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  1. Premature aging syndrome.

    Science.gov (United States)

    Coppedè, Fabio

    2012-01-01

    Hutchinson-Gilford progeria syndrome and Werner syndrome are two of the best characterized human progeroid diseases with clinical features mimicking physiological aging at an early age. Both disorders have been the focus of intense research in recent years since they might provide insights into the pathology of normal human aging. The chapter contains a detailed description of the clinical features of both disorders and then it focuses on the genetics, the resulting biochemical alterations at the protein level and the most recent findings and hypotheses concerning the molecular basis of the premature aging phenotypes. A description of available diagnostic and therapeutic approaches is included.

  2. Néstor-Guillermo progeria syndrome: a novel premature aging condition with early onset and chronic development caused by BANF1 mutations.

    Science.gov (United States)

    Cabanillas, Rubén; Cadiñanos, Juan; Villameytide, José A F; Pérez, Mercedes; Longo, Jesús; Richard, José M; Alvarez, Rebeca; Durán, Noelia S; Illán, Rafael; González, Daniel J; López-Otín, Carlos

    2011-11-01

    Progeria syndromes are rare disorders that involve premature aging. Mutations in BANF1 have been recently reported to cause a new hereditary progeroid syndrome that we now propose to call the Néstor-Guillermo progeria syndrome (NGPS). We describe herein the clinical features of the first two NGPS patients, who phenocopy features of classic progerias (i.e., Hutchinson-Gilford progeria syndrome or mandibuloacral dysplasia), such as aged appearance, growth retardation, decreased subcutaneous fat, thin limbs, and stiff joints. However, these NGPS patients have a distinctive phenotype. In their early adulthood (32 and 24 years of age), they have no signs of cardiovascular impairment, diabetes mellitus, or hypertriglyceridemia. In contrast, they suffer profound skeletal abnormalities that affect their quality of life. The observed differences are of utmost importance to patients and their families and palliation of osseous manifestations is a priority, given their relatively long lifespan. We define NGPS as a chronic progeria because of its slow clinical course and relatively long survival, despite its early onset. Understanding the differences between progeria syndromes might contribute to the development of treatment strategies for common skeletal conditions, as well as aging itself.

  3. Prematurely aged children: molecular alterations leading to Hutchinson-Gilford progeria and Werner syndromes.

    Science.gov (United States)

    Domínguez-Gerpe, Lourdes; Araújo-Vilar, David

    2008-12-01

    Ageing is thought to be a polygenic and stochastic process in which multiple mechanisms operate at the same time. At the level of the individual organism ageing is associated with a progressive deterioration of health and quality of life, sharing common features such as: alopecia and grey hair, loss of audition, macular degeneration, neurodegeneration, cardiovascular diseases, osteoporosis, cataract formation, type-2 diabetes, lipodystrophies; a generally increased susceptibility to infection, autoimmune disorders and diseases such as cancer; and an impaired ability to cope with stress. Recent studies of mechanisms involved in the ageing process are contributing to the identification of genes involved in longevity. Monogenic heritable disorders causing premature ageing, and animal models have contributed to the understanding of some of the characteristic organism-level features associated with human ageing. Werner syndrome and Hutchinson-Gilford progeria syndrome are the best characterized human disorders. Werner syndrome patients have a median life expectancy of 47 years with clinical conditions from the second decade of life. Hutchinson-Gilford progeria syndrome patients die at a median age of 11-13 years with clinical conditions appearing soon after birth. In both syndromes, alterations in specific genes have been identified, with mutations in the WRN and LMNA genes respectively being the most closely associated with each syndrome. Results from molecular studies strongly suggest an increase in DNA damage and cell senescence as the underlying mechanism of pathological premature ageing in these two human syndromes. The same general mechanism has also been observed in human cells undergoing the normal ageing process. In the present article the molecular mechanisms currently proposed for explaining these two syndromes, which may also partly explain the normal ageing process, are reviewed.

  4. LMNA-Associated Cardiocutaneous Progeria: a Novel Autosomal Dominant Premature Aging Syndrome with Late Onset

    Science.gov (United States)

    Kane, Megan S.; Lindsay, Mark E.; Judge, Daniel P.; Barrowman, Jemima; Rhys, Colette Ap; Simonson, Lisa; Dietz, Harry C.; Michaelis, Susan

    2013-01-01

    Hutchinson-Gilford Progeria Syndrome (HGPS) is a well-characterized premature aging disorder caused by mutations in LMNA, the gene encoding the nuclear scaffold proteins lamin A and C. In HGPS and related progerias, processing of prelamin A is blocked at a critical step mediated by the zinc metalloprotease ZMPSTE24. Emerging evidence indicates that LMNA-linked progerias can be grouped into two classes: 1) the processing-deficient, early onset “typical” progerias (e.g. HGPS), and 2) the processing-proficient “atypical” progeria syndromes (APS) that are later in onset. Here we describe a novel progeria syndrome with prominent cutaneous and cardiovascular manifestations belonging to the second class. We suggest the name LMNA-associated cardiocutaneous progeria syndrome (LCPS) for this disorder. Affected patients are normal at birth but undergo progressive cutaneous changes in childhood and die in middle age of cardiovascular complications, including accelerated atherosclerosis, calcific valve disease, and cardiomyopathy. In addition, the proband demonstrated cancer susceptibility, a phenotype rarely described for LMNA-based progeria disorders. The LMNA mutation that causes LCPS is a heterozygous missense mutation resulting in an amino acid substitution (D300G) in the coiled-coil domain of lamin A/C. In skin fibroblasts isolated from the proband, the processing and levels of lamin A and C are normal. However, nuclear morphology is aberrant and rescued by treatment with farnesyltransferase inhibitors (FTIs), as is also the case for HGPS and other laminopathies. Our findings advance knowledge of human LMNA progeria syndromes, and raise the possibility that typical and atypical progerias may converge upon a common mechanism to cause premature aging disease. PMID:23666920

  5. LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset.

    Science.gov (United States)

    Kane, Megan S; Lindsay, Mark E; Judge, Daniel P; Barrowman, Jemima; Ap Rhys, Colette; Simonson, Lisa; Dietz, Harry C; Michaelis, Susan

    2013-07-01

    Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disorder caused by mutations in LMNA, which encodes the nuclear scaffold proteins lamin A and C. In HGPS and related progerias, processing of prelamin A is blocked at a critical step mediated by the zinc metalloprotease ZMPSTE24. LMNA-linked progerias can be grouped into two classes: (1) the processing-deficient, early onset "typical" progerias (e.g., HGPS), and (2) the processing-proficient "atypical" progeria syndromes (APS) that are later in onset. Here we describe a previously unrecognized progeria syndrome with prominent cutaneous and cardiovascular manifestations belonging to the second class. We suggest the name LMNA-associated cardiocutaneous progeria syndrome (LCPS) for this disorder. Affected patients are normal at birth but undergo progressive cutaneous changes in childhood and die in middle age of cardiovascular complications, including accelerated atherosclerosis, calcific valve disease, and cardiomyopathy. In addition, the proband demonstrated cancer susceptibility, a phenotype rarely described for LMNA-based progeria disorders. The LMNA mutation that caused LCPS in this family is a heterozygous c.899A>G (p.D300G) mutation predicted to alter the coiled-coil domain of lamin A/C. In skin fibroblasts isolated from the proband, the processing and levels of lamin A and C are normal. However, nuclear morphology is aberrant and rescued by treatment with farnesyltransferase inhibitors, as is also the case for HGPS and other laminopathies. Our findings advance knowledge of human LMNA progeria syndromes, and raise the possibility that typical and atypical progerias may converge upon a common mechanism to cause premature aging disease.

  6. Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome

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    Heyn, Holger; Moran, Sebastian; Esteller, Manel

    2013-01-01

    DNA methylation gradiently changes with age and is likely to be involved in aging-related processes with subsequent phenotype changes and increased susceptibility to certain diseases. The Hutchinson-Gilford Progeria (HGP) and Werner Syndrome (WS) are two premature aging diseases showing features of common natural aging early in life. Mutations in the LMNA and WRN genes were associated to disease onset; however, for a subset of patients the underlying causative mechanisms remain elusive. We aimed to evaluate the role of epigenetic alteration on premature aging diseases by performing comprehensive DNA methylation profiling of HGP and WS patients. We observed profound changes in the DNA methylation landscapes of WRN and LMNA mutant patients, which were narrowed down to a set of aging related genes and processes. Although of low overall variance, non-mutant patients revealed differential DNA methylation at distinct loci. Hence, we propose DNA methylation to have an impact on premature aging diseases. PMID:23257959

  7. Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome.

    Science.gov (United States)

    Heyn, Holger; Moran, Sebastian; Esteller, Manel

    2013-01-01

    DNA methylation gradiently changes with age and is likely to be involved in aging-related processes with subsequent phenotype changes and increased susceptibility to certain diseases. The Hutchinson-Gilford Progeria (HGP) and Werner Syndrome (WS) are two premature aging diseases showing features of common natural aging early in life. Mutations in the LMNA and WRN genes were associated to disease onset; however, for a subset of patients the underlying causative mechanisms remain elusive. We aimed to evaluate the role of epigenetic alteration on premature aging diseases by performing comprehensive DNA methylation profiling of HGP and WS patients. We observed profound changes in the DNA methylation landscapes of WRN and LMNA mutant patients, which were narrowed down to a set of aging related genes and processes. Although of low overall variance, non-mutant patients revealed differential DNA methylation at distinct loci. Hence, we propose DNA methylation to have an impact on premature aging diseases.

  8. The relationship between premature ageing and immune responses in the oral cavity of Down syndrome

    Directory of Open Access Journals (Sweden)

    Yoko Tanaka

    2010-02-01

    Full Text Available Down syndrome (DS is the most common chromosomal disorder resulting in various abnormalities such as mental retardation, immunodeficiency and physical abnormities. Especially, abnormality of the immune function is important pathological features in this syndrome, and leads to increased susceptibility to viral or bacterial infections. Interestingly, several studies have showed that they have high susceptibility of severe periodontal disease, even though they have lower or equal prevalence of dental caries. Many studies have attempted to clarify this phenomenon but it remains unsolved. It is also well known that DS is a premature ageing syndrome. DS has been considered as a model of precocious, abnormal ageing of immune function in human. Age-related declines in immune function cause more susceptibility to infections in the elderly. In addition, it is well known that ageing is related with telomere shortening. Furthermore, DS has an accelerated telomere shortening. However, there are only a few reports that focus on the relations among ageing, telomere length and high susceptibility of oral infectious disease in individuals with DS. Therefore, we summarize our current knowledge on the relations between the oral disease and immunodeficiency in individuals with DS taking account of telomere shortening and ageing.

  9. Telomerase Protects Werner Syndrome Lineage-Specific Stem Cells from Premature Aging

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    Hoi-Hung Cheung

    2014-04-01

    Full Text Available Werner syndrome (WS patients exhibit premature aging predominantly in mesenchyme-derived tissues, but not in neural lineages, a consequence of telomere dysfunction and accelerated senescence. The cause of this lineage-specific aging remains unknown. Here, we document that reprogramming of WS fibroblasts to pluripotency elongated telomere length and prevented telomere dysfunction. To obtain mechanistic insight into the origin of tissue-specific aging, we differentiated iPSCs to mesenchymal stem cells (MSCs and neural stem/progenitor cells (NPCs. We observed recurrence of premature senescence associated with accelerated telomere attrition and defective synthesis of the lagging strand telomeres in MSCs, but not in NPCs. We postulate this “aging” discrepancy is regulated by telomerase. Expression of hTERT or p53 knockdown ameliorated the accelerated aging phenotypein MSC, whereas inhibition of telomerase sensitized NPCs to DNA damage. Our findings unveil a role for telomerase in the protection of accelerated aging in a specific lineage of stem cells.

  10. Radiological Diagnosis of a Rare Premature Aging Genetic Disorder: Progeria (Hutchinson-Gilford Syndrome

    Directory of Open Access Journals (Sweden)

    Haji Mohammed Nazir

    2017-01-01

    Full Text Available Hutchinson-Gilford Progeria Syndrome (HGPS is a rare disease with a combination of short stature, bone abnormalities, premature ageing, and skin changes. Though the physical appearance of these patients is characteristic, there is little emphasis on the characteristic radiological features. In this paper, we report a 16-year-old boy with clinical and radiological features of this rare genetic disorder. He had a characteristic facial appearance with a large head, large eyes, thin nose with beaked tip, small chin, protruding ears, prominent scalp veins, and absence of hair.

  11. Uremia causes premature ageing of the T cell compartment in end-stage renal disease patients

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    Meijers Ruud WJ

    2012-09-01

    Full Text Available Abstract Background End-stage renal disease (ESRD patients treated with renal replacement therapy (RRT have premature immunologically aged T cells which may underlie uremia-associated immune dysfunction. The aim of this study was to investigate whether uremia was able to induce premature ageing of the T cell compartment. For this purpose, we examined the degree of premature immunological T cell ageing by examining the T cell differentiation status, thymic output via T cell receptor excision circle (TREC content and proliferative history via relative telomere length in ESRD patients not on RRT. Results Compared to healthy controls, these patients already had a lower TREC content and an increased T cell differentiation accompanied by shorter telomeres. RRT was able to enhance CD8+ T cell differentiation and to reduce CD8+ T cell telomere length in young dialysis patients. An increased differentiation status of memory CD4+ T cells was also noted in young dialysis patients. Conclusion Based on these results we can conclude that uremia already causes premature immunological ageing of the T cell system and RRT further increases immunological ageing of the CD8+ T cell compartment in particular in young ESRD patients.

  12. Investigation into the human premature ageing disease, Hutchinson Gilford Progeria syndrome, using hTERT immortalised fibroblasts

    OpenAIRE

    Worthington, Gemma Louise

    2016-01-01

    This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London Hutchinson Gilford Progeria syndrome (HGPS) is a rare premature ageing disease affecting children. 80% of “classic” HGPS patients share the same mutation in the LMNA gene that gives rise to characteristics similar to normal human ageing and they usually die in their teens from heart attacks or strokes. Cells taken from progeria patients have a short replicative lifespan in culture an...

  13. Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective.

    Science.gov (United States)

    Cau, Pierre; Navarro, Claire; Harhouri, Karim; Roll, Patrice; Sigaudy, Sabine; Kaspi, Elise; Perrin, Sophie; De Sandre-Giovannoli, Annachiara; Lévy, Nicolas

    2014-05-01

    Lamin A-related progeroid syndromes are genetically determined, extremely rare and severe. In the past ten years, our knowledge and perspectives for these diseases has widely progressed, through the progressive dissection of their pathophysiological mechanisms leading to precocious and accelerated aging, from the genes mutations discovery until therapeutic trials in affected children. A-type lamins are major actors in several structural and functional activities at the nuclear periphery, as they are major components of the nuclear lamina. However, while this is usually poorly considered, they also play a key role within the rest of the nucleoplasm, whose defects are related to cell senescence. Although nuclear shape and nuclear envelope deformities are obvious and visible events, nuclear matrix disorganization and abnormal composition certainly represent the most important causes of cell defects with dramatic pathological consequences. Therefore, lamin-associated diseases should be better referred as laminopathies instead of envelopathies, this later being too restrictive, considering neither the key structural and functional roles of soluble lamins in the entire nucleoplasm, nor the nuclear matrix contribution to the pathophysiology of lamin-associated disorders and in particular in defective lamin A processing-associated aging diseases. Based on both our understanding of pathophysiological mechanisms and the biological and clinical consequences of progeria and related diseases, therapeutic trials have been conducted in patients and were terminated less than 10 years after the gene discovery, a quite fast issue for a genetic disease. Pharmacological drugs have been repurposed and used to decrease the toxicity of the accumulated, unprocessed and truncated prelaminA in progeria. To date, none of them may be considered as a cure for progeria and these clinical strategies were essentially designed toward reducing a subset of the most dramatic and morbid features

  14. Mutations in EXOSC2 are associated with a novel syndrome characterised by retinitis pigmentosa, progressive hearing loss, premature ageing, short stature, mild intellectual disability and distinctive gestalt.

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    Di Donato, Nataliya; Neuhann, Teresa; Kahlert, Anne-Karin; Klink, Barbara; Hackmann, Karl; Neuhann, Irmingard; Novotna, Barbora; Schallner, Jens; Krause, Claudia; Glass, Ian A; Parnell, Shawn E; Benet-Pages, Anna; Nissen, Anke M; Berger, Wolfgang; Altmüller, Janine; Thiele, Holger; Weber, Bernhard H F; Schrock, Evelin; Dobyns, William B; Bier, Andrea; Rump, Andreas

    2016-06-01

    Retinitis pigmentosa in combination with hearing loss can be a feature of different Mendelian disorders. We describe a novel syndrome caused by biallelic mutations in the 'exosome component 2' (EXOSC2) gene. Clinical ascertainment of three similar affected patients followed by whole exome sequencing. Three individuals from two unrelated German families presented with a novel Mendelian disorder encompassing childhood myopia, early onset retinitis pigmentosa, progressive sensorineural hearing loss, hypothyroidism, short stature, brachydactyly, recognisable facial gestalt, premature ageing and mild intellectual disability. Whole exome sequencing revealed homozygous or compound heterozygous missense variants in the EXOSC2 gene in all three patients. EXOSC2 encodes the 'ribosomal RNA-processing protein 4' (RRP4)-one of the core components of the RNA exosome. The RNA exosome is a multiprotein complex that plays key roles in RNA processing and degradation. Intriguingly, the EXOSC2-associated phenotype shows only minimal overlap with the previously reported diseases associated with mutations in the RNA exosome core component genes EXOSC3 and EXOSC8. We report a novel condition that is probably caused by altered RNA exosome function and expands the spectrum of clinical consequences of impaired RNA metabolism. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. Progeria: A rare genetic premature ageing disorder

    OpenAIRE

    Jitendra Kumar Sinha; Shampa Ghosh; Manchala Raghunath

    2014-01-01

    Progeria is characterized by clinical features that mimic premature ageing. Although the mutation responsible for this syndrome has been deciphered, the mechanism of its action remains elusive. Progeria research has gained momentum particularly in the last two decades because of the possibility of revealing evidences about the ageing process in normal and other pathophysiological conditions. Various experimental models, both in vivo and in vitro, have been developed in an effort to understand...

  16. Increased release and activity of matrix metalloproteinase-9 in patients with mandibuloacral dysplasia type A, a rare premature ageing syndrome.

    Science.gov (United States)

    Lombardi, F; Fasciglione, G F; D'Apice, M R; Vielle, A; D'Adamo, M; Sbraccia, P; Marini, S; Borgiani, P; Coletta, M; Novelli, G

    2008-10-01

    Mandibuloacral dysplasia type A (MADA; OMIM 248370), a rare disorder caused by mutation in the LMNA gene, is characterized by post-natal growth retardation, craniofacial and skeletal anomalies (mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of cranial sutures, low bone mass and joint contractures), cutaneous changes and partial lipodystrophy. Little is known about the molecular mechanisms by which LMNA mutations produce bone alterations. An altered bone extracellular matrix (ECM) remodelling could play a pivotal role in this disorder and influence part of the typical bone phenotype observed in patients. Therefore, we have focused our investigation on matrix metalloproteinases (MMPs), which are degradative enzymes involved in ECM degradation and ECM remodelling, thus likely contributing to the altered bone mineral density and bone metabolism values seen in five MADA patients. We evaluated the serum levels of several MMPs involved in bone development, remodelling and homeostasis, such as MMP-9, -2, -3, -8 and -13, and found that only the 82 kDa active enzyme forms of MMP-9 are significantly higher in MADA sera compared with healthy controls (n = 16). The serum level of MMP-3 was instead lower in all patients. No significant differences were observed between controls and MADA patients for the serum levels of MMP-2, -8 and -13 and of tissue inhibitor of metalloproteinase 2, a natural inhibitor of MMP-9. Similarly, normal serum levels of tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-6 and IL-1beta were detected. These data suggest a possible involvement of MMP-9 in MADA disease, underlying the potential use in diagnosis and therapy.

  17. Accumulation of Mutant Lamin A Causes Progressive Changes in Nuclear Architecture in Hutchinson-Gilford Progeria Syndrome

    National Research Council Canada - National Science Library

    Robert D. Goldman; Dale K. Shumaker; Michael R. Erdos; Maria Eriksson; Anne E. Goldman; Leslie B. Gordon; Yosef Gruenbaum; Satya Khuon; Melissa Mendez; Renée Varga; Francis S. Collins

    2004-01-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder, commonly caused by a point mutation in the lamin A gene that results in a protein lacking 50 aa near the C terminus, denoted LAΔ50...

  18. Progeria: a rare genetic premature ageing disorder.

    Science.gov (United States)

    Sinha, Jitendra Kumar; Ghosh, Shampa; Raghunath, Manchala

    2014-05-01

    Progeria is characterized by clinical features that mimic premature ageing. Although the mutation responsible for this syndrome has been deciphered, the mechanism of its action remains elusive. Progeria research has gained momentum particularly in the last two decades because of the possibility of revealing evidences about the ageing process in normal and other pathophysiological conditions. Various experimental models, both in vivo and in vitro, have been developed in an effort to understand the cellular and molecular basis of a number of clinically heterogeneous rare genetic disorders that come under the umbrella of progeroid syndromes (PSs). As per the latest clinical trial reports, Lonafarnib, a farnesyltranferase inhibitor, is a potent 'drug of hope' for Hutchinson-Gilford progeria syndrome (HGPS) and has been successful in facilitating weight gain and improving cardiovascular and skeletal pathologies in progeroid children. This can be considered as the dawn of a new era in progeria research and thus, an apt time to review the research developments in this area highlighting the molecular aspects, experimental models, promising drugs in trial and their implications to gain a better understanding of PSs.

  19. Progeria: A rare genetic premature ageing disorder

    Directory of Open Access Journals (Sweden)

    Jitendra Kumar Sinha

    2014-01-01

    Full Text Available Progeria is characterized by clinical features that mimic premature ageing. Although the mutation responsible for this syndrome has been deciphered, the mechanism of its action remains elusive. Progeria research has gained momentum particularly in the last two decades because of the possibility of revealing evidences about the ageing process in normal and other pathophysiological conditions. Various experimental models, both in vivo and in vitro, have been developed in an effort to understand the cellular and molecular basis of a number of clinically heterogeneous rare genetic disorders that come under the umbrella of progeroid syndromes (PSs. As per the latest clinical trial reports, Lonafarnib, a farnesyltranferase inhibitor, is a potent ′drug of hope′ for Hutchinson-Gilford progeria syndrome (HGPS and has been successful in facilitating weight gain and improving cardiovascular and skeletal pathologies in progeroid children. This can be considered as the dawn of a new era in progeria research and thus, an apt time to review the research developments in this area highlighting the molecular aspects, experimental models, promising drugs in trial and their implications to gain a better understanding of PSs.

  20. The epidemiology of premature aging and associated comorbidities

    Directory of Open Access Journals (Sweden)

    Coppedè F

    2013-08-01

    Full Text Available Fabio Coppedè Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy Abstract: Hutchinson–Gilford Progeria Syndrome and Werner syndrome, also known as childhood- and adulthood-progeria, respectively, represent two of the best characterized human progeroid diseases with clinical features mimicking physiological aging at an early age. The discovery of their genetic basis has led to the identification of several gene mutations leading to a spectrum of progeroid phenotypes ranging from moderate and mild–severe to very aggressive forms. In parallel, the creation of disease registers and databases provided available data for the design of relatively large-scale epidemiological studies, thereby allowing a better understanding of the nature and frequency of the premature aging-associated signs and symptoms. The aim of this article is to review the most recent findings concerning the epidemiology of premature aging disorders, their genetic basis, and the most recent reports on the frequency of associated diseases. Keywords: Hutchinson–Gilford Progeria Syndrome, Werner syndrome, premature aging disorders, epidemiology, cardiovascular diseases, cancer, atherosclerosis, genetics, sign and symptoms

  1. What Causes Down Syndrome?

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    ... Information Clinical Trials Resources and Publications What causes Down syndrome? Skip sharing on social media links Share this: ... Down Syndrome Registry​ . Chromosomal Changes That Can Cause Down Syndrome Research shows that three types of chromosomal changes ...

  2. Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson–Gilford progeria syndrome

    National Research Council Canada - National Science Library

    Leslie B. Gordon; Monica E. Kleinman; David T. Miller; Donna S. Neuberg; Anita Giobbie-Hurder; Marie Gerhard-Herman; Leslie B. Smoot; Catherine M. Gordon; Robert Cleveland; Brian D. Snyder; Brian Fligor; W. Robert Bishop; Paul Statkevich; Amy Regen; Andrew Sonis; Susan Riley; Christine Ploski; Annette Correia; Nicolle Quinn; Nicole J. Ullrich; Ara Nazarian; Marilyn G. Liang; Susanna Y. Huh; Armin Schwartzman; Mark W. Kieran

    2012-01-01

    Hutchinson–Gilford progeria syndrome (HGPS) is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA that produces the farnesylated aberrant lamin A protein, progerin...

  3. Premature aging in telomerase-deficient zebrafish

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    Monique Anchelin

    2013-09-01

    The study of telomere biology is crucial to the understanding of aging and cancer. In the pursuit of greater knowledge in the field of human telomere biology, the mouse has been used extensively as a model. However, there are fundamental differences between mouse and human cells. Therefore, additional models are required. In light of this, we have characterized telomerase-deficient zebrafish (Danio rerio as the second vertebrate model for human telomerase-driven diseases. We found that telomerase-deficient zebrafish show p53-dependent premature aging and reduced lifespan in the first generation, as occurs in humans but not in mice, probably reflecting the similar telomere length in fish and humans. Among these aging symptoms, spinal curvature, liver and retina degeneration, and infertility were the most remarkable. Although the second-generation embryos died in early developmental stages, restoration of telomerase activity rescued telomere length and survival, indicating that telomerase dosage is crucial. Importantly, this model also reproduces the disease anticipation observed in humans with dyskeratosis congenita (DC. Thus, telomerase haploinsufficiency leads to anticipation phenomenon in longevity, which is related to telomere shortening and, specifically, with the proportion of short telomeres. Furthermore, p53 was induced by telomere attrition, leading to growth arrest and apoptosis. Importantly, genetic inhibition of p53 rescued the adverse effects of telomere loss, indicating that the molecular mechanisms induced by telomere shortening are conserved from fish to mammals. The partial rescue of telomere length and longevity by restoration of telomerase activity, together with the feasibility of the zebrafish for high-throughput chemical screening, both point to the usefulness of this model for the discovery of new drugs able to reactivate telomerase in individuals with DC.

  4. Molecular insights into the premature aging disease progeria.

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    Vidak, Sandra; Foisner, Roland

    2016-04-01

    Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare premature aging disease presenting many features resembling the normal aging process. HGPS patients die before the age of 20 years due to cardiovascular problems and heart failure. HGPS is linked to mutations in the LMNA gene encoding the intermediate filament protein lamin A. Lamin A is a major component of the nuclear lamina, a scaffold structure at the nuclear envelope that defines mechanochemical properties of the nucleus and is involved in chromatin organization and epigenetic regulation. Lamin A is also present in the nuclear interior where it fulfills lamina-independent functions in cell signaling and gene regulation. The most common LMNA mutation linked to HGPS leads to mis-splicing of the LMNA mRNA and produces a mutant lamin A protein called progerin that tightly associates with the inner nuclear membrane and affects the dynamic properties of lamins. Progerin expression impairs many important cellular processes providing insight into potential disease mechanisms. These include changes in mechanosignaling, altered chromatin organization and impaired genome stability, and changes in signaling pathways, leading to impaired regulation of adult stem cells, defective extracellular matrix production and premature cell senescence. In this review, we discuss these pathways and their potential contribution to the disease pathologies as well as therapeutic approaches used in preclinical and clinical tests.

  5. Premature aging and cancer in nucleotide excision repair-disorders

    NARCIS (Netherlands)

    K.E.M. Diderich (Karin); M. Alanazi; J.H.J. Hoeijmakers (Jan)

    2011-01-01

    textabstractDuring the past decades, the major impact of DNA damage on cancer as 'disease of the genes' has become abundantly apparent. In addition to cancer, recent years have also uncovered a very strong association of DNA damage with many features of (premature) aging. The notion that DNA repair

  6. Werner综合征小鼠模型在早衰与肿瘤研究中的应用%Utilization of Werner syndrome mouse model in studying premature aging and tumor

    Institute of Scientific and Technical Information of China (English)

    贾舒婷; 杨世华; 罗瑛

    2009-01-01

    Werner综合征(Werner syndrome,ws)是一种罕见的人类常染色体隐性遗传疾病,一直以来该病作为研究人类早老综合征的典型病例而受到关注.Werner蛋白(WRN)是Werner综合征中突变的核蛋白,最近的生化及遗传学研究证明WRN在DNA复制,DNA损伤修复以及端粒的维持方面起着重要的作用.文章综述了Wemer综合征的分子遗传学机理及端粒和WRN在Werner综合征发病中的重要作用.通过双敲除Wrn与端粒酶基因建立的小鼠模型忠实地再现了人类Werner综合征,这种Werner综合征小鼠模型因其同时具有早衰与肿瘤表型而在研究人类肿瘤及衰老的相关性中起到的独特作用.

  7. Restless Legs Syndrome -- Causes and Symptoms

    Science.gov (United States)

    ... Overview & Facts Causes & Symptoms Self-Tests & Diagnosis Treatment Restless Legs Syndrome - Causes & Symptoms Causes What causes of restless legs syndrome varies from person to person. In some cases ...

  8. Premature ageing prevention: limitations and perspectives of pharmacological interventions.

    Science.gov (United States)

    Anisimov, Vladimir N

    2006-11-01

    A significant increase of the elderly in populations of developed countries is followed by increase morbidity and mortality from main age-related diseases--cardiovascular and neuro-degenerative, cancer, diabetes mellitus, declining in a resistance to infections. Obviously, the development of means of the prevention of the premature ageing and these diseases in humans are crucial at present. However, data on such type means rather scarce, contradictory and often not reliable from the points of view of the adequacy of the experiments to current scientific requirements, as well as the interpretation of the results and safety. Available data on the life span extension and adverse effects of chemical compounds and drugs suggested as geroprotectors are critically analyzed: antidiabetic drugs, growth and thyroid hormones, glucocorticoids, DHEA, sex steroids and contraceptives, melatonin and peptide preparations modulating the pineal gland, antioxidants, chelate agents and lathyrogens, adaptogens and herbs, neurotropic drugs, inhibitors of monoamine oxidase, immunomodulators and some other. Most of the results could not convincingly evidence the life span extension and safety of the suggested geroprotectors. We believe that it is necessary to establish an international program for the expert evaluation of the life span extension potential of pharmacological interventions for humans. The scope of the program should be to evaluate chemical, immunological, dietary and behavioural interventions that may lead to life span extension or retard premature ageing and the objective--preparation of critical reviews and evaluations on evidence of the life span extending properties of a wide range of potential geroprotectors and strategies by international groups of working experts. The program may assist national and international authorities in devising programs of health promotion and premature ageing prevention.

  9. Sjogren's Syndrome: Can It Cause Recurrent UTIs?

    Science.gov (United States)

    ... it cause recurrent UTIs? Since being diagnosed with Sjogren's syndrome last year, I've had three urinary tract infections. Is there any evidence that Sjogren's syndrome causes recurrent UTIs? Answers from April Chang-Miller, ...

  10. Ataxia-telangiectasia (A-T): An emerging dimension of premature ageing.

    Science.gov (United States)

    Shiloh, Yosef; Lederman, Howard M

    2017-01-01

    A-T is a prototype genome instability syndrome and a multifaceted disease. A-T leads to neurodegeneration - primarily cerebellar atrophy, immunodeficiency, oculocutaneous telangiectasia (dilated blood vessels), vestigial thymus and gonads, endocrine abnormalities, cancer predisposition and varying sensitivity to DNA damaging agents, particularly those that induce DNA double-strand breaks. With the recent increase in life expectancy of A-T patients, the premature ageing component of this disease is gaining greater awareness. The complex A-T phenotype reflects the ever growing number of functions assigned to the protein encoded by the responsible gene - the homeostatic protein kinase, ATM. The quest to thoroughly understand the complex A-T phenotype may reveal yet elusive ATM functions. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Vanishing honey bees: Is the dying of adult worker bees a consequence of short telomeres and premature aging?

    Science.gov (United States)

    Stindl, Reinhard; Stindl, Wolfgang

    2010-10-01

    Einstein is often quoted to have said that without the bee, mankind would have but 4years to live. It is highly unlikely that he made this comment, which was even mentioned in a Lancet article on honey bees. However, the current vanishing of the bees can have serious consequences for human health, because 35% of the human diet is thought to benefit from pollination. Colony collapse disorder (CCD) in honey bees is characterized by the rapid decline of the adult bee population, leaving the brood and the queen poorly or completely unattended, with no dead bodies in or around the hive. A large study found no evidence that the presence or amount of any individual pesticide or infectious agent occurred more frequently or abundantly in CCD-affected colonies. The growing consensus is that honey bees are suffering from comprised immune systems, which allow various infectious pathogens to invade. The question remains, what causes immunosuppression in many colonies of Apis mellifera in North America and Europe? Telomeres are protective DNA structures located at eukaryotic chromosome tips that shorten in the somatic tissues of animals with age. Lifelong tissue regeneration takes place in Apis mellifera, and worker bees have been shown to senesce. In humans, a vast amount of literature has accumulated on exhausted telomere reserves causing impaired tissue regeneration and age-associated diseases, specifically cancer and immunosuppression. Therefore, we propose a new causative mechanism for the vanishing of the bees: critically short telomeres in long-lived winter bees. We term this the telomere premature aging syndrome. Copyright 2010 Elsevier Ltd. All rights reserved.

  12. Radiation nephritis causing nephrotic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Jennette, J.C.; Ordonez, N.G.

    1983-12-01

    Clinical symptoms of acute radiation nephritis with nephrotic syndrome developed in a fifty-six-year-old woman after abdominal radiation therapy for an astrocytoma of the spinal cord. The diagnosis of radiation nephritis was confirmed by renal biopsy. To our knowledge, this is the first documented case of radiation nephritis associated with nephrotic syndrome.

  13. The Reasons and Prevention of Ovarian Premature Aging%卵巢早衰的原因与预防

    Institute of Scientific and Technical Information of China (English)

    李莉

    2014-01-01

    Objective To analyze the factors that cause ovarian premature aging so as to provide a basis for clinical prevention and treatment of ovarian premature aging. Methods A questionnaire was used to investigate the 100 cases in the observation group and the control group, and the data was treated by logistic regression analysis. Results 12 variables such as the number of induced abortion, drinking, smoking, marital status, family and social relationship, bean products, mood, taking corticosteroids and so on are related to the occurrence of ovarian premature aging. Multiple factors analysis showed that marital status (OR = 6.03), number of induced abortion (OR = 2.14), smoking (OR =3.26), hair coloring (OR =2.74), mood (OR= 0.16), vegetables (OR = 0.34), mumps (OR = 10.23), and other factors are closely associated with ovarian premature aging. Conclusion Many factors can cause ovarian premature aging, so effective measures should be taken clinically to strengthen the prevention and treatment, thereby reducing the incidence of the disease and promoting the recovery of the patients as early as possible.%目的:分析卵巢早衰发生因素,为临床卵巢早衰的防治提供一定的依据。方法采用问卷调查方式对观察组和健康对照组共100例进行logistic回归分析。结果卵巢早衰发生因素与人工流产次数、饮酒、吸烟、婚姻状况以及家人社会相处关系、豆制品、心情和服用糖皮质激素等12个变量相关。多因素分析表明,婚姻状况(OR=6.03)、人工流产次数(OR=2.14)、吸烟(OR=3.26)、染发(OR=2.74)、心情(OR=0.16)、蔬菜(OR=0.34)、腮腺炎(OR=10.23)等因素与卵巢早衰密切相关。结论卵巢早衰发生因素较多,临床应采取有效的措施加强预防,治疗,以降低发病率,促进患者早日康复。

  14. Hydrogen sulfide restores a normal morphological phenotype in Werner syndrome fibroblasts, attenuates oxidative damage and modulates mTOR pathway

    NARCIS (Netherlands)

    Talaei, F.; van Praag, V. M.; Henning, R. H.

    2013-01-01

    Werner syndrome (WS) protein is involved in DNA repair and its truncation causes Werner syndrome, an autosomal recessive genetic disorder with a premature aging phenotype. WRN protein mutation is currently known as the primary cause of WS. In cultured WS fibroblasts, we found an increase in cytosoli

  15. Hydrogen sulfide restores a normal morphological phenotype in Werner syndrome fibroblasts, attenuates oxidative damage and modulates mTOR pathway

    NARCIS (Netherlands)

    Talaei, F.; van Praag, V. M.; Henning, R. H.

    2013-01-01

    Werner syndrome (WS) protein is involved in DNA repair and its truncation causes Werner syndrome, an autosomal recessive genetic disorder with a premature aging phenotype. WRN protein mutation is currently known as the primary cause of WS. In cultured WS fibroblasts, we found an increase in cytosoli

  16. Muscle wasting in myotonic dystrophies: a model of premature aging.

    Science.gov (United States)

    Mateos-Aierdi, Alba Judith; Goicoechea, Maria; Aiastui, Ana; Fernández-Torrón, Roberto; Garcia-Puga, Mikel; Matheu, Ander; López de Munain, Adolfo

    2015-01-01

    Myotonic dystrophy type 1 (DM1 or Steinert's disease) and type 2 (DM2) are multisystem disorders of genetic origin. Progressive muscular weakness, atrophy and myotonia are the most prominent neuromuscular features of these diseases, while other clinical manifestations such as cardiomyopathy, insulin resistance and cataracts are also common. From a clinical perspective, most DM symptoms are interpreted as a result of an accelerated aging (cataracts, muscular weakness and atrophy, cognitive decline, metabolic dysfunction, etc.), including an increased risk of developing tumors. From this point of view, DM1 could be described as a progeroid syndrome since a notable age-dependent dysfunction of all systems occurs. The underlying molecular disorder in DM1 consists of the existence of a pathological (CTG) triplet expansion in the 3' untranslated region (UTR) of the Dystrophia Myotonica Protein Kinase (DMPK) gene, whereas (CCTG)n repeats in the first intron of the Cellular Nucleic acid Binding Protein/Zinc Finger Protein 9 (CNBP/ZNF9) gene cause DM2. The expansions are transcribed into (CUG)n and (CCUG)n-containing RNA, respectively, which form secondary structures and sequester RNA-binding proteins, such as the splicing factor muscleblind-like protein (MBNL), forming nuclear aggregates known as foci. Other splicing factors, such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of downstream genes linked to the clinical features of these diseases. Skeletal muscle regeneration relies on muscle progenitor cells, known as satellite cells, which are activated after muscle damage, and which proliferate and differentiate to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction seems to be a common feature of both age-dependent muscle degeneration (sarcopenia) and muscle wasting in DM and other muscle degenerative diseases. This review aims to describe the cellular, molecular and macrostructural processes involved in the muscular

  17. Muscle wasting in myotonic dystrophies: a model of premature aging.

    Directory of Open Access Journals (Sweden)

    Alba Judith eMateos-Aierdi

    2015-07-01

    Full Text Available Myotonic dystrophy type I (DM1 or Steinert’s disease and type II (DM2 are multisystem disorders of genetic origin. Progressive muscular weakness, atrophy and myotonia are the most prominent neuromuscular features of these diseases, and other clinical manifestations such as cardiomyopathy, insulin-resistance and cataracts are also common. From a clinical perspective, most DM symptoms are interpreted as a result of an accelerated aging (cataracts, muscular weakness and atrophy, cognitive decline, metabolic dysfunction, etc., including an increased risk of developing tumors. From this point of view, DM1 could be described as a progeroid syndrome since a notable age-dependent dysfunction of all systems occurs. The underlying molecular disorder in DM1 consists of the existence of a pathological (CTGn triplet expansion in the 3’ untranslated region of the DMPK gene, whereas (CCTGn repeats in the first intron of the CNBP/ZNF9 gene cause DM2. The expansions are transcribed into (CUGn and (CCUGn-containing RNA, respectively, which form secondary structures and sequester RNA-binding proteins, such as the splicing factor muscleblind-like protein (MBNL, forming nuclear aggregates known as foci. Other splicing factors, such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of downstream genes linked to the clinical features of these diseases. Skeletal muscle regeneration relies on muscle progenitor cells, known as satellite cells, which are activated after muscle damage, and which proliferate and differentiate to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction seems to be a common feature of both age-dependent muscle degeneration (sarcopenia and muscle wasting in DM and other muscle degenerative diseases. This review aims to describe the cellular, molecular and macrostructural processes involved in the muscular degeneration seen in DM patients, highlighting the similarities found with muscle aging.

  18. Acute compartment syndrome caused by uncontrolled hypothyroidism.

    Science.gov (United States)

    Modi, Anar; Amin, Hari; Salzman, Matthew; Morgan, Farah

    2017-06-01

    Acute compartment syndrome is increased tissue pressure exceeding perfusion pressure in a closed compartment resulting in nerve and muscle ischemia. Common precipitating causes are crush injuries, burns, substance abuse, osseous or vascular limb trauma. This is a case of 42year old female with history of hypothyroidism who presented to emergency room with acute onset of severe pain and swelling in right lower extremity. Physical examination was concerning for acute compartment syndrome of right leg which was confirmed by demonstration of elevated compartmental pressures. No precipitating causes were readily identified. Further laboratory testing revealed uncontrolled hypothyroidism. Management included emergent fasciotomy and initiating thyroid hormone replacement. This case represents a rare association between acute compartment syndrome and uncontrolled hypothyroidism. We also discuss the pathogenesis of compartment syndrome in hypothyroid patients and emphasize the importance of evaluating for less common causes, particularly in setting of non-traumatic compartment syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Transformation Resistance in a Premature Aging Disorder Identifies a Tumor-Protective Function of BRD4

    Directory of Open Access Journals (Sweden)

    Patricia Fernandez

    2014-10-01

    Full Text Available Advanced age and DNA damage accumulation are prominent risk factors for cancer. The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS provides a unique opportunity for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neoplastic transformation. Resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells, leading to inhibition of oncogenic dedifferentiation. BRD4 also inhibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals. BRD4-mediated tumor protection is clinically relevant given that a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific roles for BRD4 in tumorigenesis.

  20. Mutations in ANTXR1 Cause GAPO Syndrome

    NARCIS (Netherlands)

    Stranecky, V.; Hoischen, A.; Hartmannova, H.; Zaki, M.S.; Chaudhary, A.; Zudaire, E.; Noskova, L.; Baresova, V.; Pristoupilova, A.; Hodanova, K.; Sovova, J.; Hulkova, H.; Piherova, L.; Hehir-Kwa, J.Y.; Silva, D. De; Senanayake, M.P.; Farrag, S.; Zeman, J.; Martasek, P.; Baxova, A.; Afifi, H.H.; Croix, B. St.; Brunner, H.G.; Temtamy, S.; Kmoch, S.

    2013-01-01

    The genetic cause of GAPO syndrome, a condition characterized by growth retardation, alopecia, pseudoanodontia, and progressive visual impairment, has not previously been identified. We studied four ethnically unrelated affected individuals and identified homozygous nonsense mutations (c.262C>T [

  1. Prelamin A accumulation and stress conditions induce impaired Oct-1 activity and autophagy in prematurely aged human mesenchymal stem cell.

    Science.gov (United States)

    Infante, Arantza; Gago, Andrea; de Eguino, Garbiñe Ruiz; Calvo-Fernández, Teresa; Gómez-Vallejo, Vanessa; Llop, Jordi; Schlangen, Karin; Fullaondo, Ane; Aransay, Ana M; Martín, Abraham; Rodríguez, Clara I

    2014-04-01

    Aging, a time-dependent functional decline of biological processes, is the primary risk factor in developing diseases such as cancer, cardiovascular or degenerative diseases. There is a real need to understand the human aging process in order to increase the length of disease-free life, also known as "health span". Accumulation of progerin and prelamin A are the hallmark of a group of premature aging diseases but have also been found during normal cellular aging strongly suggesting similar mechanisms between healthy aging and LMNA-linked progeroid syndromes. How this toxic accumulation contributes to aging (physiological or pathological) remains unclear. Since affected tissues in age-associated disorders and in pathological aging are mainly of mesenchymal origin we propose a model of human aging based on mesenchymal stem cells (hMSCs) which accumulate prelamin A. We demonstrate that prelamin A-accumulating hMSCs have a premature aging phenotype which affects their functional competence in vivo. The combination of prelamin A accumulation and stress conditions enhance the aging phenotype by dysregulating the activity of the octamer binding protein Oct-1This experimental model has been fundamental to identify a new role for Oct-1 in hMSCs aging.

  2. Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Goldman, Robert D; Shumaker, Dale K; Erdos, Michael R; Eriksson, Maria; Goldman, Anne E; Gordon, Leslie B; Gruenbaum, Yosef; Khuon, Satya; Mendez, Melissa; Varga, Renée; Collins, Francis S

    2004-06-15

    Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder, commonly caused by a point mutation in the lamin A gene that results in a protein lacking 50 aa near the C terminus, denoted LADelta50. Here we show by light and electron microscopy that HGPS is associated with significant changes in nuclear shape, including lobulation of the nuclear envelope, thickening of the nuclear lamina, loss of peripheral heterochromatin, and clustering of nuclear pores. These structural defects worsen as HGPS cells age in culture, and their severity correlates with an apparent increase in LADelta50. Introduction of LADelta50 into normal cells by transfection or protein injection induces the same changes. We hypothesize that these alterations in nuclear structure are due to a concentration-dependent dominant-negative effect of LADelta50, leading to the disruption of lamin-related functions ranging from the maintenance of nuclear shape to regulation of gene expression and DNA replication.

  3. Chronic Fatigue Syndrome (CFS): Causes

    Science.gov (United States)

    ... patients and in persons with related disorders like fibromyalgia. Cortisol suppresses inflammation and cellular immune activation, and ... 1994 Case Definition Causes Who's at Risk? Symptoms Diagnosis Patient Examination Process Step 1 Step 2 Step ...

  4. A rare cause of Cushing's syndrome

    DEFF Research Database (Denmark)

    Folkestad, Lars; Andersen, Marianne Skovsager; Nielsen, Anne Lerberg;

    2014-01-01

    Excess glucocorticoid levels cause Cushing's syndrome (CS) and may be due to pituitary, adrenal or ectopic tumours. Adrenocorticotropic hormone (ACTH) levels are useful in identifying adrenal tumours. In rare cases, ACTH-producing phaeochromocytomas are the cause of CS. We present two cases of ACTH...

  5. Premature aging in mice activates a systemic metabolic response involving autophagy induction.

    Science.gov (United States)

    Mariño, Guillermo; Ugalde, Alejandro P; Salvador-Montoliu, Natalia; Varela, Ignacio; Quirós, Pedro M; Cadiñanos, Juan; van der Pluijm, Ingrid; Freije, José M P; López-Otín, Carlos

    2008-07-15

    Autophagy is a highly regulated intracellular process involved in the turnover of most cellular constituents and in the maintenance of cellular homeostasis. It is well-established that the basal autophagic activity of living cells decreases with age, thus contributing to the accumulation of damaged macromolecules during aging. Conversely, the activity of this catabolic pathway is required for lifespan extension in animal models such as Caenorhabditis elegans and Drosophila melanogaster. In this work, we describe the unexpected finding that Zmpste24-null mice, which show accelerated aging and are a reliable model of human Hutchinson-Gilford progeria, exhibit an extensive basal activation of autophagy instead of the characteristic decline in this process occurring during normal aging. We also show that this autophagic increase is associated with a series of changes in lipid and glucose metabolic pathways, which resemble those occurring in diverse situations reported to prolong lifespan. These Zmpste24(-/-) mice metabolic alterations are also linked to substantial changes in circulating blood parameters, such as leptin, glucose, insulin or adiponectin which in turn lead to peripheral LKB1-AMPK activation and mTOR inhibition. On the basis of these results, we propose that nuclear abnormalities causing premature aging in Zmpste24(-/-) mice trigger a metabolic response involving the activation of autophagy. However, the chronic activation of this catabolic pathway may turn an originally intended pro-survival strategy into a pro-aging mechanism and could contribute to the systemic degeneration and weakening observed in these progeroid mice.

  6. Genetics Home Reference: Werner syndrome

    Science.gov (United States)

    ... for This Condition Adult premature aging syndrome Adult Progeria Werner's Syndrome Werners Syndrome WS Related Information How ... BK, Monnat RJ Jr. Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human progeroid diseases. Nat ...

  7. Hutchinson-Gilford progeria syndrome caused by an LMNA mutation: a case report.

    Science.gov (United States)

    Chu, Yan; Xu, Zi-Gang; Xu, Zhe; Ma, Lin

    2015-01-01

    Hutchinson-Gilford progeria syndrome is a rare genetic disorder characterized by premature aging of the skin, bones, heart, and blood vessels. We report a 6-year-old boy who was born at full term but presented with scleroderma-like appearance at 1 month of age and gradually developed clinical manifestations of progeria. He had characteristic facial features of prominent eyes, scalp, and leg veins; loss of scalp hair, eyebrows, and eyelashes; stunted growth; scleroderma-like changes of the skin; and a premature aged appearance. Metabolic investigations showed transient methylmalonic aciduria, and genetic testing of the peripheral blood identified the c.1824C>T heterozygous LMNA mutation. The present case is reported because of its rarity.

  8. An uncommon cause of anaemia: Sheehan's syndrome.

    Science.gov (United States)

    Melchardt, Thomas; Namberger, Konrad; Weiss, Lukas; Egle, Alexander; Faber, Viktoria; Greil, Richard

    2010-12-01

    Ischemic pituitary necrosis due to severe postpartum haemorrhage called Sheehan's syndrome is a rare cause of hypopituitarism in the western world, but much more common in developing countries. A 45-year-old female patient being a war refugee from Chechnya with severe anaemia and fatigue was diagnosed at our outpatient department with Sheehan's syndrome after severe postpartum haemorrhage and emergency hysterectomy 15 years ago. Panhypopituitarism was adequately treated with substitution of hydrocortisone, thyroxine and transdermal oestrogen which resulted in haemoglobin increase to nearly normal levels and symptoms improved immediately. Severe anaemia caused by panhypopituitarism shows the importance of the hormonal system for erythropoiesis. Clinical and basic scientific evidence indicates thyroidal hormones to be the main cause.

  9. Superior mesenteric artery syndrome causing growth retardation

    Directory of Open Access Journals (Sweden)

    Halil İbrahim Taşcı

    2013-03-01

    Full Text Available Superior mesenteric artery syndrome is a rare and lifethreateningclinical condition caused by the compressionof the third portion of the duodenum between the aortaand the superior mesenteric artery’s proximal part. Thiscompression may lead to chronic intermittent, acute totalor partial obstruction. Sudden weight-loss and the relateddecrease in the fat tissue are considered to be the etiologicalreason of acute stenosis. Weight-loss accompaniedby nausea, vomiting, anorexia, epigastric pain, andbloating are the leading complaints. Barium radiographs,computerized tomography, conventional angiography,tomographic and magnetic resonance angiography areused in the diagnosis. There are medical and surgical approachesto treatment. We hereby present the case ofa patient with superior mesenteric artery syndrome withdelayed diagnosis.Key words: superior mesenteric artery syndrome, nausea-vomiting, anorexia

  10. A Solitary Plasmocytoma Case Causing Horner Syndrome

    Directory of Open Access Journals (Sweden)

    Mustafa Vayvada

    2014-08-01

    Full Text Available Solitary plasmacytoma is a rare plasma cell tumour, when seen in the chest wall, it is important to diagnose since the treatment scheme and prognosis will vary, compared to primary malignant tumours of the chest wall. A 60-year-old male presented to our clinic with left shoulder pain radiating to the left axilla. Horner%u2019s syndrome symptoms were present, in further examination a chest wall mass located in the left upper lung lobe region was detected. Histopathologic diagnosis was solitary plasmocytoma via video-assisted thoracoscopy. The primary tumor of the rib malignancy causing Horner%u2019s syndrome is discussed with reference to the relevant literature.

  11. Piriformis syndrome: a cause of nondiscogenic sciatica.

    Science.gov (United States)

    Cass, Shane P

    2015-01-01

    Piriformis syndrome is a nondiscogenic cause of sciatica from compression of the sciatic nerve through or around the piriformis muscle. Patients typically have sciatica, buttocks pain, and worse pain with sitting. They usually have normal neurological examination results and negative straight leg raising test results. Flexion, adduction, and internal rotation of the hip, Freiberg sign, Pace sign, and direct palpation of the piriformis cause pain and may reproduce symptoms. Imaging and neurodiagnostic studies are typically normal and are used to rule out other etiologies for sciatica. Conservative treatment, including medication and physiotherapy, is usually helpful for the majority of patients. For recalcitrant cases, corticosteroid and botulinum toxin injections may be attempted. Ultrasound and other imaging modalities likely improve accuracy of injections. Piriformis tenotomy and decompression of the sciatic nerve can be done for those who do not respond.

  12. Cerebellar mutism syndrome: cause and rehabilitation.

    Science.gov (United States)

    Catsman-Berrevoets, Coriene E

    2017-04-01

    Mutism of cerebellar origin may occur in the context of various causes but is most frequent in children after resection of a large midline cerebellar tumour. In this review, the endeavour to reach a consensus on name and definition of postoperative mutism of cerebellar origin and associated symptoms is highlighted. In addition, progress in understanding of cause and risk factors for the syndrome is discussed as well as the rehabilitation issues. Consensus on the term cerebellar mutism syndrome (CMS) has been reached. The exact pathogenesis of CMS remains unclear. Recently, attention was drawn to the hypothesis that thermal injury might be an important mechanism in the pathogenesis of CMS. Diffusion tensor imaging tractography was found to visualize the damage to relevant pathways that are associated with persistent impairments after recovery of CMS. There is still no established treatment for CMS to date. By reaching a consensus on terminology and description of CMS, a firm basis has been created for future research. The pathogenesis of CMS seems multifactorial and important risk factors have been found. However, CMS cannot be effectively prevented yet and no established or specific treatment is available, apart from very general rehabilitation and cognitive interventions.

  13. Hyperthyroidism caused by acquired immune deficiency syndrome.

    Science.gov (United States)

    Wang, J-J; Zhou, J-J; Yuan, X-L; Li, C-Y; Sheng, H; Su, B; Sheng, C-J; Qu, S; Li, H

    2014-01-01

    Acquired immune deficiency syndrome (AIDS) is an immune deficiency disease. The etiology of hyperthyroidism, which can also be immune-related, is usually divided into six classical categories, including hypophyseal, hypothalamic, thyroid, neoplastic, autoimmune and inflammatory hyperthyroidism. Hyperthyroidism is a rare complication of highly active antimicrobial therapy (HAART) for human immunodeficiency virus (HIV). Hyperthyroidism caused directly by AIDS has not been previously reported. A 29-year-old man who complained of dyspnea and asthenia for 1 month, recurrent fever for more than 20 days, and breathlessness for 1 week was admitted to our hospital. The thyroid function test showed that the level of free thyroxine (FT4) was higher than normal and that the level of thyroid-stimulating hormone (TSH) was below normal. He was diagnosed with hyperthyroidism. Additional investigations revealed a low serum albumin level and chest infection, along with diffuse lung fibrosis. Within 1 month, he experienced significant weight loss, no hand tremors, intolerance of heat, and perspiration proneness. We recommended an HIV examination; subsequently, AIDS was diagnosed based on the laboratory parameters. This is the first reported case of hyperthyroidism caused by AIDS. AIDS may cause hyperthyroidism by immunization regulation with complex, atypical, and easily ignored symptoms. Although hyperthyroidism is rare in patients with AIDS, clinicians should be aware of this potential interaction and should carefully monitor thyroid function in HIV-positive patients.

  14. Ischemic syndromes causing dizziness and vertigo.

    Science.gov (United States)

    Choi, K-D; Lee, H; Kim, J-S

    2016-01-01

    Dizziness/vertigo and imbalance are the most common symptoms of vertebrobasilar ischemia. Even though dizziness/vertigo usually accompanies other neurologic symptoms and signs in cerebrovascular disorders, a diagnosis of isolated vascular vertigo is increasing markedly by virtue of recent developments in clinical neurotology and neuroimaging. It is important to differentiate isolated vertigo of a vascular cause from more benign disorders involving the inner ear, since therapeutic strategies and prognosis differ between these two conditions. Over the last decade, we have achieved a marked development in the understanding and diagnosis of vascular dizziness/vertigo. Introduction of diffusion-weighted magnetic resonance imaging (MRI) has greatly enhanced detection of infarctions in patients with vascular dizziness/vertigo, especially in the posterior-circulation territories. However, well-organized bedside neurotologic evaluation is even more sensitive than MRI in detecting acute infarction as a cause of spontaneous prolonged vertigo. Furthermore, detailed evaluation of strategic infarctions has elucidated the function of various vestibular structures of the brainstem and cerebellum. In contrast, diagnosis of isolated labyrinthine infarction still remains a challenge. This diagnostic difficulty also applies to isolated transient dizziness/vertigo of vascular origin. Regarding the common nonlacunar mechanisms in the acute vestibular syndrome from small infarctions, individual strategies may be indicated to prevent recurrences of stroke in patients with vascular vertigo. © 2016 Elsevier B.V. All rights reserved.

  15. Premature ageing of the immune system underlies immunodeficiency in ataxia telangiectasia.

    Science.gov (United States)

    Exley, Andrew Robert; Buckenham, Samantha; Hodges, Elizabeth; Hallam, Robert; Byrd, Phil; Last, James; Trinder, Claire; Harris, Susan; Screaton, Nicholas; Williams, Anthony P; Taylor, A Malcolm R; Shneerson, John M

    2011-07-01

    ATM kinase modulates pathways implicated in premature ageing and ATM genotype predicts survival, yet immunodeficiency in ataxia telangiectasia is regarded as mild and unrelated to age. We address this paradox in a molecularly characterised sequential adult cohort with classical and mild variant ataxia telangiectasia. Immunodeficiency has the characteristics of premature ageing across multiple cellular and molecular immune parameters. This immune ageing occurs without previous CMV infection. Age predicts immunodeficiency in genetically homogeneous ataxia telangiectasia, and in comparison with controls, calendar age is exceeded by immunological age defined by thymic naïve CD4+ T cell levels. Applying ataxia telangiectasia as a model of immune ageing, pneumococcal vaccine responses, characteristically deficient in physiological ageing, are predicted by thymic naïve CD4+ T cell levels. These data suggest inherited defects of DNA repair may provide valuable insight into physiological ageing. Thymic naïve CD4+ T cells may provide a biomarker for vaccine responsiveness in elderly cohorts. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Characterization of monoaminergic systems in brain regions of prematurely ageing mice.

    Science.gov (United States)

    De la Fuente, Monica; Hernanz, Angel; Medina, Sonia; Guayerbas, Noelia; Fernández, Beatriz; Viveros, Maria Paz

    2003-07-01

    We have previously shown that differences in life span among members of Swiss mouse populations appear to be related to their exploration of a T-maze, with a slow exploration ("slow mice") being linked to increased levels of emotionality/anxiety, an impaired immune function and a shorter life span. Thus, we proposed the slow mice as prematurely ageing mice (PAM). We have now compared the monoaminergic systems of the PAM and of the non-prematurely ageing mice (NPAM), in discrete brain regions. PAM had decreased noradrenaline (NA) levels in all the brain regions analysed, whereas the 3-methoxy-4-hydroxyphenyl glycol (MHPG)/NA ratios were not significantly modified. PAM also showed decreased serotonine (5-HT) levels in hypothalamus, striatum and midbrain, as well as increased 5-hydroxyindol-3-acetic acid (5-HIAA)/5-HT ratios in hypothalamus and hippocampus. The dopamine (DA) content was lower in PAM in most regions, whereas the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA and homovanillic acid (HVA)/DA ratios were either increased or unchanged depending on the region analysed. In most cases, the differences between PAM and NPAM involved both sexes. One exception was the hypothalamus where the differences only affected the male mice. The neurochemical alterations found in PAM resemble some changes reported for aged animals and are related with their behavioural features.

  17. Homeostatic imbalance between apoptosis and cell renewal in the liver of premature aging Xpd mice.

    Science.gov (United States)

    Park, Jung Yoon; Cho, Mi-Ook; Leonard, Shanique; Calder, Brent; Mian, I Saira; Kim, Woo Ho; Wijnhoven, Susan; van Steeg, Harry; Mitchell, James; van der Horst, Gijsbertus T J; Hoeijmakers, Jan; Cohen, Pinchas; Vijg, Jan; Suh, Yousin

    2008-06-11

    Unrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. Xpd(TTD) mice, harboring defects in nucleotide excision repair and transcription due to a mutation in the Xpd gene (R722W), display severe symptoms of premature aging but have a reduced incidence of cancer. To gain further insight into the molecular basis of the mutant-specific manifestation of age-related phenotypes, we used comparative microarray analysis of young and old female livers to discover gene expression signatures distinguishing Xpd(TTD) mice from their age-matched wild type controls. We found a transcription signature of increased apoptosis in the Xpd(TTD) mice, which was confirmed by in situ immunohistochemical analysis and found to be accompanied by increased proliferation. However, apoptosis rate exceeded the rate of proliferation, resulting in homeostatic imbalance. Interestingly, a metabolic response signature was observed involving decreased energy metabolism and reduced IGF-1 signaling, a major modulator of life span. We conclude that while the increased apoptotic response to endogenous DNA damage contributes to the accelerated aging phenotypes and the reduced cancer incidence observed in the Xpd(TTD) mice, the signature of reduced energy metabolism is likely to reflect a compensatory adjustment to limit the increased genotoxic stress in these mutants. These results support a general model for premature aging in DNA repair deficient mice based on cellular responses to DNA damage that impair normal tissue homeostasis.

  18. Homeostatic imbalance between apoptosis and cell renewal in the liver of premature aging Xpd mice.

    Directory of Open Access Journals (Sweden)

    Jung Yoon Park

    Full Text Available Unrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. Xpd(TTD mice, harboring defects in nucleotide excision repair and transcription due to a mutation in the Xpd gene (R722W, display severe symptoms of premature aging but have a reduced incidence of cancer. To gain further insight into the molecular basis of the mutant-specific manifestation of age-related phenotypes, we used comparative microarray analysis of young and old female livers to discover gene expression signatures distinguishing Xpd(TTD mice from their age-matched wild type controls. We found a transcription signature of increased apoptosis in the Xpd(TTD mice, which was confirmed by in situ immunohistochemical analysis and found to be accompanied by increased proliferation. However, apoptosis rate exceeded the rate of proliferation, resulting in homeostatic imbalance. Interestingly, a metabolic response signature was observed involving decreased energy metabolism and reduced IGF-1 signaling, a major modulator of life span. We conclude that while the increased apoptotic response to endogenous DNA damage contributes to the accelerated aging phenotypes and the reduced cancer incidence observed in the Xpd(TTD mice, the signature of reduced energy metabolism is likely to reflect a compensatory adjustment to limit the increased genotoxic stress in these mutants. These results support a general model for premature aging in DNA repair deficient mice based on cellular responses to DNA damage that impair normal tissue homeostasis.

  19. Mutations in ZBTB20 cause Primrose syndrome.

    Science.gov (United States)

    Cordeddu, Viviana; Redeker, Bert; Stellacci, Emilia; Jongejan, Aldo; Fragale, Alessandra; Bradley, Ted E J; Anselmi, Massimiliano; Ciolfi, Andrea; Cecchetti, Serena; Muto, Valentina; Bernardini, Laura; Azage, Meron; Carvalho, Daniel R; Espay, Alberto J; Male, Alison; Molin, Anna-Maja; Posmyk, Renata; Battisti, Carla; Casertano, Alberto; Melis, Daniela; van Kampen, Antoine; Baas, Frank; Mannens, Marcel M; Bocchinfuso, Gianfranco; Stella, Lorenzo; Tartaglia, Marco; Hennekam, Raoul C

    2014-08-01

    Primrose syndrome and 3q13.31 microdeletion syndrome are clinically related disorders characterized by tall stature, macrocephaly, intellectual disability, disturbed behavior and unusual facial features, with diabetes, deafness, progressive muscle wasting and ectopic calcifications specifically occurring in the former. We report that missense mutations in ZBTB20, residing within the 3q13.31 microdeletion syndrome critical region, underlie Primrose syndrome. This finding establishes a genetic link between these disorders and delineates the impact of ZBTB20 dysregulation on development, growth and metabolism.

  20. Goldenhar syndrome: a cause of secondary immunodeficiency?

    Directory of Open Access Journals (Sweden)

    De Golovine Serge

    2012-07-01

    Full Text Available Abstract Goldenhar syndrome (GS results from an aberrant development of the 1st and 2nd branchial arches. There is a wide range of clinical manifestations, the most common being microtia, hemifacial microsomia, epibulbar dermoids and vertebral malformations. We present two cases of GS and secondary immunodeficiency due to anatomical defects characteristic of this disorder. Case 1 (3-year-old female averaged 6 episodes of sinusitis and otitis media per year. Case 2 (7-year-old female also had recurrent otitis media, an episode of bacterial pneumonia, and 2 episodes of bacterial meningitis. Their immune evaluation included a complete blood count with differential, serum immunoglobulin levels and specific antibody concentrations, lymphocyte phenotyping, and mitogen and antigen responses, the results of which were all within normal ranges. Both children demonstrated major structural abnormalities of the inner and middle ear structures, retention of fluid in mastoid air cells, and chronic sinusitis by computed tomography. These two cases illustrate how a genetically-associated deviation of the middle ear cleft can cause recurrent infections and chronic inflammation of the middle ear and adjacent sinuses, even meninges, leading to a greatly reduced quality of life for the child and parents.

  1. Biliary stone causing afferent loop syndrome and pancreatitis

    Institute of Scientific and Technical Information of China (English)

    André Roncon Dias; Roberto Iglesias Lopes

    2006-01-01

    We report the case of an 84-year-old female who had a partial gastrectomy with Billroth-Ⅱ anastomosis 24years ago for a benign peptic ulcer who now presented an acute pancreatitis secondary to an afferent loop syndrome. The syndrome was caused by a gallstone that migrated through a cholecystoenteric fistula. This is the first description in the literature of a biliary stone causing afferent loop syndrome.

  2. Gene expression and DNA repair in progeroid syndromes and human aging.

    Science.gov (United States)

    Kyng, Kasper J; Bohr, Vilhelm A

    2005-11-01

    Human progeroid syndromes are caused by mutations in single genes accelerating some but not all features of normal aging. Most progeroid disorders are linked to defects in genome maintenance, and while it remains unknown if similar processes underlie normal and premature aging, they provide useful models for the study of aging. Altered transcription is speculated to play a causative role in aging, and is involved in the pathology of most if not all progeroid syndromes. Previous studies demonstrate that there is a similar pattern of gene expression changes in primary cells from old and Werner syndrome compared to young suggesting a presence of common cellular aging mechanisms in old and progeria. Here we review the role of transcription in progeroid syndromes and discuss the implications of similar transcription aberrations in normal and premature aging.

  3. Toxic anterior segment syndrome: common causes.

    Science.gov (United States)

    Cutler Peck, Carolee M; Brubaker, Jacob; Clouser, Sue; Danford, Chris; Edelhauser, Henry E; Mamalis, Nick

    2010-07-01

    To identify the most common risk factors associated with toxic anterior segment syndrome (TASS). Ophthalmic surgical centers in the United States, Argentina, Brazil, Italy, Mexico, Spain, and Romania. A TASS questionnaire on instrument cleaning and reprocessing and extraocular and intraocular products used during cataract surgery was placed on the American Society of Cataract and Refractive Surgery web site. A retrospective analysis of questionnaires submitted by surgical centers reporting cases of TASS was performed between June 1, 2007, and May 31, 2009, to identify commonly held practices that could cause TASS. Members of the TASS Task Force made site visits between October 1, 2005, and May 31, 2009, and the findings were evaluated. Data from 77 questionnaires and 54 site visits were analyzed. The reporting centers performed 50 114 cataract surgeries and reported 909 cases of TASS. From January 1, 2006, to date, the 54 centers reported 367 cases in 143 919 procedures; 61% occurred in early 2006. Common practices associated with TASS included inadequate flushing of phaco and irrigation/aspiration handpieces, use of enzymatic cleansers, detergents at the wrong concentration, ultrasonic bath, antibiotic agents in balanced salt solution, preserved epinephrine, inappropriate agents for skin prep, and powdered gloves. Reuse of single-use products and poor instrument maintenance and processing were other risk factors. The survey identified commonly held practices associated with TASS. Understanding these findings and the safe alternatives will allow surgical center personnel to change their practices as needed to prevent TASS. No author has a financial or proprietary interest in any material or method mentioned. Copyright 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  4. GDF11 administration does not extend lifespan in a mouse model of premature aging

    Science.gov (United States)

    Freitas-Rodríguez, Sandra; Rodríguez, Francisco; Folgueras, Alicia R.

    2016-01-01

    GDF11 has recently emerged as a powerful anti-aging candidate, found in young blood, capable of rejuvenating a number of aged tissues, such as heart, skeletal muscle and brain. However, recent reports have shown contradictory data questioning its capacity to reverse age-related tissue dysfunction. The availability of a mouse model of accelerated aging, which shares most of the features occurring in physiological aging, gives us an excellent opportunity to test in vivo therapies aimed at extending lifespan both in pathological and normal aging. On this basis, we wondered whether the proposed anti-aging functions of GDF11 would have an overall effect on longevity. We first confirmed the existence of a reduction in GDF11/8 levels in our mouse model of accelerated aging compared with wild-type littermates. However, we show herein that GDF11 daily administration does not extend lifespan of premature-aged mice. PMID:27507054

  5. Psychosis as a late manifestation of Sheehan's syndrome.

    Science.gov (United States)

    Reddy, Mukku Shiva Shanker; Nahar, Abhinav; Thippeswamy, Harish; Kumar, Chaturvedi Santosh

    2017-02-01

    Sheehan's syndrome occurs as a result of ischemic pituitary necrosis due to severe postpartum haemorrhage. It is one of the most common causes of hypopituitarism in underdeveloped or developing countries. Characteristic manifestations include failure to lactate or to resume menses, genital and axillary hair loss, asthenia and weakness, fine wrinkles around the eyes and lips, signs of premature aging, dry skin, hypopigmentation and other evidence of hypopituitarism. Uncommonly it can present with psychosis. There are only few case reports of psychoses in patients with Sheehan's syndrome. Our case report illustrates the relationship between psychosis and Sheehan's syndrome. The treatment challenges in managing Sheehan's syndrome and psychosis are discussed.

  6. Contact urticaria syndrome caused by haptens

    OpenAIRE

    Gomułka, Krzysztof; Panaszek, Bernard

    2014-01-01

    In the group of urticaria, contact urticaria syndrome is a particular variety. In these patients, appearance of typical skin lesions is preceded by contact of the skin and mucous membranes with various inhaled allergens, nutrients or contact details. Furthermore, symptoms connected with contact urticaria syndrome are characterized by gradual, stepwise waveform, which can be easily generalized – patients may develop systemic symptoms similar to those found in the angioedema, asthma or anaphyla...

  7. A rare cause of pancytopenia: Sheehan′s syndrome

    Directory of Open Access Journals (Sweden)

    Mustafa Volkan Demir

    2015-01-01

    Full Text Available Sheehan′s syndrome is characterized by varying degrees of anterior pituitary dysfunction due to postpartum ischemic necrosis of the pituitary gland after massive bleeding. Pancytopenia is rarely observed in patients with Sheehan′s syndrome. We present a patient of Sheehan′s syndrome presenting with pancytopenia. Complete recovery of pancytopenia was observed after the treatment. Clinicians should consider the possibility of hypopituitarism as a cause of pancytopenia and indicate a series of hormonal examinations. A high index of suspicion is required in women with pancytopenia for possible treatable cause like Sheehan′s syndrome.

  8. A rare cause of acute coronary syndrome: Kounis syndrome.

    Science.gov (United States)

    Almeida, João; Ferreira, Sara; Malheiro, Joana; Fonseca, Paulo; Caeiro, Daniel; Dias, Adelaide; Ribeiro, José; Gama, Vasco

    2016-12-01

    Kounis syndrome is an acute coronary syndrome in the context of a hypersensitivity reaction. The main pathophysiological mechanism appears to be coronary vasospasm. We report the case of a patient with a history of allergy to quinolones, who was given ciprofloxacin before an elective surgical procedure and during drug administration developed symptoms and electrocardiographic changes suggestive of ST-segment elevation acute coronary syndrome. The drug was suspended and coronary angiography excluded epicardial coronary disease. Two hours after withdrawal of the drug the symptoms and ST elevation had resolved completely.

  9. A rare cause of pancytopenia: Sheehan′s syndrome

    OpenAIRE

    Mustafa Volkan Demir; Selçuk Yaylaci; Tuba Öztürk Demir; Tayfun Temiz; Ahmet Bilal Genç

    2015-01-01

    Sheehan′s syndrome is characterized by varying degrees of anterior pituitary dysfunction due to postpartum ischemic necrosis of the pituitary gland after massive bleeding. Pancytopenia is rarely observed in patients with Sheehan′s syndrome. We present a patient of Sheehan′s syndrome presenting with pancytopenia. Complete recovery of pancytopenia was observed after the treatment. Clinicians should consider the possibility of hypopituitarism as a cause of pancytopenia and indicate a series of h...

  10. Homeostatic imbalance between apoptosis and cell renewal in the liver of premature aging XpdTTD mice

    NARCIS (Netherlands)

    J.Y. Park; M.O. Cho; S. Leonard (Shanique); B. Calder (Brent); I.S. Mian (Saira); W.H. Kim (Woo); S.W.P. Wijnhoven (Susan); H. van Steeg (Harry); J.R. Mitchell (James); G.T.J. van der Horst (Gijsbertus); J.H.J. Hoeijmakers (Jan); P. Cohen (Pinchas); J. Vijg (Jan); Y. Suh (Yousin)

    2008-01-01

    textabstractUnrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. XpdTTDmice, harboring defects in nucleotide excision repair and transcription due to a mutation in the Xpd gene (R722W), display severe symptoms of premature aging but have a rduced incidence

  11. Homeostatic imbalance between apoptosis and cell renewal in the liver of premature aging XpdTTD mice

    NARCIS (Netherlands)

    J.Y. Park; M.O. Cho; S. Leonard (Shanique); B. Calder (Brent); I.S. Mian (Saira); W.H. Kim (Woo); S.W.P. Wijnhoven (Susan); H. van Steeg (Harry); J.R. Mitchell (James); G.T.J. van der Horst (Gijsbertus); J.H.J. Hoeijmakers (Jan); P. Cohen (Pinchas); J. Vijg (Jan); Y. Suh (Yousin)

    2008-01-01

    textabstractUnrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. XpdTTDmice, harboring defects in nucleotide excision repair and transcription due to a mutation in the Xpd gene (R722W), display severe symptoms of premature aging but have a rduced incidence

  12. NRMT1 knockout mice exhibit phenotypes associated with impaired DNA repair and premature aging.

    Science.gov (United States)

    Bonsignore, Lindsay A; Tooley, John G; Van Hoose, Patrick M; Wang, Eugenia; Cheng, Alan; Cole, Marsha P; Schaner Tooley, Christine E

    2015-03-01

    Though defective genome maintenance and DNA repair have long been known to promote phenotypes of premature aging, the role protein methylation plays in these processes is only now emerging. We have recently identified the first N-terminal methyltransferase, NRMT1, which regulates protein-DNA interactions and is necessary for both accurate mitotic division and nucleotide excision repair. To demonstrate if complete loss of NRMT1 subsequently resulted in developmental or aging phenotypes, we constructed the first NRMT1 knockout (Nrmt1(-/-)) mouse. The majority of these mice die shortly after birth. However, the ones that survive, exhibit decreased body size, female-specific infertility, kyphosis, decreased mitochondrial function, and early-onset liver degeneration; phenotypes characteristic of other mouse models deficient in DNA repair. The livers from Nrmt1(-/-) mice produce less reactive oxygen species (ROS) than wild type controls, and Nrmt1(-/-) mouse embryonic fibroblasts show a decreased capacity for handling oxidative damage. This indicates that decreased mitochondrial function may benefit Nrmt1(-/-) mice and protect them from excess internal ROS and subsequent DNA damage. These studies position the NRMT1 knockout mouse as a useful new system for studying the effects of genomic instability and defective DNA damage repair on organismal and tissue-specific aging.

  13. Infectious causes of sudden infant death syndrome.

    Science.gov (United States)

    Alfelali, Mohammad; Khandaker, Gulam

    2014-12-01

    Investigators have long suspected the role of infection in sudden infant death syndrome (SIDS). Evidence of infectious associations with SIDS is accentuated through the presence of markers of infection and inflammation on autopsy of SIDS infants and isolates of some bacteria and viruses. Several observational studies have looked into the relation between seasonality and incidence of SIDS, which often showed a winter peak. These all may suggest an infectious aetiology of SIDS. In this review we have summarised the current literature on infectious aetiologies of SIDS by looking at viral, bacterial, genetic and environmental factors which are believed to be associated with SIDS.

  14. Shoulder impingement syndrome : evaluation of the causes with MRI

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yong Ho; Song, In Sup; Chung, Hun Young; Yoon, Sang Jin; Kim, Yang Soo; Shim, Hyung Jin; Choi, Young Hee; Lee, Jong Beum; Lee, Yong Chul; Kim, Kun Sang [Chungang Univ. College of Medicine, Seoul (Korea, Republic of); Choi, Yun Sun [Eulji Hospital, College of Medicine, Seoul (Korea, Republic of)

    1999-12-01

    Various mechanical causes which induce shoulder impingement syndrome have been identified with the help of MRI. The aim of this study is to evaluate the incidence of such causes. A total of 54 patients with clinically confirmed shoulder impingement syndrome and a normal control group(n=20) without symptoms were included. We evaluated the incidence of hook shaped acromion, low lying acromion, downward slope of the acromion, subacromial spur, acromioclavicular joint hypertrophy, coracoacromial ligament hypertrophy, high cuff muscle bulk, and os acromiale. Among the 54 patients, the following conditions were present: acromioclavicular joint hypertrophy(n=36), coracoacromial ligament hypertrophy(n=20), subacromial spur(n=18), downward sloping of the acromion(n=16), hook shaped acromion(n=11), relatively high cuff muscle bulk(n=6), low lying acromion relative to the clavicle(n=3), and os acromiale(n=1). In the normal control group there were nine cases of acromioclavicular joint hypertrophy, nine of coracoacromial ligament hypertrophy, nine of downward sloping acromion, and three of low lying acromion, but hook shaped acromion, high cuff muscle bulk, and os acromiale were not found. Among 54 patients, the syndrome was due to five simultancous causes in one patient, four causes in two, three causes in 12, two causes in 22, and one cause in 17. Hook shaped acromion and subacromial spur are the statistically significant causes of shoulder impingement syndrome. In 69% of patients, the condition was due to more than one cause.

  15. Symptoms and Causes of Irritable Bowel Syndrome

    Science.gov (United States)

    ... of sugars or bile acids may cause symptoms. Mental Health Problems Psychological, or mental health, problems such ... Blood Diseases Diagnostic Tests La información de la salud en español Health Statistics Healthy Moments Radio Broadcast ...

  16. A nonsense mutation in FMR1 causing fragile X syndrome

    DEFF Research Database (Denmark)

    Grønskov, Karen; Brøndum-Nielsen, Karen; Dedic, Alma

    2011-01-01

    Fragile X syndrome is a common cause of inherited intellectual disability. It is caused by lack of the FMR1 gene product FMRP. The most frequent cause is the expansion of a CGG repeat located in the 5'UTR of FMR1. Alleles with 200 or more repeats become hypermethylated and transcriptionally silent...... mutation p.Ser27X, in a patient with classical clinical symptoms of fragile X syndrome. The mother who carried the mutation in heterozygous form presented with mild intellectual impairment. We conclude that further studies including western blot and DNA sequence analysis of the FMR1 gene should....... Only few patients with intragenic point mutations in FMR1 have been reported and, currently, routine analysis of patients referred for fragile X syndrome includes solely analysis for repeat expansion and methylation status. We identified a substitution in exon 2 of FMR1, c.80C>A, causing a nonsense...

  17. Parinaud's oculoglandular syndrome and possibly causing cortical cataract

    OpenAIRE

    Mariana Heid Rocha Hemerly; Marcelo Berno Mattos; Fábio Petersen Saraiva; Fellipe Berno Mattos

    2014-01-01

    According to the World Health Organization, cataract is the leading cause of blindness and visual impairment throughout the world. However, the etiology of cataracts often remains unknown. This report describes the development of cortical cataract in a patient after Parinaud's oculoglandular syndrome caused by the fungus Sporothrix schenckii.

  18. Parinaud's oculoglandular syndrome and possibly causing cortical cataract

    Directory of Open Access Journals (Sweden)

    Mariana Heid Rocha Hemerly

    2014-06-01

    Full Text Available According to the World Health Organization, cataract is the leading cause of blindness and visual impairment throughout the world. However, the etiology of cataracts often remains unknown. This report describes the development of cortical cataract in a patient after Parinaud's oculoglandular syndrome caused by the fungus Sporothrix schenckii.

  19. Mutations in KCTD1 cause scalp-ear-nipple syndrome.

    Science.gov (United States)

    Marneros, Alexander G; Beck, Anita E; Turner, Emily H; McMillin, Margaret J; Edwards, Matthew J; Field, Michael; de Macena Sobreira, Nara Lygia; Perez, Ana Beatriz A; Fortes, Jose A R; Lampe, Anne K; Giovannucci Uzielli, Maria Luisa; Gordon, Christopher T; Plessis, Ghislaine; Le Merrer, Martine; Amiel, Jeanne; Reichenberger, Ernst; Shively, Kathryn M; Cerrato, Felecia; Labow, Brian I; Tabor, Holly K; Smith, Joshua D; Shendure, Jay; Nickerson, Deborah A; Bamshad, Michael J

    2013-04-04

    Scalp-ear-nipple (SEN) syndrome is a rare, autosomal-dominant disorder characterized by cutis aplasia of the scalp; minor anomalies of the external ears, digits, and nails; and malformations of the breast. We used linkage analysis and exome sequencing of a multiplex family affected by SEN syndrome to identify potassium-channel tetramerization-domain-containing 1 (KCTD1) mutations that cause SEN syndrome. Evaluation of a total of ten families affected by SEN syndrome revealed KCTD1 missense mutations in each family tested. All of the mutations occurred in a KCTD1 region encoding a highly conserved bric-a-brac, tram track, and broad complex (BTB) domain that is required for transcriptional repressor activity. KCTD1 inhibits the transactivation of the transcription factor AP-2α (TFAP2A) via its BTB domain, and mutations in TFAP2A cause cutis aplasia in individuals with branchiooculofacial syndrome (BOFS), suggesting a potential overlap in the pathogenesis of SEN syndrome and BOFS. The identification of KCTD1 mutations in SEN syndrome reveals a role for this BTB-domain-containing transcriptional repressor during ectodermal development.

  20. Genetic, chromosomal, and syndromic causes of neural tube defects

    Science.gov (United States)

    Seidahmed, Mohammed Z.; Abdelbasit, Omer B.; Shaheed, Meeralebbae M.; Alhussein, Khalid A.; Miqdad, Abeer M.; Samadi, Abdulmohsen S.; Khalil, Mohammed I.; Al-Mardawi, Elham; Salih, Mustafa A.

    2014-01-01

    Objective: To ascertain the incidence, and describe the various forms of neural tube defects (NTDs) due to genetic, chromosomal, and syndromic causes. Methods: We carried out a retrospective analysis of data retrieved from the medical records of newborn infants admitted to the Neonatal Intensive Care Unit with NTDs and their mothers spanning 14 years (1996-2009) at the Security Forces Hospital, Riyadh, Saudi Arabia. The cases were ascertained by a perinatologist, neonatologist, geneticist, radiologist, and neurologist. The literature was reviewed via a MEDLINE search. Only liveborn babies were included. Permission from the Educational Committee at the Security Forces Hospital was obtained prior to the collection of data. Results: Out of 103 infants with NTDs admitted during this period, 20 (19.4%) were found to have an underlying genetic syndromic, chromosomal and/or other anomalies. There were 5 cases of Meckel-Gruber syndrome, 2 Joubert syndrome, one Waardenburg syndrome, one Walker-Warburg syndrome, 2 chromosomal disorders, 2 caudal regression, one amniotic band disruption sequence, one associated with omphalocele, one with diaphragmatic hernia, and 4 with multiple congenital anomalies. Conclusions: There is a high rate of underlying genetic syndromic and/or chromosomal causes of NTDs in the Saudi Arabian population due to the high consanguinity rate. Identification of such association can lead to more accurate provisions of genetic counseling to the family including preimplantation genetic diagnosis or early termination of pregnancies associated with lethal conditions. PMID:25551112

  1. Methylene Blue Causing Serotonin Syndrome Following Cystocele Repair.

    Science.gov (United States)

    Kapadia, Kailash; Cheung, Felix; Lee, Wai; Thalappillil, Richard; Florence, F Barry; Kim, Jason

    2016-11-01

    Methylene blue is an intravenously administered agent that may potentiate serotonin syndrome. The usage of methylene blue to evaluate ureters for injuries and patency during urological surgeries is recognized as common practice. However, there is no mention of serotonin syndrome caused by methylene blue in urological literature or for urological surgery. We report the first urological case in order to raise awareness of the risk for serotonin toxicity with utilizing methylene blue.

  2. Methylene Blue Causing Serotonin Syndrome Following Cystocele Repair

    Directory of Open Access Journals (Sweden)

    Kailash Kapadia

    2016-11-01

    Full Text Available Methylene blue is an intravenously administered agent that may potentiate serotonin syndrome. The usage of methylene blue to evaluate ureters for injuries and patency during urological surgeries is recognized as common practice. However, there is no mention of serotonin syndrome caused by methylene blue in urological literature or for urological surgery. We report the first urological case in order to raise awareness of the risk for serotonin toxicity with utilizing methylene blue.

  3. A Rare Cause of Macroscobic Hematuria: Nutcracker Syndrome

    Directory of Open Access Journals (Sweden)

    Nilgün Selçuk Duru

    2015-03-01

    Full Text Available Nutcracker syndrome caused by compression of the left renal vein between the abdominal aorta and the superior mesenteric artery is a rare anatomo-pathological condition. The patients have symptoms such as hematuria, proteinuria, and left flank pain. In this paper, we report a 13-year-old boy who presented with macroscopic haematuria. Routine laboratory tests for the evaluation of hematuria were normal. Abdominal computed tomography revealed that the left renal vein was compressed between the aorta and the superior mesenteric artery. A diagnosis of nutcracker syndrome was established. If Nutcracker syndrome is considered in the differential diagnosis of haematuria, it is easily diagnosed by imaging techniques.

  4. An unusual cause of intraoperative acute superior vena cava syndrome

    Directory of Open Access Journals (Sweden)

    Adam W Amundson

    2013-01-01

    Full Text Available Acute intraoperative superior vena cava (SVC syndrome is an exceedingly rare complication in the cardiac surgical population. We describe the case of a 71-year-old female undergoing multi-vessel coronary artery bypass grafting who developed acute intraoperative SVC syndrome following internal thoracic artery harvest retractor placement. Her symptoms included severe plethora, facial engorgement and scleral edema, which was associated with hypotension and severe elevation of central venous pressure. Transesophageal echocardiography was crucial in the diagnosis, management, and optimal retractor placement ensuring adequate SVC flow. Potential causes of intraoperative SVC syndrome are reviewed as well as management options.

  5. Premature Aging of the Microcirculation in Patients with Advanced Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Oanh H.D. Thang

    2012-11-01

    Full Text Available Background: Increasing age and advanced chronic kidney disease (CKD are both associated with an attenuated vasodilator response of the skin microcirculation. In the present study, we investigated the effect of aging on microvascular reactivity in patients with advanced CKD. Methods: Acetylcholine (ACh-mediated endothelium-dependent vasodilation and sodium nitroprusside (SNP-mediated endothelium-independent vasodilation were assessed by iontophoresis combined with laser Doppler flowmetry. Microvascular function was compared between 52 patients with advanced CKD (stage 4–5: n = 16; end-stage renal disease: n = 36 and 33 healthy control subjects. As aging has an important effect on microvascular function, both control subjects and CKD patients were divided in subgroups younger and older than 45 years. Linear regression analysis was applied to assess potential associations between microvascular function and various demographic and clinical parameters. Results: There were three main findings. (1 In young patients with advanced CKD, both ACh- and SNP-mediated vasodilations were impaired if compared to young healthy controls (p = 0.04 and p = 0.056, respectively. (2 In young patients with advanced CKD, microvascular function was similar to old healthy controls and elderly patients with advanced CKD. (3 Whereas age was inversely associated with microvascular function in healthy controls (log ACh-mediated vasodilation R = –0.41; p = 0.02 and log SNP-mediated vasodilation R = –0.38; p = 0.03, no such relation was found in patients with advanced CKD. Conclusions: Our results are consistent with premature aging of the microvascular vasodilatory capacity in patients with advanced CKD.

  6. Infraclavicular subpectoral lipoma causing thoracic outlet syndrome

    Directory of Open Access Journals (Sweden)

    Stefano Elia

    2015-01-01

    Conclusion: Although benign soft tissue tumors infraclavicular subpectoral lipomas may exert pressure on neurovascular surrounding structures during their progressive expansion and cause TOS. Therefore, a thorough preoperative study by radiological imaging such as MRI or neurophysiological test should always be performed in order to prevent unintentional lesions of the involved axillo-subclavicular plexus and plan correct surgical procedure.

  7. [Brucellosis as a cause of hemophagocytic syndrome].

    Science.gov (United States)

    Aydın, Saliha; Günal, Özgür; Taşkın, Mehmet Hakan; Atilla, Aynur; Kılıç, Süleyman Sırrı

    2015-04-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of excessive inflammation and tissue destruction due to abnormal immune activation and inflammation. HLH can occur primarily due to genetic etiology, or secondarily associated with malignancies, autoimmmune diseases or infections. There are a number of reports that revealed the relationship of hemophagocytosis with brucellosis. In this report, we described a brucellosis-related HLH case. A 73-year-old male who work as farmer was admitted to our hospital with the complaints of fever continuing for 10 days, loss of appetite and back pain. Physical examination revealed right upper quadrant tenderness and hepatomegaly. Since the patient exhibited five of the diagnostic criteria for HLH (fever, hepatosplenomegaly, bicytopenia, hypertriglyceridemia and high ferritin level), he was diagnosed as secondary HLH. PCR, microscopic agglutination and indirect fluorescent antibody tests gave negative results for the diagnosis of Crimean-Congo hemorrhagic fever, leptospirosis and Q fever, respectively. On the other hand, Rose Bengal test for brucellosis was positive, while standard tube agglutination test (STA) was negative. The patient's serum yielded a very high positive (1/1280) result when Coombs' test was performed in terms of the possibility of blocking antibodies or prozone phenomenon. Additionally, B.melitensis was isolated from his blood culture on the sixth day. The patient was treated with doxycycline and rifampicin, and on the 10th day of antibiotic therapy the patient was discharged and recommended to complete his treatment up to 6 weeks. In conclusion, in patients with secondary HLH symptoms especially in the endemic areas, brucellosis should be considered as a predisposing infection.

  8. Intrasynovial lipoma causing trigger wrist and carpal tunnel syndrome.

    Science.gov (United States)

    Imai, Shinji; Kodama, Narihito; Matsusue, Yoshitaka

    2008-01-01

    Triggering of the flexor tendon at the wrist is rare. We report a case of intrasynovial lipoma that caused a trigger wrist. As far as we know it is unique in that the intrasynovial lipoma simultaneously caused carpal tunnel syndrome. The massive tenosynovitis and adhesion of flexors tendons after the locking of the intrasynovial lipoma may have resulted from inflammation caused by attrition within the carpal tunnel.

  9. Premature Aging-related Peripheral Neuropathy in a Mouse Model of Progeria

    Science.gov (United States)

    Goss, James R.; Stolz, Donna Beer; Robinson, Andria Rasile; Zhang, Mingdi; Arbujas, Norma; Robbins, Paul D.; Glorioso, Joseph C.; Niedernhofer, Laura J.

    2011-01-01

    Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1−/Δ mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1−/Δ mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies. PMID:21596054

  10. Premature aging-related peripheral neuropathy in a mouse model of progeria.

    Science.gov (United States)

    Goss, James R; Stolz, Donna Beer; Robinson, Andria Rasile; Zhang, Mingdi; Arbujas, Norma; Robbins, Paul D; Glorioso, Joseph C; Niedernhofer, Laura J

    2011-08-01

    Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1(-/Δ) mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1(-/Δ) mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies.

  11. A Rare Cause of Secondary Hypertension: Conn Syndrom

    Directory of Open Access Journals (Sweden)

    Samet Sayilan

    2016-01-01

    Full Text Available Hypertension, is classified as primary (essential or secondary based on whether there is an identifiable cause. When it is determined a certain underlying cause of hypertension it is categorized as secondary hypertension. Conn%u2019s syndrome (primary hyperaldosteronism, a disorder of adrenal cortex characterized by exces aldosterone secretion, is an endocrine disorder that causes hypertension and it is seen in about 0.1% of all patients with hypertension. It can be caused by either unilateral disease (i.e. adenoma in one adrenal gland or bilateral disease (i.e. hyperplasia in both adrenal glands. Conn%u2019s syndrome secondary to bilateral adrenal adenoma, a cause of secondary hypertension, was presented in this articleas it is rarely reported in the literature.

  12. Compartment syndrome causes systemic inflammation in a rat.

    Science.gov (United States)

    Lawendy, A-R; Bihari, A; Sanders, D W; Badhwar, A; Cepinskas, G

    2016-08-01

    Compartment syndrome results from increased intra-compartmental pressure (ICP) causing local tissue ischaemia and cell death, but the systemic effects are not well described. We hypothesised that compartment syndrome would have a profound effect not only on the affected limb, but also on remote organs. Using a rat model of compartment syndrome, its systemic effects on the viability of hepatocytes and on inflammation and circulation were directly visualised using intravital video microscopy. We found that hepatocellular injury was significantly higher in the compartment syndrome group (192 PI-labelled cells/10(-1) mm(3), standard error of the mean (sem) 51) compared with controls (30 PI-labelled cells/10(-1) mm(3), sem 12, p compartment syndrome group (5 leukocytes/30s/10 000 μm(2), sem 1) than controls (0.2 leukocytes/30 s/10 000 μm(2), sem 0.2, p Compartment syndrome can be accompanied by severe systemic inflammation and end organ damage. This study provides evidence of the relationship between compartment syndrome in a limb and systemic inflammation and dysfunction in a remote organ. Cite this article: Bone Joint J 2016; 98-B:1132-7. ©2016 The British Editorial Society of Bone & Joint Surgery.

  13. Dumping syndrome, a cause of acquired glycogenic hepatopathy.

    Science.gov (United States)

    Resnick, Jeffrey M; Zador, Ivan; Fish, Daryl L

    2011-01-01

    A 2-year-old boy, having undergone fundoplication for gastroesophageal reflux disease and fed by gastrostomy, presented with recurrent emesis, syncope with hypoglycemia, and persistently elevated serum liver transaminase levels. Liver biopsy revealed hepatocellular glycogenosis by light and electron microscopy. Further evaluation showed no evidence of diabetes mellitus, glycogen storage disease, or corticosteroid use. Since the hyperglycemic-hyperinsulinemic state of dumping syndrome would provide a mechanism for hepatocellular glycogenosis, the biopsy findings prompted consideration of dumping syndrome. Metabolic evaluation confirmed the diagnosis of dumping syndrome, and appropriate dietary management led to sustained resolution of symptomatology and hypertransaminasemia. Dumping syndrome is proposed to be a cause of hepatocellular glycogenosis, the latter representing a form of acquired glycogenic hepatopathy.

  14. Unilateral facial paralysis caused by Ramsay Hunt syndrome.

    Science.gov (United States)

    Pereira, Flávia P; Guskuma, Marcos H; Luvizuto, Eloá R; Faco, Eduardo F S; Magro-Filho, Osvaldo; Hochuli-Vieira, Eduardo

    2011-09-01

    The Ramsay Hunt syndrome is a rare disease caused by an infection of the geniculate ganglion by the varicella-zoster virus. The main clinical features of the syndrome are as follows: Bell palsy unilateral or bilateral, vesicular eruptions on the ears, ear pain, dizziness, preauricular swelling, tingling, tearing, loss of taste sensation, and nystagmus. We describe a 23-year-old white woman, who presented with facial paralysis on the left side of the face, pain, fever, ear pain, and swelling in the neck and auricular region on the left side. She received appropriate treatment with acyclovir, vitamin B complex, and CMP nucleus. After 30 days after presentation, the patient did not show any signs or symptoms of the syndrome. At follow-up at 1 year, she showed no relapse of the syndrome.

  15. Positive Apraclonidine Test in Horner Syndrome Caused by Thalamic Hemorrhage.

    Science.gov (United States)

    Kauh, Courtney Y; Bursztyn, Lulu L C D

    2015-09-01

    Reversal of anisocoria following instillation of apraclonidine 0.5% has been reported in Horner syndrome caused by lesions of the central and peripheral nervous system. The shortest documented latency between symptom onset and a positive apraclonidine test is 36 hours, occurring in a patient with a pontomedullary infarct. We present the case of a 69-year-old man with Horner syndrome due to thalamic hemorrhage in whom apraclonidine testing demonstrated reversal of anisocoria 4 days after symptom onset. This is the first reported case of a positive apraclonidine test in a Horner syndrome caused by a lesion at this site. It suggests that apraclonidine testing is useful in confirming the diagnosis within days of onset even in a lesion located at the most proximal portion of the oculosympathetic pathway.

  16. Causes of infertility in men with Down syndrome.

    Science.gov (United States)

    Stefanidis, K; Belitsos, P; Fotinos, A; Makris, N; Loutradis, D; Antsaklis, A

    2011-10-01

    Men with Down syndrome are considered as infertile although the causes of infertility are not known in detail yet. Although this constitutes a general rule there are three confirmed cases of parenting by fathers with Down syndrome. Many investigators have addressed the causes of infertility and their studies indicate that the causes may be hormonal deficits, morphological alterations of the gonads, abnormal spermatogenesis, psychological and social factors related to the mental retardation. It is obvious that the extra chromosome 21 has a detrimental direct and indirect effect on the reproductive capacity of the affected male patient. But the definite cause of the insufficient and inadequate spermatogenesis remains to be discovered. © 2011 Blackwell Verlag GmbH.

  17. Nasu-Hakola Syndrome: An Unusual Cause of Pathological Fractures

    Directory of Open Access Journals (Sweden)

    Jaykar R. Panchmatia

    2012-01-01

    Full Text Available Nasu-Hakola syndrome is a hereditary cause of pathological fractures. Uniquely, patients also develop neuropsychiatric symptoms and signs. The disease is ultimately fatal. We propose a management strategy for pathological fractures in sufferers based on the stage of the disease.

  18. Kingella kingae causing septic arthritis in Felty's syndrome.

    Science.gov (United States)

    Lewis, D A; Settas, L

    1983-08-01

    A case of septic arthritis of the elbow caused by Kingella kingae, a Gram-negative bacillus, is described. The patient had long-standing, severe rheumatoid arthritis and Felty's syndrome. This appears to be the first report from the United Kingdom of Kingella kingae as the aetiological agent of septic arthritis.

  19. Kingella kingae causing septic arthritis in Felty's syndrome.

    OpenAIRE

    Lewis, D A; Settas, L

    1983-01-01

    A case of septic arthritis of the elbow caused by Kingella kingae, a Gram-negative bacillus, is described. The patient had long-standing, severe rheumatoid arthritis and Felty's syndrome. This appears to be the first report from the United Kingdom of Kingella kingae as the aetiological agent of septic arthritis.

  20. Acute carpal tunnel syndrome caused by peritendinitis calcarea. Case report.

    Science.gov (United States)

    Boström, L; Svartengren, G

    1993-01-01

    Two women presented with similar symptoms of acute pain in the hand that was diagnosed as acute carpal tunnel syndrome caused by peritendinitis calcarea. Radiological examinations in both cases showed calcifications in the carpal tunnel. Both patients were operated on immediately and the median nerve was decompressed. Both were completely relieved of pain after operation and hand function returned to normal.

  1. The syndrome of inappropriate antidiuretic hormone: prevalence, causes and consequences.

    Science.gov (United States)

    Hannon, M J; Thompson, C J

    2010-06-01

    Hyponatraemia is the commonest electrolyte abnormality found in hospital inpatients, and is associated with a greatly increased morbidity and mortality. The syndrome of inappropriate antidiuretic hormone (SIADH) is the most frequent cause of hyponatraemia in hospital inpatients. SIADH is the clinical and biochemical manifestation of a wide range of disease processes, and every case warrants investigation of the underlying cause. In this review, we will examine the prevalence, pathophysiology, clinical characteristics and clinical consequences of hyponatraemia due to SIADH.

  2. The syndrome of inappropriate antidiuretic hormone: prevalence, causes and consequences.

    LENUS (Irish Health Repository)

    Hannon, M J

    2010-06-01

    Hyponatraemia is the commonest electrolyte abnormality found in hospital inpatients, and is associated with a greatly increased morbidity and mortality. The syndrome of inappropriate antidiuretic hormone (SIADH) is the most frequent cause of hyponatraemia in hospital inpatients. SIADH is the clinical and biochemical manifestation of a wide range of disease processes, and every case warrants investigation of the underlying cause. In this review, we will examine the prevalence, pathophysiology, clinical characteristics and clinical consequences of hyponatraemia due to SIADH.

  3. Trismus Pseudocamptodactyly Syndrome: A Sporadic Cause of Trismus

    Directory of Open Access Journals (Sweden)

    Prathima Sreenivasan

    2013-01-01

    Full Text Available Trismus pseudocamptodactyly syndrome is a very rare autosomal dominant inherited disorder characterized by the inability to completely open the mouth (trismus and the presence of abnormally short tendon units causing the fingers to curve (camptodactyly. Early diagnosis and management of this condition is important to prevent facial deformities in the patient. Reporting such a case is important as case reports are one of the sources of data for calculating the prevalence of rare diseases. Here, we report a case of trismus pseudocamptodactyly syndrome in an eight-year-old boy with a brief review of the literature.

  4. Gluteal compartment syndrome after prostatectomy caused by incorrect positioning.

    Science.gov (United States)

    Heyn, Jens; Ladurner, R; Ozimek, A; Vogel, T; Hallfeldt, K K; Mussack, T

    2006-04-28

    Gluteal compartment syndrome is an uncommon and rare disease. Most reasonable causes for the development of this disease are trauma, drug induced coma, Ehlers-Danlos syndrome, sickle cell associated muscle infarction, incorrect positioning during surgical procedures and prolonged pressure in patients with altered consciousness levels. The diagnosis requires a high index of suspicion, especially in postoperative patient where sedation or peridural anaesthesia can confound the neurological examination. Early signs include gluteal tenderness, decrease in vibratory sensation during clinical examination and increasing CK in laboratory findings. We present a case of a 52 year-old patient, who developed gluteal compartment syndrome after radical prostatectomy in lithotomic position. After operation, diuresis decreased [pain in the gluteal region and both thighs. His thighs and the gluteal region were swollen. Passive stretch of the thighs caused enormous pain. The compartment pressure was 92 mmHg. Therefore, emergency fasciotomy was performed successfully. The gluteal compartment syndrome was most likely caused by elevated pressure on the gluteal muscle during operation. We suggest heightened awareness of positioning the patient on the operating table is important especially in obese patients with lengthy operating procedures.

  5. Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome.

    Science.gov (United States)

    Boyden, Lynn M; Kam, Chen Y; Hernández-Martín, Angela; Zhou, Jing; Craiglow, Brittany G; Sidbury, Robert; Mathes, Erin F; Maguiness, Sheilagh M; Crumrine, Debra A; Williams, Mary L; Hu, Ronghua; Lifton, Richard P; Elias, Peter M; Green, Kathleen J; Choate, Keith A

    2016-01-15

    Disorders of keratinization (DOK) show marked genotypic and phenotypic heterogeneity. In most cases, disease is primarily cutaneous, and further clinical evaluation is therefore rarely pursued. We have identified subjects with a novel DOK featuring erythrokeratodermia and initially-asymptomatic, progressive, potentially fatal cardiomyopathy, a finding not previously associated with erythrokeratodermia. We show that de novo missense mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous disorder, which we term erythrokeratodermia-cardiomyopathy (EKC) syndrome. We demonstrate that DSP mutations in our EKC syndrome subjects affect localization of desmosomal proteins and connexin 43 in the skin, and result in desmosome aggregation, widening of intercellular spaces, and lipid secretory defects. DSP encodes desmoplakin, a primary component of desmosomes, intercellular adhesion junctions most abundant in the epidermis and heart. Though mutations in DSP are known to cause other disorders, our cohort features the unique clinical finding of severe whole-body erythrokeratodermia, with distinct effects on localization of desmosomal proteins and connexin 43. These findings add a severe, previously undescribed syndrome featuring erythrokeratodermia and cardiomyopathy to the spectrum of disease caused by mutation in DSP, and identify a specific region of the protein critical to the pathobiology of EKC syndrome and to DSP function in the heart and skin. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Single Gene and Syndromic Causes of Obesity: Illustrative Examples.

    Science.gov (United States)

    Butler, Merlin G

    2016-01-01

    Obesity is a significant health problem in westernized societies, particularly in the United States where it has reached epidemic proportions in both adults and children. The prevalence of childhood obesity has doubled in the past 30 years. The causation is complex with multiple sources, including an obesity promoting environment with plentiful highly dense food sources and overall decreased physical activity noted for much of the general population, but genetic factors clearly play a role. Advances in genetic technology using candidate gene approaches, genome-wide association studies, structural and expression microarrays, and next generation sequencing have led to the discovery of hundreds of genes recognized as contributing to obesity. Polygenic and monogenic causes of obesity are now recognized including dozens of examples of syndromic obesity with Prader-Willi syndrome, as a classical example and recognized as the most common known cause of life-threatening obesity. Genetic factors playing a role in the causation of obesity will be discussed along with the growing evidence of single genes and the continuum between monogenic and polygenic obesity. The clinical and genetic aspects of four classical but rare obesity-related syndromes (ie, Prader-Willi, Alström, fragile X, and Albright hereditary osteodystrophy) will be described and illustrated in this review of single gene and syndromic causes of obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Cubital tunnel syndrome caused by hypertrophic burn scarring: Sonographic envisage

    Directory of Open Access Journals (Sweden)

    Alparslan Bayram Carli

    2015-08-01

    Full Text Available In nerve entrapment syndromes, an electrodiagnostic study during physical examination would usually suffice to assess localization of injury. However, in daily clinical practice, sometimes it may be necessary to depict the insight; in other words to use an imaging tool. From this point of view, with its manifold advantages, ultrasound (US is superior to other imaging technologies such as magnetic resonance imaging (MRI. According to a study, US increased the sensitivity of electrodiagnostic studies from 78% to 98%. By presenting a patient with cubital tunnel syndrome caused by hypertrophic scarring, we wanted to highlight the complementary role of US in nerve entrapment syndromes in confirming the entrapment, as well as the usefulness of it in the follow-up period of burn patients. [Hand Microsurg 2015; 4(2.000: 44-46

  8. Prevalence and causes of back pain syndromes in children

    Directory of Open Access Journals (Sweden)

    A.A. Smirnova

    2014-01-01

    Full Text Available We present a review of literature devoted to epidemiology, and the nosological and syndromal structure of back pain in children. The data of our own study of school-aged children with back pain are presented. The structure of back pain syndromes in 105 children has been analyzed using the medical aid appealability data. The results of a comprehensive clinical and instrumental study demonstrated that the children mostly had lumbosacral pain (52.4% of cases; neck pain was observed in 29.5% of cases; while thoracic pain syndromes were observed in 18.1% of cases. Congenital defect of the connective tissue was diagnosed in 16.19% of children; congenital abnormalities of the spine, in 15.2%; scoliosis (idiopathic and secondary, in 8.6%; and Scheuermann-Mau's disease, in 5.71%. The conclusion has been made about the high prevalence of back pain in schoolchildren. Muscular tonic syndromes were prevailing in the clinical structure in children; radicular syndromes were less frequent. Musculoskeletal disorders were the main causes of back pain. Congenital defect of the connective tissue was often observed, which was revealed as functional instability of the vertebral motor segment, spondylolisthesis due to weak ligaments, and disc protrusions. Congenital abnormalities of the spine, scoliosis, and Scheuermann-Mau' disease were observed less often. 

  9. Lipoma causing Guyon's canal syndrome: a case report and review

    Directory of Open Access Journals (Sweden)

    Narayanathu Chellappantilla Sreekumar

    2014-12-01

    Full Text Available Compression of the ulnar nerve in Guyon's canal leads to Guyon's canal syndrome. Lipoma is a rare cause of such compressions with only 12 cases reported previously. We report a 55-year-old man who presented with swelling in the left hand with decreased sensation in the ring and little fingers. Magnetic resonance imaging revealed high signals in T1-weighted and T2-weighted images with suppression of the short T1 inversion recovery signal, suggestive of lipoma. On exploration a well-encapsulated, dumbbell-shaped, fatty tumor was seen in the hypothenar space and Guyon's canal. The tumor was enucleated in toto. At 6-month follow-up, the patient had fully regained sensation. A review of the literature is presented for similar cases where a lipoma was the cause of Guyon's canal syndrome.

  10. Therapeutic Management of Hypothenar Hammer Syndrome Causing Ulnar Nerve Entrapment

    Directory of Open Access Journals (Sweden)

    Emanuele Cigna

    2010-01-01

    Full Text Available Introduction. The hypothenar hammer syndrome is a rare traumatic vascular disease of the hand. Method and Materials. We report the case of a 43-years-old man with a painful tumefaction of the left hypothenar region. The ulnar artery appeared thrombosed clinically and radiologically. The patient underwent surgery to resolve the ulnar nerve compression and revascularise the artery. Results. The symptoms disappeared immediately after surgery. The arterial flow was reestablished. Postoperatively on day 20, a new thrombosis of the ulnar artery occurred. Conclusion. Hypothenar hammer syndrome is caused by repetitive trauma to the heel of the hand. The alterations of the vessel due to its chronic inflammation caused an acute compression of the ulnar nerve at the Guyon's canal and, in our case, do not allow a permanent revascularisation of the ulnar artery.

  11. Trismus Pseudocamptodactyly Syndrome: A Sporadic Cause of Trismus

    OpenAIRE

    Prathima Sreenivasan; Peedikayil, Faizal C.; Sumal V. Raj; Manasa Anand Meundi

    2013-01-01

    Trismus pseudocamptodactyly syndrome is a very rare autosomal dominant inherited disorder characterized by the inability to completely open the mouth (trismus) and the presence of abnormally short tendon units causing the fingers to curve (camptodactyly). Early diagnosis and management of this condition is important to prevent facial deformities in the patient. Reporting such a case is important as case reports are one of the sources of data for calculating the prevalence of rare diseases. He...

  12. Intronic splicing mutations in PTCH1 cause Gorlin syndrome.

    Science.gov (United States)

    Bholah, Zaynab; Smith, Miriam J; Byers, Helen J; Miles, Emma K; Evans, D Gareth; Newman, William G

    2014-09-01

    Gorlin syndrome is an autosomal dominant disorder characterized by multiple early-onset basal cell carcinoma, odontogenic keratocysts and skeletal abnormalities. It is caused by heterozygous mutations in the tumour suppressor PTCH1. Routine clinical genetic testing, by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) to confirm a clinical diagnosis of Gorlin syndrome, identifies a mutation in 60-90 % of cases. We undertook RNA analysis on lymphocytes from ten individuals diagnosed with Gorlin syndrome, but without known PTCH1 mutations by exonic sequencing or MLPA. Two altered PTCH1 transcripts were identified. Genomic DNA sequence analysis identified an intron 7 mutation c.1068-10T>A, which created a strong cryptic splice acceptor site, leading to an intronic insertion of eight bases; this is predicted to create a frameshift p.(His358Alafs*12). Secondly, a deep intronic mutation c.2561-2057A>G caused an inframe insertion of 78 intronic bases in the cDNA transcript, leading to a premature stop codon p.(Gly854fs*3). The mutations are predicted to cause loss of function of PTCH1, consistent with its tumour suppressor function. The findings indicate the importance of RNA analysis to detect intronic mutations in PTCH1 not identified by routine screening techniques.

  13. Homeostatic Imbalance between Apoptosis and Cell Renewal in the Liver of Premature Aging XpdTTD Mice

    Science.gov (United States)

    Park, Jung Yoon; Cho, Mi-Ook; Leonard, Shanique; Calder, Brent; Mian, I. Saira; Kim, Woo Ho; Wijnhoven, Susan; van Steeg, Harry; Mitchell, James; van der Horst, Gijsbertus T. J.; Hoeijmakers, Jan; Cohen, Pinchas; Vijg, Jan; Suh, Yousin

    2008-01-01

    Unrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. XpdTTD mice, harboring defects in nucleotide excision repair and transcription due to a mutation in the Xpd gene (R722W), display severe symptoms of premature aging but have a reduced incidence of cancer. To gain further insight into the molecular basis of the mutant-specific manifestation of age-related phenotypes, we used comparative microarray analysis of young and old female livers to discover gene expression signatures distinguishing XpdTTD mice from their age-matched wild type controls. We found a transcription signature of increased apoptosis in the XpdTTD mice, which was confirmed by in situ immunohistochemical analysis and found to be accompanied by increased proliferation. However, apoptosis rate exceeded the rate of proliferation, resulting in homeostatic imbalance. Interestingly, a metabolic response signature was observed involving decreased energy metabolism and reduced IGF-1 signaling, a major modulator of life span. We conclude that while the increased apoptotic response to endogenous DNA damage contributes to the accelerated aging phenotypes and the reduced cancer incidence observed in the XpdTTD mice, the signature of reduced energy metabolism is likely to reflect a compensatory adjustment to limit the increased genotoxic stress in these mutants. These results support a general model for premature aging in DNA repair deficient mice based on cellular responses to DNA damage that impair normal tissue homeostasis. PMID:18545656

  14. Gitelman's syndrome as a cause of poorly controlled hypokalemia.

    Science.gov (United States)

    Dimitrijevic, Z; Salinger-Martinovic, S; Mitic, B; Nikolic, V

    2015-01-01

    Gitelman's syndrome is a rare autosomal recessive tubulopathy caused by a defect of the thiazide-sensitive sodium chloride co-transporter at the distal tubule, leading to hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria and low-to-normal blood pressure. Clinical features include transient periods of muscle weakness and tetany, dizziness, abdominal pains and constipation. Patients can also present with convulsions due to severe metabolic alkalosis or hypomagnesemia. Therefore, early recognition and treatment are important. Diagnosis of Gitelman's syndrome is usually made incidentally during adolescence or early adulthood based on clinical and biochemical findings. In this paper we present the case of a 23-year-old female patient referred to our nephrology department for severe hypokalemia. Complementary evaluation revealed hypokalemia, hypomagnesemia, metabolic alkalosis, increased chloride and sodium urinary excretion and reduced urinary calcium excretion with normal renal function. A diagnosis of Gitelman syndrome was established. Treatment included magnesium and potassium salts and potassium saving diuretics. In general, the long-term prognosis of Gitelman's syndrome is good if the patient adhere with the treatment.

  15. Cerebral Salt-Wasting Syndrome Caused by Minor Head Injury.

    Science.gov (United States)

    Fukuoka, Toshiki; Tsurumi, Yuko; Tsurumi, Arihito

    2017-01-01

    A 34-year-old woman was admitted to hospital after sustaining a head injury in a motor vehicle accident (day 1). No signs of neurological deficit, skull fracture, brain contusion, or intracranial bleeding were evident. She was discharged without symptoms on day 4. However, headache and nausea worsened on day 8, at which time serum sodium level was noted to be 121 mEq/L. Treatment with sodium chloride was initiated, but serum sodium decreased to 116 mEq/L on day 9. Body weight decreased in proportion to the decrease in serum sodium. Cerebral salt-wasting syndrome was diagnosed. This case represents the first illustration of severe hyponatremia related to cerebral salt-wasting syndrome caused by a minor head injury.

  16. Cerebral Salt-Wasting Syndrome Caused by Minor Head Injury

    Directory of Open Access Journals (Sweden)

    Toshiki Fukuoka

    2017-01-01

    Full Text Available A 34-year-old woman was admitted to hospital after sustaining a head injury in a motor vehicle accident (day 1. No signs of neurological deficit, skull fracture, brain contusion, or intracranial bleeding were evident. She was discharged without symptoms on day 4. However, headache and nausea worsened on day 8, at which time serum sodium level was noted to be 121 mEq/L. Treatment with sodium chloride was initiated, but serum sodium decreased to 116 mEq/L on day 9. Body weight decreased in proportion to the decrease in serum sodium. Cerebral salt-wasting syndrome was diagnosed. This case represents the first illustration of severe hyponatremia related to cerebral salt-wasting syndrome caused by a minor head injury.

  17. Frontal mucocele with intracranial extension causing frontal lobe syndrome.

    Science.gov (United States)

    Weidmayer, Sara

    2015-06-01

    Mucoceles are mucus-containing cysts that form in paranasal sinuses; although mucoceles themselves are benign, this case report highlights the extensive damage they can cause as their expansion may lead to bony erosion and extension of the mucocele into the orbit and cranium; it also presents a rarely reported instance of frontal sinus mucocele leading to frontal lobe syndrome. A thorough discussion and review of mucoceles is included. A 68-year-old white man presented with intermittent diplopia and a pressure sensation in the right eye. He had a history of chronic sinusitis and had had endoscopic sinus surgery 5 years prior. A maxillofacial computed tomography scan revealed a large right frontal sinus mucocele, which had caused erosion along the medial wall of the right orbit and the outer and inner tables of the right frontal sinus. The mucocele had protruded both into the right orbit and intracranially, causing mass effect on the frontal lobe, which led to frontal lobe syndrome. The patient was successfully treated with endoscopic right ethmoidectomy, radial frontal sinusotomy, marsupialization of the mucocele, and transcutaneous irrigation. Paranasal sinus mucoceles may expand and lead to bony erosion and can become very invasive in surrounding structures such as the orbit and cranium. This case not only exhibits a very rare presentation of frontal sinus mucocele with intracranial extension and frontal lobe mass effect causing a frontal lobe syndrome but also demonstrates many of the ocular and visual complications commonly associated with paranasal sinus mucoceles. Early identification and surgical intervention is vital for preventing and reducing morbidity associated with invasive mucoceles, and the patient must be followed regularly to monitor for recurrence.

  18. Alcohol-induced Cushing syndrome. Hypercortisolism caused by alcohol abuse.

    Science.gov (United States)

    Besemer, F; Pereira, A M; Smit, J W A

    2011-01-01

    Cushing's syndrome (CS), a rare syndrome caused by overexposure to glucocorticoids, is difficult to diagnose. The underlying causes of CS include pituitary and ectopic adrenocorticotropic hormone (ACTH) producing tumours and adrenal adenomas or hyperplasia. Alcoholism, however, can cause similar symptoms, giving rise to a so-called pseudo-Cushing state, which aggravates the differential diagnostic dilemmas of CS. To document any specific clinical or biochemical features of alcohol-induced CS. A Medline computer-aided search was performed to identify studies that have attempted to differentiate between alcohol-induced pseudo-Cushing and CS. Only original articles, not reviews, written in English were included. A total of 62 articles were included. Clinical and biochemical abnormalities mimicking increased hypothalamus-pituitary-adrenal (HPA) axis activity were found in the majority of the patients, although the severity of the changes varied widely. The most frequently occurring abnormalities were: insufficient suppression after low-dose dexamethasone or increased 24-hour urinary free cortisol (UFC). After alcohol withdrawal, cortisol decreased and dexamethasone-induced suppression of cortisol increased. No differences were noted between alcoholic and control subjects after an ACTH stimulation test, insulin tolerance test or metyrapone test. Differences were found after a naloxone test and hexarelin test. Studies using corticotropin-releasing hormone stimulation and tests after ethanol ingestion revealed inconclusive results. There is no clear definition for the alcohol-induced pseudo-Cushing state, and hitherto studies fail to provide clues to differentiate between pseudo-Cushing and Cushing's syndrome. Only cessation of alcohol can normalise biochemical abnormalities and regress hypercortisolic symptoms.

  19. A model of premature aging in mice based on altered stress-related behavioral response and immunosenescence.

    Science.gov (United States)

    Viveros, María-Paz; Arranz, Lorena; Hernanz, Angel; Miquel, Jaime; De la Fuente, Mónica

    2007-01-01

    The intensity of behavioral and neuroendocrine responses to stressful stimuli in rodent strains seems to be inversely related to their life span. We have previously shown that interindividual differences in members of outbred Swiss and inbred BALB/c mouse populations, both male and female, may be related to their behavior in a simple T-maze test. The animals that explore the maze slowly show impaired neuromuscular vigor and coordination, decreased locomotor activity, increased level of emotionality/anxiety, decreased levels of brain biogenic amines as well as immunosenescence and decreased life span, when compared to their control counterparts, which quickly explore the maze. These traits are similar to some of the alterations previously observed in aging animals and therefore we proposed that those 'slow mice' are biologically older than the fast animals and may be a model of prematurely aging mice (PAM). Although most of our work on this model has been performed on chronologically adult-mature animals, we have also shown that certain characteristics of PAM, such as increased anxiety and deficient immune response, are already present in chronologically young animals. Thus, it is tempting to hypothesize that chronic hyperreactivity to stress (trait anxiety) leading to immune dysfunction may have a causal relationship with impaired health and premature aging. In view of the link between oxidative stress and the aging process, the redox state of peritoneal leukocytes from PAM has been studied, showing an oxidative stress situation. In the present work we have determined the levels of a key antioxidant, reduced glutathione (GSH), and the oxidant malondialdehyde (MDA), a marker of lipid peroxidation, both in the spleen and brain of male and female PAM and non-PAM (NPAM). We found that GSH and MDA are decreased and increased, respectively, in PAM with respect to NPAM. Moreover, diet supplementation with antioxidants showed to be an effective strategy for protection

  20. [Cyriax's syndrome. A cause of diagnostic error in abdominal pains].

    Science.gov (United States)

    Monnin, J L; Pierrugues, R; Bories, P; Michel, H

    The slipping rib syndrome is characterized by upper abdominal pain due to irritation of the intercostal nerve by incomplete dislocation of the costal cartilage of the 8th, 9th, or 10th ribs. Twenty-three new cases are reported and the literature is reviewed. Diagnosis is only clinical. The pain is precipitated by movement and certain postures; it is faithfully reproduced by pressure on one particular point of the costal margin and is relieved by local injection of an anaesthetic. Pain from a slipping rib is usually attributed to visceral causes, which is a source of diagnostic errors.

  1. Proteus syndrome: A rare cause of gigantic limb

    Directory of Open Access Journals (Sweden)

    Nandini Chakrabarti

    2014-01-01

    Full Text Available A congenital disorder with variable manifestations, including partial gigantism of the hands and feet with hypertrophy of soles, nevi, hemihypertrophy, gynecomastia, macrocephaly and other skull abnormalities, and abdominal lipomatosis. The cause is unknown, although a genetic origin, generally of autosomal-dominant transmission, has been conjectured. Symptoms can be treated, but there is no known cure. We present the case of a young male with grotesque overgrowth of the right lower limb, splenomegaly and multiple nevi. Angiography revealed venous malformation within the limb. The findings are in conformity to the criteria for the Proteus syndrome.

  2. [Hemolytic uremic syndrome caused by enterohaemorrhagic Escherichia coli].

    Science.gov (United States)

    Ibarra, Cristina; Goldstein, Jorge; Silberstein, Claudia; Zotta, Elsa; Belardo, Marcela; Repetto, Horacio A

    2008-10-01

    Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, plaquetopenia and kidney damage. It is the leading cause of acute renal failure in pediatric age and the second for chronic renal failure. Shiga toxin-producing Escherichia coli (STEC) is the first etiologic agent of HUS being its main reservoir cattle and transmitted via contaminated food. At present, there is no specific treatment to reduce the progression of HUS. The study of the mechanisms by which STEC infects and Shiga toxin induces HUS can help to find new strategies to prevent this disease.

  3. Unusual cause of childhood anemia: Imerslund grasbeck syndrome

    Directory of Open Access Journals (Sweden)

    Kishan Prasad Hosapatna Laxminarayana

    2011-01-01

    Full Text Available Imerslund Grasbeck syndrome (IGS is a rare autosomal recessive childhood disorder characterized by selective Vitamin (vit B 12 malabsorption with asymptomatic proteinuria without any structural renal pathology. The patients stay healthy for decades with life-long parenteral vit B12. We report a case of young female who presented with pancytopenia and proteinuria, evaluated in local hospitals as chronic hemolytic anemia (autoimmune cause, finally diagnosed as IGS on complete evaluation. She was treated with injectable vit B12 (1000 μg cyanocobalalmin and showed drastic recovery. IGS should be considered in patients with megaloblastic anemia not responding to oral vit B12 and associated proteinuria.

  4. Loss of HtrA2/Omi activity in non-neuronal tissues of adult mice causes premature aging.

    Science.gov (United States)

    Kang, S; Louboutin, J-P; Datta, P; Landel, C P; Martinez, D; Zervos, A S; Strayer, D S; Fernandes-Alnemri, T; Alnemri, E S

    2013-02-01

    mnd2 mice die prematurely as a result of neurodegeneration 30-40 days after birth due to loss of the enzymatic activity of the mitochondrial quality control protease HtrA2/Omi. Here, we show that transgenic expression of human HtrA2/Omi in the central nervous system of mnd2 mice rescues them from neurodegeneration and prevents their premature death. Interestingly, adult transgenic mnd2 mice develop accelerated aging phenotypes, such as premature weight loss, hair loss, reduced fertility, curvature of the spine, heart enlargement, increased autophagy, and death by 12-17 months of age. These mice also have elevated levels of clonally expanded mitochondrial DNA (mtDNA) deletions in their tissues. Our results provide direct genetic evidence linking mitochondrial protein quality control to mtDNA deletions and aging in mammals.

  5. Prehospital Dextrose Extravasation Causing Forearm Compartment Syndrome: A Case Report.

    Science.gov (United States)

    Chinn, Matthew; Colella, M Riccardo

    2017-01-01

    A 57-year-old woman was found at home by paramedics to be hypoglycemic with altered mental status. She had multiple attempts at IV access and eventually a 22G IV was established and D50 was infused into her right forearm. Extravasation of the dextrose was noted after approximately 12 g of the medication was infused. She was given a dose of glucagon intramuscularly and her mental status improved. Shortly after her arrival to the emergency department, she was noted to have findings of compartment syndrome of her forearm at the site of the dextrose extravasation. She was evaluated by plastic surgery and taken to the operating room for emergent fasciotomy. She recovered well from the operation. D50 is well known to cause phlebitis and local skin necrosis as a complication. This case illustrates the danger of compartment syndrome after D50 extravasation. It is the first documented case of prehospital dextrose extravasation leading to compartment syndrome. There may be safer alternatives to D50 administration and providers must be acutely aware to monitor for D50 infusion complications.

  6. Subacromial Impingement Syndrome Caused by a Voluminous Subdeltoid Lipoma

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Murray

    2014-01-01

    Full Text Available Subacromial impingement syndrome is a clinical diagnosis encompassing a spectrum of possible etiologies, including subacromial bursitis, rotator cuff tendinopathy, and partial- to full-thickness rotator cuff tears. This report presents an unusual case of subdeltoid lipoma causing extrinsic compression and subacromial impingement syndrome. The patient, a 60-year-old man, presented to our institution with a few years' history of nontraumatic, posteriorly localized throbbing pain in his right shoulder. Despite a well-followed 6-months physiotherapy program, the patient was still suffering from his right shoulder. The MRI scan revealed a well-circumscribed 6 cm × 2 cm × 5 cm homogenous lesion compatible with a subdeltoid intermuscular lipoma. The mass was excised en bloc, and subsequent histopathologic examination confirmed a benign lipoma. At 6-months follow-up, the patient was asymptomatic with a complete return to his activities. Based on this case and a review of the literature, a subacromial lipoma has to be included in the differential diagnosis of a subacromial impingement syndrome refractory to nonoperative treatment. Complementary imaging modalities are required only after a failed conservative management to assess the exact etiology and successfully direct the surgical treatment.

  7. Sporadic premature aging in a Japanese monkey: a primate model for progeria.

    Directory of Open Access Journals (Sweden)

    Takao Oishi

    Full Text Available In our institute, we have recently found a child Japanese monkey who is characterized by deep wrinkles of the skin and cataract of bilateral eyes. Numbers of analyses were performed to identify symptoms representing different aspects of aging. In this monkey, the cell cycle of fibroblasts at early passage was significantly extended as compared to a normal control. Moreover, both the appearance of senescent cells and the deficiency in DNA repair were observed. Also, pathological examination showed that this monkey has poikiloderma with superficial telangiectasia, and biochemical assay confirmed that levels of HbA1c and urinary hyaluronan were higher than those of other (child, adult, and aged monkey groups. Of particular interest was that our MRI analysis revealed expansion of the cerebral sulci and lateral ventricles probably due to shrinkage of the cerebral cortex and the hippocampus. In addition, the conduction velocity of a peripheral sensory but not motor nerve was lower than in adult and child monkeys, and as low as in aged monkeys. However, we could not detect any individual-unique mutations of known genes responsible for major progeroid syndromes. The present results indicate that the monkey suffers from a kind of progeria that is not necessarily typical to human progeroid syndromes.

  8. Sporadic premature aging in a Japanese monkey: a primate model for progeria.

    Science.gov (United States)

    Oishi, Takao; Imai, Hiroo; Go, Yasuhiro; Imamura, Masanori; Hirai, Hirohisa; Takada, Masahiko

    2014-01-01

    In our institute, we have recently found a child Japanese monkey who is characterized by deep wrinkles of the skin and cataract of bilateral eyes. Numbers of analyses were performed to identify symptoms representing different aspects of aging. In this monkey, the cell cycle of fibroblasts at early passage was significantly extended as compared to a normal control. Moreover, both the appearance of senescent cells and the deficiency in DNA repair were observed. Also, pathological examination showed that this monkey has poikiloderma with superficial telangiectasia, and biochemical assay confirmed that levels of HbA1c and urinary hyaluronan were higher than those of other (child, adult, and aged) monkey groups. Of particular interest was that our MRI analysis revealed expansion of the cerebral sulci and lateral ventricles probably due to shrinkage of the cerebral cortex and the hippocampus. In addition, the conduction velocity of a peripheral sensory but not motor nerve was lower than in adult and child monkeys, and as low as in aged monkeys. However, we could not detect any individual-unique mutations of known genes responsible for major progeroid syndromes. The present results indicate that the monkey suffers from a kind of progeria that is not necessarily typical to human progeroid syndromes.

  9. CtIP Mutations Cause Seckel and Jawad Syndromes.

    Directory of Open Access Journals (Sweden)

    Per Qvist

    2011-10-01

    Full Text Available Seckel syndrome is a recessively inherited dwarfism disorder characterized by microcephaly and a unique head profile. Genetically, it constitutes a heterogeneous condition, with several loci mapped (SCKL1-5 but only three disease genes identified: the ATR, CENPJ, and CEP152 genes that control cellular responses to DNA damage. We previously mapped a Seckel syndrome locus to chromosome 18p11.31-q11.2 (SCKL2. Here, we report two mutations in the CtIP (RBBP8 gene within this locus that result in expression of C-terminally truncated forms of CtIP. We propose that these mutations are the molecular cause of the disease observed in the previously described SCKL2 family and in an additional unrelated family diagnosed with a similar form of congenital microcephaly termed Jawad syndrome. While an exonic frameshift mutation was found in the Jawad family, the SCKL2 family carries a splicing mutation that yields a dominant-negative form of CtIP. Further characterization of cell lines derived from the SCKL2 family revealed defective DNA damage induced formation of single-stranded DNA, a critical co-factor for ATR activation. Accordingly, SCKL2 cells present a lowered apoptopic threshold and hypersensitivity to DNA damage. Notably, over-expression of a comparable truncated CtIP variant in non-Seckel cells recapitulates SCKL2 cellular phenotypes in a dose-dependent manner. This work thus identifies CtIP as a disease gene for Seckel and Jawad syndromes and defines a new type of genetic disease mechanism in which a dominant negative mutation yields a recessively inherited disorder.

  10. CtIP Mutations Cause Seckel and Jawad Syndromes.

    Directory of Open Access Journals (Sweden)

    Per Qvist

    2011-10-01

    Full Text Available Seckel syndrome is a recessively inherited dwarfism disorder characterized by microcephaly and a unique head profile. Genetically, it constitutes a heterogeneous condition, with several loci mapped (SCKL1-5 but only three disease genes identified: the ATR, CENPJ, and CEP152 genes that control cellular responses to DNA damage. We previously mapped a Seckel syndrome locus to chromosome 18p11.31-q11.2 (SCKL2. Here, we report two mutations in the CtIP (RBBP8 gene within this locus that result in expression of C-terminally truncated forms of CtIP. We propose that these mutations are the molecular cause of the disease observed in the previously described SCKL2 family and in an additional unrelated family diagnosed with a similar form of congenital microcephaly termed Jawad syndrome. While an exonic frameshift mutation was found in the Jawad family, the SCKL2 family carries a splicing mutation that yields a dominant-negative form of CtIP. Further characterization of cell lines derived from the SCKL2 family revealed defective DNA damage induced formation of single-stranded DNA, a critical co-factor for ATR activation. Accordingly, SCKL2 cells present a lowered apoptopic threshold and hypersensitivity to DNA damage. Notably, over-expression of a comparable truncated CtIP variant in non-Seckel cells recapitulates SCKL2 cellular phenotypes in a dose-dependent manner. This work thus identifies CtIP as a disease gene for Seckel and Jawad syndromes and defines a new type of genetic disease mechanism in which a dominant negative mutation yields a recessively inherited disorder.

  11. Pallister-Killian syndrome: an unusual cause of epileptic spasms.

    Science.gov (United States)

    Sánchez-Carpintero, Rocio; McLellan, Ailsa; Parmeggiani, Lucio; Cockwell, Annette E; Ellis, Richard J; Cross, J Helen; Eckhardt, Susan; Guerrini, Renzo

    2005-11-01

    Pallister-Killian syndrome (PKS) is a rare, sporadic, genetic disorder characterized by dysmorphic features, learning disability, and epilepsy. It is caused by a mosaic supernumerary isochromosome 12p (i[12p]). The i(12p) is rarely found in peripheral blood but it is present in skin fibroblasts. Recognition is essential for cytogenetic diagnosis. We describe a male aged 2 years 6 months and a female aged 11 years with PKS and epileptic spasms (ES). This type of seizure is not unusual in patients with brain malformations and with severe developmental delay, but it is sometimes difficult to recognize without video-electroencephalogram studies and could be mistaken for other types of seizure or behavioural manifestations. In these two patients with PKS, spasms had late onset, persisted beyond infancy, and were drug resistant. Clinicians should be aware of this possibility in PKS, which appears to be a rare cause of ES.

  12. Intracranial hemorrhage revealing pseudohypoparathyroidism as a cause of fahr syndrome.

    Science.gov (United States)

    Swami, Abhijit; Kar, Giridhari

    2011-01-01

    Pseudohypoparathyroidism is an infrequently encountered disease. It is one of the causes of Fahr syndrome which also is a rare clinical entity caused by multiple diseases. A 4-year-old man hospitalized for sudden onset left hemiparesis and hypertension was diagnosed to have right thalamic and midbrain hemorrhage on plain CT scan of the head which also revealed co-existent extensive intracranial calcifications involving the basal ganglia and cerebellum bilaterally. General physical examination revealed features of Albright hereditary osteodystrophy, goitre, hypertension, left hemiparesis, and signs of cerebellar dysfunction. Laboratory findings suggested hypocalcemia, hyperphosphatemia along with high TSH, low FT(4), low FT(3), and high anti-TPO antibody. Though bilateral intracranial calcifications are usually encountered as an incidental radiological finding in the CT scan of brain, in this case, the patient admitted for thalamic and midbrain hemorrhage was on investigation for associated intracranial calcification, and goitre was also found to have coexisting pseudohypoparathyroidism and autoimmune hypothyroidism.

  13. Leg Weakness Caused by Bilateral Piriformis Syndrome: A Case Report.

    Science.gov (United States)

    Moon, Hee Bong; Nam, Ki Yeun; Kwon, Bum Sun; Park, Jin Woo; Ryu, Gi Hyeong; Lee, Ho Jun; Kim, Chang Jae

    2015-12-01

    Piriformis syndrome (PS) is an uncommon neuromuscular disorder caused by the piriformis muscle (PM) compressing the sciatic nerve (SN). The main symptom of PS is sciatica, which worsens with certain triggering conditions. Because the pathophysiology is poorly understood, there are no definite diagnostic and therapeutic choices for PS. This case report presents a young woman who mainly complained of bilateral leg weakness. Electromyography revealed bilateral sciatic neuropathy and magnetic resonance imaging confirmed structural lesions causing entrapment of the bilateral SNs. After a laborious diagnosis of bilateral PS, she underwent PM releasing surgery. Few PS cases present with bilateral symptoms and leg weakness. Therefore, in such cases, a high level of suspicion is necessary for accurate and prompt diagnosis and treatment.

  14. [Neuroleptic malignant syndrome : Rare cause of fever of unknown origin].

    Science.gov (United States)

    Chackupurakal, R; Wild, U; Kamm, M; Wappler, F; Reske, D; Sakka, S G

    2015-07-01

    Neuroleptic malignant syndrome (NMS) is a possible cause of fever of unknown origin (FUO) and is a potentially fatal adverse effect of various drugs, especially of neuroleptics. First generation antipsychotics, such as received by the patient described in this article, are more likely to cause NMS than second generation antipsychotics. The key symptoms are the development of severe muscle rigidity and elevated temperature associated with the use of neuroleptic medication. Malignant catatonia (MC) is an important differential diagnosis of NMS. While neuroleptics can trigger NMS and must be immediately discontinued if NMS occurs, neuroleptic therapy represents the first line treatment for MC. This article describes the case of a patient with schizoaffective disorder where initially the diagnosis of NMS was not clear. Eventually, fever and a markedly elevated serum creatine kinase (CK) led to the correct diagnosis and the appropriate therapy with dantrolene, bromocriptine and amantadine. Furthermore, a thorough review of the currently available literature on NMS is provided.

  15. Intracranial Hemorrhage Revealing Pseudohypoparathyroidism as a Cause of Fahr Syndrome

    Directory of Open Access Journals (Sweden)

    Abhijit Swami

    2011-01-01

    Full Text Available Pseudohypoparathyroidism is an infrequently encountered disease. It is one of the causes of Fahr syndrome which also is a rare clinical entity caused by multiple diseases. A 4-year-old man hospitalized for sudden onset left hemiparesis and hypertension was diagnosed to have right thalamic and midbrain hemorrhage on plain CT scan of the head which also revealed co-existent extensive intracranial calcifications involving the basal ganglia and cerebellum bilaterally. General physical examination revealed features of Albright hereditary osteodystrophy, goitre, hypertension, left hemiparesis, and signs of cerebellar dysfunction. Laboratory findings suggested hypocalcemia, hyperphosphatemia along with high TSH, low FT4, low FT3, and high anti-TPO antibody. Though bilateral intracranial calcifications are usually encountered as an incidental radiological finding in the CT scan of brain, in this case, the patient admitted for thalamic and midbrain hemorrhage was on investigation for associated intracranial calcification, and goitre was also found to have coexisting pseudohypoparathyroidism and autoimmune hypothyroidism.

  16. Disruption of PTPRO Causes Childhood-Onset Nephrotic Syndrome

    Science.gov (United States)

    Ozaltin, Fatih; Ibsirlioglu, Tulin; Taskiran, Ekim Z.; Baydar, Dilek Ertoy; Kaymaz, Figen; Buyukcelik, Mithat; Kilic, Beltinge Demircioglu; Balat, Ayse; Iatropoulos, Paraskevas; Asan, Esin; Akarsu, Nurten A.; Schaefer, Franz; Yilmaz, Engin; Bakkaloglu, Ayşin

    2011-01-01

    Idiopathic nephrotic syndrome (INS) is a genetically heterogeneous group of disorders characterized by proteinuria, hypoalbuminemia, and edema. Because it typically results in end-stage kidney disease, the steroid-resistant subtype (SRNS) of INS is especially important when it occurs in children. The present study included 29 affected and 22 normal individuals from 17 SRNS families; genome-wide analysis was performed with Affymetrix 250K SNP arrays followed by homozygosity mapping. A large homozygous stretch on chromosomal region 12p12 was identified in one consanguineous family with two affected siblings. Direct sequencing of protein tyrosine phosphatase receptor type O (PTPRO; also known as glomerular epithelial protein-1 [GLEPP1]) showed homozygous c.2627+1G>T donor splice-site mutation. This mutation causes skipping of the evolutionarily conserved exon 16 (p.Glu854_Trp876del) at the RNA level. Immunohistochemistry with GLEPP1 antibody showed a similar staining pattern in the podocytes of the diseased and control kidney tissues. We used a highly polymorphic intragenic DNA marker—D12S1303—to search for homozygosity in 120 Turkish and 13 non-Turkish individuals in the PodoNet registry. This analysis yielded 17 candidate families, and a distinct homozygous c.2745+1G>A donor splice-site mutation in PTPRO was further identified via DNA sequencing in a second Turkish family. This mutation causes skipping of exon 19, and this introduces a premature stop codon at the very beginning of exon 20 (p.Asn888Lysfs∗3) and causes degradation of mRNA via nonsense-mediated decay. Immunohistochemical analysis showed complete absence of immunoreactive PTPRO. Ultrastructural alterations, such as diffuse foot process fusion and extensive microvillus transformation of podocytes, were observed via electron microscopy in both families. The present study introduces mutations in PTPRO as another cause of autosomal-recessive nephrotic syndrome. PMID:21722858

  17. Acute compartment syndrome of the forearm caused by calcific tendinitis of the distal biceps.

    Science.gov (United States)

    Garayoa, Santiago Amillo; Romero-Muñoz, Luis M; Pons-Villanueva, Juan

    2010-12-01

    Acute compartment syndrome of the forearm requires immediate treatment to avoid damage of the soft tissues and a poor functional outcome for the forearm. Muscular and bone lesions are the main causes of acute compartment syndromes. We report a case of acute compartment syndrome of the forearm caused by a calcific tendinitis of the distal biceps.

  18. Phenotype-Dependent Coexpression Gene Clusters: Application to Normal and Premature Ageing.

    Science.gov (United States)

    Wang, Kun; Das, Avinash; Xiong, Zheng-Mei; Cao, Kan; Hannenhalli, Sridhar

    2015-01-01

    Hutchinson Gilford progeria syndrome (HGPS) is a rare genetic disease with symptoms of aging at a very early age. Its molecular basis is not entirely clear, although profound gene expression changes have been reported, and there are some known and other presumed overlaps with normal aging process. Identification of genes with agingor HGPS-associated expression changes is thus an important problem. However, standard regression approaches are currently unsuitable for this task due to limited sample sizes, thus motivating development of alternative approaches. Here, we report a novel iterative multiple regression approach that leverages co-expressed gene clusters to identify gene clusters whose expression co-varies with age and/or HGPS. We have applied our approach to novel RNA-seq profiles in fibroblast cell cultures at three different cellular ages, both from HGPS patients and normal samples. After establishing the robustness of our approach, we perform a comparative investigation of biological processes underlying normal aging and HGPS. Our results recapitulate previously known processes underlying aging as well as suggest numerous unique processes underlying aging and HGPS. The approach could also be useful in detecting phenotype-dependent co-expression gene clusters in other contexts with limited sample sizes.

  19. Homozygous Nonsense Mutations in TWIST2 Cause Setleis Syndrome

    Science.gov (United States)

    Tukel, Turgut; Šošić, Dražen; Al-Gazali, Lihadh I.; Erazo, Mónica; Casasnovas, Jose; Franco, Hector L.; Richardson, James A.; Olson, Eric N.; Cadilla, Carmen L.; Desnick, Robert J.

    2010-01-01

    The focal facial dermal dysplasias (FFDDs) are a group of inherited developmental disorders in which the characteristic diagnostic feature is bitemporal scar-like lesions that resemble forceps marks. To date, the genetic defects underlying these ectodermal dysplasias have not been determined. To identify the gene defect causing autosomal-recessive Setleis syndrome (type III FFDD), homozygosity mapping was performed with genomic DNAs from five affected individuals and 26 members of the consanguineous Puerto Rican (PR) family originally described by Setleis and colleagues. Microsatellites D2S1397 and D2S2968 were homozygous in all affected individuals, mapping the disease locus to 2q37.3. Haplotype analyses of additional markers in the PR family and a consanguineous Arab family further limited the disease locus to ∼3 Mb between D2S2949 and D2S2253. Of the 29 candidate genes in this region, the bHLH transcription factor, TWIST2, was initially sequenced on the basis of its known involvement in murine facial development. Homozygous TWIST2 nonsense mutations, c.324C>T and c.486C>T, were identified in the affected members of the Arab and PR families, respectively. Characterization of the expressed mutant proteins, p.Q65X and p.Q119X, by electrophoretic mobility shift assays and immunoblot analyses indicated that they were truncated and unstable. Notably, Setleis syndrome patients and Twist2 knockout mice have similar facial features, indicating the gene's conserved role in mammalian development. Although human TWIST2 and TWIST1 encode highly homologous bHLH transcription factors, the finding that TWIST2 recessive mutations cause an FFDD and dominant TWIST1 mutations cause Saethre-Chotzen craniocynostosis suggests that they function independently in skin and bone development. PMID:20691403

  20. A novel ICK mutation causes ciliary disruption and lethal endocrine-cerebro-osteodysplasia syndrome

    OpenAIRE

    Kayserili Karabey, Hülya; Oud, M.M.; Bonnard, C.; Mans, D.A.; Altunoğlu, U.; Tohari, S.; Ng, A.Y.J.; Eskin, A.; Lee, H.; Rupar, C.A.; Wagenaar, N.P.; Wu, K.M.; Lahiry, P.; Pazour, G.J.; Nelson, S.F.; Hegele, R.A.; Roepman, R; Venkatesh, B.; Siu, V.M.; Reversade, B.; Arts, H.H.

    2016-01-01

    Background: Endocrine-cerebro-osteodysplasia (ECO) syndrome [MIM:612651] caused by a recessive mutation (p.R272Q) in Intestinal cell kinase (ICK) shows significant clinical overlap with ciliary disorders. Similarities are strongest between ECO syndrome, the Majewski and Mohr-Majewski short-rib thoracic dysplasia (SRTD) with polydactyly syndromes, and hydrolethalus syndrome. In this study, we present a novel homozygous ICK mutation in a fetus with ECO syndrome and compare the effect of this mu...

  1. Rare cause of natural death in forensic setting: hemophagocytic syndrome.

    Science.gov (United States)

    Ondruschka, B; Habeck, J-O; Hädrich, C; Dreßler, J; Bayer, R

    2016-05-01

    We report about the case of a sudden unexpected death of a 25-year-old male suffering from infectious disease. An autopsy was ordered with no final premortem diagnosis. Microscopic and microbiological examination revealed a pneumococcal bronchopneumonia and hemophagocytic lesions in the bone marrow. After integrating clinical and autopsy reports as well as additional postmortem investigations, the cause of death was found to be infectious-triggered hemophagocytic syndrome (HPS) with a final cytokine storm. This seems to be the first reported fatal case of a reactive form of HPS associated to Streptococcus pneumoniae to the best of our knowledge. HPS is a dangerous hyperinflammation with highly characteristic, but nonspecific, laboratory findings and symptoms. Autopsies in such cases must be carefully performed and include systematic tissue sampling done by an experienced pathologist.

  2. Impact of Oxidative Stress in Premature Aging and Iron Overload in Hemodialysis Patients

    Science.gov (United States)

    Hernández Vázquez, Wendy Ivett; Solorio-Meza, Sergio; Albarrán-Tamayo, Froylán; Ramos-Rodríguez, Edna; Benítez- Bribiesca, Luis

    2016-01-01

    Background. Increased oxidative stress is a well described feature of patients in hemodialysis. Their need for multiple blood transfusions and supplemental iron causes a significant iron overload that has recently been associated with increased oxidation of polyunsaturated lipids and accelerated aging due to DNA damage caused by telomere shortening. Methods. A total of 70 patients were evaluated concomitantly, 35 volunteers with ferritin levels below 500 ng/mL (Group A) and 35 volunteers with ferritin levels higher than 500 ng/mL (Group B). A sample of venous blood was taken to extract DNA from leukocytes and to measure relative telomere length by real-time PCR. Results. Patients in Group B had significantly higher plasma TBARS (p = 0.008), carbonyls (p = 0.0004), and urea (p = 0.02) compared with those in Group A. Telomeres were significantly shorter in Group B, 0.66 (SD, 0.051), compared with 0.75 (SD, 0.155) in Group A (p = 0.0017). We observed a statistically significant association between relative telomere length and ferritin levels (r = −0.37, p = 0.001). Relative telomere length was inversely related to time on hemodialysis (r = −0.27, p = 0.02). Conclusions. Our findings demonstrate that iron overload was associated with increased levels of oxidative stress and shorter relative telomere length. PMID:27800120

  3. Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Ullrich, Nicole J; Gordon, Leslie B

    2015-01-01

    Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare, uniformly fatal, segmental "premature aging" disease in which children exhibit phenotypes that may give us insights into the aging process at both the cellular and organismal levels. Initial presentation in early childhood is primarily based on growth and dermatologic findings. Primary morbidity and mortality for children with HGPS is from atherosclerotic cardiovascular disease and strokes with death occurring at an average age of 14.6 years. There is increasing data to support a unique phenotype of the craniofacial and cerebrovascular anatomy that accompanies the premature aging process. Strokes in HGPS can occur downstream of carotid artery and/or vertebral artery occlusion, stenosis, and calcification, with prominent collateral vessel formation. Both large and small vessel disease are present, and strokes are often clinically silent. Despite the presence of multisystem premature aging, children with HGPS do not appear to have cognitive deterioration, suggesting that some aspects of brain function may be protected from the deleterious effects of progerin, the disease-causing protein. Based on limited autopsy material, there is no pathologic evidence of dementia or Alzheimer-type changes. In a transgenic mouse model of progeria with expression of the most common HGPS mutation in brain, skin, bone, and heart, there are distortions of neuronal nuclei at the ultrastructural level with irregular shape and severe invaginations, but no evidence of inclusions or aberrant tau in brain sections. Importantly, the nuclear distortions did not result in significant changes in gene expression in hippocampal neurons. This chapter will discuss both preclinical and clinical aspects of the genetics, pathobiology, clinical phenotype, clinical care, and treatment of HGPS, with special attention toward neurologic and cutaneous findings.

  4. A high-fat diet and NAD+ activate sirt1 to rescue premature aging in cockayne syndrome

    DEFF Research Database (Denmark)

    Scheibye-Knudsen, Morten; Mitchell, Sarah J.; Fang, Evandro F.;

    2014-01-01

    SIRT1 activity and mitochondrial dysfunction. Notably, β-hydroxybutyrate levels are increased by the high-fat diet, and β-hydroxybutyrate, PARP inhibition, or NAD+ supplementation can activate SIRT1 and rescue CS-associated phenotypes. Mechanistically, CSB can displace activated PARP1 from damaged DNA...... to limit its activity. This study connects two emerging longevity metabolites, β-hydroxybutyrate and NAD+, through the deacetylase SIRT1 and suggests possible interventions for CS....

  5. Evidence of a normal mean telomere fragment length in patients with Ullrich-Turner syndrome

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Gravholt, Claus Højbjerg; Kassem, M

    2001-01-01

    Clinical and epidemiological studies suggest that premature ageing and increased morbidity and mortality is present in Ullrich-Turner syndrome. We studied telomere restriction fragment length (TRFL) in 30 women with Ullrich-Turner syndrome and 30 age-matched control women. All Turner women had...... with excessive telomere loss, at least when studied in peripheral blood leucocytes, and thus quite different from other premature ageing syndromes....

  6. The medial tibial stress syndrome. A cause of shin splints.

    Science.gov (United States)

    Mubarak, S J; Gould, R N; Lee, Y F; Schmidt, D A; Hargens, A R

    1982-01-01

    The medial tibial stress syndrome is a symptom complex seen in athletes who complain of exercise-induced pain along the distal posterior-medial aspect of the tibia. Intramuscular pressures within the posterior compartments of the leg were measured in 12 patients with this disorder. These pressures were not elevated and therefore this syndrome is a not a compartment syndrome. Available information suggests that the medial tibial stress syndrome most likely represents a periostitis at this location of the leg.

  7. A rare cause of acromegaly: McCune-Albright syndrome

    Directory of Open Access Journals (Sweden)

    Erdal Bodakçi

    2015-06-01

    Full Text Available McCune-Albright syndrome is characterized by polyostatic fibrous dysplasia, brown spots on the skin (café au lait pigmentation and autonomous endocrine hyperfunction. Early puberty and other endocrinological manifestations, such as acromegaly, gigantism and hypercortisolism are widely observed in the syndrome. Acromegaly is seen in 20% of patients. We report a case of acromegaly accompanied with this syndrome.

  8. The superior vena cava syndrome caused by malignant disease

    Energy Technology Data Exchange (ETDEWEB)

    Eren, Suat [Department of Radiology, Faculty of Medicine, Atatuerk University, 25240 Erzurum (Turkey)]. E-mail: suateren@atauni.edu.tr; Karaman, Adem [Department of Radiology, Faculty of Medicine, Atatuerk University, 25240 Erzurum (Turkey); Okur, Adnan [Department of Radiology, Faculty of Medicine, Atatuerk University, 25240 Erzurum (Turkey)

    2006-07-15

    Objective: The superior vena cava (SVC) obstruction by malignant diseases is either by direct invasion and compression or by tumour thrombus of the SVC. Whatever is its cause, obstruction of the SVC causes elevated pressure in the veins draining into the SVC and increased or reversed blood flow through collateral vessels. Severity of the syndrome depends on the collateral vascular system development. Therefore, imaging of the collateral veins with variable location and connection is important in determining the extension and management of the disease. Our aims are to describe collateral vessels of the superior vena cava syndrome (SVCS) related with the malignant diseases and to assess the ability of multi-detector row CT with multiplanar and 3D volume rendering techniques in determining and describing collateral circulations. Materials and methods: We present CT angiography findings of seven patients with small cell carcinoma of the lung (n = 2), squamous cell carcinoma of the lung (n = 3), Hodgkin disease of the thorax (n = 1), and squamous cell carcinoma of the oesophagus (n = 1). The patients received contrast-enhanced CT scans of the chest and abdomen on a multi-detector row CT during breath holding at suspended inspiration. Results: CT images revealed the cause and level of the SVC obstruction in all patients with axial and multiplanar reconstructed images. The SVC showed total obstruction in five patients and partial obstruction in two patients. The most common experienced collateral vessels were azygos vein (6), intercostal veins (6), mediastinal veins (6), paravertebral veins (5), hemiazygos vein (5), thoracoepigastric vein (5), internal mammary vein (5), thoracoacromioclavicular venous plexus (5), and anterior chest wall veins (5). While one case showed the portal-systemic shunt, V. cordis media and sinus coronarius with phrenic veins were enlarged in two cases, and the left adrenal vein was enlarged in a patient. In one case, the azygos vein with reversed

  9. Mitochondrial disorder caused Charles Darwin's cyclic vomiting syndrome.

    Science.gov (United States)

    Finsterer, Josef; Hayman, John

    2014-01-08

    Charles Darwin (CD), "father of modern biology," suffered from multisystem illness from early adulthood. The most disabling manifestation was cyclic vomiting syndrome (CVS). This study aims at finding the possible cause of CVS in CD. A literature search using the PubMed database was carried out, and CD's complaints, as reported in his personal writings and those of his relatives, friends, colleagues, biographers, were compared with various manifestations of mitochondrial disorders (MIDs), known to cause CVS, described in the literature. Organ tissues involved in CD's disease were brain, nerves, muscles, vestibular apparatus, heart, gut, and skin. Cerebral manifestations included episodic headache, visual disturbance, episodic memory loss, periodic paralysis, hysterical crying, panic attacks, and episodes of depression. Manifestations of polyneuropathy included numbness, paresthesias, increased sweating, temperature sensitivity, and arterial hypotension. Muscular manifestations included periods of exhaustion, easy fatigability, myalgia, and muscle twitching. Cardiac manifestations included episodes of palpitations and chest pain. Gastrointestinal manifestations were CVS, dental problems, abnormal seasickness, eructation, belching, and flatulence. Dermatological manifestations included painful lips, dermatitis, eczema, and facial edema. Treatments with beneficial effects to his complaints were rest, relaxation, heat, and hydrotherapy. CVS in CD was most likely due to a multisystem, nonsyndromic MID. This diagnosis is based upon the multisystem nature of his disease, the fact that CVS is most frequently the manifestation of a MID, the family history, the variable phenotypic expression between affected family members, the fact that symptoms were triggered by stress, and that only few symptoms could not be explained by a MID.

  10. A rare cause of tall stature: Sotos syndrome

    Directory of Open Access Journals (Sweden)

    Nagehan Aslan

    2014-12-01

    Full Text Available Sotos syndrome is an excessive growth syndrome and is characterized by macrocephaly, typical facial appearance and mental retardation. The majority of cases are sporadic, autosomal dominant inheritance pattern matching families have been reported. Syndrome responsible for gen encodes the nuclear receptor-binding SET domain1 (NSD1 protein. This rare genetic syndrome firstly described by Sotos et al. in 1964 at five cases with excessive height, acromegalic appearance and mild mental retardation. Hairline high forehead, macrocephaly, frontal bossing, long and thin face, frontotemporal hair sparseness, down slanting palpebral fissures and prominent mandible creating characteristic facial appearance and advanced bone age and varying degrees of mental retardation are other diagnostic criteria. Cardiovascular, central nervous system and genitourinary system anomalies may be associated with syndrome. In this case report we presenting a case who admitted to our clinic because of the rapid growth and mild mental retardation and diagnosed with Sotos syndrome for emphasize the importance of growth monitoring.

  11. An Aggressive Sphenoid Wing Meningioma Causing Foster Kennedy Syndrome

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    Harpreet S. Walia

    2012-01-01

    Full Text Available Foster Kennedy syndrome is a rare neurological condition with ophthalmic significance that can manifest as acute visual loss. It is classically characterised by unilateral optic nerve atrophy and contralateral papilledema resulting from an intracranial neoplasm. Physicians should consider Foster Kennedy syndrome in patients who present with visual loss and who have a history of intracranial neoplasm. In addition to ophthalmologic examination, neuroimaging is essential for the diagnosis of Foster Kennedy syndrome.

  12. Wallenberg Syndrome: An Exceptional Cause of Acute Vertigo in Children.

    Science.gov (United States)

    Ehresmann, Aude Ménétrey; Van, Hélène Cao; Merlini, Laura; Fluss, Joel

    2016-01-01

    The assessment of acute vertigo in childhood is often challenging, but fortunately a central cause is rarely identified. We present the case of a 7-year-old boy who developed, after a mild head trauma, a rotary vertigo associated with nausea and vomiting. A posttraumatic peripheral vestibular dysfunction was first suspected but not confirmed by an otoneurological evaluation. When subtle neurological signs were elicited, a brain magnetic resonance imaging was promptly requested. This showed a small infarct on the lateral posterior left part of the medulla oblongata of the brainstem, typical of Wallenberg syndrome. Vascular imaging was normal and no defined etiology was found. The child was started on prophylactic acetylsalicylic acid. The rapid disappearance of vertigo was noted. On follow-up at 6 months, there has been no recurrence and neurological examination was fully normal. Our case extends the differential diagnosis of acute vertigo in childhood that rarely includes the possibility of a brainstem infarct whose recognition through appropriate clinical examination is nevertheless capital for appropriate investigations and management. Georg Thieme Verlag KG Stuttgart · New York.

  13. Seizure-triggered Takotsubo syndrome rarely causes SUDEP.

    Science.gov (United States)

    Finsterer, Josef; Bersano, Anna

    2015-09-01

    Since almost 20 y it is known that seizures may trigger Takotsubo syndrome (TTS). Since then it has been repeatedly proposed that TTS could be the cause of sudden unexpected death in epilepsy (SUDEP). A review of the so far reported cases of seizure-triggered TTS was carried out to see how often seizure-triggered TTS is fatal. Altogether 59 papers were identified which reported altogether 74 patients with seizure-triggered TTS. Age was reported in 70 patients and ranged from 18 to 82 y. Gender was reported in 70 cases and was female in 60 cases (86%). The type of triggering seizure was reported in 47 cases. In 28 patients (60%) the trigger was a generalized tonic clonic seizure, in 15 cases (32%) a generalized status epilepticus, and in 3 cases a complex partial seizure. The outcome was mentioned in 63 of the 74 patients. Full recovery was reported in 61 cases (97%), incomplete recovery in none of the patients, and a fatal outcome in 2 patients (3%). Fatalities are rare in patients experiencing seizure-triggered TTS. This is why seizure-triggered TTS does not seem to play a major role in the pathogenesis of SUDEP. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  14. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome

    Science.gov (United States)

    Lemaire, Mathieu; Frémeaux-Bacchi, Véronique; Schaefer, Franz; Choi, Murim; Tang, Wai Ho; Le Quintrec, Moglie; Fakhouri, Fadi; Taque, Sophie; Nobili, François; Martinez, Frank; Ji, Weizhen; Overton, John D.; Mane, Shrikant M.; Nürnberg, Gudrun; Altmüller, Janine; Thiele, Holger; Morin, Denis; Deschenes, Georges; Baudouin, Véronique; Llanas, Brigitte; Collard, Laure; Majid, Mohammed A.; Simkova, Eva; Nürnberg, Peter; Rioux-Leclerc, Nathalie; Moeckel, Gilbert W.; Gubler, Marie Claire; Hwa, John; Loirat, Chantal; Lifton, Richard P.

    2013-01-01

    Pathologic thrombosis is a major cause of mortality. Hemolytic-uremic syndrome (HUS) features episodes of small vessel thrombosis resulting in microangiopathic hemolytic anemia, thrombocytopenia and renal failure1. Atypical HUS (aHUS) can result from genetic or autoimmune factors2 that lead to pathologic complement cascade activation3. By exome sequencing we identify recessive mutations in DGKE (diacylglycerol kinase epsilon) that co-segregate with aHUS in 9 unrelated kindreds, defining a distinctive Mendelian disease. Affected patients present with aHUS before age 1, have persistent hypertension, hematuria and proteinuria (sometimes nephrotic range), and develop chronic kidney disease with age. DGKE is found in endothelium, platelets, and podocytes. Arachidonic acid-containing diacylglycerols (DAG) activate protein kinase C, which promotes thrombosis. DGKE normally inactivates DAG signaling. We infer that loss of DGKE function results in a pro-thrombotic state. These findings identify a new mechanism of pathologic thrombosis and kidney failure and have immediate implications for treatment of aHUS patients. PMID:23542698

  15. Mitochondrial disorder caused Charles Darwin's cyclic vomiting syndrome

    Directory of Open Access Journals (Sweden)

    Finsterer J

    2014-01-01

    Full Text Available Josef Finsterer,1 John Hayman21Krankenanstalt Rudolfstiftng, Vienna, Austria; 2Department of Pathology, University of Melbourne, Victoria, AustraliaBackground: Charles Darwin (CD, “father of modern biology,” suffered from multisystem illness from early adulthood. The most disabling manifestation was cyclic vomiting syndrome (CVS. This study aims at finding the possible cause of CVS in CD.Methods: A literature search using the PubMed database was carried out, and CD's complaints, as reported in his personal writings and those of his relatives, friends, colleagues, biographers, were compared with various manifestations of mitochondrial disorders (MIDs, known to cause CVS, described in the literature.Results: Organ tissues involved in CD's disease were brain, nerves, muscles, vestibular apparatus, heart, gut, and skin. Cerebral manifestations included episodic headache, visual disturbance, episodic memory loss, periodic paralysis, hysterical crying, panic attacks, and episodes of depression. Manifestations of polyneuropathy included numbness, paresthesias, increased sweating, temperature sensitivity, and arterial hypotension. Muscular manifestations included periods of exhaustion, easy fatigability, myalgia, and muscle twitching. Cardiac manifestations included episodes of palpitations and chest pain. Gastrointestinal manifestations were CVS, dental problems, abnormal seasickness, eructation, belching, and flatulence. Dermatological manifestations included painful lips, dermatitis, eczema, and facial edema. Treatments with beneficial effects to his complaints were rest, relaxation, heat, and hydrotherapy.Conclusion: CVS in CD was most likely due to a multisystem, nonsyndromic MID. This diagnosis is based upon the multisystem nature of his disease, the fact that CVS is most frequently the manifestation of a MID, the family history, the variable phenotypic expression between affected family members, the fact that symptoms were triggered by stress

  16. Cellular defects caused by hypomorphic variants of the Bloom syndrome helicase gene BLM.

    Science.gov (United States)

    Shastri, Vivek M; Schmidt, Kristina H

    2016-01-01

    Bloom syndrome is an autosomal recessive disorder characterized by extraordinary cancer incidence early in life and an average life expectancy of ~27 years. Premature stop codons in BLM, which encodes a DNA helicase that functions in DNA double-strand-break repair, make up the vast majority of Bloom syndrome mutations, with only 13 single amino acid changes identified in the syndrome. Sequencing projects have identified nearly one hundred single nucleotide variants in BLM that cause amino acid changes of uncertain significance. Here, in addition to identifying five BLM variants incapable of complementing certain defects of Bloom syndrome cells, making them candidates for new Bloom syndrome causing mutations, we characterize a new class of BLM variants that cause some, but not all, cellular defects of Bloom syndrome. We find elevated sister-chromatid exchanges, a delayed DNA damage response and inefficient DNA repair. Conversely, hydroxyurea sensitivity and quadriradial chromosome accumulation, both characteristic of Bloom syndrome cells, are absent. These intermediate variants affect sites in BLM that function in ATP hydrolysis and in contacting double-stranded DNA. Allele frequency and cellular defects suggest candidates for new Bloom syndrome causing mutations, and intermediate BLM variants that are hypomorphic which, instead of causing Bloom syndrome, may increase a person's risk for cancer or possibly other Bloom-syndrome-associated disorders, such as type-2 diabetes.

  17. Coracoid syndrome: a neglected cause of anterior shoulder pain

    Science.gov (United States)

    GIGANTE, ANTONIO; BOTTEGONI, CARLO; BARBADORO, PAMELA

    2016-01-01

    Purpose the present prospective open-label study was designed to gain further insights into a condition thought to constitute a neglected but not uncommon syndrome characterized by anterior shoulder pain and tenderness to palpation over the apex of the coracoid process, not related to rotator cuff or pectoralis minor tendinopathy, long head of the biceps tendon disorders, or instability. The aim was to clarify its prevalence, clinical characteristics, differential diagnosis and response to corticosteroid injections. Methods patients with primary anterior shoulder pain precisely reproduced by deep pressure on the apex of the coracoid process were recruited. Patients with clinical or instrumental signs of other shoulder disorders were excluded. Patients were given an injection of triamcinolone acetonide 40 mg/ml 1 ml at the coracoid trigger point. They were evaluated after 15, 30 and 60 days and at 2 years using Equal Visual Analog Scale (EQ-VAS) and the Italian version of the Simple Shoulder Test (SST). Results between January 1 and December 31 2010, we treated 15 patients aged 26–66 years. The majority were women (86.67%). At 15 days, 6 (40%) patients reported complete resolution of their symptoms, while 9 (60%) complained of residual symptoms and received another injection. At 30 days, 14 (93.33%) patients were pain-free and very satisfied. At 2 years, the 14 patients who had been asymptomatic at 30 days reported that they had experienced no further pain or impaired shoulder function. The analysis of variance for repeated measures showed a significant effect of time on EQ-VAS and SST scores. Conclusions the present study documents the existence, and characteristics, of a “coracoid syndrome” characterized by anterior shoulder pain and tenderness to palpation over the apex of the coracoid process and showed that the pain is usually amenable to steroid treatment. This syndrome should be clearly distinguished from anterior shoulder pain due to other causes, in

  18. Drowning as a Cause of Death in Angelman Syndrome.

    Science.gov (United States)

    Ishmael, Holly A.; Begleiter, Michael L.; Butler, Merlin G.

    2002-01-01

    This study reports on a 9-year-old boy previously diagnosed with Angelman syndrome who died unexpectedly by drowning in a shallow backyard wading pool. The case illustrates the fascination with water by individuals with Angelman syndrome and highlights that this fascination may lead to death. The need for supervision is stressed. (Contains 5…

  19. Rapunzel Syndrome: a rare cause of acute small bowel obstruction

    Directory of Open Access Journals (Sweden)

    Dr. Vipul D Yagnik

    2010-07-01

    Full Text Available The Rapunzel syndrome is a very rare condition where trichobezoar has extended up to the small bowel. Here we are reporting a rare case of Rapunzel syndrome in an adolescent girl with history of trichophagia who presented with small bowel obstruction. Patient underwent exploratory laparotomy and bezoar was removed through gastrotomy. Post-operative course was unremarkable.

  20. Abernethy syndrome, a rare cause of hypoxemia: A case report

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    Manoj Kumar Sahu

    2015-01-01

    Full Text Available Abernethy syndrome (congenital extrahepatic portosystemic shunt (CEPS II as an etiology of hepatopulmonary syndrome (HPS is uncommon. The severe hypoxemia and its consequences become incapacitating for the patient. Early shunt closure resolves hypoxemia and clinical symptomatology and prevents irreversible changes in pulmonary vasculature.

  1. De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome

    NARCIS (Netherlands)

    Burrage, L.C.; Charng, W.L.; Eldomery, M.K.; Willer, J.R.; Davis, E.E.; Lugtenberg, D.; Zhu, W.; Leduc, M.S.; Akdemir, Z.C.; Azamian, M.; Zapata, G.; Hernandez, P.P.; Schoots, J.; Munnik, S.A. de; Roepman, R.; Pearring, J.N.; Jhangiani, S.; Katsanis, N.; Vissers, L.E.L.M.; Brunner, H.G.; Beaudet, A.L.; Rosenfeld, J.A.; Muzny, D.M.; Gibbs, R.A.; Eng, C.M.; Xia, F.; Lalani, S.R.; Lupski, J.R.; Bongers, E.M.H.F.; Yang, Y

    2015-01-01

    Meier-Gorlin syndrome (MGS) is a genetically heterogeneous primordial dwarfism syndrome known to be caused by biallelic loss-of-function mutations in one of five genes encoding pre-replication complex proteins: ORC1, ORC4, ORC6, CDT1, and CDC6. Mutations in these genes cause disruption of the origin

  2. Anterior throat pain syndromes: causes for undiagnosed craniofacial pain.

    Science.gov (United States)

    Shankland, Wesley E

    2010-01-01

    It is not uncommon for practitioners who treat craniofacial pain to see patients with undiagnosed throat and submandibular pain. Usually, these patients will already have been seen by their primary care physician and frequently, several others doctors including otolaryngologists, oral and maxillofacial surgeons, and even neurologists. Far too often these patients have three common features: 1. they have endured multiple expensive diagnostic tests; 2. they have received treatment of multiple courses of antibiotics; and 3. no specific diagnosis for their pain complaints has been determined and their pain persists. In this article, five disorders, Ernest syndrome, Eagle's syndrome, carotid artery syndrome, hyoid bone syndrome and superior pharyngeal constrictor syndrome are briefly described. All five produce common symptoms, making diagnosis difficult, which is often followed by ineffective or no treatment being provided to the patient. Diagnostic criteria and suggested treatment modalities are also presented.

  3. Food protein induced enterocolitis syndrome caused by rice beverage.

    Science.gov (United States)

    Caminiti, Lucia; Salzano, Giuseppina; Crisafulli, Giuseppe; Porcaro, Federica; Pajno, Giovanni Battista

    2013-05-14

    Food protein-induced enterocolitis syndrome (FPIES) is an uncommon and potentially severe non IgE-mediated gastrointestinal food allergy. It is usually caused by cow's milk or soy proteins, but may also be triggered by ingestion of solid foods. The diagnosis is made on the basis of clinical history and symptoms. Management of acute phase requires fluid resuscitation and intravenous steroids administration, but avoidance of offending foods is the only effective therapeutic option.Infant with FPIES presented to our emergency department with vomiting, watery stools, hypothension and metabolic acidosis after ingestion of rice beverage. Intravenous fluids and steroids were administered with good clinical response. Subsequently, a double blind placebo control food challenge (DBPCFC) was performed using rice beverage and hydrolyzed formula (eHF) as placebo. The "rice based formula" induced emesis, diarrhoea and lethargy. Laboratory investigations reveal an increase of absolute count of neutrophils and the presence of faecal eosinophils. The patient was treated with both intravenous hydration and steroids. According to Powell criteria, oral food challenge was considered positive and diagnosis of FPIES induced by rice beverage was made. Patient was discharged at home with the indication to avoid rice and any rice beverage as well as to reintroduce hydrolyzed formula. A case of FPIES induced by rice beverage has never been reported. The present case clearly shows that also beverage containing rice proteins can be responsible of FPIES. For this reason, the use of rice beverage as cow's milk substitute for the treatment of non IgE-mediated food allergy should be avoided.

  4. Intermediate Phenotype between ADULT Syndrome and EEC Syndrome Caused by R243Q Mutation in TP63

    Science.gov (United States)

    Ueda, Koichi; Satoh, Chisei; Maekawa, Ryuta; Yoshiura, Koh-ichiro; Iseki, Sachiko

    2016-01-01

    Summary: A patient who had ectrodactyly, dry skin, exfoliative dermatitis, and hypodontia with peg-shaped teeth, but not cleft lip and palate, is described. Ectrodactyly with a tooth anomaly is recognized in both acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome and ectrodactyly-ectodermal dysplasia-cleft (EEC) syndrome. These 2 syndromes are caused by heterozygous mutations in the transcriptional factor gene p63. Mutation analysis of p63 gene showed a heterozygous mutation c.728G>A, p.Arg243Gln (previously referred to as R204Q) in the patient, but not in his parents. Therefore, this was a sporadic case of the p63 mutation–associated disorder. Although the mutation has been mostly reported in EEC syndrome patients, the present case did not have cleft lip and palate. Furthermore, the present case did not exhibit freckling or some of the other ectodermal dysplasia phenotypes typical of ADULT syndrome. The concept of ELA syndrome proposed by Prontera in 2011 resolves the problem confronted in diagnosing the present case. ELA syndrome is an acronym of EEC/limb–mammary syndrome/ADULT syndromes, and these 3 syndromes are united into a unique entity. This system can classify p63 mutation–associated disorders simply without interfering with treatment. PMID:28293528

  5. [Stiff baby syndrome is a rare cause of neonatal hypertonicity].

    Science.gov (United States)

    Rønne, Maria Sode; Nielsen, Preben Berg; Mogensen, Christian Backer

    2014-02-24

    Stiff baby syndrome (hyperekplexia) is a rare genetic disorder. The condition can easily be misdiagnosed as epilepsy or severe sepsis because of hypertonicity and seizure-like episodes and has an increased risk of severe apnoea and sudden infant death. Tapping of the nasal bridge inducing a startle response is the clinical hallmark. We report cases of two sisters born with stiff baby syndrome with hypertonicity, exaggerated startle reaction and cyanosis. The syndrome has a good prognosis if treated with clonazepam and both cases were developmental normal after one year.

  6. GITELMAN SYNDROME AS A RARE CAUSE OF HYPOKALEMIA - CASE REPORT

    Directory of Open Access Journals (Sweden)

    Zorica Dimitrijević

    2014-09-01

    Full Text Available Gitelman syndrome is a rare autosomal recessive tubulopathy leading to hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria and low-to-normal blood pressure. Clinical signs are mostly secondary to chronic hypokalemia and include dizziness, fatigue, constipation and weakness. Patients can also present with muscle cramps, tetany and convulsions due to severe metabolic alkalosis or hypomagnesemia. Therefore, early recognition and treatment are important. Diagnosis of Gitelman syndrome is usually made incidentally during adolescence or early adulthood based on clinical and biochemical findings. In this paper we report a case of a young women with classic Gitelman syndrome. Treatment included magnesium and potassium salts and potassium saving diuretics. In general, the long-term prognosis of Gitelman syndrome is excellent. However, the severity of fatigue may seriously hamper some patients in their daily activities.

  7. A Rare Cause of Pheochromocytoma; Neurofibromatosis Type 1-Noonan Syndrome

    Directory of Open Access Journals (Sweden)

    Mazhar Müslüm Tuna

    2014-09-01

    Full Text Available Neurofibromatosis (NF Type 1 (NF-1 is an autosomal dominant disease with a prevalence of about 1/3000. NF-1 is a neurocutaneous syndrome characterized by cafe au lait macules, neurofibroma, optic glioma, lisch nodules, and symptoms involving other systems. Noonan syndrome (NS is a clinically heterogeneous disorder predominantly characterized by dysmorphic facial features, congenital heart disease, proportionate post-natal short stature, neck abnormalities, and chest deformities. NF-NS is a very rare overlapping syndrome sharing many features of both syndromes. Coexistence of pheochromocytoma, which can be life-threatening if not treated properly, is also a very rare complication of this disorder. Here, we report a patient who was admitted with a mass in the right upper quadrant and was diagnosed with pheochromocytoma and NFNS. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 227-31

  8. Acute radiation syndrome caused by accidental radiation exposure - therapeutic principles

    Directory of Open Access Journals (Sweden)

    Dörr Harald

    2011-11-01

    Full Text Available Abstract Fortunately radiation accidents are infrequent occurrences, but since they have the potential of large scale events like the nuclear accidents of Chernobyl and Fukushima, preparatory planning of the medical management of radiation accident victims is very important. Radiation accidents can result in different types of radiation exposure for which the diagnostic and therapeutic measures, as well as the outcomes, differ. The clinical course of acute radiation syndrome depends on the absorbed radiation dose and its distribution. Multi-organ-involvement and multi-organ-failure need be taken into account. The most vulnerable organ system to radiation exposure is the hematopoietic system. In addition to hematopoietic syndrome, radiation induced damage to the skin plays an important role in diagnostics and the treatment of radiation accident victims. The most important therapeutic principles with special reference to hematopoietic syndrome and cutaneous radiation syndrome are reviewed.

  9. Blind loop syndrome: an unusual cause of panniculitis.

    Science.gov (United States)

    Caux, F; Halimi, C; Kevorkian, J P; Pinquier, L; Dubertret, L; Segrestaa, J M

    1997-11-01

    We describe a 52-year-old woman with panniculitis and blind loop syndrome. She had undergone a gastrectomy for peptic ulcer 4 years before. Tender erythematous nodules on her palms and soles were associated with diarrhea and weight loss. A biopsy specimen revealed septal and lobular panniculitis. A glucose hydrogen breath test was consistent with bacterial overgrowth. These results were consistent with panniculitis associated with a blind loop syndrome. Only four cases of this association have been reported previously.

  10. Late Onset Cobalamin Disorder and Hemolytic Uremic Syndrome: A Rare Cause of Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Gianluigi Ardissino

    2017-01-01

    Full Text Available Hemolytic uremic syndrome (HUS is an unrare and severe thrombotic microangiopathy (TMA caused by several pathogenetic mechanisms among which Shiga toxin-producing Escherichia coli infections and complement dysregulation are the most common. However, very rarely and particularly in neonates and infants, disorders of cobalamin metabolism (CblC can present with or be complicated by TMA. Herein we describe a case of atypical HUS (aHUS related to CblC disease which first presented in a previously healthy boy at age of 13.6 years. The clinical picture was initially dominated by nephrotic range proteinuria and severe hypertension followed by renal failure. The specific treatment with high dose of hydroxycobalamin rapidly obtained the remission of TMA and the complete recovery of renal function. We conclude that plasma homocysteine and methionine determinations together with urine organic acid analysis should be included in the diagnostic work-up of any patient with TMA and/or nephrotic syndrome regardless of age.

  11. Cortisol--cause and cure for metabolic syndrome?

    Science.gov (United States)

    Walker, B R

    2006-12-01

    Similarities between the metabolic syndrome and Cushing's syndrome, and reversibility of the features of Cushing's syndrome, suggest that cortisol may contribute to the pathophysiology of both conditions and that reducing cortisol action may provide a novel therapeutic approach in the metabolic syndrome. There is substantial evidence that circulating cortisol concentrations are higher in people with hypertension and glucose intolerance. The basis for this activation of the hypothalamic-pituitary-adrenal axis remains uncertain, but it may be attributable to 'programming' effects of events in early life, since it is associated with low birth weight. In obese people, intracellular cortisol levels within adipose tissue are further amplified by increased local regeneration of cortisol by the enzyme 11beta-HSD type 1. In mice, transgenic manipulations of 11beta-HSD1 have potent effects on obesity and associated features of the metabolic syndrome. Promising preclinical data suggest that novel 11beta-HSD1 inhibitors will have a role in lowering intracellular cortisol levels as a treatment for the metabolic syndrome. In addition to their metabolic effects, glucocorticoids act in the blood vessel wall. Pharmacoepidemiological studies suggest that glucocorticoid excess is an independent risk factor for cardiovascular disease. Recent data suggest that 11beta-HSD1 within the blood vessel wall influences vascular remodelling and angiogenesis, for example in the myocardium following coronary artery occlusion. Thus, glucocorticoid signalling provides a potentially tractable system to influence both risk factors for, and the outcome of, Type 2 diabetes and cardiovascular disease.

  12. Dental and craniofacial characteristics in a patient with Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Reichert, Christoph; Gölz, Lina; Götz, Werner; Wolf, Michael; Deschner, James; Jäger, Andreas

    2014-07-01

    The Hutchinson-Gilford progeria syndrome (HGPS) is an exceptionally rare medical disorder caused by mutations in the lamin A/C gene. Affected patients display typical features of premature aging. Beside general medical disorders, these patients have several specific features related to the craniofacial phenotype and the oral cavity. In this article, the dental and craniofacial characteristics of a 9-year-old girl with HGPS are presented. It is the first report addressing orthodontic tooth movement and microbiological features in a HGPS patient. We describe and discuss pathologic findings and provide a detailed histology of the teeth which had to be extracted during initial treatment.

  13. Rabson Mendenhall Syndrome caused by a novel missense mutation.

    Science.gov (United States)

    Sinnarajah, Krishnapradeep; Dayasiri, M B K C; Dissanayake, N D W; Kudagammana, S T; Jayaweera, A H H M

    2016-01-01

    Rabson Mendenhall syndrome is a rare endocrine condition characterized by severe insulin resistance and hyperglycemia. It occurs due to mutations in the insulin receptor gene. Few mutations which are associated with Rabson Mendenhall syndrome have been identified and reported in the past. The management of this condition is extremely challenging and will need multi-disciplinary approach. An 11 year old boy presented with polyuria and polydipsia. He was noted to have coarse facies, severe acanthosis nigricans, hypertrichosis, retarded growth and developmental delay. Investigations revealed severe hyperglycemia which was poorly responsive to high doses of insulin. A diagnosis of Rabson Mendenhall syndrome was suspected based on his physical characteristics in the presence of insulin resistance. Genetic studies revealed a homozygous missense mutation in the Insulin receptor gene confirming the diagnosis of Rabson Mendenhall syndrome. This is a novel mutation which has not been reported previously. Rabson Mendenhall syndrome should be suspected in a patient with characteristic physical features, severe hyperglycemia and insulin resistance. The genetic studies will not only confirm the diagnosis but also will help in counselling. Wider collaboration is needed to identify definitive treatment options for managing this rare condition.

  14. A Rare Cause for Cervical Pain: Eagle's Syndrome

    Directory of Open Access Journals (Sweden)

    Massimo Politi

    2009-01-01

    Full Text Available Patients with pharyngodynia and neck pain symptoms can lead to an extensive differential diagnosis. Eagle's syndrome must be taken in account. Eagle defined “stylalgia” as an autonomous entity related to abnormal length of the styloid process or to mineralization of the stylohyoid ligament complex. The stylohyoid complex derives from Reichert's cartilage of the second branchial arch. The styloyd process is an elongated conical projection of the temporal bone that lies anteriorly to the mastoid process. The incidence of Eagle's syndrome varies among population. Usually asymptomatic, it occurs in adult patients. It is characterized by pharyngodynia localized in the tonsillar fossa and sometimes accompanied by disphagia, odynophagia, foreign body sensation, and temporary voice changes. In some cases, the stylohyoid apparatus compresses the internal and/or the external carotid arteries and their perivascular sympathetic fibers, resulting in a persistent pain irradiating in the carotid territory. The pathogenesis of the syndrome is still under discussion.

  15. GAUCHER´S DISEASE: A RARE CAUSE OF FANCONI SYNDROME?

    Directory of Open Access Journals (Sweden)

    Musso CG

    2007-01-01

    Full Text Available Gaucher´s disease consists of a genetic autosomic recesive alteration that leads to a reduction in the acid glucosil-ceramide beta-glucosidase enzyme. This enzyme brakes the glucosilceramide, a substance from which many esphingo and glucolipids are synthesized. Even though the renal compromise is not frequent in Gaucher disease, proteinuria (in nephrotic range or not and glomerulonephritis have been described in this illness.Fanconi syndrome is charaterized by a dysfunction in the proximal tubular reabsorption. Among the etiologies of Fanconi syndrome there are many metabolic diseases, but no association has been described yet in the literature between Fanconi syndrome and Gaucher disease. We present the following case report where this association was observed.

  16. Unusual Cause of Horner Syndrome 13 Years After In Situ Ductal Carcinoma.

    Science.gov (United States)

    Zhou, Di; Ibrahim, Mohannad; Malach, Daniel; Tomsak, Robert L

    2016-06-01

    Horner syndrome can be caused by a wide range of pathologies along the sympathetic nerve chain, from the hypothalamus to the orbit. Imaging workup of Horner syndrome is necessary given the potential for deadly lesions, especially in a patient with a previous cancer history. The authors report a case of a woman who presented with a preganglionic Horner syndrome secondary to vertebral metastasis from previously diagnosed breast cancer that involved the neural foramina at T1 and T2.

  17. [Pellegrini-Stieda syndrome as a cause of knee pain].

    Science.gov (United States)

    Santos Sánchez, J A; Ramos Pascua, L R; García Casado, D; Bermúdez López, C

    2012-01-01

    Calcification in the soft tissue next to the medial femoral condyle after a history of trauma around the knee is a recognized radiographic finding-PS (Pellegrini-Stieda) sign. When this is associated with pain and a restricted range of motion it is known as the PS syndrome. We describe two cases of PS syndrome, treated conservatively with rest and physiotherapy, as well as the radiographic and ultrasound findings, and the many theories proposed in attempts to explain the pathogenesis of PS disease.

  18. [Sneddon syndrome: a rare cause of vascular dementia].

    Science.gov (United States)

    Lavernhe, S; Richard, A; Varvat, J; Garnier, P; Dirson, S; Thomas-Antérion, C

    2013-02-01

    Few vascular dementias are diagnosed in memory clinic consultations. One type, a rare etiology, Sneddon syndrome, can lead patients to consult for an isolated memory complaint. We report the cases of two patients, aged 63 and 66 years, who presented frontocortical cognitive profile and behavior disorders. Seronegative Sneddon syndrome, complicated with dementia, was diagnosed in each case by noticing an association between, on MRI, an atrophy and several ischemic cerebrovascular accident aftermaths, and a livedo racemosa. Management of vascular risks factors improves the prognosis.

  19. Prevalence and causes of back pain syndromes in children

    OpenAIRE

    Smirnova, A. A.; O.L. Lapochkin; M.A. Lobov; M.N. Borisova

    2014-01-01

    We present a review of literature devoted to epidemiology, and the nosological and syndromal structure of back pain in children. The data of our own study of school-aged children with back pain are presented. The structure of back pain syndromes in 105 children has been analyzed using the medical aid appealability data. The results of a comprehensive clinical and instrumental study demonstrated that the children mostly had lumbosacral pain (52.4% of cases); neck pain was observed in 29.5% of ...

  20. Plummer-Vinson syndrome: an unusual cause of dysphagia.

    Science.gov (United States)

    Ganesh, R; Janakiraman, L; Sathiyasekaran, M

    2008-06-01

    Plummer-Vinson syndrome, comprising a triad of dysphagia, iron deficiency anaemia and cricoid webs, is rarely reported in children. It is important to identify this condition not only to provide relief of symptoms by iron supplementation but also to include these children in surveillance programmes for oesophageal squamous cell carcinoma.

  1. Cantu syndrome is caused by mutations in ABCC9

    NARCIS (Netherlands)

    Bon, B.W. van; Gilissen, C.; Grange, D.K.; Hennekam, R.C.; Kayserili, H.; Engels, H.; Reutter, H.; Ostergaard, J.R.; Morava, E.; Tsiakas, K.; Isidor, B.; Merrer, M. le; Eser, M.; Wieskamp, N.; Vries, P. de; Steehouwer, M.; Veltman, J.A.; Robertson, S.P.; Brunner, H.G.; Vries, B.B. de; Hoischen, A.

    2012-01-01

    Cantu syndrome is a rare disorder characterized by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. Using an exome-sequencing approach applied to one proband-parent trio and three unrelated single cases, we identified heterozygous mutations in ABCC9

  2. Staphylococcal Toxic Shock Syndrome Caused by Tampon Use

    Directory of Open Access Journals (Sweden)

    Cian McDermott

    2015-01-01

    Full Text Available The authors report a case of near-fatal sepsis with multiorgan failure resulting from a Staphylococcal tampon-associated toxic shock syndrome, requiring a lengthy critical care admission. Successful treatment of this condition focuses on early identification, source control, and administration of antimicrobial agents. Intravenous immunoglobulin therapy used early may prevent widespread tissue necrosis.

  3. Autoimmune lymphoproliferative syndrome (ALPS): a rare cause of immune cytopenia.

    Science.gov (United States)

    John, M Joseph; Rajasekhar, Reena; Mathews, Vikram

    2008-02-01

    Autoimmune Lymphoproliferative syndrome (ALPS) is an inherited disorder manifesting with autoimmune cytopenia, lymphadenopathy and splenomegaly. The differential diagnosis includes infections, autoimmune disorders or malignancies. The disease is characterized by accumulation of double negative (CD3+ CD4- CD8-) T cells (DNT) in the peripheral blood. We describe a case and review the literature.

  4. A defect in dystrophin causes a novel porcine stress syndrome

    Science.gov (United States)

    Two sibling barrows were identified in the USMARC swine herd that died from apparent symptoms of a stress syndrome after transport to a research location at 12 weeks of age. The symptoms included open-mouth breathing, skin discoloration, vocalization and loss of mobility. The original mating was rep...

  5. Blastomyces gilchristii as Cause of Fatal Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Dalcin, Daniel; Rothstein, Aaron; Spinato, Joanna; Escott, Nicholas; Kus, Julianne V

    2016-02-01

    Since the 2013 description of Blastomyces gilchristii, research describing the virulence or clinical outcome of B. gilchristii infection has been lacking. We report molecular evidence of B. gilchristii as an etiologic agent of fatal acute respiratory distress syndrome. B. gilchristii infection was confirmed by PCR and sequence analysis.

  6. Dominant missense mutations in ABCC9 cause Cantu syndrome

    NARCIS (Netherlands)

    Harakalova, M.; van Harssel, J.J.; Terhal, P.A.; van Lieshout, S.; Duran, K.; Renkens, I.; Amor, D.J.; Wilson, L.C.; Kirk, E.P.; Turner, C.L.; Shears, D.; Garcia-Minaur, S.; Lees, M.M.; Ross, A.; Venselaar, H.; Vriend, G.; Takanari, H.; Rook, M.B.; van der Heyden, M.A.; Asselbergs, F.W.; Breur, H.M.; Swinkels, M.E.; Scurr, I.J.; Smithson, S.F.; Knoers, N.V.; van der Smagt, J.J.; Nijman, I.J.; Kloosterman, W.P.; van Haelst, M.M.; van Haaften, G.; Cuppen, E.

    2012-01-01

    Cantu syndrome is characterized by congenital hypertrichosis, distinctive facial features, osteochondrodysplasia and cardiac defects. By using family-based exome sequencing, we identified a de novo mutation in ABCC9. Subsequently, we discovered novel dominant missense mutations in ABCC9 in 14 of the

  7. Dominant missense mutations in ABCC9 cause Cantu syndrome.

    NARCIS (Netherlands)

    Harakalova, M.; Harssel, J.J. van; Terhal, P.A.; Lieshout, S. van; Duran, K.; Renkens, I.; Amor, D.J.; Wilson, L.C.; Kirk, E.P.; Turner, C.L.; Shears, D.; Garcia-Minaur, S.; Lees, M.M.; Ross, A.; Venselaar, H.; Vriend, G.; Takanari, H.; Rook, M.B.; Heyden, M.A. van der; Asselbergs, F.W.; Breur, H.M.; Swinkels, M.E.; Scurr, I.J.; Smithson, S.F.; Knoers, N.V.A.M.; Smagt, J.J. van der; Nijman, I.J.; Kloosterman, W.P.; Haelst, M.M. van; Haaften, G. van; Cuppen, E.

    2012-01-01

    Cantu syndrome is characterized by congenital hypertrichosis, distinctive facial features, osteochondrodysplasia and cardiac defects. By using family-based exome sequencing, we identified a de novo mutation in ABCC9. Subsequently, we discovered novel dominant missense mutations in ABCC9 in 14 of the

  8. KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes

    NARCIS (Netherlands)

    A. Putoux; S. Thomas; K.L.M. Coene; E.E. Davis; Y. Alanay; G. Ogur; E. Uz; D. Buzas; C. Gomes; S. Patrier; C.L. Bennett; N. Elkhartoufi; M.-H. Saint Frison; L. Rigonnot; N. Joye; S. Pruvost; G.E. Utine; K. Boduroglu; P. Nitschke; L. Fertitta; C. Thauvin-Robinet; A. Munnich; V. Cormier-Daire; R. Hennekam; E. Colin; N.A. Akarsu; C. Bole-Feysot; N. Cagnard; A. Schmitt; N. Goudin; S. Lyonnet; F. Encha-Razavi; J.P. Siffroi; M. Winey; N. Katsanis; M. Gonzales; M. Vekemans; P.L. Beales; T. Attie-Bitach

    2011-01-01

    KIF7, the human ortholog of Drosophila Costal2, is a key component of the Hedgehog signaling pathway. Here we report mutations in KIF7 in individuals with hydrolethalus and acrocallosal syndromes, two multiple malformation disorders with overlapping features that include polydactyly, brain abnormali

  9. Gerstmann's syndrome: can cardiac myxoma be the cause?

    Science.gov (United States)

    Sakellaridis, Timothy; Argiriou, Michalis; Koukis, Ioannis; Panagiotakopoulos, Vicror; Spiliotopoulos, Constantinos; Dimakopoulou, Antonia; Charitos, Christos

    2008-01-01

    Cardiac myxomas are primary cardiac tumours. Clinical presentations vary. Central nervous embolism has been a constant association. We describe a case of a 40-year-old female who presented with neurological signs and symptoms of Gerstmann's syndrome secondary to a left atrial myxoma.

  10. Determining the Amount, Timing and Causes of Mortality among Infants with Down Syndrome

    Science.gov (United States)

    Goldman, S. E.; Urbano, R. C.; Hodapp, R. M.

    2011-01-01

    Objective: To examine the amount, timing and causes/correlates of infant mortality among newborns with Down syndrome. Methods: Using the Tennessee Department of Health Birth, Hospital Discharge and Death records, infants were identified who were born with Down syndrome from 1990 to 2006. Those who died during the first year were separated into…

  11. A novel ICK mutation causes ciliary disruption and lethal endocrine-cerebro-osteodysplasia syndrome

    NARCIS (Netherlands)

    Oud, M.M.; Bonnard, C.; Mans, D.A.; Altunoglu, U.; Tohari, S.; Ng, A.Y.; Eskin, A.; Lee, H.; Rupar, C.A.; Wagenaar, N.P. de; Wu, K.M.; Lahiry, P.; Pazour, G.J.; Nelson, S.F.; Hegele, R.A.; Roepman, R.; Kayserili, H.; Venkatesh, B.; Siu, V.M.; Reversade, B.; Arts, H.H.

    2016-01-01

    BACKGROUND: Endocrine-cerebro-osteodysplasia (ECO) syndrome [MIM:612651] caused by a recessive mutation (p.R272Q) in Intestinal cell kinase (ICK) shows significant clinical overlap with ciliary disorders. Similarities are strongest between ECO syndrome, the Majewski and Mohr-Majewski short-rib

  12. TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome

    NARCIS (Netherlands)

    Lambacher, N.J.; Bruel, A.L.; Dam, T.J. van; Szymanska, K.; Slaats, G.G.; Kuhns, S.; McManus, G.J.; Kennedy, J.E.; Gaff, K.; Wu, K.M.; Lee, R. van der; Burglen, L.; Doummar, D.; Riviere, J.B.; Faivre, L.; Attie-Bitach, T.; Saunier, S.; Curd, A.; Peckham, M.; Giles, R.H.; Johnson, C.A.; Huynen, M.A.; Thauvin-Robinet, C.; Blacque, O.E.

    2016-01-01

    The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signalling by facilitating a protein diffusion barrier at the ciliary base. TZ defects cause ciliopathies such as Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome (JBTS). However, t

  13. Determining the Amount, Timing and Causes of Mortality among Infants with Down Syndrome

    Science.gov (United States)

    Goldman, S. E.; Urbano, R. C.; Hodapp, R. M.

    2011-01-01

    Objective: To examine the amount, timing and causes/correlates of infant mortality among newborns with Down syndrome. Methods: Using the Tennessee Department of Health Birth, Hospital Discharge and Death records, infants were identified who were born with Down syndrome from 1990 to 2006. Those who died during the first year were separated into…

  14. A novel ICK mutation causes ciliary disruption and lethal endocrine-cerebro-osteodysplasia syndrome

    NARCIS (Netherlands)

    Oud, M.M.; Bonnard, C.; Mans, D.A.; Altunoglu, U.; Tohari, S.; Ng, A.Y.; Eskin, A.; Lee, H.; Rupar, C.A.; Wagenaar, N.P. de; Wu, K.M.; Lahiry, P.; Pazour, G.J.; Nelson, S.F.; Hegele, R.A.; Roepman, R.; Kayserili, H.; Venkatesh, B.; Siu, V.M.; Reversade, B.; Arts, H.H.

    2016-01-01

    BACKGROUND: Endocrine-cerebro-osteodysplasia (ECO) syndrome [MIM:612651] caused by a recessive mutation (p.R272Q) in Intestinal cell kinase (ICK) shows significant clinical overlap with ciliary disorders. Similarities are strongest between ECO syndrome, the Majewski and Mohr-Majewski short-rib thora

  15. TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome

    NARCIS (Netherlands)

    Lambacher, N.J.; Bruel, A.L.; Dam, T.J. van; Szymanska, K.; Slaats, G.G.; Kuhns, S.; McManus, G.J.; Kennedy, J.E.; Gaff, K.; Wu, K.M.; Lee, R. van der; Burglen, L.; Doummar, D.; Riviere, J.B.; Faivre, L.; Attie-Bitach, T.; Saunier, S.; Curd, A.; Peckham, M.; Giles, R.H.; Johnson, C.A.; Huynen, M.A.; Thauvin-Robinet, C.; Blacque, O.E.

    2016-01-01

    The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signalling by facilitating a protein diffusion barrier at the ciliary base. TZ defects cause ciliopathies such as Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome (JBTS). However,

  16. [A case of sustained cholestasis caused by acute A viral hepatitis in Dubin-Johnson syndrome].

    Science.gov (United States)

    Ra, Sang Ho; Sung, Se Yong; Jung, Ho Yeon; Cha, Jae Hwang; Baik, Soon Koo; Cho, Mee Yon; Kim, Moon Young

    2012-04-01

    Dubin-Johnson syndrome is a rare clinical entity. It shows intermittent symptoms such as chronic or intermittent jaundice, abdominal pain, weakness, nausea, vomiting, anorexia and diarrhea. Symptoms are precipitated or aggravated by pregnancy, alcoholism, surgical procedures and intercurrent disease. Chronic idiopathic jaundice is typical of Dubin-Johnson syndrome and its prognosis is good. We describe a case of prolonged cholestasis for more than 10 months caused by acute A viral hepatitis in a patient with Dubin-Johnson syndrome. It is a first report of cholestasis complicated by acute A viral hepatitis in a patient with Dubin-Johnson syndrome.

  17. Superior mesenteric artery (SMA) syndrome: an unusual cause of intestinal obstruction in palliative care.

    Science.gov (United States)

    So, Chun-Yan; Chan, Kwok-Ying; Au, Ho-Yan; Chan, Man-Lui; Lai, Theresa

    2017-01-01

    Superior mesenteric artery (SMA) syndrome is an uncommon cause of intestinal obstruction and seldom been mentioned in palliative care. Hereby, we reported a case of SMA syndrome who presented with symptoms of upper intestinal obstruction in a 68-year-old patient; subsequent CT findings were classical of SMA syndrome. The patient's history of poliomyelitis and recent significant weight loss were the predisposing factors for SMA syndrome. It also highlights the importance of monitoring signs and symptoms of intestinal obstruction in such patients before considering switching to oral feeding.

  18. A Rare Cause of Abdominal Mass: Rapunzel Syndrome

    Directory of Open Access Journals (Sweden)

    Feyzullah Uçmak

    2016-03-01

    Full Text Available Bezoar is a condition in which foods or fibers that are not absorbed in the gastrointestinal system usually accumu­late in the stomach. It usually develops in persons with gastrointestinal motility disorders, anatomic changes or psychiatric disorders. Trichobezoar is the accumulation of hair in the gastric chamber among people with psychi­atric disorders such as trichotillomania and trichophagia. Rapunzel syndrome, however, is a rare form of trichobe­zoar extending from the stomach to the small intestine. In this paper, we present a rare case of 15-year old girl diagnosed with Rapunzel syndrome on admission due to abdominal pain and abdominal mass. J Clin Exp Invest 2016; 7 (1: 87-90

  19. Fulminant infection and toxic shock syndrome caused by Streptococcus pyogenes.

    Science.gov (United States)

    Fox, Kevin L; Born, Michael W; Cohen, Merrill A

    2002-05-01

    Two patients presented to the Emergency Department (ED) with features of toxic shock syndrome, including hypotension, acute respiratory distress syndrome (ARDS), renal and hepatic insufficiency and disseminated intravascular coagulation (DIC). Computed tomography (CT) scan identified the source of infection in one patient. At laparotomy, pelvic peritonitis and massive edema of the pelvic retroperitoneal tissue was found. The other patient had myonecrosis of the forearm necessitating amputation. Intra-operative cultures of tissue in each case yielded Streptococcus pyogenes, Group A. These patients were treated early with clindamycin and intensive supportive care as well as surgery, and both made a full recovery. Because of the necessity of early recognition of the varied presentation of these infections, the clinical features as well as essential interventions are emphasized. We review the pathophysiology of invasive Group A streptococcal infection to increase awareness of these uncommon but fulminant and often lethal infections.

  20. Mutations in TMEM231 cause Meckel-Gruber syndrome.

    Science.gov (United States)

    Shaheen, Ranad; Ansari, Shinu; Mardawi, Elham Al; Alshammari, Muneera J; Alkuraya, Fowzan S

    2013-03-01

    Meckel-Gruber syndrome (MKS) is a genetically heterogeneous severe ciliopathy characterised by early lethality, occipital encephalocele, polydactyly, and polycystic kidney disease. To report genetic analysis results in two families in which all known MKS diseases genes have been excluded. In two consanguineous families with classical MKS in which autozygome-guided sequencing of previously reported MKS genes was negative, we performed exome sequencing followed by autozygome filtration. We identified one novel splicing mutation in TMEM231, which led to complete degradation of the mutant transcript in one family, and a novel missense mutation in the other, both in the homozygous state. TMEM231 represents a novel MKS locus. The very recent identification of TMEM231 mutations in Joubert syndrome supports the growing appreciation of the overlap in the molecular pathogenesis between these two ciliopathies.

  1. Mutations in TMEM231 cause Meckel–Gruber syndrome

    Science.gov (United States)

    Shaheen, Ranad; Ansari, Shinu; Mardawi, Elham AL; Alshammari, Muneera J; Alkuraya, Fowzan S

    2013-01-01

    Background Meckel–Gruber syndrome (MKS) is a genetically heterogeneous severe ciliopathy characterised by early lethality, occipital encephalocele, polydactyly, and polycystic kidney disease. Purpose To report genetic analysis results in two families in which all known MKS diseases genes have been excluded. Methods In two consanguineous families with classical MKS in which autozygome-guided sequencing of previously reported MKS genes was negative, we performed exome sequencing followed by autozygome filtration. Results We identified one novel splicing mutation in TMEM231, which led to complete degradation of the mutant transcript in one family, and a novel missense mutation in the other, both in the homozygous state. Conclusions TMEM231 represents a novel MKS locus. The very recent identification of TMEM231 mutations in Joubert syndrome supports the growing appreciation of the overlap in the molecular pathogenesis between these two ciliopathies. PMID:23349226

  2. Cervical Disc Herniation Causing Brown-Séquard's Syndrome: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Tarush Rustagi

    2011-01-01

    Full Text Available Brown-Séquard's syndrome (BSS is caused by hemisection or hemicompression of the cord leading to ipsilateral motor deficit and contralateral sensory loss. Cervical disc herniation has been reported to be a rare cause of Brown-Séquard's syndrome. We describe a rare case of multilevel cervical disc herniation presenting as BSS. The condition was confirmed by MRI scan. Cervical corpectomy, decompression, and fusion gave a satisfying result. Pertinent literature has been reviewed.

  3. Cervical Disc Herniation Causing Brown-Séquard's Syndrome: A Case Report and Literature Review

    Science.gov (United States)

    Rustagi, Tarush; Badve, Siddharth; Maniar, Hemil; Parekh, Aseem N.

    2011-01-01

    Brown-Séquard's syndrome (BSS) is caused by hemisection or hemicompression of the cord leading to ipsilateral motor deficit and contralateral sensory loss. Cervical disc herniation has been reported to be a rare cause of Brown-Séquard's syndrome. We describe a rare case of multilevel cervical disc herniation presenting as BSS. The condition was confirmed by MRI scan. Cervical corpectomy, decompression, and fusion gave a satisfying result. Pertinent literature has been reviewed. PMID:23259105

  4. Cervical Disc Herniation Causing Brown-Séquard's Syndrome: A Case Report and Literature Review.

    Science.gov (United States)

    Rustagi, Tarush; Badve, Siddharth; Maniar, Hemil; Parekh, Aseem N

    2011-01-01

    Brown-Séquard's syndrome (BSS) is caused by hemisection or hemicompression of the cord leading to ipsilateral motor deficit and contralateral sensory loss. Cervical disc herniation has been reported to be a rare cause of Brown-Séquard's syndrome. We describe a rare case of multilevel cervical disc herniation presenting as BSS. The condition was confirmed by MRI scan. Cervical corpectomy, decompression, and fusion gave a satisfying result. Pertinent literature has been reviewed.

  5. Therapeutic Management of Hypothenar Hammer Syndrome Causing Ulnar Nerve Entrapment

    OpenAIRE

    2010-01-01

    Introduction. The hypothenar hammer syndrome is a rare traumatic vascular disease of the hand. Method and Materials. We report the case of a 43-years-old man with a painful tumefaction of the left hypothenar region. The ulnar artery appeared thrombosed clinically and radiologically. The patient underwent surgery to resolve the ulnar nerve compression and revascularise the artery. Results. The symptoms disappeared immediately after surgery. The arterial flow was reestablished. Postoperatively ...

  6. Piriformis syndrome surgery causing severe sciatic nerve injury.

    Science.gov (United States)

    Justice, Phillip E; Katirji, Bashar; Preston, David C; Grossman, Gerald E

    2012-09-01

    Piriformis syndrome is a controversial entrapment neuropathy in which the sciatic nerve is thought to be compressed by the piriformis muscle. Two patients developed severe left sciatic neuropathy after piriformis muscle release. One had a total sciatic nerve lesion, whereas the second had a predominantly high common peroneal nerve lesion. Follow-up studies showed reinnervation of the hamstrings only. We conclude that piriformis muscle surgery may be hazardous and result in devastating sciatic nerve injury.

  7. AORTIC ANEURYSM: A RARE CAUSE OF ORTNER’S SYNDROME

    OpenAIRE

    2014-01-01

    A 60 year old male patient presented with hoarseness of voice lasting for 2 months. First he was examined by the otorhinolaryngologist of our hospital, who noticed absence of movements of the left vocal cord. Chest X-ray showed a large opacity in the left upper zone and the patient was referred to the pulmonologist. His general physical examination was unremarkable not having any stigmata of Marfan's or Ehler Danlos syndrome. On chest auscultation, a systolic flow murmur was ...

  8. Delineation of a clinical syndrome caused by mosaic trisomy 15

    Energy Technology Data Exchange (ETDEWEB)

    Buehler, E.M.; Bienz, G.; Straumann, E.; Bosceh, N. [Univ. Children`s Hospital, Basel (Switzerland)

    1996-03-15

    We report on a boy with mosaic trisomy 15. The clinical manifestations are compared with those of the few cases reported up to now. A clinical syndrome is delineated consisting of a characteristic shape of the nose and other minor craniofacial anomalies, as well as typical deformities of the hands and feet. Different degrees of mosaicism may explain the more or less severe manifestations in individual patients. 10 refs., 4 figs., 1 tab.

  9. Novel EYA1 variants causing Branchio-oto-renal syndrome.

    Science.gov (United States)

    Klingbeil, Kyle D; Greenland, Christopher M; Arslan, Selcuk; Llamos Paneque, Arianne; Gurkan, Hakan; Demir Ulusal, Selma; Maroofian, Reza; Carrera-Gonzalez, Andrea; Montufar-Armendariz, Stefany; Paredes, Rosario; Elcioglu, Nursel; Menendez, Ibis; Behnam, Mahdiyeh; Foster, Joseph; Guo, Shengru; Escarfuller, Sebastian; Cengiz, Filiz Basak; Duman, Duygu; Bademci, Guney; Tekin, Mustafa

    2017-07-01

    Branchio-oto-renal (BOR) syndrome is an autosomal dominant genetic disorder characterized by second branchial arch anomalies, hearing impairment, and renal malformations. Pathogenic mutations have been discovered in several genes such as EYA1, SIX5, and SIX1. However, nearly half of those affected reveal no pathogenic variant by traditional genetic testing. Whole Exome sequencing and/or Sanger sequencing performed in 10 unrelated families from Turkey, Iran, Ecuador, and USA with BOR syndrome in this study. We identified causative DNA variants in six families including novel c.525delT, c.979T > C, and c.1768delG and a previously reported c.1779A > T variants in EYA1. Two large heterozygous deletions involving EYA1 were detected in additional two families. Whole exome sequencing did not reveal a causative variant in the remaining four families. A variety of DNA changes including large deletions underlie BOR syndrome in different populations, which can be detected with comprehensive genetic testing. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. A Lemierre syndrome variant caused by Klebsiella pneumoniae

    Directory of Open Access Journals (Sweden)

    Yih-Jeng Tsai

    2012-07-01

    Full Text Available Lemierre syndrome is an extremely rare disease characterized by oropharyngeal infection, septicemia, internal jugular vein thrombosis, and skip lesions. The most common causative pathogen is Fusobacterium necrophorum. We reported a 45-year-old woman who presented with left neck painful swelling and septicemia. Magnetic resonance imaging of the head and neck demonstrated venous thrombosis extending from the left internal jugular vein to the sigmoid sinus. During admission we discovered that the patient had uncontrolled diabetes mellitus. We also found a metastatic lesion through chest radiography. Klebsiella pneumoniae was cultivated from both blood samples and pus from deep neck spaces. Surgical drainage, early and adequate antibiotic treatment, anticoagulation, and strict control of blood glucose led to the patient's complete recovery. Because Lemierre syndrome is a forgotten disease in the era of antibiotics, awareness of the signs and symptoms of this disease is important because of its associated high mortality rate. This case illustrated that the presence of K pneumoniae can lead to Lemierre syndrome.

  11. Cubital tunnel syndrome due to heterotrophic ossification caused by radial head fracture: A case report

    Directory of Open Access Journals (Sweden)

    Seyitali Gumustas

    2014-04-01

    Full Text Available Compression of the ulnar nerve in the cubital tunnel is the second most common nerve entrapment syndrome in the upper extremity after carpal tunnel syndrome. Although various etiologies have been described, heterotrophic ossification is rarely seen. Heterotrophic ossification should be kept in mind as a cause of ulnar nerve entrapment after elbow trauma. Early diagnosis and surgical intervention are important in such cases before completion of the maturation phase. We report a case of heterotrophic ossification due to elbow trauma that caused cubital tunnel syndrome. [Hand Microsurg 2014; 3(1.000: 24-28

  12. An unusual cause of the quadrilateral space impingement syndrome by a bone spike

    Energy Technology Data Exchange (ETDEWEB)

    Amin, Mohammed F.; Berst, Matthew; El-Khoury, George Y. [University of Iowa Hospitals and Clinics, Radiology, Iowa City, IO (United States)

    2006-12-15

    The quadrilateral space impingement syndrome is a clinical syndrome resulting from compression of the axillary nerve and the posterior circumflex humeral artery, with subsequent focal atrophy of the teres minor, with or without involvement of portions of the deltoid muscle. This entity has many etiologies. We are reporting a case of this syndrome caused by a bone spike from a malunited old scapular fracture following a motor vehicle accident. The bone spike impinged on the axillary nerve as it passes through the quadrilateral space, causing focal atrophy of the teres minor muscle. The abnormality was well demonstrated by MD-CT. (orig.)

  13. Assessment of bleeding disorders in Sheehan's syndrome: are bleeding disorders the underlying cause of Sheehan's syndrome?

    Science.gov (United States)

    Gokalp, Deniz; Tuzcu, Alpaslan; Bahceci, Mithat; Ayyildiz, Orhan; Erdemoglu, Mahmut; Alpagat, Gulistan

    2011-01-01

    Sheehan's syndrome (SS) is an adenopituitary insufficiency caused by hypovolemia secondary to excessive blood loss during or after childbirth. However, the mechanism of postpartum hemorrhage and ischemia is not clear. We aimed to evaluate the bleeding disorders among patients with SS, in comparison with healthy controls. In addition, we investigated underlying causes in postpartum hemorrhage that begin the event. The present study was conducted at the Dicle University School of Medicine. Forty-eight patients with SS and 50 age-matched female healthy controls were included. Biochemical and hormonal variables were measured, as was platelet function by means of closure times (PFA-100 testing using collagen plus epinephrine and collagen plus ADP), von Willebrand factor (vWF) level, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), and coagulation factors. Although PT and INR were significantly higher in patients with SS (both P<0.01), aPTT and levels of fibrinogen, vWF, and factors II, V, VII, VIII, IX, X, XI, and XII did not differ significantly. Closure times with collagen/epinephrine and collagen/ADP also did not differ significantly between patients with SS and control patients. The nonspecific etiology and presence of excessive postpartum hemorrhage in patients with SS suggest that coagulation disorders may play a role in their predisposition to bleeding. The increased PT and INR noted might implicate bleeding diathesis as the underlying etiology, although no significant decreases were noted in factor levels. Further studies are needed to elucidate this complex mechanism of this disorder.

  14. Gastric sarcoidosis mimicking irritable bowel syndrome-Cause not association?

    Institute of Scientific and Technical Information of China (English)

    John Samuel Leeds; Mark Edward McAlindon; Eleanor Lorenz; Asha Kumari Dube; David Surendran Sanders

    2006-01-01

    Sarcoidosis is a systemic disease of unknown aetiology that may affect any organ in the body. The gastrointestinal tract however is only rarely affected outside the liver. Symptoms may be non-specific.Irritable bowel syndrome (IBS) is a common diagnosis.The recognition of TBS is aided by the use of the Rome Ⅱ criteria - in the absence of organic disease. We describe the first case of a patient with gastric sarcoidosis who presented with IBS symptoms but subsequently responded to immunosuppressive therapy.

  15. A RARE CAUSE OF RESISTANT SEIZURES: DYKE DAVIDOFF MASSON SYNDROME

    Directory of Open Access Journals (Sweden)

    Biswadev Basu

    2013-11-01

    Full Text Available ABSTRACT : Dyke – Davidoff – Masson Syndrome (DDMS, is a rare clinical condition characterized by clinical triad of seizures, contralateral spastic hemiplegia or hemiparesis, with or without mental retardation. Diagnosis requires presence of cerebral hemiatrophy with homolateral hypertrophy of the skull and sinuses on brain imaging. Here we report a case of DDMS in a 16 year old girl who presented with seizures and hemiparesis.MRI of her brain showed hemiatrophy involving the left cerebral hemisphere with enlargement of ipsilateral sinuses and ventricles

  16. Atypicality in presentation of neuroleptic malignant syndrome caused by olanzapine

    Directory of Open Access Journals (Sweden)

    Mishra Biswaranjan

    2007-10-01

    Full Text Available Neuroleptic malignant syndrome (NMS is the most serious of acute neurological side effects produced by antipsychotic medication, characterized by hyperthermia, rigidity, altered consciousness and autonomic dysfunction, the prevalence of which varies from 0.4-1.4%. NMS is usually seen in treatment with high potency typical antipsychotics and very rarely with atypical antipsychotics. However, NMS cases have been reported with risperidone, clozapine, olanzapine and quetiapine. The presentations of NMS have often varied, and we report another atypicality in presentation of NMS due to olanzapine use.

  17. Rituximab as a possible cause of posterior reversible encephalopathy syndrome

    Directory of Open Access Journals (Sweden)

    Ahmed Imran Siddiqi

    2011-09-01

    Full Text Available A 66-year-old woman presented with new onset generalisedtonic-clonic seizures following her first dose ofchemotherapy comprising Rituximab, Cyclophosphamide,Hydroxydaunorubicin, Oncovin and Prednisolone (R-CHOP10 days earlier for non-Hodgkin’s lymphoma. On admission,computed tomography (CT scan of the cranium showed noabnormality. The CT was repeated within 48 hours as thepatient developed status epilepticus and papilledema; therepeat scan showed characteristics of posterior reversibleencephalopathy syndrome (PRES. Association of rituximabwith this condition was suspected as there was norecurrence of PRES after receiving two more cycles of CHOPwithout rituximab. Contrary to previously published casereports, this patient had a delayed clinical presentation.

  18. Acute Compartment Syndrome in Orthopedics: Causes, Diagnosis, and Management

    Science.gov (United States)

    Raza, Hasnain; Mahapatra, Anant

    2015-01-01

    Almost all orthopaedic surgeons come across acute compartment syndrome (ACS) in their clinical practice. Diagnosis of ACS mostly relies on clinical findings. If the diagnosis is missed and left untreated, it can lead to serious consequences which can endanger limb and life of the patient and also risk the clinician to face lawsuits. This review article highlights the characteristic features of ACS which will help an orthopaedic surgeon to understand the pathophysiology, natural history, high risk patients, diagnosis, and surgical management of the condition. PMID:25688303

  19. SUPERIOR MESENTERIC ARTERY SYNDROME - AN UNUSUAL CAUSE OF DUODENAL OBSTRUCTION

    OpenAIRE

    Sahu SK, , , , , , ,; Singh PK; Ray J; Uniyal M; Sharma C; Sekhar C; Kapruwan H; Sachan PK

    2012-01-01

    Superior mesenteric artery (SMA) arising from aorta at the level of first lumbar vertebra usually takes an angular downward course from ventral surface of aorta. It is through this vascular angle that the 3rd part of duodenum passes at the level of 4th lumbar vertebra. Fat and lymphatics around SMA maintains the angle at 25° to 60° with a mean of 450 and provide protection against duodenal compression. In Superior Mesenteric Artery Syndrome, the SMA-aorta angle in narrowed down to 7° to 22° w...

  20. Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis)

    NARCIS (Netherlands)

    Doherty, D.; Parisi, M. A.; Finn, L. S.; Gunay-Aygun, M.; Al-Mateen, M.; Bates, D.; Clericuzio, C.; Demir, H.; Dorschner, M.; van Essen, A. J.; Gahl, W. A.; Gentile, M.; Gorden, N. T.; Hikida, A.; Knutzen, D.; Ozyurek, H.; Phelps, I.; Rosenthal, P.; Verloes, A.; Weigand, H.; Chance, P. F.; Dobyns, W. B.; Glass, I. A.

    2010-01-01

    Objective To identify genetic causes of COACH syndrome Background COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia, Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a spect

  1. Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the genetic overlap with the lethal ciliopathy Meckel syndrome

    National Research Council Canada - National Science Library

    Romani, Marta; Micalizzi, Alessia; Kraoua, Ichraf; Dotti, Maria Teresa; Cavallin, Mara; Sztriha, László; Ruta, Rosario; Mancini, Francesca; Mazza, Tommaso; Castellana, Stefano; Hanene, Benrhouma; Carluccio, Maria Alessandra; Darra, Francesca; Máté, Adrienn; Zimmermann, Alíz; Gouider-Khouja, Neziha; Valente, Enza Maria

    2014-01-01

    ... (the "molar tooth sign"), and variable multiorgan involvement. To date, 24 genes have been found mutated in Joubert syndrome, of which 13 also cause Meckel syndrome, a lethal ciliopathy with kidney, liver and skeletal involvement...

  2. Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis)

    NARCIS (Netherlands)

    Doherty, D.; Parisi, M. A.; Finn, L. S.; Gunay-Aygun, M.; Al-Mateen, M.; Bates, D.; Clericuzio, C.; Demir, H.; Dorschner, M.; van Essen, A. J.; Gahl, W. A.; Gentile, M.; Gorden, N. T.; Hikida, A.; Knutzen, D.; Ozyurek, H.; Phelps, I.; Rosenthal, P.; Verloes, A.; Weigand, H.; Chance, P. F.; Dobyns, W. B.; Glass, I. A.

    Objective To identify genetic causes of COACH syndrome Background COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia, Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a

  3. Early repolarization syndrome: A cause of sudden cardiac death

    Institute of Scientific and Technical Information of China (English)

    Abdi; Ali; Nida; Butt; Azeem; S; Sheikh

    2015-01-01

    Early repolarization syndrome(ERS), demonstrated as J-point elevation on an electrocardiograph, was formerly thought to be a benign entity, but the recent studies have demonstrated that it can be linked to a considerable risk of life- threatening arrhythmias and sudden cardiac death(SCD). Early repolarization characteristics associated with SCD include high-amplitude J-point elevation, horizontal and/or downslopping ST segments, and inferior and/or lateral leads location. The prevalence of ERS varies between 3% and 24%, depending on age, sex and J-point elevation(0.05 m V vs 0.1 m V) being the main determinants.ERS patients are sporadic and they are at a higher risk of having recurrent cardiac events. Implantable cardioverter-defibrillator implantation and isoproterenol are the suggested therapies in this set of patients. On the other hand, asymptomatic patients with ERS are common and have a better prognosis. The risk stratification in asymptomatic patients with ERS still remains a grey area. This review provides an outline of the up-to-date evidence associated with ERS and the risk of life- threatening arrhythmias. Further prospective studies are required to elucidate the mechanisms of ventricular arrhythmogenesis in patients with ERS.

  4. Iatrogenic Cushing syndrome caused by ocular glucocorticoids in a child.

    Science.gov (United States)

    Messina, Maria Francesca; Valenzise, Mariella; Aversa, Salvatore; Arrigo, Teresa; De Luca, Filippo

    2009-01-01

    A boy aged 7.6 years presented to our Unit of Paediatric Endocrinology for evaluation of obesity. Progressive weight gain (10 kg) started 6 months earlier after an accidental penetrating orbital injury on the right eye. During this period the child has been treated with oral betamethasone (0.5 mg/day) for 1 month and dexamethasone 2% ocular drops (2 hourly by day) for 6 months. Physical examination showed he was 113.5 cm in height (-1.5 SD), weight 36.0 kg, blood pressure 110/90 mmHg (90th centile), body mass index 28 (+5 SD), truncal obesity, buffalo hump, "moon-face", increased lanugo hair and supraclavicular fullness. Endocrinological work-up revealed undetectable levels of basal adrenocorticotropic hormone (ACTH), basal and ACTH-stimulated cortisol and 24 h urine excretion cortisol, confirming the diagnosis of iatrogenic Cushing syndrome. The abrupt withdrawal of ocular glucocorticoids by the parents evoked two adrenal crises; 4 months later the patient recovered. In conclusion, we would alert doctors that every formulation of glucocorticoids, no ocular drops excluded, can determine severe systemic side effects and iatrogenic Cushing syndrome.

  5. PFAPA syndrome: a rare cause of periodic fever.

    Science.gov (United States)

    Kurtaran, Hanifi; Karadağ, Ahmet; Catal, Ferhat; Aktaş, Davut

    2004-01-01

    PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, adenopathy) is characterized by abrupt onset of fever, malaise, aphthous stomatitis, tonsillitis, pharyngitis and cervical adenopathy. The age of onset of the disease is four years, with a range of 6 months to 7 years. The syndrome is sporadic and nonhereditary. Long-term sequelae do not develop. A nine- year-old boy presented with sore throat, fever and oral aphthae. After taking a throat culture, he was prescribed oral antipyretic and was called for a follow-up visit the next day. As the culture result was negative, he was given a single dose prednisolone with the suspected diagnosis of PFAPA. Twenty-four hours later his temperature was 36.8 degrees C, with all his complaints regressed. Twenty-two days later the patient was again admitted to our hospital with the same complaints. Again, single dose oral prednisolone was given after a throat culture. On the next day the patient was free of all symptoms and the culture was again normal. To our knowledge this is the first PFAPA case report from Turkey in the literature.

  6. A defect in dystrophin causes a novel porcine stress syndrome

    Directory of Open Access Journals (Sweden)

    Nonneman Dan J

    2012-06-01

    Full Text Available Abstract Background Losses of slaughter-weight pigs due to transport stress are both welfare and economic concerns to pork producers. Historically, the HAL-1843 mutation in ryanodine receptor 1 was considered responsible for most of the losses; however, DNA testing has effectively eliminated this mutation from commercial herds. We identified two sibling barrows in the USMARC swine herd that died from apparent symptoms of a stress syndrome after transport at 12 weeks of age. The symptoms included open-mouth breathing, skin discoloration, vocalization and loss of mobility. Results We repeated the original mating along with sire-daughter matings to produce additional offspring. At 8 weeks of age, heart rate and electrocardiographs (ECG were monitored during isoflurane anesthesia challenge (3% for 3 min. Four males from the original sire-dam mating and two males from a sire-daughter mating died after one minute of anesthesia. Animals from additional litters were identified as having a stress response, sometimes resulting in death, during regular processing and weighing. Affected animals had elevated plasma creatine phosphokinase (CPK levels before and immediately after isoflurane challenge and cardiac arrhythmias. A pedigree containing 250 pigs, including 49 affected animals, was genotyped with the Illumina PorcineSNP60 Beadchip and only one chromosomal region, SSCX at 25.1-27.7 Mb over the dystrophin gene (DMD, was significantly associated with the syndrome. An arginine to tryptophan (R1958W polymorphism in exon 41 of DMD was the most significant marker associated with stress susceptibility. Immunoblots of affected heart and skeletal muscle showed a dramatic reduction of dystrophin protein and histopathology of affected hearts indicated muscle fiber degeneration. Conclusions A novel stress syndrome was characterized in pigs and the causative genetic factor most likely resides within DMD that results in less dystrophin protein and cardiac

  7. MEIG’S SYNDROME: A CAUSE OF DIAGNOSTIC DILEMMA

    Directory of Open Access Journals (Sweden)

    Rooplekha

    2014-10-01

    Full Text Available A postmenopausal 50yrs old para3 presented with abdominal pain and distension; decreased appetite and breathlessness. She was provisionally diagnosed as malignant ovarian tumor with secondaries. On USG 16x14 cm size well defined heterogeneous mass lesion was seen in left adnexa with internal vascularity; mild ascitis; right sided pleural effusion. MRI abdomen and pelvis showed large 19.1 x 12.7 cm mass with multiple septations and peripheral nodules. USG guided FNAC showed scanty inflammatory cells with proteinaceous fluid background, malignant cells were not seen. Pleural and ascitic fluid tap showed inflammatory and mesothelial cell but no malignant cell. Clinical and investigation profile suggest the Meigs’s syndrome. Left side salpingo-ovariectomy done and the desired section were sent for histomorphological evaluation. Histology reported ovarian fibroma and thus confirm the diagnosis.

  8. Lynch Syndrome Caused by Germline PMS2 Mutations

    DEFF Research Database (Denmark)

    Ten Broeke, Sanne W; Brohet, Richard M; Tops, Carli M

    2015-01-01

    . Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome-associated cancers. RESULTS: The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52......PURPOSE: The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. METHODS: Data were collected from 98...... years, and there was a significant difference in mean age of CRC between the probands (mean, 47 years; range, 26 to 68 years) and other family members with a PMS2 mutation (mean, 58 years; range, 31 to 86 years; P

  9. Piriformis syndrome--a rare cause of extraspinal sciatica.

    Science.gov (United States)

    Arooj, Shumaila; Azeemuddin, Muhammad

    2014-08-01

    Piriformis syndrome is a rare entity resulting in severe unilateral isolated buttock pain shooting in nature, non discogenic in origin. MR imaging of pelvis plays an important role in such patients to see the normal anatomy of piriformis muscle and its relationship with sciatic nerve. A 35-year-old woman presented with one year history of radiating leg pain with normal MR lumbosacral spine. MRI pelvis showed an abnormal orientation of left sciatic nerve through cleaved fibers of the piriformis muscle. The patient's symptoms were relieved by surgical decompression. The purpose of this case report is to show the role and importance of MR imaging for tracing sciatic nerve and its relationship to the Piriformis muscle. MR imaging of pelvis for sciatic nerve plays an important role in symptomatic patients with isolated buttock pain having normal MRI lumbosacral spine.

  10. Fetal alcohol syndromecauses, diagnostic criteria and prevalence

    Directory of Open Access Journals (Sweden)

    Agata Horecka-Lewitowicz

    2014-04-01

    Full Text Available Fetal alcohol syndrome (FAS is the outcome of alcohol exposition in the prenatal period. It is irreversible. In Poland, FAS is becoming more and more common, the diagnostic tools are limited though. It is recommended to use the 4-Digit Diagnostic Code, which evaluates the 4 basic FAS symptoms: growth retardation, dysmorphic appearance, damage to the central nervous system and prenatal alcohol exposure. It has been confirmed that there is no safe amount of alcohol for a mother to drink while carrying a baby. To put it another way, only a complete lack of alcohol consumption is a guarantee that the baby will not suffer from FAS. It is necessary for society to know that even the smallest amount of alcohol is bad for the foetus. A number of people still believe that, for example, red wine is good and healthy for both the mother and child.

  11. A Rare Cause of Mucocutaneous Pigmentation: Laugier Hunziker Syndrome

    Directory of Open Access Journals (Sweden)

    Gonca Meriç

    2011-11-01

    Full Text Available Laugier Hunziker syndrome (LHS is a rare, acquired pigmentation disorder characterized by macular melonotic pigmentation of the oral mucous membranes and lips frequently associated with longitudinal melanonychia. LHS is known to be an entirely benign condition with no underlying systemic abnormalities or malignant predisposition. However, it is very important to make a differential diagnosis with other mucocutaneous pigmentary disorders which require detailed examination, treatment and follow up. LHS is seen very rarely and to our knowledge, approximately 100 cases have been described in the literature, to date. There are only seven cases reported from the our country, based on the literature search in PubMed and Turkish Dermatological journals, avaliable on the web. Herein we report a 54-year-old woman diagnosed as having LHS, with hyperpigmented macular lesions of the tongue, lip, buccal mucosa, gingiva and palms and soles.

  12. Primary bimorphic adrenocortical disease: cause of hypercortisolism in McCune-Albright syndrome.

    Science.gov (United States)

    Carney, J Aidan; Young, William F; Stratakis, Constantine A

    2011-09-01

    McCune-Albright syndrome (polyostotic fibrous dysplasia, café-au-lait skin spots, and precocious puberty) is a genetically mosaic disorder with populations of mutant and normal cells in affected organs. Cushing syndrome, a rare feature of the condition, usually affects infants and is the result of corticotropin-independent primary bilateral adrenal disease, usually interpreted as nodular adrenocortical hyperplasia. In this study of 9 patients with Cushing syndrome and McCune-Albright syndrome, light microscopy revealed a characteristic bimorphic pattern of diffuse and nodular hyperplasia and a distinctive form of cortical atrophy with apparent zona glomerulosa hyperplasia in 8 patients, all very young. The pattern could be explained by the presence of a mosaic distribution of mutant and normal cells in the adrenal glands. The findings are different from those in inherited or other forms of genetically caused Cushing syndrome. The ninth patient, aged 17 years, had an adrenal adenoma and diffuse cortical hyperplasia in each adrenal gland.

  13. An often unrecognized cause of thunderclap headache : reversible cerebral vasoconstriction syndrome

    NARCIS (Netherlands)

    Koopman, K; Teune, L K; ter Laan, M; Uyttenboogaart, M; Vroomen, P C; De Keyser, J; Luijckx, G J

    2008-01-01

    Thunderclap headache (TCH) can have several causes of which subarachnoid hemorrhage (SAH) is most common and well known. A rare cause of TCH is the reversible cerebral vasoconstriction syndrome (RCVS) which is characterized by a reversible segmental vasoconstriction of the intracranial vessels. We d

  14. Case study: Gluteal compartment syndrome as a cause of lumbosacral radiculoplexopathy and complex regional pain syndrome.

    Science.gov (United States)

    Lederman, Andrew; Turk, David; Howard, Antonio; Reddy, Srinivas; Stern, Michelle

    2016-01-01

    We present the case of a 24 yr old male who was diagnosed with gluteal compartment syndrome and was subsequently found to have developed lumbosacral radiculoplexopathy and complex regional pain syndrome. The patient's gluteal compartment syndrome was diagnosed within 24 h of presentation to the emergency room, and he underwent emergent compartment release. While recovering postoperatively, persistent weakness was noted in the right lower limb. Results of electrodiagnostic testing were consistent with a lumbosacral radiculoplexopathy. After admission to inpatient rehabilitation, the patient complained of pain, burning sensation, and numbness in the distal right lower limb. Based on clinical findings, he was diagnosed with complex regional pain syndrome type II, or causalgia, and was referred for a lumbar sympathetic block under fluoroscopic guidance. Sympathetic block resulted in relief of the patient's symptoms. He was discharged home with good pain control on oral medications.

  15. Vascular compression syndrome of sciatic nerve caused by gluteal varicosities.

    Science.gov (United States)

    Hu, Ming-Hsiao; Wu, Kuan-Wen; Jian, Yu-Ming; Wang, Chen-Ti; Wu, I-Hui; Yang, Shu-Hua

    2010-11-01

    Sciatica is defined as pain or discomfort along the regions innervated by the sciatic nerve. Compression or irritation of lumbar spinal roots, most commonly because of lumbar disc herniation or spinal stenosis, causes sciatica in the vast majority of cases. Although it is rather uncommon, many pathologies have reported to cause nondiscogenic sciatica. A 70-year-old woman presented with intractable sciatic pain which was not elicited by posture change or cough. Sitting on the affected side provoked more pain than standing or walking. Magnetic resonance imaging revealed both spondylolisthesis with lumbar stenosis and compression of the gluteal portion of the sciatic nerve by varicotic gluteal veins. Given the atypical presentation of spinal root compression, gluteal vascular compressive neuropathy was suspected. Ligation and resection of varicotic vein resulted in relief of the patient's pain. To our knowledge, cases with varicosity-caused sciatica were limited in the literature review.

  16. Serotonin syndrome caused by fentanyl and methadone in a burn injury.

    Science.gov (United States)

    Hillman, Ashley D; Witenko, Corey J; Sultan, Said M; Gala, Gary

    2015-01-01

    Serotonin syndrome is a syndrome identified by a triad of altered mental status, neuromuscular overactivity, and autonomic instability caused by the overstimulation of serotonin in the central nervous system and periphery. Serotonin syndrome may be provoked with the addition or increase in serotonergic agents such as selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors as well as other agents with serotonergic properties. Some narcotics, including fentanyl and methadone, have these properties and may be associated with the development of serotonin syndrome when used in conjunction with other agents. Currently, there are no identified case reports of narcotics as the sole agent causing serotonin syndrome. This report provides a brief overview of serotonin syndrome, particularly with cases involving administration of narcotics such as fentanyl and methadone. The case described is the first report associated with fentanyl and methadone without the coadministration of other serotonergic agents, and a possible drug interaction with voriconazole is discussed. This raises awareness of using multiple serotonergic narcotics and the potential precipitation of serotonin syndrome.

  17. Pyridoxine for Prevention of Hand-Foot Syndrome Caused by Chemotherapy: A Systematic Review

    OpenAIRE

    2013-01-01

    BACKGROUND: Hand-foot syndrome (HFS) is a relatively frequent dermatologic toxic reaction to certain anti-cancer chemotherapies. The syndrome can evolve into a distressing condition that limits function and affects quality of life. Pyridoxine (vitamin B6) has been used empirically for the prevention of HFS caused by anti-cancer therapy. However, evidence of its efficacy remains controversial. METHODOLOGY//PRINCIPAL FINDINGS: Systematic literature searches were conducted on the Cochrane Librar...

  18. Microtia Reconstruction and Postsurgical Grisel’s Syndrome: A Rare Cause of Torticollis in a Child

    Directory of Open Access Journals (Sweden)

    Jay Ching Chieh Wang, MD

    2014-06-01

    Full Text Available Summary: Grisel’s syndrome is an unusual but important cause of torticollis which may be encountered in a pediatric plastic surgery practice, where craniofacial and oropharyngeal surgeries are commonly performed. Grisel’s syndrome is characterized by painful torticollis and limited cervical rotation, and the diagnosis is confirmed via radiologic imaging. Initial management of Grisel’s syndrome is with anti-inflammatories and in some cases antibiotics. In unresolving or recurrent cases, more invasive treatments, such as cervical collar, halo, or surgical arthrodesis, may be considered.

  19. Laugier-hunziker syndrome: an uncommon cause of oral pigmentation and a review of the literature.

    Science.gov (United States)

    Montebugnoli, Lucio; Grelli, Ivana; Cervellati, Fabio; Misciali, Cosimo; Raone, Beatrice

    2010-01-01

    Laugier-Hunziker syndrome is a rare benign condition characterized by diffuse oral hyperpigmentation associated with pigmentation of the nails. The syndrome must be included in the differential diagnosis of diffuse oral pigmentation to exclude other conditions with systemic implications. We describe a 43-year-old white woman with the clinical and histological features of Laugier-Hunziker syndrome associated with toenail pigmentation. The correct clinical identification avoids the need for detailed investigations and treatment. We also review the potential causes of oral pigmentation.

  20. Laugier-Hunziker Syndrome: An Uncommon Cause of Oral Pigmentation and a Review of the Literature

    Directory of Open Access Journals (Sweden)

    Lucio Montebugnoli

    2010-01-01

    Full Text Available Laugier-Hunziker syndrome is a rare benign condition characterized by diffuse oral hyperpigmentation associated with pigmentation of the nails. The syndrome must be included in the differential diagnosis of diffuse oral pigmentation to exclude other conditions with systemic implications. We describe a 43-year-old white woman with the clinical and histological features of Laugier-Hunziker syndrome associated with toenail pigmentation. The correct clinical identification avoids the need for detailed investigations and treatment. We also review the potential causes of oral pigmentation.

  1. Serotonin syndrome caused by minimum doses of SSRIS in a patient with spinal cord injury

    OpenAIRE

    Satoh, Koichiro; Takano, Shizuko; Onogi, Takashi; Ohtsuki, Koji; Kobayashi, Toshio

    2006-01-01

    There have been only a few reports of serotonin syndrome developing after mono-therapy with a selective serotonin reuptake inhibitor (SSRI). We report a case of serotonin syndrome caused by long-term therapy with fluvoxamine prior to treatment with paroxetine. An 18-year-old man with spinal cord injury (SCI) at thoracic level 2-3 presented with onset of serotonin syndrome after taking fluvoxamine (50 mg per day) for 8 weeks prior to treatment with paroxetine (10 mg per day) for 6 days. He had...

  2. AORTIC ANEURYSM: A RARE CAUSE OF ORTNER’S SYNDROME

    Directory of Open Access Journals (Sweden)

    Sukanta

    2014-11-01

    Full Text Available A 60 year old male patient presented with hoarseness of voice lasting for 2 months. First he was examined by the otorhinolaryngologist of our hospital, who noticed absence of movements of the left vocal cord. Chest X-ray showed a large opacity in the left upper zone and the patient was referred to the pulmonologist. His general physical examination was unremarkable not having any stigmata of Marfan's or Ehler Danlos syndrome. On chest auscultation, a systolic flow murmur was audible and there was decreased breath sound in the left infraclavicular area. Bronchoscopy revealed absence of movement of left vocal cord. His trans-thoracic echocardiography revealed degenerative aortic and mitral valve disease with mild aortic regurgitation and mild mitral regurgitation with dilated aortic aneurysm. A contrast enhanced CT scan of thorax and CT Angio Aortogram revealed fusiform aneurysmal dilatation of the arch of aorta with diameter of 6.2 cm over a length of 12.3 cm showing intraluminal partial thrombus with wall calcification. The patient was advised to undergo surgery. However, after detailed discussion with him and his family, they decided for medical management in view of his advanced age

  3. Empty Follicle Syndrome: The Possible Cause of Occurrence

    Directory of Open Access Journals (Sweden)

    Tahereh Madani

    2015-11-01

    Full Text Available Objectives: Empty follicle syndrome (EFS, although rare, is a disappointing condition in which no oocytes are retrieved from mature follicle after ovulation induction in in vitro fertilization (IVF cycles. The aim of this study was to estimate the incidence and factors associated with EFS. Methods: All cycles resulting in EFS from May 2012 to September 2013 were retrospectively identified at a tertiary referral infertility center. Among the 3,356 cycles performed, 58 (1.7% women who underwent their first IVF cycle and had no oocyte retrieval were enrolled in the study. Three different stimulation protocols (long, antagonist, and miniflare were mainly used for induction of follicular growth. Data relating to the age, follicle stimulating hormone (FSH level, anti-Müllerain hormone (AMH level, and the number of ampules and follicles for each patient was obtained. Results: Out of 58 individuals, 10 (17.2% showed false type and 48 (82.8% showed genuine EFS. The most frequent findings in our study were diminished ovarian reserve, low anti-Müllerian hormone (AMH; ≤0.5 ng/mL, and less than four mature follicles, indicating EFS in 1.7% of the patients. Conclusion: Low serum AMH levels and a small number of follicles after ovarian stimulation is the manifestation of diminished ovarian reserve. Thus, we suggest that EFS could be a manifestation of low ovarian reserve.

  4. Capecitabine caused cardiogenic shock through induction of global takotsubo syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Y-Hassan, Shams, E-mail: shams.younis-hassan@karolinska.se; Tornvall, Per; Törnerud, Mattias; Henareh, Loghman

    2013-01-15

    5-Fluorouracil (5-FU) and its oral pro-drug capecitabine are widely used in oncology for the treatment of various solid tumours, including colorectal cancers. Cardiotoxicity to these drugs is not an uncommon adverse effect and has been reported in 1%–18% of patients. Capecitabine has been reported to trigger mid-apical Takotsubo syndrome (TS). We describe here the case of a 55-year-old man who presented with cardiogenic shock and ECG signs of ST-elevation myocardial infarction. The symptoms began 28 h after the commencement of capecitabine adjuvant therapy, following a radical right-sided hemicolectomy for low-differentiated adenocarcinoma of the caecum. Echocardiography showed severe global left ventricular dysfunction. Cardiac magnetic resonance imaging showed no signs of late gadolinium enhancement. These clinical, cardiac image study findings and the course of the disease with full recovery within one week were consistent with global TS triggered by the adjuvant therapy capecitabine and presenting with a life-threatening cardiogenic shock. Moreover, we have demonstrated the speedy dynamic of the left ventricular wall motion abnormality with global TS at presentation and basal (inverted) TS findings 4 days later on.

  5. Perimenstrual asthma : A syndrome without known cause or cure

    NARCIS (Netherlands)

    Vrieze, A; Postma, DS; Kerstjens, HAM

    Perimenstrual worsening of asthma has been documented in 30% to 40% of asthmatic women. This increase in symptoms has been backed up by increased health care use perimenstrually, as well as by cyclic variation in peak expiratory flows. The cause of perimenstrual asthma (PMA) remains unclear.

  6. Perimenstrual asthma : A syndrome without known cause or cure

    NARCIS (Netherlands)

    Vrieze, A; Postma, DS; Kerstjens, HAM

    2003-01-01

    Perimenstrual worsening of asthma has been documented in 30% to 40% of asthmatic women. This increase in symptoms has been backed up by increased health care use perimenstrually, as well as by cyclic variation in peak expiratory flows. The cause of perimenstrual asthma (PMA) remains unclear. Fluctua

  7. A novel ICK mutation causes ciliary disruption and lethal endocrine-cerebro-osteodysplasia syndrome.

    Science.gov (United States)

    Oud, Machteld M; Bonnard, Carine; Mans, Dorus A; Altunoglu, Umut; Tohari, Sumanty; Ng, Alvin Yu Jin; Eskin, Ascia; Lee, Hane; Rupar, C Anthony; de Wagenaar, Nathalie P; Wu, Ka Man; Lahiry, Piya; Pazour, Gregory J; Nelson, Stanley F; Hegele, Robert A; Roepman, Ronald; Kayserili, Hülya; Venkatesh, Byrappa; Siu, Victoria M; Reversade, Bruno; Arts, Heleen H

    2016-01-01

    Endocrine-cerebro-osteodysplasia (ECO) syndrome [MIM:612651] caused by a recessive mutation (p.R272Q) in Intestinal cell kinase (ICK) shows significant clinical overlap with ciliary disorders. Similarities are strongest between ECO syndrome, the Majewski and Mohr-Majewski short-rib thoracic dysplasia (SRTD) with polydactyly syndromes, and hydrolethalus syndrome. In this study, we present a novel homozygous ICK mutation in a fetus with ECO syndrome and compare the effect of this mutation with the previously reported ICK variant on ciliogenesis and cilium morphology. Through homozygosity mapping and whole-exome sequencing, we identified a second variant (c.358G > T; p.G120C) in ICK in a Turkish fetus presenting with ECO syndrome. In vitro studies of wild-type and mutant mRFP-ICK (p.G120C and p.R272Q) revealed that, in contrast to the wild-type protein that localizes along the ciliary axoneme and/or is present in the ciliary base, mutant proteins rather enrich in the ciliary tip. In addition, immunocytochemistry revealed a decreased number of cilia in ICK p.R272Q-affected cells. Through identification of a novel ICK mutation, we confirm that disruption of ICK causes ECO syndrome, which clinically overlaps with the spectrum of ciliopathies. Expression of ICK-mutated proteins result in an abnormal ciliary localization compared to wild-type protein. Primary fibroblasts derived from an individual with ECO syndrome display ciliogenesis defects. In aggregate, our findings are consistent with recent reports that show that ICK regulates ciliary biology in vitro and in mice, confirming that ECO syndrome is a severe ciliopathy.

  8. [Orbital compartment syndrome. The most frequent cause of blindness following facial trauma].

    Science.gov (United States)

    Klenk, Gusztáv; Katona, József; Kenderfi, Gábor; Lestyán, János; Gombos, Katalin; Hirschberg, Andor

    2017-09-01

    Although orbital compartment syndrome is a rare condition, it is still the most common cause of blindness following simple or complicated facial fractures. Its pathomechanism is similar to the compartment syndrome in the limb. Little extra fluid (blood, oedema, brain, foreign body) in a non-space yielding space results with increasingly higher pressures within a short period of time. Unless urgent surgical intervention is performed the blocked circulation of the central retinal artery will result irreversible ophthalmic nerve damage and blindness. Aim, material and method: A retrospective analysis of ten years, 2007-2017, in our hospital among those patients referred to us with facial-head trauma combined with blindness. 571 patients had fractures involving the orbit. 23 patients become blind from different reasons. The most common cause was orbital compartment syndrome in 17 patients; all had retrobulbar haematomas as well. 6 patients with retrobulbar haematoma did not develop compartment syndrome. Compartment syndrome was found among patient with extensive and minimal fractures such as with large and minimal haematomas. Early lateral canthotomy and decompression saved 7 patients from blindness. We can not predict and do not know why some patients develop orbital compartment syndrome. Compartment syndrome seems independent from fracture mechanism, comminution, dislocation, amount of orbital bleeding. All patients are in potential risk with midface fractures. We have a high suspicion that orbital compartment syndrome has been somehow missed out in the recommended textbooks of our medical universities and in the postgraduate trainings. Thus compartment syndrome is not recognized. Teaching, training and early surgical decompression is the only solution to save the blind eye. Orv Hetil. 2017; 158(36): 1410-1420.

  9. Malabsorption syndrome as a rare cause of nephrocalcinosis.

    Science.gov (United States)

    Abreu, Rui; Bento, Cláudia; Oliveira, Luís; Morgado, Teresa

    2016-01-01

    Nephrocalcinosis is characterized by calcification of kidney parenchyma and can be caused by an increased amount of calcium, phosphate or oxalate in urinary excretion. We report a 35-year-old female with nephrocalcinosis. She had fitful steatorrhea since last year. Physical examination was normal. Analytic exams found normal renal function and ionogram. Primary hyperparathyroidism, renal tubular acidosis and sarcoidosis were excluded. Urinalysis showed mild hematuria, without proteinuria and 24-hour urine collection exhibited hyperoxaluria. Patient was submitted to an endoscopy and duodenal biopsy whose histology sustained the diagnosis of celiac disease. Fluid intake increase and gluten and oxalate free diet were initiated.

  10. [Anastomotic false-diverticulum causing an atypical dumping syndrome. A case report].

    Science.gov (United States)

    Covarelli, P; Esperti, L; Fratto, A; Cerroni, M; Marianeschi, P; Cristofani, R

    2003-02-01

    Aim of the study is to evaluate the causes of dumping syndromes following partial gastrectomies, and to report an unusual feature of dumping. A case of early dumping due to diverticular-like dilation of gastro-jejunal anastomosis is described with preoperative imaging and intraoperative picture. The surgical correction led to complete clinical remission; the common causes and physiopathological bases of dumping are reviewed and the role of en-Y gastro-jejunal reconstruction is underlined in order to reduce the risk of developing the syndrome.

  11. A giant trichobezoar causing rapunzel syndrome in a 12-year-old female

    Directory of Open Access Journals (Sweden)

    Nadeem Ul Nazeer Kawoosa

    2011-01-01

    Full Text Available Bezoar is a tightly packed collection of undigested material that is unable to exit the stomach. Most bezoars are of indigestible organic matter such as hair-trichobezoars; or vegetable and fruit-phytobezoars; or a combination of both. Trichobezoars commonly occur in patients with psychiatric disturbances who chew and swallow their own hair. In very rare cases, the Rapunzel syndrome hair extends through the pylorus into the small bowel causing symptom and sign of partial or complete gastric outlet obstruction. A case report of trichobezoar in the stomach causing Rapunzel syndrome in a 12-year-old female is reported.

  12. Marfan syndrome caused by a novel FBN1 mutation with associated pigmentary glaucoma.

    Science.gov (United States)

    Kuchtey, John; Chang, Ta Chen; Panagis, Lampros; Kuchtey, Rachel W

    2013-04-01

    Mutations in fibrillin-1 (FBN1) cause a wide spectrum of disorders, including Marfan syndrome, which have in common defects in fibrillin-1 microfibrils. Ectopia lentis and myopia are frequently observed ocular manifestations of Marfan syndrome. Glaucoma is also associated with Marfan syndrome, though the form of glaucoma has not been well-characterized. In this report, ocular examination of a patient diagnosed with Marfan syndrome based on family history and aortic dilatation was performed, including measurement of facility of aqueous humor outflow by tonography. The patient did not have ectopia lentis at the age of 42 years. Based on optic nerve appearance, reduced outflow facility, elevated IOP with open angles and clear signs of pigment dispersion, the patient was diagnosed with pigmentary glaucoma. The patient was heterozygous for a novel truncating mutation in FBN1, p.Leu72Ter. Histology of normal human eyes revealed abundant expression of elastic fibers and fibrillin-1 in aqueous humor outflow structures. This is the first report of a patient with Marfan syndrome that is caused by a confirmed FBN1 mutation with associated pigmentary glaucoma. In addition to identifying a novel mutation of FBN1 and broadening the spectrum of associated ocular phenotypes in Marfan syndrome, our findings suggest that pigmentary glaucoma may involve defects in fibrillin-1 microfibrils.

  13. [Auto-immune disorders as a possible cause of neuropsychiatric syndromes].

    Science.gov (United States)

    Martinez-Martinez, P; Molenaar, P C; Losen, M; Hoffmann, C; Stevens, J; de Witte, L D; van Amelsvoort, T; van Os, J; Rutten, B P F

    2015-01-01

    Changes that occur in the behaviour of voltage-gated ion channels and ligand-gated receptor channels due to gene mutations or auto-immune attack are the cause of channelopathies in the central and peripheral nervous system. Although the relation between molecular channel defects and clinical symptoms has been explained in the case of many neuromuscular channelopathies, the pathophysiology of auto-immunity in neuropsychiatric syndromes is still unclear. To review recent findings regarding neuronal auto-immune reactions in severe neuropsychiatric syndromes. Using PubMed, we consulted the literature published between 1990 and August 2014 relating to the occurrence of auto-immune antibodies in severe and persistent neuropsychiatric syndromes. Auto-antibodies have only limited access to the central nervous system, but if they do enter the system they can, in some cases, cause disease. We discuss recent findings regarding the occurrence of auto-antibodies against ligand-activated receptor channels and potassium channels in neuropsychiatric and neurological syndromes, including schizophrenia and limbic encephalitis. Although the occurrence of several auto-antibodies in schizophrenia has been confirmed, there is still no proof of a causal relationship in the syndrome. We still have no evidence of the prevalence of auto-immunity in neuropsychiatric syndromes. The discovery that an antibody against an ion channel is associated with some neuropsychiatric disorders may mean that in future it will be possible to treat patients by means of immunosuppression, which could lead to an improvement in a patient's cognitive abilities.

  14. 阳虚生风论%Theory of Feng-Syndrome Caused by Yang Deficiency

    Institute of Scientific and Technical Information of China (English)

    潘远根

    2016-01-01

    The treatment of Feng-syndrome in TCM frequently focused on the wind syndromes caused by the strong hot, the hyperactivity of Yang, the Yin deficiency and the blood deficiency, but the Feng syndrome rarely deals with Yang deficiency. In this paper, we puts forward the Feng syndromes also caused by Yang deficiency and briefly discusses on it in the theory, the type of diseases and the syndrome differentiation, and then, to break down the syndrome differentiating keys with some clinical cases.%中医论风证的辨证治疗,向来仅注重火热、阳亢、阴虚、血虚等引起的风证,绝少论及阳虚动风。本文从阳虚生风的理论、病证类型、辨证要点等方面简要论述了阳虚阴盛同样引起动风证,并例举临床病例以详解辨证关键。

  15. The SAPHO syndrome in children: a rare cause of hyperostosis and osteitis.

    Science.gov (United States)

    Letts, M; Davidson, D; Birdi, N; Joseph, M

    1999-01-01

    The SAPHO syndrome is a rare constellation of signs and symptoms characterized by synovitis, acne, pustulosis, hyperostosis, and osteitis. The most common musculoskeletal complaints are hyperostosis, causing pain, tenderness, and swelling of the anterior chest wall, although any part of the axial and appendicular skeleton may be affected. There is a great degree of variability in the dermatologic involvement of this syndrome. A combination of clinical, radiographic, and pathological investigation is required to establish the correct diagnosis. No single treatment has been found to be effective, although nonsteroidal antiinflammatory drugs have been the most frequently used. Because there is no mention of SAPHO syndrome in the English orthopaedic literature, and pediatric orthopaedic surgeons may be the first caregivers to treat these children, we thought it appropriate to share our experience with a 5-year-old boy with SAPHO syndrome recently under our care.

  16. Deregulation of Fas ligand expression as a novel cause of autoimmune lymphoproliferative syndrome-like disease.

    Science.gov (United States)

    Nabhani, Schafiq; Ginzel, Sebastian; Miskin, Hagit; Revel-Vilk, Shoshana; Harlev, Dan; Fleckenstein, Bernhard; Hönscheid, Andrea; Oommen, Prasad T; Kuhlen, Michaela; Thiele, Ralf; Laws, Hans-Jürgen; Borkhardt, Arndt; Stepensky, Polina; Fischer, Ute

    2015-09-01

    Autoimmune lymphoproliferative syndrome is frequently caused by mutations in genes involved in the Fas death receptor pathway, but for 20-30% of patients the genetic defect is unknown. We observed that treatment of healthy T cells with interleukin-12 induces upregulation of Fas ligand and Fas ligand-dependent apoptosis. Consistently, interleukin-12 could not induce apoptosis in Fas ligand-deficient T cells from patients with autoimmune lymphoproliferative syndrome. We hypothesized that defects in the interleukin-12 signaling pathway may cause a similar phenotype as that caused by mutations of the Fas ligand gene. To test this, we analyzed 20 patients with autoimmune lymphoproliferative syndrome of unknown cause by whole-exome sequencing. We identified a homozygous nonsense mutation (c.698G>A, p.R212*) in the interleukin-12/interleukin-23 receptor-component IL12RB1 in one of these patients. The mutation led to IL12RB1 protein truncation and loss of cell surface expression. Interleukin-12 and -23 signaling was completely abrogated as demonstrated by deficient STAT4 phosphorylation and interferon γ production. Interleukin-12-mediated expression of membrane-bound and soluble Fas ligand was lacking and basal expression was much lower than in healthy controls. The patient presented with the classical symptoms of autoimmune lymphoproliferative syndrome: chronic non-malignant, non-infectious lymphadenopathy, splenomegaly, hepatomegaly, elevated numbers of double-negative T cells, autoimmune cytopenias, and increased levels of vitamin B12 and interleukin-10. Sanger sequencing and whole-exome sequencing excluded the presence of germline or somatic mutations in genes known to be associated with the autoimmune lymphoproliferative syndrome. Our data suggest that deficient regulation of Fas ligand expression by regulators such as the interleukin-12 signaling pathway may be an alternative cause of autoimmune lymphoproliferative syndrome-like disease. Copyright© Ferrata Storti

  17. Dyke-Davidoff-Masson Syndrome. An unusual cause of status epilepticus.

    Science.gov (United States)

    Zawar, Ifrah; Khan, Ashfa A; Sultan, Tipu; Rathore, Ahsan W

    2015-10-01

    The Dyke-Davidoff-Masson Syndrome (DDMS) results from an insult to the growing brain in utero or early infancy, which lead to loss of neurons compromising the growth of the brain. Clinical presentation includes seizures, hemiparesis, facial asymmetry, and learning disability. Radiological findings include cerebral atrophy on one side. Here, we present a case with status epilepticus who had underlying DDMS. It is a rare syndrome and uncommon cause for status epilepticus. Infections of CNS, hypoxic ischemic encephalopathy, intracranial bleed, trauma, congenital vascular malformations are the common causes of this syndrome. Diagnosis is established after clinical history, examination, and MRI. Intractable seizures can be controlled with appropriate anticonvulsants. Subsequently, these children may require physiotherapy, speech therapy, and occupational therapy in addition to the anticonvulsant medication. Outcome is better if the seizures are controlled.

  18. Diaphragm paralysis causing ventilatory failure in an adult with the rigid spine syndrome.

    Science.gov (United States)

    Efthimiou, J; McLelland, J; Round, J; Gribbin, H R; Loh, L; Spiro, S G

    1987-12-01

    A syndrome consisting of a rigid spine and myopathy predominantly affecting proximal limb muscles has been previously described in children, and as with most neuromuscular disorders, the respiratory muscles appear to be affected only at an advanced stage in the disease. We describe an adult male with this syndrome who presented with ventilatory failure caused by severe respiratory muscle weakness and who demonstrated profound nocturnal arterial oxygen desaturation, particularly during rapid eye movement sleep. Treatment with negative pressure ventilation initially resulted in only modest improvements in symptoms, blood gas tensions, and nocturnal desaturation. The cause of this only partial improvement was upper airway obstruction provoked by the mode of ventilatory support used. After tracheostomy there was a dramatic and sustained improvement in symptoms and blood gas tensions and complete abolition of nocturnal arterial oxygen desaturation. This is the first report of an adult with the rigid spine syndrome presenting with ventilatory failure and cor pulmonale due to severe respiratory muscle weakness.

  19. Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany

    DEFF Research Database (Denmark)

    Rasko, David A; Webster, Dale R; Sahl, Jason W

    2011-01-01

    A large outbreak of diarrhea and the hemolytic-uremic syndrome caused by an unusual serotype of Shiga-toxin-producing Escherichia coli (O104:H4) began in Germany in May 2011. As of July 22, a large number of cases of diarrhea caused by Shiga-toxin-producing E. coli have been reported--3167 without...... the hemolytic-uremic syndrome (16 deaths) and 908 with the hemolytic-uremic syndrome (34 deaths)--indicating that this strain is notably more virulent than most of the Shiga-toxin-producing E. coli strains. Preliminary genetic characterization of the outbreak strain suggested that, unlike most of these strains......, it should be classified within the enteroaggregative pathotype of E. coli....

  20. Scheie syndrome

    Science.gov (United States)

    ... Hurler syndrome) MPS II (Hunter syndrome) MPS IV (Morquio syndrome) MPS III (Sanfilippo syndrome) Causes Scheie syndrome ... Autosomal recessive Cloudy cornea Hearing loss Hurler syndrome Morquio syndrome Review Date 4/20/2015 Updated by: ...

  1. Acute forearm compressive myopathy syndrome secondary to upper limb entrapment: an unusual cause of renal failure.

    Science.gov (United States)

    Tachtsi, Maria D; Kalogirou, Thomas E; Atmatzidis, Stefanos K; Papadimitriou, Dimitrios K; Atmatzidis, Konstantinos S

    2011-05-01

    Compressive myopathy syndrome (SCM) is a syndrome characterized by the lesion of skeletal muscle resulting in subsequent release of intracellular contents (myoglobin, creatine phosphokinase, potassium, etc.) into the circulatory system, which can cause potentially lethal complications. There are numerous causes that can lead to SCM resulting to acute rhabdomyolysis, and many patients present with multiple causes. The most common potentially lethal complication is acute renal failure. The occurrence of acute rhabdomyolysis should be considered as a possibility in any patient who can remain stationary for long periods, or is in a coma, or is intoxicated in any form. We report the rare case of a 26-year-old patient who developed SCM caused by ischemia reperfusion, with subsequent acute rhabdomyolysis and acute renal failure after prolonged compression of the right upper extremity.

  2. Hutchinson-Gilford progeria syndrome

    OpenAIRE

    Amar Singh Bhukya; Bellum Siva Nagi Reddy

    2015-01-01

    Hutchinson-Gilford Progeria syndrome (HGPS) is a rare pediatric genetic syndrome associated with a characteristic aged appearance very early in life, generally leading to death in the second decade of life. Apart from premature aging, the other notable characteristics of children with HGPS include extreme short stature, prominent superficial veins, poor weight gain, alopecia, as well as various skeletal and cardiovascular pathologies associated with advanced age. The pattern of inheritance of...

  3. The spectrum of mutations in UBE3A causing Angelman syndrome

    NARCIS (Netherlands)

    P. Fang (Ping); E. Lev-Lehman (Efrat); T.-F. Tsai (Ting-Fen); N. Matsuura (Nobuo); S. Benton (Sabrina); J.S. Sutcliffe (James); S.L. Christian (Susan); T. Kubota (Takeo); D.J.J. Halley (Dicky); E.J. Meijers-Heijboer (Hanne); S. Langlois (Sylvie); J.M. Graham (John); J. Beuten (Joke); P.J. Willems (Patrick); A.M. Ledbetter (Andrew M.); L. Beaudet (Lucille)

    1999-01-01

    textabstractAngelman syndrome (AS) is characterized by mental retardation, absence of speech, seizures and motor dysfunction. AS is caused by maternal deletions for chromosome 15q11-q13, paternal uniparental disomy (UPD), imprinting defects or loss-of-function mutations in the UBE3A locus which

  4. Upstream SLC2A1 translation initiation causes GLUT1 deficiency syndrome

    NARCIS (Netherlands)

    Willemsen, M.A.A.P.; Vissers, L.E.L.M.; Verbeek, M.M.; Bon, B.W.M. van; Geuer, S.; Gilissen, C.F.; Klepper, J.; Kwint, M.P.; Leen, W.G.; Pennings, M.; Wevers, R.A.; Veltman, J.A.; Kamsteeg, E.J.

    2017-01-01

    Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder with a complex phenotypic spectrum but simple biomarkers in cerebrospinal fluid. The disorder is caused by impaired glucose transport into the brain resulting from variants in SCL2A1. In 10% of GLUT1DS patients, a

  5. DIARRHEA, UROSEPSIS AND HEMOLYTIC UREMIC SYNDROME CAUSED BY THE SAME HETEROPATHOGENIC ESCHERICHIA COLI STRAIN

    NARCIS (Netherlands)

    Ang, C. Wim; Bouts, Antonia H. M.; Rossen, John W. A.; Van der Kuip, Martijn; Van Heerde, Marc; Bokenkamp, Arend

    2016-01-01

    We describe an 8-month-old girl with diarrhea, urosepsis and hemolytic uremic syndrome caused by Escherichia coli. Typing of cultured E. coli strains from urine and blood revealed the presence of virulence factors from multiple pathotypes of E. coli. This case exemplifies the genome plasticity of E.

  6. High-sensitivity sequencing reveals multi-organ somatic mosaicism causing DICER1 syndrome

    NARCIS (Netherlands)

    de Kock, Leanne; Wang, Yu Chang; Revil, Timothée; Badescu, Dunarel; Rivera, Barbara; Sabbaghian, Nelly; Wu, Mona; Weber, Evan; Sandoval, Claudio; Hopman, Saskia M J; Merks, Johannes H M; van Hagen, Johanna M.; Bouts, Antonia H M; Plager, David A.; Ramasubramanian, Aparna; Forsmark, Linus; Doyle, Kristine L.; Toler, Tonja; Callahan, Janine; Engelenberg, Charlotte; Soglio, Dorothée Bouron Dal; Priest, John R.; Ragoussis, Jiannis; Foulkes, William D.

    2016-01-01

    Background Somatic mosaicism is being increasingly recognised as an important cause of non-Mendelian presentations of hereditary syndromes. A previous wholeexome sequencing study using DNA derived from peripheral blood identified mosaic mutations in DICER1 in two children with overgrowth and develop

  7. Travel-related Streptococcal toxic shock syndrome caused by emm type 78 Streptococcus pyogenes.

    Science.gov (United States)

    Tappe, Dennis; Schulze, Marco H; van der Linden, Mark; Ziegler, Uwe; Müller, Andreas; Stich, August

    2011-08-01

    Streptococcal toxic shock syndrome is a serious health problem in developed and developing countries. We here report a case of severe protracted disease after a minor skin infection in a young traveler returning from West Malaysia which was caused by an unusual emm-type strain harboring speG and smeZ superantigen genes.

  8. Species determination of pine nuts in commercial samples causing pine nut syndrome

    DEFF Research Database (Denmark)

    Mikkelsen, Aase Æ.; Jessen, Flemming; Ballin, Nicolai Z.

    2014-01-01

    Consumption of pine nuts from the species of Pinus armandii has been reported to cause dysgeusia, commonly known as pine mouth, or pine nut syndrome (PNS). However, the number of reports on pine nut consumptions of the different species and PNS is limited. This leaves open the possibility...

  9. OTORHINOLARYNGOLOGIC CAUSES OF CLAUDE-BERNARD-HÖRNER SYNDROME: THREE CASES REPORT

    Directory of Open Access Journals (Sweden)

    R. de la Fuente Cañibano

    2010-01-01

    Full Text Available The syndrome of Claude-Bernard-Hörner is caused by the sinpatical injury of thebranches ascending innervation of the stellate ganglion and the iris smooth muscle eyelid. His triad is the presence of ptosis, myosis and enoftalmos. It may be accompanied by anhidrosis, pupillary dilation heterocromía delayed in the congenital case.

  10. Autoimmune hemolytic anemia, as part of Evans' syndrome, caused by cold reactive IgG autoantibodies

    NARCIS (Netherlands)

    Jaarsma, AS; Muis, N; DeGraaf, SSN

    1996-01-01

    We describe a boy with Evans' syndrome, consisting of immune thrombocytopenic purpura at age 2 and autoimmune hemolytic anemia (AIHA) at age 4. AIHA was caused by cold Ige autoantibodies. This is unusual because AIHA is generally associated with either warm IgG antibodies or cold IgM antibodies. Tre

  11. Diarrhea, Urosepsis and Hemolytic Uremic Syndrome Caused by the Same Heteropathogenic Escherichia coli Strain.

    Science.gov (United States)

    Ang, C Wim; Bouts, Antonia H M; Rossen, John W A; Van der Kuip, Martijn; Van Heerde, Marc; Bökenkamp, Arend

    2016-09-01

    We describe an 8-month-old girl with diarrhea, urosepsis and hemolytic uremic syndrome caused by Escherichia coli. Typing of cultured E. coli strains from urine and blood revealed the presence of virulence factors from multiple pathotypes of E. coli. This case exemplifies the genome plasticity of E. coli and the resulting heteropathogenic strains.

  12. OTORHINOLARYNGOLOGIC CAUSES OF CLAUDE-BERNARD-HÖRNER SYNDROME: THREE CASES REPORT

    OpenAIRE

    R. de la Fuente Cañibano; A. Muñoz Herrera

    2010-01-01

    The syndrome of Claude-Bernard-Hörner is caused by the sinpatical injury of thebranches ascending innervation of the stellate ganglion and the iris smooth muscle eyelid. His triad is the presence of ptosis, myosis and enoftalmos. It may be accompanied by anhidrosis, pupillary dilation heterocromía delayed in the congenital case.

  13. Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome.

    Science.gov (United States)

    Kress, Wolfram; Schropp, Christian; Lieb, Gabriele; Petersen, Birgit; Büsse-Ratzka, Maria; Kunz, Jürgen; Reinhart, Edeltraut; Schäfer, Wolf-Dieter; Sold, Johanna; Hoppe, Florian; Pahnke, Jan; Trusen, Andreas; Sörensen, Niels; Krauss, Jürgen; Collmann, Hartmut

    2006-01-01

    The Saethre-Chotzen syndrome (SCS) is an autosomal dominant craniosynostosis syndrome with uni- or bilateral coronal synostosis and mild limb deformities. It is caused by loss-of-function mutations of the TWIST 1 gene. In an attempt to delineate functional features separating SCS from Muenke's syndrome, we screened patients presenting with coronal suture synostosis for mutations in the TWIST 1 gene, and for the Pro250Arg mutation in FGFR3. Within a total of 124 independent pedigrees, 39 (71 patients) were identified to carry 25 different mutations of TWIST 1 including 14 novel mutations, to which six whole gene deletions were added. The 71 patients were compared with 42 subjects from 24 pedigrees carrying the Pro250Arg mutation in FGFR3 and 65 subjects from 61 pedigrees without a detectable mutation. Classical SCS associated with a TWIST 1 mutation could be separated phenotypically from the Muenke phenotype on the basis of the following features: low-set frontal hairline, gross ptosis of eyelids, subnormal ear length, dilated parietal foramina, interdigital webbing, and hallux valgus or broad great toe with bifid distal phalanx. Functional differences were even more important: intracranial hypertension as a consequence of early progressive multisutural fusion was a significant problem in SCS only, while mental delay and sensorineural hearing loss were associated with the Muenke's syndrome. Contrary to previous reports, SCS patients with complete loss of one TWIST allele showed normal mental development.

  14. Causes of Death in Prader-Willi Syndrome: Prader-Willi Syndrome Association (USA) 40-Year Mortality Survey

    Science.gov (United States)

    Butler, Merlin G.; Manzardo, Ann M.; Heinemann, Janalee; Loker, Carolyn; Loker, James

    2016-01-01

    Background Prader-Willi syndrome (PWS) is a rare complex neurodevelopmental genetic disorder that is associated with hyperphagia and morbid obesity in humans leading to a shortened life expectancy. This report summarizes the primary causes of death and evaluates mortality trends in a large cohort of individuals with PWS. Methods PWSA (USA) mortality syndrome-specific database of death reports was collected through a cursory bereavement program for PWSA(USA) families using a brief survey created in 1999. Causes of death were descriptively characterized and statistically examined using Cox Proportional Hazards. Results A total of 486 deaths were reported (263 males, 217 females, 6 unknown) between 1973 and 2015 with mean age of 29.5 ± 16 years (2mo–67yrs), 70% occurring in adulthood. Respiratory failure was the most common cause accounting for 31% of all deaths. Males were at increased risk for presumed hyperphagia-related accidents/injuries compared to females and cardiopulmonary factors. PWS maternal disomy 15 genetic subtype showed an increased risk of death from cardiopulmonary factors compared to the deletion subtype. Conclusions These findings highlight the heightened vulnerability towards obesity and hyperphagia-related mortality in PWS. Future research is needed to address critical vulnerabilities such as gender and genetic subtype in the cause of death in PWS. PMID:27854358

  15. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome.

    Science.gov (United States)

    Wiseman, Frances K; Al-Janabi, Tamara; Hardy, John; Karmiloff-Smith, Annette; Nizetic, Dean; Tybulewicz, Victor L J; Fisher, Elizabeth M C; Strydom, André

    2015-09-01

    Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP)--an Alzheimer disease risk factor--although the possession of extra copies of other chromosome 21 genes may also play a part. Further study of the mechanisms underlying the development of Alzheimer disease in people with Down syndrome could provide insights into the mechanisms that cause dementia in the general population.

  16. Clinical and radiologic review of uncommon cause of profound iron deficiency anemia: Median arcuate ligament syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Gunduz, Yasemin; Asil, Kiyasrttin; Aksoy, Yakup Ersel; Ayhan, Lacin Tatli [Dept. of Radiology, Sakarya University Medical Faculty, Sakarya (Turkmenistan)

    2014-08-15

    Median arcuate ligament syndrome is an anatomic and clinical entity characterized by dynamic compression of the proximal celiac artery by the median arcuate ligament, which leads to postprandial epigastric pain, vomiting, and weight loss. These symptoms are usually nonspecific and are easily misdiagnosed as functional dyspepsia, peptic ulcer disease, or gastropathy. In this report, we presented a 72-year-old male patient with celiac artery compression syndrome causing recurrent abdominal pain associated with gastric ulcer and iron deficiency anemia. This association is relatively uncommon and therefore not well determined. In addition, we reported the CT angiography findings and three-dimensional reconstructions of this rare case.

  17. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

    Science.gov (United States)

    Wiseman, Frances K.; Al-Janabi, Tamara; Hardy, John; Karmiloff-Smith, Annette; Nizetic, Dean; Tybulewicz, Victor L. J.; Fisher, Elizabeth M. C.; Strydom, André

    2015-01-01

    Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP) — an Alzheimer disease risk factor — although the possession of extra copies of other chromosome 21 genes may also play a part. Further study of the mechanisms underlying the development of Alzheimer disease in people with Down syndrome could provide insights into the mechanisms that cause dementia in the general population. PMID:26243569

  18. Neuroleptic Malignant Syndrome Caused by a Combination of Carbamazepine and Amitriptyline

    Directory of Open Access Journals (Sweden)

    A. Bruce Janati

    2012-01-01

    Full Text Available A 32-year-old female, with a history of secondarily-generalized convulsive epilepsy, mental retardation, and a psychiatric illness, developed neuroleptic malignant syndrome while receiving carbamazepine and amitriptyline concurrently. We hypothesize that the addition of amitriptyline to carbamazepine caused a decrease in the serum level of carbamazepine, resulting in NMS. We conclude that combination therapy with carbamazepine and amitriptyline should be avoided in patients who are predisposed to NMS. The purpose of this paper is to warn physicians against combination therapy with carbamazepine and tricyclic antidepressants which may be conducive to neuroleptic malignant syndrome in susceptible patients.

  19. "Sagging heart syndrome": a cause of acute lead dislodgment in two patients.

    Science.gov (United States)

    Iskos, D; Lurie, K G; Shultz, J J; Fabian, W H; Benditt, D G

    1999-02-01

    Acute passive fixation atrial lead dislodgment occurred due to an unexpected and marked postural descent of the heart after permanent pacemaker implantation in two patients. Sagging of the heart in these two individuals may have been related to a history of morbid obesity followed by weight loss of over 100 pounds. Lead replacement with active fixation leads was required in both cases. The term "sagging heart syndrome" is proposed to describe this clinical entity. In certain adult populations, such as in patients with a history of significant weight loss, the "sagging heart syndrome" may represent a previously unrecognized cause of acute lead dislodgment.

  20. DRESS syndrome secondary to ibuprofen as a cause of hyperacute liver failure

    Directory of Open Access Journals (Sweden)

    Valentín Roales-Gómez

    2014-08-01

    Full Text Available Acute liver failure has a high mortality and its most frequent cause in Spain is viral infection. In this article, we present a case of fulminant liver failure. The failure is secondary to an idiosyncratic reaction to ibuprofen, an entity included in the DRESS syndrome. This syndrome plays a key role in the differential diagnosis of acute liver failure, since its unfortunate course often requires liver transplantation as the only useful therapeutic weapon. This case illustrates the need for an efficient coordination between hospitals as a key factor for improving the prognosis.

  1. Laugier-hunziker syndrome: a rare cause of oral and acral pigmentation.

    Science.gov (United States)

    Sachdeva, Silonie; Sachdeva, Shabina; Kapoor, Pranav

    2011-01-01

    Laugier-Hunziker syndrome (LHS) is an acquired, benign pigmentary skin condition involving oral cavity including lower lip in the form of brown black macules 1-5 mm in size, frequently associated with longitudinal melanonychia. There is no underlying systemic abnormality or malignant predisposition associated with LHS, and therefore the prognosis is good. Important differential diagnoses include Peutz Jeghers syndrome and Addison's disease among other causes of oral and acral pigmentation. Treatment is sought mainly for cosmetic reasons and Q-switched Nd-Yag laser/ Q-switched alexandrite therapy and cryosurgery have been tried with varying success.

  2. Laugier-hunziker syndrome: A rare cause of oral and acral pigmentation

    Directory of Open Access Journals (Sweden)

    Silonie Sachdeva

    2011-01-01

    Full Text Available Laugier-Hunziker syndrome (LHS is an acquired, benign pigmentary skin condition involving oral cavity including lower lip in the form of brown black macules 1-5 mm in size, frequently associated with longitudinal melanonychia. There is no underlying systemic abnormality or malignant predisposition associated with LHS, and therefore the prognosis is good. Important differential diagnoses include Peutz Jeghers syndrome and Addison′s disease among other causes of oral and acral pigmentation. Treatment is sought mainly for cosmetic reasons and Q-switched Nd-Yag laser/ Q-switched alexandrite therapy and cryosurgery have been tried with varying success.

  3. Budd-chiari syndrome caused by diaphragmatic hernia of the liver: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jae Min; Yoon, Jung Won; Kim, Jae Wook; Chung, Woo Kyoung; Chung, Hee Sun; Kim, Joo Hyung; Choi, Jun Ho; Kim, Seung Ho [Armed Forces Capital Hospital, Seongnam (Korea, Republic of)

    2007-01-15

    Budd-Chiari syndrome is an uncommon disorder, and it is caused by obstruction of the hepatic venous out-flow or inferior vena cava above the hepatic vein. It may result from a large number of conditions, including primary congenital obstructions of the hepatic veins or inferior vena cava by webs or bands. Secondary causes include trauma, polycythemia vera, chronic leukemia, pregnancy, tumors and use of oral contraceptives. No definitive etiologic factors have been identified in two thirds of all cases. We recently experienced a case of Budd-Chiari syndrome caused by diaphragmatic hernia in 21-year-old man. Postoperative follow up CT showed normal venous flow after reintroduction of the liver into the abdominal cavity and closure of the diaphragm defect.

  4. Neuroendocrine carcinoma of the ampulla of Vater causing ectopic adrenocorticotropic hormone-dependent Cushing's syndrome

    Science.gov (United States)

    KATO, AKIHISA; HAYASHI, KAZUKI; NAITOH, ITARU; SENO, KYOJI; OKADA, YUKIKO; BAN, TESSHIN; KONDO, HIROMU; NISHI, YUJI; UMEMURA, SHUICHIRO; HORI, YASUKI; NATSUME, MAKOTO; JOH, TAKASHI

    2016-01-01

    Ectopic adrenocorticotropic hormone (ACTH) is rarely secreted by neuroendocrine tumors. Although neuroendocrine tumors may occur at any site in the gastrointestinal system, they very rarely occur in the ampulla of Vater and have a poor prognosis. The present study described the first Cushing's syndrome as a result of ectopic ACTH arising from the ampulla of Vater neuroendocrine carcinoma. A 69-year-old female was admitted with clinical features of Cushing's syndrome, confirmed biochemically by hypokalemia, and elevated levels of ACTH and cortisol. In further investigations, a tumor of the ampulla of Vater and liver metastases were detected. Pathological analysis of the biopsy confirmed a neuroendocrine carcinoma, which was immunohistochemically positive for chromogranin A, synaptophysin, cluster of differentiation 56 and ACTH. Therefore, the present study diagnosed a functional and metastatic neuroendocrine carcinoma of the ampulla of Vater with ectopic ACTH production causing Cushing's syndrome. The patient succumbed to mortality 4 months later, despite administration of combined chemotherapy with irinotecan and cisplatin. PMID:27330779

  5. Internal carotid dissection caused by an elongated styloid process (Eagle syndrome).

    Science.gov (United States)

    Sveinsson, Olafur; Kostulas, Nikolaos; Herrman, Lars

    2013-06-11

    Eagle syndrome (symptoms associated with an elongated styloid process (SP)) is commonly divided into two presentations. First, the so-called classic Eagle syndrome where patients can present with unilateral sore throat, dysphagia, tinnitus, unilateral facial and neck pain and otalgia. Second, there is the vascular or stylocarotid form of Eagle syndrome in which the elongated SP is in contact with the extracranial internal carotid artery. We describe two cases of internal carotid artery dissection associated with an elongated SP. One is a patient with ischaemic stroke and another with transient ischaemic attacks caused by an elongated SP. A surgical resection of the SP was performed on the former patient. Both patients were treated with anticoagulation and recovered well. A literature search only revealed two prior descriptions of carotid dissection in the context of an elongated SP.

  6. Refeeding syndrome as an unusual cause of anion gap metabolic acidosis.

    Science.gov (United States)

    Singla, Manish; Perry, Alexandra; Lavery, Eric

    2012-11-01

    Refeeding syndrome is characterized by hypophosphatemia in the setting of malnutrition. It is commonly seen in patients with anorexia, alcoholism, or malignancy, and it is often a missed diagnosis. Because of the potential morbidity associated with missing the diagnosis of refeeding syndrome, it is important to monitor for this disease in any malnourished patient. We present a case of a 49-year-old male with chronic alcohol abuse who presented for alcohol detoxification and was found to have low phosphate, potassium, and magnesium on presentation, in addition to an elevated anion gap of unclear etiology. After extensive workup to evaluate the cause of his elevated anion gap and worsening of his electrolyte abnormalities despite replenishment, it was felt his symptoms were a result of refeeding syndrome. After oral intake was held and aggressive electrolyte replenishment was performed for 24 hours, the patient's anion gap closed and his electrolyte levels stabilized. This case demonstrates a unique presentation of refeeding syndrome given the patient's profound metabolic acidosis that provided a clue toward his eventual diagnosis. The standard workup for an anion gap metabolic acidosis was negative, and it was not until his refeeding syndrome had been treated that the anion gap closed.

  7. The biochemistry of vitamin B6 is basic to the cause of the Chinese restaurant syndrome.

    Science.gov (United States)

    Folkers, K; Shizukuishi, S; Willis, R; Scudder, S L; Takemura, K; Longenecker, J B

    1984-03-01

    The concept of this basic research was that monosodium L-glutamate could reveal a deficiency of vitamin B6 by the neurological reactions known as the Chinese Restaurant Syndrome. An other amino acid, tryptophan, administered to subjects, is known to reveal a deficiency of vitamin B6 by the excretory xanthurenic acid, etc. The presence and degree of a deficiency of vitamin B6 in 155 students on no supplemental B6 was determined by the differential assay of aspartate transaminase of erythrocytes which also allows each subject to be a control. Twenty-seven of 155 students had extraordinarily low basal specific activities of the transaminase, less than 0.26 mumol pyruvate/(h X 10(8) erythrocytes). These 27 were challenged with glutamate and a placebo. Twelve of 27 revealed the Chinese Restaurant Syndrome, and 15 did not. By double blind trials, the 12 "responders" were treated with pyridoxine and a placebo for twelve weeks, and then were rechallenged with glutamate and a placebo. Decoding showed 3 of 12 received placebo to pyridoxine and then revealed the symptoms of the syndrome again to glutamate; 9 of 12 received pyridoxine and then 8 of 9 failed to respond to glutamate. These results show, p less than 0.01, that the symptoms of the Chinese Restaurant Syndrome to oral glutamate fail to reoccur after treatment which pyridoxine, and that the biochemistry of vitamin B6 is basic to the cause of the Chinese Restaurant Syndrome.

  8. Glucocorticoid- and androgen-secreting black adrenocortical adenomas: unique cause of corticotropin-independent Cushing syndrome.

    Science.gov (United States)

    Tanaka, Satoshi; Tanabe, Akiyo; Aiba, Motohiko; Hizuka, Naomi; Takano, Kazue; Zhang, Jun; Young, William F

    2011-01-01

    To describe the unique association of corticotropin-independent Cushing syndrome caused by cortisol- and androgen-secreting black adrenal cortical adenomas with myelolipomatous change. We report the clinical, laboratory, radiologic, and pathologic findings from 2 patients who presented with androgen excess and typical signs and symptoms of Cushing syndrome. Endocrine investigations showed high serum cortisol concentrations that lacked diurnal rhythm, undetectable plasma corticotropin concentrations, and absence of serum cortisol suppression after overnight dexamethasone suppression tests. Serum levels of adrenal androgens were elevated. Computed tomography of the abdomen revealed unilateral adrenal masses (largest lesional diameters 4.0 and 3.1 cm). On the basis of the plurihormonal hypersecretion and the imaging characteristics, adrenocortical carcinoma was considered as a possible diagnosis. However, histopathologic analysis in both patients revealed black adrenal cortical adenomas with myelolipomatous change. After surgery, adrenal androgens normalized, and the signs and symptoms of Cushing syndrome and androgen excess resolved. There was no evidence of recurrent disease at last follow-up. A unique form of corticotropin-independent Cushing syndrome is described: cortisol- and androgen-secreting black adrenal cortical adenomas with myelolipomatous change. Although most patients with corticotropin-independent Cushing syndrome associated with androgen excess prove to have adrenocortical carcinoma, the clinician should be aware of the possibility of benign, black adrenal adenomas in this clinical setting.

  9. Artery of Percheron Infarction as an Unusual Cause of Korsakoff’s Syndrome

    Directory of Open Access Journals (Sweden)

    Yongxing Zhou

    2015-01-01

    Full Text Available The Korsakoff syndrome is defined as “an abnormal mental state in which memory and learning are affected out of all proportion to other cognitive functions in an otherwise alert and responsive patient.” Confabulation refers to false or erroneous memories arising, not deliberately, in the context of a neurological amnesia and is often thought of as pathognomonic of the Korsakoff syndrome. Although the exact pathophysiology is unknown, various studies have identified brain lesions in the thalami, mammillary bodies, and frontal cortex. We report a case of a 68-year-old male presenting with acute altered mental status on July 16, 2015. The neuropsychological dysfunctions included prominent Korsakoff’s syndrome, which became apparent when the altered mental status resolved. Amnesia was accompanied by prominent confabulation, disorientation, and lack of insight into his own disability. Neuroradiological data indicated that the intralaminar and dorsomedial nuclei in bilateral thalami were infarcted by occlusion of the artery of Percheron. We believe that ours is one of few reported cases of Korsakoff syndrome in a patient with infarction involving the territory of the artery of Percheron. We conclude that bilateral thalamic lesions could cause Korsakoff’s syndrome and the intralaminar and dorsomedial nuclei might be important structures in the pathogenesis of confabulation.

  10. MKS1 mutations cause Joubert syndrome with agenesis of the corpus callosum.

    Science.gov (United States)

    Bader, Ingrid; Decker, E; Mayr, J A; Lunzer, V; Koch, J; Boltshauser, E; Sperl, W; Pietsch, P; Ertl-Wagner, B; Bolz, H; Bergmann, C; Rittinger, O

    2016-08-01

    Joubert syndrome (JS) is a clinically and genetically heterogeneous ciliopathy characterized by episodic hyperpnea and apnea, hypotonia, ataxia, cognitive impairment and ocular motor apraxia. The "molar tooth sign" is pathognomonic of this condition. Mutations in the MKS1 gene are a major cause of Meckel-Gruber syndrome (MKS), the most common form of syndromic neural tube defects, frequently resulting in perinatal lethality. We present the phenotype and genotype of a child with severe JS and agenesis of the corpus callosum (ACC). In our patient, a next generation sequencing (NGS) approach revealed the following two variants of the MKS1 gene: first, a novel missense variant [ c.240G > T (p.Trp80Cys)], which affects a residue that is evolutionarily highly conserved in mammals and ciliates; second, a 29 bp deletion in intron 15 [c.1408-35_1408-7del29], a founder mutation, which in a homozygous state constitutes the major cause of MKS in Finland. We review the MKS1-variants in all of the eleven JS patients reported to date and compare these patients to our case. To our knowledge, this is the first patient with Joubert syndrome and agenesis of the corpus callosum where a potentially causal genotype is provided. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. DNA repair defects and genome instability in Hutchinson-Gilford Progeria Syndrome.

    Science.gov (United States)

    Gonzalo, Susana; Kreienkamp, Ray

    2015-06-01

    The integrity of the nuclear lamina has emerged as an important factor in the maintenance of genome stability. In particular, mutations in the LMNA gene, encoding A-type lamins (lamin A/C), alter nuclear morphology and function, and cause genomic instability. LMNA gene mutations are associated with a variety of degenerative diseases and devastating premature aging syndromes such as Hutchinson-Gilford Progeria Syndrome (HGPS) and Restrictive Dermopathy (RD). HGPS is a severe laminopathy, with patients dying in their teens from myocardial infarction or stroke. HGPS patient-derived cells exhibit nuclear shape abnormalities, changes in epigenetic regulation and gene expression, telomere shortening, genome instability, and premature senescence. This review highlights recent advances in identifying molecular mechanisms that contribute to the pathophysiology of HGPS, with a special emphasis on DNA repair defects and genome instability.

  12. Aging of Hutchinson-Gilford progeria syndrome fibroblasts is characterised by hyperproliferation and increased apoptosis.

    Science.gov (United States)

    Bridger, Joanna M; Kill, Ian R

    2004-05-01

    Hutchinson-Gilford progeria syndrome is a rare genetic disorder that mimics certain aspects of aging prematurely. Recent work has revealed that mutations in the lamin A gene are a cause of the disease. We show here that cellular aging of Hutchinson-Gilford progeria syndrome fibroblasts is characterised by a period of hyperproliferation and terminates with a large increase in the rate of apoptosis. The occurrence of cells with abnormal nuclear morphology reported by others is shown to be a result of cell division since the fraction of these abnormalities increases with cellular age. Similarly, the proportion of cells with an abnormal or absent A-type lamina increases with age. These data provide clues as to the cellular basis for premature aging in HGPS and support the view that cellular senescence and tissue homeostasis are important factors in the normal aging process.

  13. Cockayne Syndrome group B protein stimulates NEIL2 DNA glycosylase activity

    DEFF Research Database (Denmark)

    Aamann, Maria Diget; Hvitby, Christina Poulsen; Popuri, Venkateswarlu

    2014-01-01

    Cockayne Syndrome is a segmental premature aging syndrome, which can be caused by loss of function of the CSB protein. CSB is essential for genome maintenance and has numerous interaction partners with established roles in different DNA repair pathways including transcription coupled nucleotide...... excision repair and base excision repair. Here, we describe a new interaction partner for CSB, the DNA glycosylase NEIL2. Using both cell extracts and recombinant proteins, CSB and NEIL2 were found to physically interact independently of DNA. We further found that CSB is able to stimulate NEIL2 glycosylase...... in a DNA bubble structure using whole cell extracts. Taken together, our data supports a biological role for CSB and NEIL2 in transcription associated base excision repair....

  14. The Haglund painful heel syndrome. Experimental investigation of cause and therapeutic implications.

    Science.gov (United States)

    Heneghan, M A; Pavlov, H

    1984-01-01

    Haglund syndrome, a common cause of pain in the posterior heel, consists of a painful swelling of the local soft tissues (the so-called pump bump) and prominence of the calcaneal bursal projection. The condition is caused by compression of the distal Achilles tendon and surrounding soft tissue between the os calcis and the posterior shoe counter. Osseous plantar projections appear to be a critical etiologic factor in Haglund syndrome. With an experimental model, it has been demonstrated that osseous projections on the plantar surface of the calcaneus adversely influence the bone-soft tissue relation of the posterior heel. Shoe heel elevation has been shown to be clinically effective in alleviating symptoms. It is demonstrated with an experimental model that elevation of the shoe heel decreases the pitch angle. This diminishes the prominence of the bursal projection and allows the foot to slip forward, displacing the posterior calcaneus away from the shoe counter.

  15. Severe Cenani-Lenz syndrome caused by loss of LRP4 function.

    Science.gov (United States)

    Kariminejad, Ariana; Stollfuß, Barbara; Li, Yun; Bögershausen, Nina; Boss, Karin; Hennekam, Raoul C M; Wollnik, Bernd

    2013-06-01

    Limb patterning and growth are complex embryonic processes in which the elaborately orchestrated interplay of diverse endocrine and paracrine factors is crucial to limb integrity. LRP4 is a lipoprotein receptor known for its regulatory effects on LRP5- and LRP6-mediated Wnt signaling, a pathway that plays a pivotal role in limb development. Recessive mutations in LRP4 have been shown to cause Cenani-Lenz syndrome, which is characterized by severe limb malformations, an unusual face, and renal abnormalities. We report on a child with severe Cenani-Lenz syndrome caused by a novel homozygous nonsense mutation in LRP4. The severity of the phenotype in a patient with absent residual LRP4 function may point to a genotype-phenotype correlation.

  16. Homozygosity for a novel truncating mutation confirms TBX15 deficiency as the cause of Cousin syndrome.

    Science.gov (United States)

    Dikoglu, Esra; Simsek-Kiper, Pelin Ozlem; Utine, Gulen Eda; Campos-Xavier, Belinda; Boduroglu, Koray; Bonafé, Luisa; Superti-Furga, Andrea; Unger, Sheila

    2013-12-01

    Cousin syndrome, also called pelviscapular dysplasia (OMIM 260660), is characterized by short stature, craniofacial dysmorphism, and multiple skeletal anomalies. Following its description in two sibs in 1982, no new cases have been observed until the observation of two unrelated cases in 2008 who were homozygous for frameshift mutations in TBX15. We investigated an adult individual with short stature, a complex craniofacial dysmorphism, malformed and rotated ears, short neck, elbow contractures, hypoacusis, and hypoplasia of scapula and pelvis on radiographs. We identified homozygosity for a novel nonsense mutation (c.841C>T) in TBX15 predicted to cause a premature stop (p.Arg281*) with truncation of the protein. This observation confirms that Cousin syndrome is a consistent and clinically recognizable phenotype caused by loss of function of TBX15.

  17. Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training

    Science.gov (United States)

    Roberts, Christian K.; Hevener, Andrea L.; Barnard, R. James

    2014-01-01

    Metabolic syndrome (MS) is a collection of cardiometabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia. Although there has been significant debate regarding the criteria and concept of the syndrome, this clustering of risk factors is unequivocally linked to an increased risk of developing type 2 diabetes and cardiovascular disease. Regardless of the true definition, based on current population estimates, nearly 100 million have MS. It is often characterized by insulin resistance, which some have suggested is a major underpinning link between physical inactivity and MS. The purpose of this review is to: (i) provide an overview of the history, causes and clinical aspects of MS, (ii) review the molecular mechanisms of insulin action and the causes of insulin resistance, and (iii) discuss the epidemiological and intervention data on the effects of exercise on MS and insulin sensitivity. PMID:23720280

  18. Unilateral acquired Brown's syndrome in systemic scleroderma: An unusual cause for diplopia.

    Science.gov (United States)

    Pawar, Neelam; Ravindran, Meenakshi; Ramakrishnan, Renagappa; Maheshwari, Devendra; Trivedi, Bhakti

    2015-11-01

    Brown's syndrome can be congenital or acquired with multiple causes. It has been described as a ocular complication in various rheumatic and nonrheumatic diseases. We describe a case of 27-year-old female patient with 5 years old history of systemic scleroderma who developed vertical diplopia, a left head tilt, and restriction of left eye on elevation in adduction. The patient responded to systemic steroids with resolution of diplopia.

  19. Unusual pharyngeal pain caused by acute coronary syndrome: a report of three cases

    Directory of Open Access Journals (Sweden)

    Takashi Anzai

    2017-01-01

    Full Text Available Most patients complaining of pharyngeal pain have an upper respiratory tract infection or other local explanation for their pain. Here we show 3 rare cases of patients visiting our Otorhinolaryngology Department who had an initial symptom of pharyngeal pain caused by acute coronary syndrome (ACS. An electrocardiogram and a cardiac biomarker test are recommended to exclude ACS with atypical presentation in cases without pharyngolaryngeal findings comparable to pharyngeal pain.

  20. Cri du chat syndrome and primary ciliary dyskinesia: a common genetic cause on chromosome 5p.

    Science.gov (United States)

    Shapiro, Adam J; Weck, Karen E; Chao, Kay C; Rosenfeld, Margaret; Nygren, Anders O H; Knowles, Michael R; Leigh, Margaret W; Zariwala, Maimoona A

    2014-10-01

    Cri du chat syndrome (CdCS) and primary ciliary dyskinesia (PCD) are rare diseases that present with frequent respiratory symptoms. PCD can be caused by hemizygous DNAH5 mutation in combination with a 5p segmental deletion attributable to CdCS on the opposite chromosome. Chronic oto-sino-pulmonary symptoms or organ laterality defects in CdCS should prompt an evaluation for PCD.

  1. A huge ovarian mucinous cystadenoma causing virilization, preterm labor, and persistent supine hypotensive syndrome during pregnancy.

    Science.gov (United States)

    Kucur, Suna Kabil; Acar, Canan; Temizkan, Osman; Ozagari, Aysim; Gozukara, Ilay; Akyol, Atif

    2016-01-01

    Mucinous cystadenoma (MC) of the ovary is an unilateral, multilocular cystic benign epithelial tumor. Supposed to be hormone responsive, MC reaches huge sizes during pregnancy. Aortocaval compression is common during pregnancy, especially when the pregnant woman is in the supine position. However, the compression recovers with a change in position. The authors report the first case of a huge mucinous cystadenoma of the ovary complicating pregnancy and causing virilization, premature labor, and persistent supine hypotensive syndrome.

  2. Gouty wrist arthritis causing carpal tunnel syndrome--a case report.

    Science.gov (United States)

    Sikkandar, M F; Sapuan, J; Singh, R; Abdullah, S

    2012-06-01

    A 63 year old male with a history of gout and hypertension presented with carpal tunnel syndrome. He gave history of bilateral wrist pain associated with numbness over the median nerve distribution of the hand. Tinels sign and Phalens test were positive with no obvious thenar muscle wasting on examination. Tophaceous deposits in the flexor tendons and within the synovium of the wrist joint was seen during surgery and this established gout as the cause of median nerve entrapment in this patient.

  3. Intrauterine device infection causing concomitant streptococcal toxic shock syndrome and pelvic abscess with Actinomyces odontolyticus bacteraemia.

    Science.gov (United States)

    Wu, Carolyn M Yu; Noska, Amanda

    2016-03-10

    Intrauterine devices (IUDs) are rarely associated with serious infections. We report an unusual concomitant infection of group A Streptococcus (GAS) causing toxic shock syndrome and pelvic abscess with Actinomyces odontolyticus associated with an IUD in a healthy 50-year-old patient. The IUD was subsequently removed and the patient recovered on the appropriate antibiotics. This case highlights the importance of clinicians' high index of suspicion of an IUD infection and prompt removal of the infected foreign body to obtain source control.

  4. Smith-Lemli-Opitz syndrome is caused by mutations in the 7-dehydrocholesterol reductase gene.

    OpenAIRE

    Waterham, H. R.; Wijburg, F.A.; Hennekam, R. C.; Vreken, P; Poll-The, B T; Dorland, L.; Duran, M.; Jira, P.E.; Smeitink, J. A.; Wevers, R. A.; Wanders, R J

    1998-01-01

    Smith-Lemli-Opitz syndrome is a frequently occurring autosomal recessive developmental disorder characterized by facial dysmorphisms, mental retardation, and multiple congenital anomalies. Biochemically, the disorder is caused by deficient activity of 7-dehydrocholesterol reductase, which catalyzes the final step in the cholesterol-biosynthesis pathway-that is, the reduction of the Delta7 double bond of 7-dehydrocholesterol to produce cholesterol. We identified a partial transcript coding for...

  5. Superior cerebellar aneurysm causing subarachnoid haemorrhage in a 17-year-old with alagille syndrome.

    LENUS (Irish Health Repository)

    O'Connell, David

    2012-04-01

    Alagille syndrome is a rare autosomal dominant condition characterised by mutation in Jagged1 gene. Intracranial aneurysms may be seen in this condition and may present as subarachnoid hemorrhage. We describe the first case of superior cerebellar aneurysm rupture causing WFNS grade 1 subarachnoid haemorrhage in a 17-year-old girl. The clinical condition and management of this rare occurrence is discussed with a review of literature.

  6. Unusual cause of ectopic secretion of adrenocorticotropic hormone: Cushing syndrome attributable to small cell prostate cancer.

    Science.gov (United States)

    Alshaikh, Omalkhaire M; Al-Mahfouz, Abdulraof A; Al-Hindi, Hindi; Mahfouz, Ali Bin; Alzahrani, Ali S

    2010-01-01

    To report a rare cause of ectopic adrenocorticotropic hormone (ACTH) secretion leading to severe Cushing syndrome. We describe the clinical presentation and management of a case of Cushing syndrome attributable to ectopic ACTH secretion from small cell cancer of the prostate. In a 70-year-old man with hypertension and diabetes, congestive heart failure developed. He was found to have severe hypokalemia (serum potassium, 1.7 mEq/L) and a huge pelvic mass on a computed tomographic scan performed because of a complaint of urinary retention. Transurethral biopsy of the prostate showed features of small cell prostate cancer. Hormonal evaluation revealed a high urine free cortisol excretion of 6,214.5 microg/d (reference range, 36 to 137), confirming the diagnosis of Cushing syndrome. A serum ACTH level was elevated at 316 ng/dL (reference range, 10 to 52). An overnight high-dose (8 mg orally) dexamethasone suppression test was positive (serum cortisol levels were 43.2 and 41 microg/dL before and after suppression, respectively), and magnetic resonance imaging of the pituitary gland disclosed no abnormalities. A prostate biopsy specimen showed small cell prostate cancer with positive staining for ACTH. The tumor was found to be unresectable, and the poor condition of the patient did not allow for bilateral adrenalectomy. He was treated with ketoconazole and metyrapone, which yielded good temporary control of his Cushing syndrome (24-hour urine free cortisol decreased to 55.2 microg/d). He received 1 cycle of chemotherapy (etoposide and cisplatin), but he died 6 months later as a result of sepsis. Small cell prostate cancer is a rare subtype that can be associated with ectopic secretion of ACTH and severe Cushing syndrome. With this subtype of prostate cancer, Cushing syndrome should be considered and appropriately managed.

  7. PIK3R1 Mutations Cause Syndromic Insulin Resistance with Lipoatrophy

    Science.gov (United States)

    Thauvin-Robinet, Christel; Auclair, Martine; Duplomb, Laurence; Caron-Debarle, Martine; Avila, Magali; St-Onge, Judith; Le Merrer, Martine; Le Luyer, Bernard; Héron, Delphine; Mathieu-Dramard, Michèle; Bitoun, Pierre; Petit, Jean-Michel; Odent, Sylvie; Amiel, Jeanne; Picot, Damien; Carmignac, Virginie; Thevenon, Julien; Callier, Patrick; Laville, Martine; Reznik, Yves; Fagour, Cédric; Nunes, Marie-Laure; Capeau, Jacqueline; Lascols, Olivier; Huet, Frédéric; Faivre, Laurence; Vigouroux, Corinne; Rivière, Jean-Baptiste

    2013-01-01

    Short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome is a developmental disorder with an unknown genetic cause and hallmarks that include insulin resistance and lack of subcutaneous fat. We ascertained two unrelated individuals with SHORT syndrome, hypothesized that the observed phenotype was most likely due to de novo mutations in the same gene, and performed whole-exome sequencing in the two probands and their unaffected parents. We then confirmed our initial observations in four other subjects with SHORT syndrome from three families, as well as 14 unrelated subjects presenting with syndromic insulin resistance and/or generalized lipoatrophy associated with dysmorphic features and growth retardation. Overall, we identified in nine affected individuals from eight families de novo or inherited PIK3R1 mutations, including a mutational hotspot (c.1945C>T [p.Arg649Trp]) present in four families. PIK3R1 encodes the p85α, p55α, and p50α regulatory subunits of class IA phosphatidylinositol 3 kinases (PI3Ks), which are known to play a key role in insulin signaling. Functional data from fibroblasts derived from individuals with PIK3R1 mutations showed severe insulin resistance for both proximal and distal PI3K-dependent signaling. Our findings extend the genetic causes of severe insulin-resistance syndromes and provide important information with respect to the function of PIK3R1 in normal development and its role in human diseases, including growth delay, Rieger anomaly and other ocular affections, insulin resistance, diabetes, paucity of fat, and ovarian cysts. PMID:23810378

  8. HANAC Syndrome Col4a1 Mutation Causes Neonate Glomerular Hyperpermeability and Adult Glomerulocystic Kidney Disease.

    Science.gov (United States)

    Chen, Zhiyong; Migeon, Tiffany; Verpont, Marie-Christine; Zaidan, Mohamad; Sado, Yoshikazu; Kerjaschki, Dontscho; Ronco, Pierre; Plaisier, Emmanuelle

    2016-04-01

    Hereditary angiopathy, nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is an autosomal dominant syndrome caused by mutations in COL4A1 that encodes the α1 chain of collagen IV, a major component of basement membranes. Patients present with cerebral small vessel disease, retinal tortuosity, muscle cramps, and kidney disease consisting of multiple renal cysts, chronic kidney failure, and sometimes hematuria. Mutations producing HANAC syndrome localize within the integrin binding site containing CB3[IV] fragment of the COL4A1 protein. To investigate the pathophysiology of HANAC syndrome, we generated mice harboring the Col4a1 p.Gly498Val mutation identified in a family with the syndrome. Col4a1 G498V mutation resulted in delayed glomerulogenesis and podocyte differentiation without reduction of nephron number, causing albuminuria and hematuria in newborns. The glomerular defects resolved within the first month, but glomerular cysts developed in 3-month-old mutant mice. Abnormal structure of Bowman's capsule was associated with metalloproteinase induction and activation of the glomerular parietal epithelial cells that abnormally expressed CD44,α-SMA, ILK, and DDR1. Inflammatory infiltrates were observed around glomeruli and arterioles. Homozygous Col4a1 G498V mutant mice additionally showed dysmorphic papillae and urinary concentration defects. These results reveal a developmental role for the α1α1α2 collagen IV molecule in the embryonic glomerular basement membrane, affecting podocyte differentiation. The observed association between molecular alteration of the collagenous network in Bowman's capsule of the mature kidney and activation of parietal epithelial cells, matrix remodeling, and inflammation may account for glomerular cyst development and CKD in patients with COL4A1-related disorders.

  9. Acute urinary retention caused by seminoma in a case of persistent Mullerian duct syndrome

    Directory of Open Access Journals (Sweden)

    Jayesh Modi

    2015-01-01

    Full Text Available Urinary symptoms have been described secondary to a pelvic mass originating from the ovary, uterus, cervix, prostate, or rectum. Persistent Mullerian duct syndrome is a rare form of intersex disorder, characterized by the presence of uterus and fallopian tubes in an otherwise 46 XY male. We report an adult male with bilateral cryptorchidism and a pelvic mass, who presented with acute urinary retention, and was diagnosed with a seminoma of the right testis, intratubular germ cell neoplasia of the left testis with the presence of Mullerian remnants. Pelvic mass was caused due to seminoma is a rare cause of urinary retention.

  10. Stem cell depletion in Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Rosengardten, Ylva; McKenna, Tomás; Grochová, Diana; Eriksson, Maria

    2011-12-01

    Hutchinson-Gilford progeria syndrome (HGPS or progeria) is a very rare genetic disorder with clinical features suggestive of premature aging. Here, we show that induced expression of the most common HGPS mutation (LMNA c.1824C>T, p.G608G) results in a decreased epidermal population of adult stem cells and impaired wound healing in mice. Isolation and growth of primary keratinocytes from these mice demonstrated a reduced proliferative potential and ability to form colonies. Downregulation of the epidermal stem cell maintenance protein p63 with accompanying activation of DNA repair and premature senescence was the probable cause of this loss of adult stem cells. Additionally, upregulation of multiple genes in major inflammatory pathways indicated an activated inflammatory response. This response has also been associated with normal aging, emphasizing the importance of studying progeria to increase the understanding of the normal aging process.

  11. Dumping Syndrome

    Science.gov (United States)

    ... System & How it Works Digestive Diseases A-Z Dumping Syndrome What is dumping syndrome? Dumping syndrome occurs when food, especially sugar, ... the colon and rectum—and anus. What causes dumping syndrome? Dumping syndrome is caused by problems with ...

  12. Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes.

    Science.gov (United States)

    Du, Xiaobing; Shen, Johnny; Kugan, Nishan; Furth, Emma E; Lombard, David B; Cheung, Catherine; Pak, Sally; Luo, Guangbin; Pignolo, Robert J; DePinho, Ronald A; Guarente, Leonard; Johnson, F Brad

    2004-10-01

    The Werner and Bloom syndromes are caused by loss-of-function mutations in WRN and BLM, respectively, which encode the RecQ family DNA helicases WRN and BLM, respectively. Persons with Werner syndrome displays premature aging of the skin, vasculature, reproductive system, and bone, and those with Bloom syndrome display more limited features of aging, including premature menopause; both syndromes involve genome instability and increased cancer. The proteins participate in recombinational repair of stalled replication forks or DNA breaks, but the precise functions of the proteins that prevent rapid aging are unknown. Accumulating evidence points to telomeres as targets of WRN and BLM, but the importance in vivo of the proteins in telomere biology has not been tested. We show that Wrn and Blm mutations each accentuate pathology in later-generation mice lacking the telomerase RNA template Terc, including acceleration of phenotypes characteristic of latest-generation Terc mutants. Furthermore, pathology not observed in Terc mutants but similar to that observed in Werner syndrome and Bloom syndrome, such as bone loss, was observed. The pathology was accompanied by enhanced telomere dysfunction, including end-to-end chromosome fusions and greater loss of telomere repeat DNA compared with Terc mutants. These findings indicate that telomere dysfunction may contribute to the pathogenesis of Werner syndrome and Bloom syndrome.

  13. Sheehan's syndrome as a rare cause of anaemia secondary to hypopituitarism.

    Science.gov (United States)

    Gokalp, Deniz; Tuzcu, Alpaslan; Bahceci, Mithat; Arikan, Senay; Bahceci, Selen; Pasa, Semir

    2009-05-01

    Although its exact mechanism is unclear, anaemia is well recognised as a feature of hypopituitarism; and anaemia is associated with Sheehan's syndrome (SS). We aimed to evaluate the frequency and severity of anaemia and other haematological changes among patients with Sheehan's syndrome, in comparison with healthy controls. Sixty-five SS patients and 55 age-matched female healthy controls were included. Biochemical and hormonal assessments and haematological evaluations were carried out, and groups were compared. The mean number of red blood cells, as well as mean haemoglobin, iron and erythropoietin levels, total iron-binding capacity and transferrin saturation were all significantly lower in SS patients compared to controls. SS patients had significantly higher rates of anaemia (80.0% vs. 25.5%, p = 0.0001), iron deficiency (44.6% vs. 5.4%, p = 0.001), leukopenia (20.0% vs. 5.4%, p = 0.015), thrombocytopenia (9.2% vs. 0.0%, p = 0.028) and bicytopenia (21.5% vs. 1.8%, p = 0.001) compared to controls. Anaemic SS patients had normochromic-normocytic anaemia (55%) or hypochromic-microcytic anaemia (45%). Anaemia is frequently associated with Sheehan's syndrome and responds to appropriate replacement therapy. Hypopituitarism should be considered as a possible cause of anaemia, and a hormone examination should be undertaken promptly, particularly in patients with anaemia resistant to therapy and/or with a history suggestive of Sheehan's syndrome.

  14. Two cases of uveitis masquerade syndrome caused by bilateral intraocular large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Jovanović Svetlana

    2013-01-01

    Full Text Available Introduction. Sometimes it is not easy to clinically recognize subtle differences between intraocular lymphoma and noninfectious uveitis. The most common lymphoma subtype involving the eye is B-cell lymphoma. Case report. We presented two patients aged 59 and 58 years with infiltration of the subretinal space with a large B-cell non-Hodgkin intraocular lymphoma. The patients originally had clinically masked syndrome in the form of intermediate uveitis. As it was a corticosteroid-resistant uveitis, we focused on the possible diagnosis of neoplastic causes of this syndrome. During hospitalization, the neurological symptoms emerged and multiple subretinal changes accompanied by yellowish white patches of retinal pigment epithelium with signs of vitritis, which made us suspect the intraocular lymphoma. Endocranial magnetic resonance imaging established tumorous infiltration in the region of the left hemisphere of the cerebellum. The histopathological finding confirmed the diagnosis of large B-cell non-Hodgkin lymphoma of risk moderate degree, immunoblast - centroblast cytological type. The other patient had clinical chronic uveitis accompanied by yellowish shaped white echographic changes of the retina and localized changes in the level of the subretina. The diagnosis of lymphoma was made by brain biopsy. Conclusion. Uveitis masquerade syndrome should be considered in all patients over 40 years with idiopathic steroid-resistant uveitis. Treatment begun on time can affect the course and improve the prognosis of uveitis masquerade syndrome (UMS and systemic disease.

  15. 3. Chromosomal instability in B-lymphoblasotoid cell lines from Werner's and Bloom's syndrome patients

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Werner's syndrome (WS) and Bloom's syndrome (BS) are rare autosomal recessive diseases in which the feature of premature aging and the elevated risk of neoplasia may be associated with genomic instability. To cha-racterize the genomic instability of WS and BS, B-lymphoblastoid cell lines (LCLs) from WS and BS patients were cytogenetically analyzed, comparing to those from healthy donors. Although all

  16. Upper gastrointestinal bleeding caused by severe esophagitis: a unique clinical syndrome.

    Science.gov (United States)

    Guntipalli, Prathima; Chason, Rebecca; Elliott, Alan; Rockey, Don C

    2014-12-01

    We have recognized a unique clinical syndrome in patients with upper gastrointestinal bleeding who are found to have severe esophagitis. We aimed to more clearly describe the clinical entity of upper gastrointestinal bleeding in patients with severe esophagitis. We conducted a retrospective matched case-control study designed to investigate clinical features in patients with carefully defined upper gastrointestinal bleeding and severe esophagitis. Patient data were captured prospectively via a Gastrointestinal Bleeding Healthcare Registry, which collects data on all patients admitted with gastrointestinal bleeding. Patients with endoscopically documented esophagitis (cases) were matched with randomly selected controls that had upper gastrointestinal bleeding caused by other lesions. Epidemiologic features in patients with esophagitis were similar to those with other causes of upper gastrointestinal bleeding. However, hematemesis was more common in patients with esophagitis 86% (102/119) than in controls 55% (196/357) (p bleeding than those without cirrhosis. We have described a unique clinical syndrome in patients with upper gastrointestinal bleeding who have erosive esophagitis. This syndrome is manifest by typical clinical features and is associated with favorable outcomes.

  17. Cole-Carpenter syndrome is caused by a heterozygous missense mutation in P4HB.

    Science.gov (United States)

    Rauch, Frank; Fahiminiya, Somayyeh; Majewski, Jacek; Carrot-Zhang, Jian; Boudko, Sergei; Glorieux, Francis; Mort, John S; Bächinger, Hans-Peter; Moffatt, Pierre

    2015-03-05

    Cole-Carpenter syndrome is a severe bone fragility disorder that is characterized by frequent fractures, craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features. To identify the cause of Cole-Carpenter syndrome in the two individuals whose clinical results were presented in the original description of this disorder, we performed whole-exome sequencing of genomic DNA samples from both individuals. The two unrelated individuals had the same heterozygous missense mutation in exon 9 of P4HB (NM_000918.3: c.1178A>G [p.Tyr393Cys]), the gene that encodes protein disulfide isomerase (PDI). In one individual, the P4HB mutation had arisen de novo, whereas in the other the mutation was transmitted from the clinically unaffected father who was a mosaic carrier of the variant. The mutation was located in the C-terminal disulfide isomerase domain of PDI, sterically close to the enzymatic center, and affected disulfide isomerase activity in vitro. Skin fibroblasts showed signs of increased endoplasmic reticulum stress, but despite the reported importance of PDI for collagen type I production, the rate of collagen type I secretion appeared normal. In conclusion, Cole-Carpenter syndrome is caused by a specific de novo mutation in P4HB that impairs the disulfide isomerase activity of PDI.

  18. Gram-positive bacterial superantigen outside-in signaling causes toxic shock syndrome.

    Science.gov (United States)

    Brosnahan, Amanda J; Schlievert, Patrick M

    2011-12-01

    Staphylococcus aureus and Streptococcus pyogenes (group A streptococci) are Gram-positive pathogens capable of producing a variety of bacterial exotoxins known as superantigens. Superantigens interact with antigen-presenting cells (APCs) and T cells to induce T cell proliferation and massive cytokine production, which leads to fever, rash, capillary leak and subsequent hypotension, the major symptoms of toxic shock syndrome. Both S. aureus and group A streptococci colonize mucosal surfaces, including the anterior nares and vagina for S. aureus, and the oropharynx and less commonly the vagina for group A streptococci. However, due to their abilities to secrete a variety of virulence factors, the organisms can also cause illnesses from the mucosa. This review provides an updated discussion of the biochemical and structural features of one group of secreted virulence factors, the staphylococcal and group A streptococcal superantigens, and their abilities to cause toxic shock syndrome from a mucosal surface. The main focus of this review, however, is the abilities of superantigens to induce cytokines and chemokines from epithelial cells, which has been linked to a dodecapeptide region that is relatively conserved among all superantigens and is distinct from the binding sites required for interactions with APCs and T cells. This phenomenon, termed outside-in signaling, acts to recruit adaptive immune cells to the submucosa, where the superantigens can then interact with those cells to initiate the final cytokine cascades that lead to toxic shock syndrome.

  19. Trousseau's Syndrome Caused by Intrahepatic Cholangiocarcinoma: An Autopsy Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Takashi Yuri

    2014-05-01

    Full Text Available An autopsy case report of Trousseau's syndrome caused by intrahepatic cholangiocarcinoma is presented, and seven previously reported cases are reviewed. A 73-year-old woman experiencing light-headedness and dementia of unknown cause for 6 months developed severe hypotonia. A hypointense lesion compatible with acute cerebral infarction was detected by magnetic resonance imaging. Abdominal computed tomography revealed an ill-defined large liver mass in the right lobe. The mass was not further investigated because of the patient's poor condition. She died of multiple organ failure, and an autopsy was conducted. Postmortem examination revealed intrahepatic cholangiocarcinoma, fibrous vegetations on the mitral valves and multiple thromboemboli in the cerebrum, spleen and rectum. Trousseau's syndrome is defined as an idiopathic thromboembolism in patients with undiagnosed or concomitantly diagnosed malignancy. This syndrome is encountered frequently in patients with mucin-producing carcinomas, while the incidence in patients with intrahepatic cholangiocarcinoma is uncommon. We found that tissue factor and mucin tumor marker (CA19-9, CA15-3 and CA-125 expression in cancer cells may be involved in the pathogenesis of thromboembolism. A patient with unexplained thromboembolism may have occult visceral malignancy; thus, mucin tumor markers may indicate the origin of a mucin-producing carcinoma, and postmortem examination may play an important role in revealing the hidden malignancy.

  20. Uniparental disomy as an unexpected cause of Meckel-Gruber syndrome: report of a case.

    Science.gov (United States)

    Bruechle, Nadia Ortiz; Steuernagel, Peter; Zerres, Klaus; Kurth, Ingo; Eggermann, Thomas; Knopp, Cordula

    2017-06-15

    Meckel-Gruber syndrome (MKS, OMIM #607361) is a rare pre- or perinatal lethal autosomal recessive ciliopathy caused by mutations in at least 12 known genes. It has a clinical and genetic overlap with other viable ciliopathies, especially Joubert syndrome and Joubert syndrome-related disorders. MKS is characterized by multicystic kidney dysplasia, central nervous system malformations (usually occipital encephalocele), ductal plate malformation of the liver, and postaxial polydactyly. We identified a homozygous mutation in TMEM67 (MKS3) in a fetus affected by MKS; however, only the mother was a carrier of the respective mutation. Genotyping with polymorphic microsatellite markers and single nucleotide polymorphism (SNP) array revealed a maternal uniparental disomy (UPD) of the entire chromosome 8 (upd(8)mat), harboring TMEM67. This is the first reported case of UPD as a cause of MKS. The possible underlying mechanisms for uniparental disomy (UPD) are reviewed. Even if rare, awareness of UPD and comprehensive work-up in the case of unexpected homozygosity for a recessive mutation is essential for accurate genetic counseling and assessment of the risk of recurrence.

  1. No evidence for pathogenic variants or maternal effect of ZFP57 as the cause of Beckwith-Wiedemann Syndrome

    DEFF Research Database (Denmark)

    Boonen, Susanne E; Hahnemann, Johanne M D; Mackay, Deborah

    2012-01-01

    Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome, which, in 50-60% of sporadic cases, is caused by hypomethylation of KCNQ1OT1 differentially methylated region (DMR) at chromosome 11p15.5. The underlying defect of this hypomethylation is largely unknown. Recently, recessive mutations...

  2. [Retention of urine caused by fecaloma in the course of a Guillain-Barre syndrome (author's transl)].

    Science.gov (United States)

    Nicolle, M H; Hugues, F C; Leche, J

    Sphincteral disorders are very rarely seen in a Guillain-Barre syndrome. The authors report a case of such a syndrome in a woman, in the course of which a retention of urine appeared making diagnosis more difficult. The cause actually was mechanical.

  3. Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients

    DEFF Research Database (Denmark)

    Hoornaert, Kristien P; Vereecke, Inge; Dewinter, Chantal;

    2010-01-01

    Stickler syndrome is an autosomal dominant connective tissue disorder caused by mutations in different collagen genes. The aim of our study was to define more precisely the phenotype and genotype of Stickler syndrome type 1 by investigating a large series of patients with a heterozygous mutation ...

  4. TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome

    NARCIS (Netherlands)

    Lambacher, Nils J; Bruel, Ange-Line; van Dam, Teunis J P; Szymańska, Katarzyna; Slaats, Gisela G; Kuhns, Stefanie; McManus, Gavin J; Kennedy, Julie E; Gaff, Karl; Wu, Ka Man; van der Lee, Robin; Burglen, Lydie; Doummar, Diane; Rivière, Jean-Baptiste; Faivre, Laurence; Attié-Bitach, Tania; Saunier, Sophie; Curd, Alistair; Peckham, Michelle; Giles, R|info:eu-repo/dai/nl/173658725; Johnson, Colin A; Huynen, Martijn A; Thauvin-Robinet, Christel; Blacque, Oliver E

    2016-01-01

    The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signalling by facilitating a protein diffusion barrier at the ciliary base. TZ defects cause ciliopathies such as Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome (JBTS). However, t

  5. TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome

    NARCIS (Netherlands)

    Lambacher, Nils J; Bruel, Ange-Line; van Dam, Teunis J P; Szymańska, Katarzyna; Slaats, Gisela G; Kuhns, Stefanie; McManus, Gavin J; Kennedy, Julie E; Gaff, Karl; Wu, Ka Man; van der Lee, Robin; Burglen, Lydie; Doummar, Diane; Rivière, Jean-Baptiste; Faivre, Laurence; Attié-Bitach, Tania; Saunier, Sophie; Curd, Alistair; Peckham, Michelle; Giles, R; Johnson, Colin A; Huynen, Martijn A; Thauvin-Robinet, Christel; Blacque, Oliver E

    The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signalling by facilitating a protein diffusion barrier at the ciliary base. TZ defects cause ciliopathies such as Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome (JBTS). However,

  6. Novel mutations in EVC cause aberrant splicing in Ellis-van Creveld syndrome.

    Science.gov (United States)

    Shi, Lisong; Luo, Chunyan; Ahmed, Mairaj K; Attaie, Ali B; Ye, Xiaoqian

    2016-04-01

    Ellis-van Creveld syndrome (EvC) is a rare autosomal recessive disorder characterized by disproportionate chondrodysplasia, postaxial polydactyly, nail dystrophy, dental abnormalities and in a proportion of patients, congenital cardiac malformations. Weyers acrofacial dysostosis (Weyers) is another dominantly inherited disorder allelic to EvC syndrome but with milder phenotypes. Both disorders can result from loss-of-function mutations in either EVC or EVC2 gene, and phenotypes associated with the two gene mutations are clinically indistinguishable. We present here a clinical and molecular analysis of a Chinese family manifested specific features of EvC syndrome. Sequencing of both EVC and EVC2 identified two novel heterozygous splice site mutations c.384+5G>C in intron 3 and c.1465-1G>A in intron 10 in EVC, which were inherited from mother and father, respectively. In vitro minigene expression assay, RT-PCR and sequencing analysis demonstrated that c.384+5G>C mutation abolished normal splice site and created a new cryptic acceptor site within exon 4, whereas c.1465-1G>A mutation affected consensus splice junction site and resulted in full exon 11 skipping. These two aberrant pre-mRNA splicing processes both produced in-frame abnormal transcripts that possibly led to abolishment of important functional domains. To our knowledge, this is the first report of EVC mutations that cause EvC syndrome in Chinese population. Our data revealed that EVC splice site mutations altered splicing pattern and helped elucidate the pathogenesis of EvC syndrome.

  7. An unusual cause of fulminant Guillain-Barré syndrome: angel's trumpet.

    Science.gov (United States)

    Sevketoglu, Esra; Tatlı, Burak; Tuğcu, Betul; Demirelli, Yasar; Hatipoglu, Sami

    2010-11-01

    A 5-year-old previously healthy boy presented with typical findings of Guillain-Barré syndrome and unilateral tonic pupil. He was placed on mechanical ventilation for 35 days for respiratory failure. Plasmapheresis and two courses of intravenous immunoglobulin therapy were given to the patient, and he experienced stepwise recovery from his illness. This case of acute motor axonal neuropathy type Guillain-Barré syndrome is novel in that the cause was established as ingestion of a toxic solanaceous plant, angel's trumpet (Brugmansia suaveolens; syn. Datura suaveolens). Understanding the signs and symptoms of angel's trumpet toxicity can allow for early diagnosis and proper case management. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Reversible cerebral vasoconstriction syndrome is a rare cause of stroke after carotid endarterectomy.

    Science.gov (United States)

    Causey, Marlin Wayne; Amans, Matthew R; Han, Sukgu; Higashida, Randall T; Conte, Michael

    2016-12-01

    Neurologic events after carotid endarterectomy (CEA) require prompt diagnosis and management to avoid potentially catastrophic sequelae. This report describes a 69-year-old gentleman who underwent a left CEA for a high-grade asymptomatic carotid stenosis with concomitant contralateral carotid occlusion. He had transient and crescendo neurologic events in the first 3 postoperative weeks that culminated in right hand weakness and paresthesia, despite dual antiplatelet therapy, maximal anticoagulation, and undergoing stenting of the endarterectomy site. Neurologic events recurred despite these measures and subsequent angiography showed reversible cerebral vasoconstriction syndrome that was successfully managed without further events. Reversible cerebral vasoconstriction syndrome is an unusual but important cause of neurologic events after CEA that requires aggressive and directed medical therapy. Published by Elsevier Inc.

  9. Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome

    DEFF Research Database (Denmark)

    Ü Basmanav, F Buket; Cau, Laura; Tafazzoli, Aylar

    2016-01-01

    Uncombable hair syndrome (UHS), also known as "spun glass hair syndrome," "pili trianguli et canaliculi," or "cheveux incoiffables" is a rare anomaly of the hair shaft that occurs in children and improves with age. UHS is characterized by dry, frizzy, spangly, and often fair hair that is resistant...... in the majority of UHS case subjects. The two enzymes PADI3 and TGM3, responsible for posttranslational protein modifications, and their target structural protein TCHH are all involved in hair shaft formation. Elucidation of the molecular outcomes of the disease-causing mutations by cell culture experiments...... and tridimensional protein models demonstrated clear differences in the structural organization and activity of mutant and wild-type proteins. Scanning electron microscopy observations revealed morphological alterations in hair coat of Padi3 knockout mice. All together, these findings elucidate the molecular genetic...

  10. Spontaneous coronary artery dissection causing acute coronary syndrome in a young patient without risk factors

    Directory of Open Access Journals (Sweden)

    Parag Chevli

    2014-09-01

    Full Text Available Spontaneous coronary artery dissection (SCAD is a rare cause of acute myocardial infarction that is more common in younger patients (under age 50 and in women. Although the etiology is not known, some predisposing conditions to SCAD are well known and include Marfan syndrome, pregnancy and peripartum state, drug abuse, and some anatomical abnormalities of the coronary arteries such as aneurysms and severe kinking. We describe a case of SCAD in a young woman who presented with sudden onset of chest pain and was admitted for the treatment of acute coronary syndrome. The coronary angiography showed dissection of the left anterior descending artery. The patient underwent successful percutaneous transluminal coronary angioplasty and stent placement.

  11. Klinefelter syndrome is a common cause for mental retardation of unknown etiology among prepubertal males.

    Science.gov (United States)

    Khalifa, M M; Struthers, J L

    2002-01-01

    Klinefelter syndrome (KS) has not typically been associated with mental retardation (MR), however, in recent years a growing body of evidence suggested that KS boys often experience language deficits and academic difficulties. In this study, we screened DNA samples from 1205 patients originally referred for fragile X syndrome (FRAX) testing, because of MR of unknown etiology and detected 8 KS patients. A similar number of males in the same age group were found to have FRAX; 3 of them had a family history of FRAX. Based on these findings, KS might be the most common cause of MR of unknown etiology among prepubertal males. Because of the significant benefits of early recognition and treatment of KS, we emphasize the importance of cytogenetic testing of all prepubertal males with cognitive impairment even without dysmorphic features.

  12. An atypical case of fragile X syndrome caused by a deletion that includes FMRI gene

    Energy Technology Data Exchange (ETDEWEB)

    Quan, F.; Zonana, J.; Gunter, K.; Peterson, K.L.; Magenis, R.E., Popovich, B.W. [Shriners Hospital for Crippled Children, Portland, OR (United States)

    1995-05-01

    Fragile X syndrome is the most common form of inherited mental retardation and results from the transcriptional inactivation of the FMR1 gene. In the vast majority of cases, this is caused by the expansion of an unstable CGG repeat in the first exon of the FMR1 gene. We describe here a phenotypically atypical case of fragile X syndrome, caused by a deletion that includes the entire FMR1 gene and {ge}9.0 Mb of flanking DNA. The proband, RK, was a 6-year-old mentally retarded male with obesity and anal atresia. A diagnosis of fragile X syndrome was established by the failure of RK`s DNA to hybridize to a 558-bp PstI-XhoI fragment (pfxa3) specific for the 5{prime}-end of the FMR1 gene. The analysis of flanking markers in the interval from Xq26.3-q28 indicated a deletion extending from between 160-500 kb distal and 9.0 Mb proximal to the FMR1 gene. High-resolution chromosome banding confirmed a deletion with breakpoints in Xq26.3 and Xq27.3. This deletion was maternally transmitted and arose as a new mutation on the grandpaternal X chromosome. The maternal transmission of the deletion was confirmed by FISH using a 34-kb cosmid (c31.4) containing most of the FMR1 gene. These results indicated that RK carried a deletion of the FMR1 region with the most proximal breakpoint described to date. This patient`s unusual clinical presentation may indicate the presence of genes located in the deleted interval proximal to the FMR1 locus that are able to modify the fragile X syndrome phenotype. 36 refs., 7 figs.

  13. Interstitial Lung Disease in Werner Syndrome: A Case Report of a 55-Year-Old Male Patient

    Directory of Open Access Journals (Sweden)

    Tiphaine Goletto

    2015-01-01

    Full Text Available Werner syndrome (WS is a progeroid or premature aging syndrome characterized by early onset of age-related pathologies and cancer. The average life expectancy of affected people is 52.8 years and tends to increase. The major causes of death are malignancy and myocardial infarction. Increased telomere attrition and decay are thought to play a causative role in the clinical and pathological manifestations of the disease. Although telomere length, with or without germline mutation, is known to be associated with interstitial lung disease, the latter is not associated with WS. To the best of our knowledge, we report the first case describing a WS patient with fatal ILD. This case suggests that older patients with WS could develop ILD. Clinical outcome of WS patients may thus be improved by counselling them regarding smoking cessation or other exposure and by proposing antifibrotic therapy.

  14. Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells.

    Science.gov (United States)

    Aliper, Alexander M; Csoka, Antonei Benjamin; Buzdin, Anton; Jetka, Tomasz; Roumiantsev, Sergey; Moskalev, Alexy; Zhavoronkov, Alex

    2015-01-01

    For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging.

  15. The prevalence and etiology of polycystic ovarian syndrome (PCOS) as a cause of female infertility in central Travancore

    OpenAIRE

    K. Roy George; N A Malini

    2014-01-01

    Recent alarming rise in the incidence of polycystic ovary syndrome (PCOS), the most common cause of female infertility is becoming a major concern among adolescent women worldwide. Altered hormonal and metabolic profiles are one of the common clinical manifestations in PCOS. The aim of the present study was to determine the prevalence and the etiology of polycystic ovary syndrome (PCOS) as a cause of female infertility in Central Travancore women, in view of their change in life s...

  16. Impact of anaemia on mortality and its causes in elderly patients with acute coronary syndromes.

    Science.gov (United States)

    Ariza-Solé, Albert; Formiga, Francesc; Salazar-Mendiguchía, Joel; Garay, Alberto; Lorente, Victòria; Sánchez-Salado, José C; Sánchez-Elvira, Guillermo; Gómez-Lara, Josep; Gómez-Hospital, Joan A; Cequier, Angel

    2015-06-01

    Prognostic impact of anaemia in the elderly with acute coronary syndromes has not been specifically analysed, and little information exists about causes of mortality in this setting. We prospectively included consecutive patients with acute coronary syndromes. Anaemia was defined as haemoglobin Anaemia was more common in the elderly (40.4% vs 19.5%, p Anaemia independently predicted overall mortality (HR 1.47, 95% CI 1.05-2.06), cardiac mortality (HR 1.76, 95% CI 1.06-2.94) and non-cardiac mortality (HR 1.59, 95% CI 1.03-2.45) in the overall cohort. In young patients the association between anaemia and mortality was significant only for non-cardiac causes. The association between anaemia and mortality was not significant in the elderly (HR 1.08, 95% CI 0.71-1.63, p 0.736). The impact of anaemia on cause specific of mortality seem to be different according to age subgroup. The association between anaemia and mortality was not observed in elderly patients from our series. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  17. Progeria syndrome: A case report

    Directory of Open Access Journals (Sweden)

    Rastogi Rajul

    2008-01-01

    Full Text Available Progeria is a rare and peculiar combination of dwarfism and premature aging. The incidence is one in several million births. It occurs sporadically and is probably an autosomal recessive syndrome. Though the clinical presentation is usually typical, conventional radiological and biochemical investigations help in confirming the diagnosis. We present a rare case of progeria with most of the radiological features as a pictorial essay.

  18. Origins of the E. coli Strain Causing an Outbreak of Hemolytic–Uremic Syndrome in Germany

    Science.gov (United States)

    Rasko, David A.; Webster, Dale R.; Sahl, Jason W.; Bashir, Ali; Boisen, Nadia; Scheutz, Flemming; Paxinos, Ellen E.; Sebra, Robert; Chin, Chen-Shan; Iliopoulos, Dimitris; Klammer, Aaron; Peluso, Paul; Lee, Lawrence; Kislyuk, Andrey O.; Bullard, James; Kasarskis, Andrew; Wang, Susanna; Eid, John; Rank, David; Redman, Julia C.; Steyert, Susan R.; Frimodt-Møller, Jakob; Struve, Carsten; Petersen, Andreas M.; Krogfelt, Karen A.; Nataro, James P.; Schadt, Eric E.; Waldor, Matthew K.

    2011-01-01

    BACKGROUND A large outbreak of diarrhea and the hemolytic–uremic syndrome caused by an unusual serotype of Shiga-toxin–producing Escherichia coli (O104:H4) began in Germany in May 2011. As of July 22, a large number of cases of diarrhea caused by Shiga-toxin–producing E. coli have been reported — 3167 without the hemolytic–uremic syndrome (16 deaths) and 908 with the hemolytic–uremic syndrome (34 deaths) — indicating that this strain is notably more virulent than most of the Shiga-toxin–producing E. coli strains. Preliminary genetic characterization of the outbreak strain suggested that, unlike most of these strains, it should be classified within the enteroaggregative pathotype of E. coli. METHODS We used third-generation, single-molecule, real-time DNA sequencing to determine the complete genome sequence of the German outbreak strain, as well as the genome sequences of seven diarrhea-associated enteroaggregative E. coli serotype O104:H4 strains from Africa and four enteroaggregative E. coli reference strains belonging to other serotypes. Genomewide comparisons were performed with the use of these enteroaggregative E. coli genomes, as well as those of 40 previously sequenced E. coli isolates. RESULTS The enteroaggregative E. coli O104:H4 strains are closely related and form a distinct clade among E. coli and enteroaggregative E. coli strains. However, the genome of the German outbreak strain can be distinguished from those of other O104:H4 strains because it contains a prophage encoding Shiga toxin 2 and a distinct set of additional virulence and antibiotic-resistance factors. CONCLUSIONS Our findings suggest that horizontal genetic exchange allowed for the emergence of the highly virulent Shiga-toxin–producing enteroaggregative E. coli O104:H4 strain that caused the German outbreak. More broadly, these findings highlight the way in which the plasticity of bacterial genomes facilitates the emergence of new pathogens. PMID:21793740

  19. De Novo ACTA2 Mutation Causes a Novel Syndrome of Multisystemic Smooth Muscle Dysfunction

    Science.gov (United States)

    Milewicz, Dianna M.; Østergaard, John R.; Ala-Kokko, Leena M.; Khan, Nadia; Grange, Dorothy K.; Mendoza-Londono, Roberto; Bradley, Timothy J.; Olney, Ann Haskins; Adès, Lesley; Maher, Joseph F.; Guo, Dongchuan; Buja, L. Maximilian; Kim, Dong; Hyland, James C.; Regalado, Ellen S.

    2011-01-01

    Smooth muscle cells (SMCs) contract to perform many physiological functions, including regulation of blood flow and pressure in arteries, contraction of the pupils, peristalsis of the gut and voiding of the bladder. SMC lineage in these organs is characterized by cellular expression of the SMC isoform of α-actin, encoded by the ACTA2 gene. We report here on a unique and de novo mutation in ACTA2, R179H, that causes a syndrome characterized by dysfunction of SMCs throughout the body, leading to aortic and cerebrovascular disease, fixed dilated pupils, hypotonic bladder, malrotation and hypoperistalsis of the gut and pulmonary hypertension. PMID:20734336

  20. De novo mutations in Plxnd1 and Rev3l cause mobius syndrome

    OpenAIRE

    Kayserili Karabey, Hülya; Tomas-Roca, Laura; Tsaalbi-Shtylik, Anastasia; Jansen, Jacob G.; Singh, Manvendra K.; Epstein, Jonathan A.; Altunoglu, Umut; Verzijl, Harriette; Soria, Laura; van Beusekom, Ellen; Roscioli, Tony; Iqbal, Zafar; Gilissen, Christian; Hoischen, Alexander; de Brouwer,Arjan P. M.; Erasmus, Corrie; Schubert, Dirk; Brunner, Han; Aytes, Antonio Perez; Marin, Faustino; Aroca, Pilar; Carta, Arturo; de Wind, Niels; Padberg, George W.; van Bokhoven, Hans

    2015-01-01

    ARTICLE Received 15 Nov 2014 | Accepted 17 Apr 2015 | Published 12 Jun 2015 De novo mutations in PLXND1 and REV3L cause Mo¨bius syndrome Laura Tomas-Roca1,2, Anastasia Tsaalbi-Shtylik3, Jacob G. Jansen3, Manvendra K. Singh4,5, Jonathan A. Epstein4, Umut Altunoglu6, Harriette Verzijl7, Laura Soria1, Ellen van Beusekom1, Tony Roscioli1,8, Zafar Iqbal1, Christian Gilissen1, Alexander Hoischen9, Arjan P.M. de Brouwer1, Corrie Erasmus7, Dirk Schubert10, Han Brunner1,11, Antoni...

  1. Autosplenectomy Causing Catastrophic Pneumococcal Meningitis in a Patient with Lupus/Antiphospholipid Antibody Syndrome.

    Science.gov (United States)

    Sheth, Khushboo; Snyder, Aaron; Wu, Ulysses; Lahiri, Bimalin; Grover, Prashant

    2016-01-01

    We present the case ofa26-year-old female who presented to the hospital with pneumococcal meningitis. A review of her records showed atrophic spleen, and a hypercoagulable workup was positive for Systemic Lupus Erythematous (SLE)/Antiphospholipid Antibody Syndrome (APS). An autosplenectomy from thrombotic occlusion of the splenic artery made her susceptible to pneumococcal meningitis. Autoimmune conditions, particularly SLE and APS, are important causes of hypercoagulable states in a young population, and earlier detection of these conditions and appropriate treatment helps to decrease morbidity and mortality among these patients.

  2. Poland's syndrome and head-and-neck tumour: an unusual association causing a reconstruction dilemma.

    Science.gov (United States)

    Gerlinger, Imre; Járai, Tamás; Lujber, László; Pytel, József

    2007-05-01

    Poland's syndrome is a rare congenital anomaly characterized by unilateral chest wall hypoplasia and ipsilateral hand abnormalities. The literature data suggest its sporadic nature. The prevailing theory concerning its cause is hypoplasia of the subclavian artery or its branches, which may lead to a range of developmental changes. Relationships have been demonstrated between tumours and Poland's syndrome and also between tumours and other developmental defects. The explanation may lie in abnormal homeobox and tumour suppressor genes. This paper presents the first literature report of a malignant tonsillo-lingual tumour with metastatic neck involvement in a patient with partial Poland's sequence. In consequence of the aplasia of the pectoralis major muscle, an alternative (a free radical forearm flap) to the routine head-and-neck reconstruction (pedicled pectoralis major flap) was necessitated following tumour excision and radical neck dissection. This case report surveys the diagnostic and therapeutic considerations when previously unnoticed Poland's syndrome is diagnosed in a patient with head-and-neck cancer. One year following major head-and-neck surgery, our patient is tumour-free.

  3. [Stevens-Johnson syndrome plus intrahepatic cholestasis caused by clindamycin or chlorpheniramine].

    Science.gov (United States)

    Sahagún Flores, J E; Soto Ortiz, J A; Tovar Méndez, C E; Cárdenas Ochoa, E C; Hernández Flores, G

    2009-05-15

    A 48-year-old woman was hospitalized with the diagnosis of hepatitis. She presented with symptoms of jaundice, headache, elevated bilirubin, and elevated hepatic enzymes. She related a recent episode of a bronchial infection that was treated during the previous eight days with paracetamol (500mg, 2 doses only), chlorpheniramine, betamethasone and clindamycin. After an initial clinical and laboratorial improvement, she began to complain of pruritus of the palms and soles. Thereafter, vesicles evolving to blisters developed and a deterioration of her general health ensued. Serologies for hepatitis A, B, and C viruses were negative. Intrahepatic cholestasis and Stevens Johnson Syndrome (SJS) were the final diagnosis. The association of the Stevens Johnson Syndrome and intrahepatic cholestasis simultaneously, related to adverse drug reactions, is very rare. The drugs reportedly involved are mainly antibiotics, such as ampicillin, vancomycin, amoxicillin/clavulinic acid and erythromycin. Other drugs involved are non-steroidal anti-inflamatory drugs, such as mefenamic acid, ibuprofen, and sulindac. The reactions can be minor or severe and can even cause death, an outcome that has been reported in patients of all races and ethnic groups, but appears to be more rare in patients of Latin origin. We present a discussion of this case and review the main characteristics of the Stevens Johnson Syndrome.

  4. Rules for distinguishing toxicants that cause type I and type II narcosis syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Veith, G.D.; Broderius, S.J. (Environmental Protection Agency, Environmental Research Laboratory-Duluth, MN (USA))

    1990-07-01

    Narcosis is a nonspecific reversible state of arrested activity of protoplasmic structures caused by a wide variety of organic chemicals. The vast majority of industrial organic chemicals can be characterized by a baseline structure-toxicity relationship as developed for diverse aquatic organisms, using only the n-octanol/water partition coefficient as a descriptor. There are, however, many apparent narcotic chemicals that are more toxic than baseline narcosis predicts. Some of these chemicals have been distinguished as polar narcotics. Joint toxic theory and isobole diagrams were used to show that chemicals strictly additive with phenol were generally more toxic than predicted by narcosis I models and characterized by a different mode of action called narcosis II syndrome. This type of toxicity is exemplified by certain amides, amines, phenols, and nitrogen heterocycles. Evidence is provided that suggests that narcosis II syndrome may result from the presence of a strong hydrogen bonding group on the molecule, and narcosis I syndrome results from hydrophobic bonding of the chemical to enzymes and/or membranes. This shift in toxic action is apparently indistinguishable for narcotic chemicals with log P greater than about 2.7. General rules for selecting the appropriate models are proposed.

  5. GBA2 Mutations Cause a Marinesco-Sjögren-Like Syndrome: Genetic and Biochemical Studies

    Science.gov (United States)

    Haugarvoll, Kristoffer; Johansson, Stefan; Rodriguez, Carlos E.; Boman, Helge; Haukanes, Bjørn Ivar; Bruland, Ove; Roque, Francisco; Jonassen, Inge; Blomqvist, Maria; Telstad, Wenche; Månsson, Jan-Eric

    2017-01-01

    Background With the advent new sequencing technologies, we now have the tools to understand the phenotypic diversity and the common occurrence of phenocopies. We used these techniques to investigate two Norwegian families with an autosomal recessive cerebellar ataxia with cataracts and mental retardation. Methods and Results Single nucleotide polymorphism (SNP) chip analysis followed by Exome sequencing identified a 2 bp homozygous deletion in GBA2 in both families, c.1528_1529del [p.Met510Valfs*17]. Furthermore, we report the biochemical characterization of GBA2 in these patients. Our studies show that a reduced activity of GBA2 is sufficient to elevate the levels of glucosylceramide to similar levels as seen in Gaucher disease. Furthermore, leucocytes seem to be the proper enzyme source for in vitro analysis of GBA2 activity. Conclusions We report GBA2 mutations causing a Marinesco-Sjögren-like syndrome in two Norwegian families. One of the families was originally diagnosed with Marinesco-Sjögren syndrome based on an autosomal recessive cerebellar ataxia with cataracts and mental retardation. Our findings highlight the phenotypic variability associated with GBA2 mutations, and suggest that patients with Marinesco-Sjögren-like syndromes should be tested for mutations in this gene. PMID:28052128

  6. Clinical study of lateral patellofemoral crush syndrome caused by military training

    Directory of Open Access Journals (Sweden)

    De-hui ZHANG

    2012-05-01

    Full Text Available Objective  To explore diagnostic method and surgical outcome of lateral patellofemoral crush syndrome caused by military training. Methods  Fifteen patients with lateral patellofemoral crush syndrome caused by military training from May 2006 to May 2008 were enrolled in this study, including 12 men (14 knees and 3 women (3 knees, aged from 22 to 43 years old with an average of 27.3 years. Randomly selected 18 healthy volunteers with similar age and gender but no knee pain symptom were selected to serve as a control group. Anteroposterior and lateral X-ray photographs of knee joint and axial photographs of the patella were taken in both groups for observing the bone architecture of the knee joint and measuring the femoral trochlear angle, patellofemoral congruence angle and patellofemoral index, and the data were compared. The 17 knee joints in patient group were treated with lateral patellar retinaculum release. Then the preoperative and postoperative pain severity was evaluated with visual analogue scale (VAS. Results  Patellofemoral congruence angle was 7.67°± 5.81° and patellofemoral index was 2.49±1.40 in patient group, while they were -2.2°±-2.71° and 1.25±0.15 in control group. The difference between two groups showed statistical significance (P < 0.05. The change in bone architecture was obvious in patient group. The preoperative pain score was 7.06±0.85, and postoperative pain score was 3.87±0.24 after 6 months and 3.01+0.17 after 1 year in patient group. The difference between preoperative pain score and postoperative pain score showed statistical significance (P < 0.05. Conclusions  Diagnosis of patellofemoral crush syndrome caused by military training requires a combination of case history, typical symptoms, objective sign and X-ray examination. Among these, X-ray examination is the fundamental auxiliary diagnostic tool for lateral patellofemoral crush syndrome, and the patellofemoral index is convenient for

  7. Aortopulmonary window parathyroid gland causing primary hyperparathyroidism in men type 1 syndrome.

    Science.gov (United States)

    Tonelli, Francesco; Biagini, Carlo; Giudici, Francesco; Cioppi, Federica; Brandi, Maria Luisa

    2016-01-01

    Primary hyperparathyroidism (HPT) is the most common endocrinopathy in Multiple Endocrine Neoplasia type 1 (MEN1) syndrome. Supernumerary and/or ectopic parathyroid glands, potentially causes of persistent or recurrent HPT after surgery, have been previously described. However, this is the first ever described case of ectopic parathyroid gland localized in the aortopulmunary window causing HPT in MEN1. After a consistent concordant pre-operative imaging assessment the patient, a 16 years old male affected by a severe hypercalcemia, underwent surgery. The parathyroid was found very deeply near the tracheal bifurcation, hidden by the aortic arch itself and for this reason not visible at the beginning of the dissection but only after being identified by palpation for its typical consistence. The intraoperative PTH decreased at normal level 10 min after removal of the ectopic gland. The patient remained with normal value of calcemia and PTH during the 10 months of follow-up.

  8. A Case of Idiopathic Hypereosinophilic Syndrome Causing Mitral Valve Papillary Muscle Rupture

    Directory of Open Access Journals (Sweden)

    Tiffany Tamse

    2015-01-01

    Full Text Available Idiopathic Hypereosinophilic Syndrome (IHES is a rare disease that can be difficult to diagnose as the differential is broad. This disease can cause significant morbidity and mortality if left untreated. Our patient is a 17-year-old adolescent female who presented with nonspecific symptoms of abdominal pain and malaise. She was incidentally found to have hypereosinophilia of 16,000 on complete blood count and nonspecific colitis and pulmonary edema on computed tomography. She went into cardiogenic shock due to papillary rupture of her mitral valve requiring extreme life support measures including intubation and extracorporal membrane oxygenation (ECMO as well as mitral valve replacement. Pathology of the valve showed eosinophilic infiltration as the underlying etiology. The patient was diagnosed with IHES after the exclusion of infectious, rheumatologic, and oncologic causes. She was treated with steroids with improvement of her symptoms and scheduled for close follow-up. In general patients with IHES that have cardiac involvement have poorer prognoses.

  9. Progress of Integrative Chinese and Western Medicine in Treating Polycystic Ovarian Syndrome Caused Infertility

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Polycystic ovarian syndrome (PCOS) is one of the most popular diseases that cause menstrual dysfunction and infertility in women. The present paper is a brief retrospection on the progress in treatment of PCOS caused infertility with integrative Chinese and Western medicine (ICWM). It can be seen from these materials that using traditional Chinese medicine (TCM) recipes formulated by Sheh-replenishing herbs or acupuncture to reinforce Gan-Shen, regulate Chong-Ren Channels in treating PCOS, stable clinical efficacy could be obtained, with less adverse reaction, though the effect initiated somewhat late. Whereas, when Shen-replenishing recipe and acupuncture are combined with hormone or ovulation promoting drugs of Western medicine, the above-mentioned shortcomings would be overcome. So, this combined therapy is frequently used in clinical practice.

  10. Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro–costo–mandibular syndrome

    Science.gov (United States)

    Lynch, Danielle C.; Revil, Timothée; Schwartzentruber, Jeremy; Bhoj, Elizabeth J.; Innes, A. Micheil; Lamont, Ryan E.; Lemire, Edmond G.; Chodirker, Bernard N.; Taylor, Juliet P.; Zackai, Elaine H.; McLeod, D. Ross; Kirk, Edwin P.; Hoover-Fong, Julie; Fleming, Leah; Savarirayan, Ravi; Boycott, Kym; MacKenzie, Alex; Brudno, Michael; Bulman, Dennis; Dyment, David; Majewski, Jacek; Jerome-Majewska, Loydie A.; Parboosingh, Jillian S.; Bernier, Francois P.

    2014-01-01

    Elucidating the function of highly conserved regulatory sequences is a significant challenge in genomics today. Certain intragenic highly conserved elements have been associated with regulating levels of core components of the spliceosome and alternative splicing of downstream genes. Here we identify mutations in one such element, a regulatory alternative exon of SNRPB as the cause of cerebro–costo–mandibular syndrome. This exon contains a premature termination codon that triggers nonsense-mediated mRNA decay when included in the transcript. These mutations cause increased inclusion of the alternative exon and decreased overall expression of SNRPB. We provide evidence for the functional importance of this conserved intragenic element in the regulation of alternative splicing and development, and suggest that the evolution of such a regulatory mechanism has contributed to the complexity of mammalian development. PMID:25047197

  11. Progress of integrative Chinese and Western medicine in treating polycystic ovarian syndrome caused infertility.

    Science.gov (United States)

    Song, Juan-juan; Yan, Miao-e; Wu, Xiao-ke; Hou, Li-hui

    2006-12-01

    Polycystic ovarian syndrome (PCOS) is one of the most popular diseases that cause menstrual dysfunction and infertility in women. The present paper is a brief retrospection on the progress in treatment of PCOS caused infertility with integrative Chinese and Western medicine (ICWM). It can be seen from these materials that using traditional Chinese medicine (TCM) recipes formulated by Shen-replenishing herbs or acupuncture to reinforce Gan-Shen, regulate Chong-Ren Channels in treating PCOS, stable clinical efficacy could be obtained, with less adverse reaction, though the effect initiated somewhat late. Whereas, when Shen-replenishing recipe and acupuncture are combined with hormone or ovulation promoting drugs of Western medicine, the above-mentioned shortcomings would be overcome. So, this combined therapy is frequently used in clinical practice.

  12. Histidine decarboxylase deficiency causes Tourette syndrome: parallel findings in humans and mice

    Science.gov (United States)

    Baldan, Lissandra Castellan; Rapanelli, Maximiliano; Crowley, Michael; Anderson, George M.; Loring, Erin; Gorczyca, Roxanne; Billingslea, Eileen; Wasylink, Suzanne; Panza, Kaitlyn E.; Ercan-Sencicek, A. Gulhan; Krusong, Kuakarun; Leventhal, Bennett L.; Ohtsu, Hiroshi; Bloch, Michael H.; Hughes, Zoë A.; Krystal, John H.; Mayes, Linda; de Araujo, Ivan; Ding, Yu-Shin; State, Matthew W.; Pittenger, Christopher

    2013-01-01

    Tourette syndrome (TS) is characterized by tics, sensorimotor gating deficiencies, and abnormalities of cortico-basal ganglia circuits. A mutation in histidine decarboxylase (Hdc), the key enzyme for the biosynthesis of histamine (HA), has been implicated as a rare genetic cause. Hdc knockout mice exhibited potentiated tic-like stereotypies, recapitulating core phenomenology of TS; these were mitigated by the dopamine D2 antagonist haloperidol, a proven pharmacotherapy, and by HA infusion into the brain. Prepulse inhibition was impaired in both mice and humans carrying Hdc mutations. HA infusion reduced striatal dopamine (DA) levels; in Hdc knockout mice, striatal DA was increased and the DA-regulated immediate early gene Fos was upregulated. Dopamine D2/D3 receptor binding was altered both in mice and in humans carrying the Hdc mutation. These data confirm HDC deficiency as a rare cause of TS and identify histamine-dopamine interactions in the basal ganglia as an important locus of pathology. PMID:24411733

  13. A New Potential Cause in the Development of Toxic Anterior Segment Syndrome: Fibrin Glue

    Directory of Open Access Journals (Sweden)

    Selçuk Sızmaz

    2014-08-01

    Full Text Available Objectives: To present a potential cause for toxic anterior segment syndrome (TASS. Materials and Methods: We report 4 cases of TASS that occurred following uneventful phacoemulsification and intraocular lens implantation. Results: The 4 cases were the first consecutive 2 cases of 2 different surgery days, 5 months apart. The most prominent sign of TASS was limbus-to-limbus corneal edema. Pain and/or intraocular pressure rise were also common. All surgical and presurgical procedures were checked after the first outbreak, whereas the second outbreak required further investigation. Fibrin glue remnants from preceding pterygium surgery with conjunctival autografting were found to be the potential cause. Despite intensive corticosteroid therapy, corneal edema did not resolve in 2 patients who underwent keratoplasty. Conclusion: TASS is a sight-threatening condition which requires thorough investigation for prevention of new cases. All steps must be carefully revised. (Turk J Ophthalmol 2014; 44: 280-3

  14. Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro-costo-mandibular syndrome.

    Science.gov (United States)

    Lynch, Danielle C; Revil, Timothée; Schwartzentruber, Jeremy; Bhoj, Elizabeth J; Innes, A Micheil; Lamont, Ryan E; Lemire, Edmond G; Chodirker, Bernard N; Taylor, Juliet P; Zackai, Elaine H; McLeod, D Ross; Kirk, Edwin P; Hoover-Fong, Julie; Fleming, Leah; Savarirayan, Ravi; Majewski, Jacek; Jerome-Majewska, Loydie A; Parboosingh, Jillian S; Bernier, Francois P

    2014-07-22

    Elucidating the function of highly conserved regulatory sequences is a significant challenge in genomics today. Certain intragenic highly conserved elements have been associated with regulating levels of core components of the spliceosome and alternative splicing of downstream genes. Here we identify mutations in one such element, a regulatory alternative exon of SNRPB as the cause of cerebro-costo-mandibular syndrome. This exon contains a premature termination codon that triggers nonsense-mediated mRNA decay when included in the transcript. These mutations cause increased inclusion of the alternative exon and decreased overall expression of SNRPB. We provide evidence for the functional importance of this conserved intragenic element in the regulation of alternative splicing and development, and suggest that the evolution of such a regulatory mechanism has contributed to the complexity of mammalian development.

  15. Vascular Quadrilateral Space Syndrome in 3 Overhead Throwing Athletes: An Underdiagnosed Cause of Digital Ischemia.

    Science.gov (United States)

    Rollo, Johnathon; Rigberg, David; Gelabert, Hugh

    2017-03-08

    Vascular quadrilateral space syndrome (vQSS) is an underdiagnosed cause of extremity ischemia, pain, and paresthesia in overhand throwing athletes. The mechanism of vQSS is thought to result from repeated abduction and external rotation of the arm leading to a distraction injury of the posterior circumflex humoral artery (PCHA) as this courses through the quadrilateral space. This trauma may cause dissection and dissecting aneurysm formation. Thrombus from this arterial injury then embolizes down the arm resulting in the symptomatic presentation. Patients were often presented after multiple embolic events, which have resulted in obliteration of digital arteries. Later stages of presentation may include ischemic ulceration and gangrene. We report 3 cases of vQSS in overhand throwing athletes. All 3 underwent surgical correction and have returned to competition. We discuss presentation, diagnosis, imaging findings, management, outcomes, and review of the literature. Prompt recognition of this syndrome is essential to optimal treatment, which includes PCHA ligation and division with or without thrombolytic therapy. Increased awareness of vQSS is needed among coaches and athletic trainers who often identify the symptoms and initiate the treatment. When treated promptly, these athletes return to baseline functional status.

  16. Aortic valve replacement for aortic stenosis with a small aortic annulus in a patient having Werner's syndrome and liver cirrhosis.

    Science.gov (United States)

    Sogawa, M; Kasuya, S; Yamamoto, K; Koshika, M; Oguma, F; Hayashi, J

    2001-12-01

    Werner's syndrome is a rare genetic disease characterized by premature aging and scleroderma-like involvement of the skin. We report a case of aortic valve replacement for severely calcified aortic valve stenosis with a small annulus in a patient suffering from Werner's syndrome and liver cirrhosis

  17. [Primary Neuroendocrine Carcinoma of Thymus Caused Cushing Syndrome: Surgical Treatment and Prognosis Analysis].

    Science.gov (United States)

    Li, Li; Chen, Yeye; Li, Shanqing; Liu, Hongsheng; Huang, Cheng; Qin, Yingzhi

    2015-07-01

    Primary neuroendocrine carcinoma of thymus (pNECT) is a rare thymic neoplasm. Some pNECTs could produce an adrenocorticotropic hormone and cause Cushing syndrome (CS). The aim os this study is to discuss the diagnostic technique and surgical management of pNECT-caused CS and analyze prognosis factors to improve the clinical experience of the disease. The outcome of surgery and follow-up of 14 cases (eight males and six females) of pNECT-caused CS were retrospectively analyzed from November 1987 to June 2013. The median age of the patients was 29, and the median duration of the disease was four months (1 month-44 months). All cases exhibited clinical evidence for the diagnosis of CS, and thoracic computed tomography (CT) was used to detect thymic tumors. Surgical treatment significantly decreased the concentration of both serum cortisol and adrenocorticotropic hormone (P<0.01) but caused one death in the perioperative period. With multidisciplinary therapy, the median survival was 38 months. pNECT-caused CS is a rare disease with aggressive characteristics and unclear prognosis. Early diagnosis and therapy is a challenge for clinicians. Thoracic CT is important for disease location and preoperative evaluation and should be routinely applied to all CS patients to allow early surgery and improved prognosis.

  18. Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system

    Directory of Open Access Journals (Sweden)

    Han Ruolan

    2008-04-01

    Full Text Available Abstract Background Cancer treatment with a variety of chemotherapeutic agents often is associated with delayed adverse neurological consequences. Despite their clinical importance, almost nothing is known about the basis for such effects. It is not even known whether the occurrence of delayed adverse effects requires exposure to multiple chemotherapeutic agents, the presence of both chemotherapeutic agents and the body's own response to cancer, prolonged damage to the blood-brain barrier, inflammation or other such changes. Nor are there any animal models that could enable the study of this important problem. Results We found that clinically relevant concentrations of 5-fluorouracil (5-FU; a widely used chemotherapeutic agent were toxic for both central nervous system (CNS progenitor cells and non-dividing oligodendrocytes in vitro and in vivo. Short-term systemic administration of 5-FU caused both acute CNS damage and a syndrome of progressively worsening delayed damage to myelinated tracts of the CNS associated with altered transcriptional regulation in oligodendrocytes and extensive myelin pathology. Functional analysis also provided the first demonstration of delayed effects of chemotherapy on the latency of impulse conduction in the auditory system, offering the possibility of non-invasive analysis of myelin damage associated with cancer treatment. Conclusions Our studies demonstrate that systemic treatment with a single chemotherapeutic agent, 5-FU, is sufficient to cause a syndrome of delayed CNS damage and provide the first animal model of delayed damage to white-matter tracts of individuals treated with systemic chemotherapy. Unlike that caused by local irradiation, the degeneration caused by 5-FU treatment did not correlate with either chronic inflammation or extensive vascular damage and appears to represent a new class of delayed degenerative damage in the CNS.

  19. Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes.

    Science.gov (United States)

    Moulson, Casey L; Fong, Loren G; Gardner, Jennifer M; Farber, Emily A; Go, Gloriosa; Passariello, Annalisa; Grange, Dorothy K; Young, Stephen G; Miner, Jeffrey H

    2007-09-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare precocious aging syndrome caused by mutations in LMNA that lead to synthesis of a mutant form of prelamin A, generally called progerin, that cannot be processed to mature lamin A. Most HGPS patients have a recurrent heterozygous de novo mutation in exon 11 of LMNA, c.1824C>T/p.G608G; this synonymous mutation activates a nearby cryptic splice donor site, resulting in synthesis of the mutant prelamin A, progerin, which lacks 50 amino acids within the carboxyl-terminal domain. Abnormal splicing is incomplete, so the mutant allele produces some normally-spliced transcripts. Nevertheless, the synthesis of progerin is sufficient to cause misshapen nuclei in cultured cells and severe disease phenotypes in affected patients. Here we present two patients with extraordinarily severe forms of progeria caused by unusual mutations in LMNA. One had a splice site mutation (c.1968+1G>A; or IVS11+1G>A), and the other had a novel synonymous coding region mutation (c.1821G>A/p.V607V). Both mutations caused very frequent use of the same exon 11 splice donor site that is activated in typical HGPS patients. As a consequence, the ratios of progerin mRNA and protein to wild-type were higher than in typical HGPS patients. Fibroblasts from both patients exhibited nuclear shape abnormalities typical of HGPS, and cells treated with a protein farnesyltransferase inhibitor exhibited fewer misshapen nuclei. Thus, farnesyltransferase inhibitors may prove to be useful even when progerin expression levels are higher than those in typical HGPS patients.

  20. Proteomic profiling of adipose tissue from Zmpste24-/- mice, a model of lipodystrophy and premature aging, reveals major changes in mitochondrial function and vimentin processing.

    Science.gov (United States)

    Peinado, Juan R; Quirós, Pedro M; Pulido, Marina R; Mariño, Guillermo; Martínez-Chantar, Maria L; Vázquez-Martínez, Rafael; Freije, José M P; López-Otín, Carlos; Malagón, María M

    2011-11-01

    Lipodystrophy is a major disease involving severe alterations of adipose tissue distribution and metabolism. Mutations in genes encoding the nuclear envelope protein lamin A or its processing enzyme, the metalloproteinase Zmpste24, cause diverse human progeroid syndromes that are commonly characterized by a selective loss of adipose tissue. Similarly to humans, mice deficient in Zmpste24 accumulate prelamin A and display phenotypic features of accelerated aging, including lipodystrophy. Herein, we report the proteome and phosphoproteome of adipose tissue as well as serum metabolome in lipodystrophy by using Zmpste24(-/-) mice as experimental model. We show that Zmpste24 deficiency enhanced lipolysis, fatty acid biogenesis and β-oxidation as well as decreased fatty acid re-esterification, thus pointing to an increased partitioning of fatty acid toward β-oxidation and away from storage that likely underlies the observed size reduction of Zmpste24-null adipocytes. Besides the mitochondrial proteins related to lipid metabolism, other protein networks related to mitochondrial function, including those involved in tricarboxylic acid cycle and oxidative phosphorylation, were up-regulated in Zmpste24(-/-) mice. These results, together with the observation of an increased mitochondrial response to oxidative stress, support the relationship between defective prelamin A processing and mitochondrial dysfunction and highlight the relevance of oxidative damage in lipoatrophy and aging. We also show that absence of Zmpste24 profoundly alters the processing of the cytoskeletal protein vimentin and identify a novel protein dysregulated in lipodystrophy, High-Mobility Group Box-1 Protein. Finally, we found several lipid derivates with important roles in energy balance, such as Lysophosphatidylcholine or 2-arachidonoylglycerol, to be dysregulated in Zmpste24(-/-) serum. Together, our findings in Zmpste24(-/-) mice may be useful to unveil the mechanisms underlying adipose tissue

  1. Defective lamin A-Rb signaling in Hutchinson-Gilford Progeria Syndrome and reversal by farnesyltransferase inhibition.

    Directory of Open Access Journals (Sweden)

    Jackleen Marji

    Full Text Available Hutchinson-Gilford Progeria Syndrome (HGPS is a rare premature aging disorder caused by a de novo heterozygous point mutation G608G (GGC>GGT within exon 11 of LMNA gene encoding A-type nuclear lamins. This mutation elicits an internal deletion of 50 amino acids in the carboxyl-terminus of prelamin A. The truncated protein, progerin, retains a farnesylated cysteine at its carboxyl terminus, a modification involved in HGPS pathogenesis. Inhibition of protein farnesylation has been shown to improve abnormal nuclear morphology and phenotype in cellular and animal models of HGPS. We analyzed global gene expression changes in fibroblasts from human subjects with HGPS and found that a lamin A-Rb signaling network is a major defective regulatory axis. Treatment of fibroblasts with a protein farnesyltransferase inhibitor reversed the gene expression defects. Our study identifies Rb as a key factor in HGPS pathogenesis and suggests that its modulation could ameliorate premature aging and possibly complications of physiological aging.

  2. SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome.

    Science.gov (United States)

    Gilfillan, Gregor D; Selmer, Kaja K; Roxrud, Ingrid; Smith, Raffaella; Kyllerman, Mårten; Eiklid, Kristin; Kroken, Mette; Mattingsdal, Morten; Egeland, Thore; Stenmark, Harald; Sjøholm, Hans; Server, Andres; Samuelsson, Lena; Christianson, Arnold; Tarpey, Patrick; Whibley, Annabel; Stratton, Michael R; Futreal, P Andrew; Teague, Jon; Edkins, Sarah; Gecz, Jozef; Turner, Gillian; Raymond, F Lucy; Schwartz, Charles; Stevenson, Roger E; Undlien, Dag E; Strømme, Petter

    2008-04-01

    Linkage analysis and DNA sequencing in a family exhibiting an X-linked mental retardation (XLMR) syndrome, characterized by microcephaly, epilepsy, ataxia, and absent speech and resembling Angelman syndrome, identified a deletion in the SLC9A6 gene encoding the Na(+)/H(+) exchanger NHE6. Subsequently, other mutations were found in a male with mental retardation (MR) who had been investigated for Angelman syndrome and in two XLMR families with epilepsy and ataxia, including the family designated as having Christianson syndrome. Therefore, mutations in SLC9A6 cause X-linked mental retardation. Additionally, males with findings suggestive of unexplained Angelman syndrome should be considered as potential candidates for SLC9A6 mutations.

  3. The pacemaker-twiddler's syndrome: an infrequent cause of pacemaker failure.

    Science.gov (United States)

    Salahuddin, Mohammad; Cader, Fathima Aaysha; Nasrin, Sahela; Chowdhury, Mashhud Zia

    2016-01-20

    The pacemaker-twiddler's syndrome is an uncommon cause of pacemaker malfunction. It occurs due to unintentional or deliberate manipulation of the pacemaker pulse generator within its skin pocket by the patient. This causes coiling of the lead and its dislodgement, resulting in failure of ventricular pacing. More commonly reported among elderly females with impaired cognition, the phenomenon usually occurs in the first year following pacemaker implantation. Treatment involves repositioning of the dislodged leads and suture fixation of the lead and pulse generator within its pocket. An 87 year old Bangladeshi lady who underwent a single chamber ventricular pacemaker (VVI mode: i.e. ventricle paced, ventricle sensed, inhibitory mode) implantation with the indication of complete heart block, and presented to us again 7 weeks later, with syncopal attacks. She admitted to repeatedly manipulating the pacemaker generator in her left pectoral region. Physical examination revealed a heart rate of 42 beats/minute, blood pressure 140/80 mmHg and bilateral crackles on lung auscultation. She had no cognitive deficit. An immediate electrocardiogram showed complete heart block with pacemaker spikes and failure to capture. Chest X-ray showed coiled and retracted right ventricular lead and rotated pulse generator. An emergent temporary pace maker was set at a rate of 60 beats per minute. Subsequently, she underwent successful lead repositioning with strong counselling to avoid further twiddling. Twiddler's syndrome should be considered as a cause of pacemaker failure in elderly patients presenting with bradyarrythmias following pacemaker implantation. Chest X-ray and electrocardiograms are simple and easily-available first line investigations for its diagnosis. Lead repositioning is required, however proper patient education and counselling against further manipulation is paramount to long-term management.

  4. Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome.

    Science.gov (United States)

    Ü Basmanav, F Buket; Cau, Laura; Tafazzoli, Aylar; Méchin, Marie-Claire; Wolf, Sabrina; Romano, Maria Teresa; Valentin, Frederic; Wiegmann, Henning; Huchenq, Anne; Kandil, Rima; Garcia Bartels, Natalie; Kilic, Arzu; George, Susannah; Ralser, Damian J; Bergner, Stefan; Ferguson, David J P; Oprisoreanu, Ana-Maria; Wehner, Maria; Thiele, Holger; Altmüller, Janine; Nürnberg, Peter; Swan, Daniel; Houniet, Darren; Büchner, Aline; Weibel, Lisa; Wagner, Nicola; Grimalt, Ramon; Bygum, Anette; Serre, Guy; Blume-Peytavi, Ulrike; Sprecher, Eli; Schoch, Susanne; Oji, Vinzenz; Hamm, Henning; Farrant, Paul; Simon, Michel; Betz, Regina C

    2016-12-01

    Uncombable hair syndrome (UHS), also known as "spun glass hair syndrome," "pili trianguli et canaliculi," or "cheveux incoiffables" is a rare anomaly of the hair shaft that occurs in children and improves with age. UHS is characterized by dry, frizzy, spangly, and often fair hair that is resistant to being combed flat. Until now, both simplex and familial UHS-affected case subjects with autosomal-dominant as well as -recessive inheritance have been reported. However, none of these case subjects were linked to a molecular genetic cause. Here, we report the identification of UHS-causative mutations located in the three genes PADI3 (peptidylarginine deiminase 3), TGM3 (transglutaminase 3), and TCHH (trichohyalin) in a total of 11 children. All of these individuals carry homozygous or compound heterozygous mutations in one of these three genes, indicating an autosomal-recessive inheritance pattern in the majority of UHS case subjects. The two enzymes PADI3 and TGM3, responsible for posttranslational protein modifications, and their target structural protein TCHH are all involved in hair shaft formation. Elucidation of the molecular outcomes of the disease-causing mutations by cell culture experiments and tridimensional protein models demonstrated clear differences in the structural organization and activity of mutant and wild-type proteins. Scanning electron microscopy observations revealed morphological alterations in hair coat of Padi3 knockout mice. All together, these findings elucidate the molecular genetic causes of UHS and shed light on its pathophysiology and hair physiology in general. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  5. Blue toe syndrome treated with sympathectomy in a patient with acute renal failure caused by cholesterol embolization

    Directory of Open Access Journals (Sweden)

    Min-Gang Kim

    2013-12-01

    Full Text Available Blue toe syndrome is the most frequent manifestation of tissue ischemia caused by cholesterol embolization (CE, which can lead to amputation of affected lower extremities, if severe. However, any effective treatment is lacking. We experienced a case of spontaneously presenting blue toe syndrome and concomitant acute renal failure in a patient with multiple atherosclerotic risk factors. CE was confirmed by renal biopsy. Despite medical treatment including prostaglandin therapy and narcotics, the toe lesion progressed to gangrene with worsening ischemic pain. Therefore, we performed lumbar sympathectomy, which provided dramatic pain relief as well as an adequate blood flow to the ischemic lower extremities, resulting in healing of the gangrenous lesion and avoiding toe amputation. This is the first reported case of a patient with intractable ischemic toe syndrome caused by CE that was treated successfully by sympathectomy. Our observations suggest that sympathectomy may be beneficial in some patients with CE-associated blue toe syndrome.

  6. Observational cohort study of ventricular arrhythmia in adults with Marfan syndrome caused by FBN1 mutations.

    Directory of Open Access Journals (Sweden)

    Ali Aydin

    Full Text Available BACKGROUND: Marfan syndrome is associated with ventricular arrhythmia but risk factors including FBN1 mutation characteristics require elucidation. METHODS AND RESULTS: We performed an observational cohort study of 80 consecutive adults (30 men, 50 women aged 42±15 years with Marfan syndrome caused by FBN1 mutations. We assessed ventricular arrhythmia on baseline ambulatory electrocardiography as >10 premature ventricular complexes per hour (>10 PVC/h, as ventricular couplets (Couplet, or as non-sustained ventricular tachycardia (nsVT, and during 31±18 months of follow-up as ventricular tachycardia (VT events (VTE such as sudden cardiac death (SCD, and sustained ventricular tachycardia (sVT. We identified >10 PVC/h in 28 (35%, Couplet/nsVT in 32 (40%, and VTE in 6 patients (8%, including 3 with SCD (4%. PVC>10/h, Couplet/nsVT, and VTE exhibited increased N-terminal pro-brain natriuretic peptide serum levels(P10/h and Couplet/nsVT also related to increased indexed end-systolic LV diameters (P = .024 and P = .020, to moderate mitral valve regurgitation (P = .018 and P = .003, and to prolonged QTc intervals (P = .001 and P = .006, respectively. Moreover, VTE related to mutations in exons 24-32 (P = .021. Kaplan-Meier analysis corroborated an association of VTE with increased NT-proBNP (P<.001 and with mutations in exons 24-32 (P<.001. CONCLUSIONS: Marfan syndrome with causative FBN1 mutations is associated with an increased risk for arrhythmia, and affected persons may require life-long monitoring. Ventricular arrhythmia on electrocardiography, signs of myocardial dysfunction and mutations in exons 24-32 may be risk factors of VTE.

  7. A Rare Cause of Bacteremia in a Pediatric Patient with Down Syndrome: Sphingomonas Paucimobilis

    Directory of Open Access Journals (Sweden)

    Mehmet Özdemir, Sevgi Pekcan, Mehmet Emin Demircili, Fatma Esenkaya Taşbent, Bahadır Feyzioğlu, Şerife Pirinç, Mahmut Baykan

    2011-01-01

    Full Text Available Sphingomonas paucimobilis, is a yellow-pigmented, aerobic, non fermentative, gram negative motile bacillus. S. paucimobilis which is widely found in nature and hospital environments rarely cause serious or life threatening infections. In this report, a case of hospital acquired bloodstream infection due to S. paucimobilis in a patient with Down syndrome who was on treatment for presumed pneumonia is presented.A one year-old child patient who was a known case of Down syndrome and had previously experienced cardiac surgery was hospitalized and treated for pneumonia. On the 12th day of hospitalization, blood cultures were taken because of a high body temperature. One of the blood cultures was positive for gram-negative rods. After 48 hour of incubation, the sub-cultures on blood agar medium yielded pure growth of a yellow, non-fermentative, gram-negative, rod-shaped bacterium. The microorganism was positive for oxidase, and esculin hydrolysis, while negative for urea and nitrate reduction, citrate utilisation and motility. The isolate had been identified as S. paucimobilis by using Vitek 2 system. The antibiotic susceptibility test was also performed with the same system and the strain was found to be susceptible to piperacillin-tazobactam and other antibiotics. Treatment with intravenous piperacilin-tazobactam (150 mg/kg/day was initiated. He responded well to the treatment and was discharged after 10 days. This case is reported to emphasize that S. paucimobilis should be kept in mind as a nosocomial infectious agent in patients with Down syndrome and immunosuppressive patients and the infections should be treated according to the sensitivity test results.

  8. Mutations of the CEP290 gene encoding a centrosomal protein cause Meckel-Gruber syndrome.

    Science.gov (United States)

    Frank, Valeska; den Hollander, Anneke I; Brüchle, Nadina Ortiz; Zonneveld, Marijke N; Nürnberg, Gudrun; Becker, Christian; Du Bois, Gabriele; Kendziorra, Heide; Roosing, Susanne; Senderek, Jan; Nürnberg, Peter; Cremers, Frans P M; Zerres, Klaus; Bergmann, Carsten

    2008-01-01

    Meckel-Gruber syndrome (MKS) is an autosomal recessive, lethal multisystemic disorder characterized by meningooccipital encephalocele, cystic kidney dysplasia, hepatobiliary ductal plate malformation, and postaxial polydactyly. Recently, genes for MKS1 and MKS3 were identified, putting MKS on the list of ciliary disorders (ciliopathies). By positional cloning in a distantly related multiplex family, we mapped a novel locus for MKS to a 3-Mb interval on 12q21. Sequencing of the CEP290 gene located in the minimal critical region showed a homozygous 1-bp deletion supposed to lead to loss of function of the encoded centrosomal protein CEP290/nephrocystin-6. CEP290 is thought to be involved in chromosome segregation and localizes to cilia, centrosomes, and the nucleus. Subsequent analysis of another consanguineous multiplex family revealed homozygous haplotypes and the same frameshift mutation. Our findings add to the increasing body of evidence that ciliopathies can cause a broad spectrum of disease phenotypes, and pleiotropic effects of CEP290 mutations range from single organ involvement with isolated Leber congenital amaurosis to Joubert syndrome and lethal early embryonic multisystemic malformations in Meckel-Gruber syndrome. We compiled clinical and genetic data of all patients with CEP290 mutations described so far. No clear-cut genotype-phenotype correlations were apparent as almost all mutations are nonsense, frameshift, or splice-site changes and scattered throughout the gene irrespective of the patients' phenotypes. Conclusively, other factors than the type and location of CEP290 mutations may underlie phenotypic variability. (c) 2007 Wiley-Liss, Inc.

  9. Reduced Euchromatin histone methyltransferase 1 causes developmental delay, hypotonia, and cranial abnormalities associated with increased bone gene expression in Kleefstra syndrome mice

    NARCIS (Netherlands)

    Balemans, M.C.M.; Ansar, M.; Oudakker, A.R.; Caam, A.P.M. van; Bakker, B.; Vitters, E.L.; Kraan, P.M. van der; Bruijn, D.R.H. de; Janssen, S.M.; Kuipers, A.J.; Huibers, M.M.; Maliepaard, Eliza M.; Walboomers, X.F.; Benevento, M.; Nadif Kasri, N.; Kleefstra, T.; Zhou, H.; Zee, C.E.E.M. van der; Bokhoven, H. van

    2014-01-01

    Haploinsufficiency of Euchromatin histone methyltransferase 1 (EHMT1), a chromatin modifying enzyme, is the cause of Kleefstra syndrome (KS). KS is an intellectual disability (ID) syndrome, with general developmental delay, hypotonia, and craniofacial dysmorphisms as additional core features. Recent

  10. Novel association of neurofibromatosis type 1-causing mutations in families with neurofibromatosis-Noonan syndrome.

    Science.gov (United States)

    Ekvall, Sara; Sjörs, Kerstin; Jonzon, Anders; Vihinen, Mauno; Annerén, Göran; Bondeson, Marie-Louise

    2014-03-01

    Neurofibromatosis-Noonan syndrome (NFNS) is a rare condition with clinical features of both neurofibromatosis type 1 (NF1) and Noonan syndrome (NS). All three syndromes belong to the RASopathies, which are caused by dysregulation of the RAS-MAPK pathway. The major gene involved in NFNS is NF1, but co-occurring NF1 and PTPN11 mutations in NFNS have been reported. Knowledge about possible involvement of additional RASopathy-associated genes in NFNS is, however, very limited. We present a comprehensive clinical and molecular analysis of eight affected individuals from three unrelated families displaying features of NF1 and NFNS. The genetic etiology of the clinical phenotypes was investigated by mutation analysis, including NF1, PTPN11, SOS1, KRAS, NRAS, BRAF, RAF1, SHOC2, SPRED1, MAP2K1, MAP2K2, and CBL. All three families harbored a heterozygous NF1 variant, where the first family had a missense variant, c.5425C>T;p.R1809C, the second family a recurrent 4bp-deletion, c.6789_6792delTTAC;p.Y2264Tfs*6, and the third family a splice-site variant, c.2991-1G>A, resulting in skipping of exon 18 and an in-frame deletion of 41 amino acids. These NF1 variants have all previously been reported in NF1 patients. Surprisingly, both c.6789_6792delTTAC and c.2991-1G>A are frequently associated with NF1, but association to NFNS has, to our knowledge, not previously been reported. Our results support the notion that NFNS represents a variant of NF1, genetically distinct from NS, and is caused by mutations in NF1, some of which also cause classical NF1. Due to phenotypic overlap between NFNS and NS, we propose screening for NF1 mutations in NS patients, preferentially when café-au-lait spots are present. © 2013 Wiley Periodicals, Inc.

  11. Identification of novel mutation in cathepsin C gene causing Papillon-Lefèvre Syndrome in Mexican patients

    OpenAIRE

    2013-01-01

    Abstract Background Papillon-Lefèvre Syndrome (PLS) is a type IV genodermatosis caused by mutations in cathepsin C (CTSC), with a worldwide prevalence of 1–4 cases per million in the general population. In México, the prevalence of this syndrome is unknown, and there are few case reports. The diagnosis of twenty patients in the state of Sinaloa highlights the need to characterize this syndrome in Mexicans. Methods To understand the basis of PLS in Mexicans, the gene expression, enzymatic acti...

  12. Identification of novel mutation in cathepsin C gene causing Papillon-Lefèvre Syndrome in Mexican patients

    OpenAIRE

    2013-01-01

    Background Papillon-Lefèvre Syndrome (PLS) is a type IV genodermatosis caused by mutations in cathepsin C (CTSC), with a worldwide prevalence of 1–4 cases per million in the general population. In México, the prevalence of this syndrome is unknown, and there are few case reports. The diagnosis of twenty patients in the state of Sinaloa highlights the need to characterize this syndrome in Mexicans. Methods To understand the basis of PLS in Mexicans, the gene expression, enzymatic activity and ...

  13. Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy

    DEFF Research Database (Denmark)

    Arndt, Anne-Karin; Schafer, Sebastian; Drenckhahn, Jorg-Detlef

    2013-01-01

    Deletion 1p36 syndrome is recognized as the most common terminal deletion syndrome. Here, we describe the loss of a gene within the deletion that is responsible for the cardiomyopathy associated with monosomy 1p36, and we confirm its role in nonsyndromic left ventricular noncompaction cardiomyopa...... of cardiomyocytes and also revealed evidence of impaired cardiomyocyte proliferative capacity. In conclusion, mutation of PRDM16 causes the cardiomyopathy in 1p36 deletion syndrome as well as a proportion of nonsyndromic LVNC and DCM....

  14. Current status of prenatal diagnosis in Cuba: causes of low prevalence of Down syndrome.

    Science.gov (United States)

    Méndez-Rosado, L A; Hechavarría-Estenoz, D; de la Torre, M E; Pimentel-Benitez, H; Hernández-Gil, J; Perez, B; Barrios-Martínez, A; Morales-Rodriguez, E; Soriano-Torres, M; Garcia, M; Suarez-Mayedo, U; Cedeño-Aparicio, N; Blanco, I; Díaz-Véliz, P; Vidal-Hernández, B; Mitjans-Torres, M; Miñoso, S; Alvarez-Espinosa, D; Reyes-Hernández, E; Angulo-Cebada, E; Torres-Palacios, M; Lozano-Lezcano, L; Lima-Rodriguez, U; Mayeta, M; Noblet, M; Benítez, Y; Lardoeyt-Ferrer, R; Yosela-Martin, S; Carbonell, P; Pérez-Ramos, M; de León, N; Perez, M; Carbonell, J

    2014-11-01

    To analyze trends in cytogenetic prenatal diagnosis in Cuba and to analyze possible causes leading to a low Down syndrome prevalence in a country where the triple test is not available. An analysis of the Cuban program in prenatal cytogenetic diagnosis from 1984 to 2012 was conducted. Results are described, with particular emphasis on indications, abnormal results, types of invasive procedures, and terminations of pregnancy. Cytogenetic prenatal diagnostic analyses (n = 75,095) were conducted; maternal age was the indication for 77.9% of the amniocenteses and chorionic villus samplings. The detection rate of chromosomally abnormal pregnancies was 2.3% for maternal age and increased to 8-9% for other indications. When a chromosomal abnormality was identified, 88.5% terminated the pregnancy. In 2002, the live birth prevalence of Down syndrome was 8.4 per 10,000 live births, and in 2012, 7 per 10,000. Prenatal diagnosis in Cuba has contributed to a significant reduction in chromosomal aberrations. The impact increased because of the demographic trends of the population, the high index of terminations of pregnancy, and the establishment of a network of cytogenetic laboratories throughout Cuba. © 2014 John Wiley & Sons, Ltd.

  15. [Brain abscess caused by Haemophilus influenzae type E in a pediatric patient suffering from Apert syndrome].

    Science.gov (United States)

    Isasmendi, Adela M; Pinheiro, José L; Escudé, Natalia García; Efrón, Adriana M; Moscoloni, María A; Hernández, Claudia M

    2014-01-01

    We report a case of a brain abscess caused by Haemophilus influenzae type e in a 12 year-old patient suffering from Apert syndrome. Apert syndrome is characterized by the premature closure of cranial sutures. In 2010 the patient suffered head trauma in the frontal area with cranial fracture and a cerebrospinal fluid fistula. In February 2013 he was admitted to hospital with fever, vomiting and generalized tonic-clonic seizure with deteriorating mental status/progressive sensory impairment. The computerized axial tomographic scan showed a right frontal lesion, perilesional edema, mild ventricular dilatation and pansinusitis. A brain abscess was diagnosed and drained. The clinical sample was then cultured. A gram negative coccobacillus was isolated and identified as Haemophilus influenzae serotype e. Empirical treatment was started with meropenem (120 mg/kg/day) and vancomycin (60 mg/kg/day), which was later switched to ceftriaxone (100 mg/kg/day) and metronidazole (500 mg/8 h) after culture results arrived. The patient was discharged in good clinical condition.

  16. Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome

    Science.gov (United States)

    Prasad, Rathi; Hadjidemetriou, Irene; Meimaridou, Eirini; Buonocore, Federica; Saleem, Moin; Hurcombe, Jenny; Bierzynska, Agnieszka; Barbagelata, Eliana; Bergadá, Ignacio; Cassinelli, Hamilton; Das, Urmi; Krone, Ruth; Hacihamdioglu, Bulent; Sari, Erkan; Yesilkaya, Ediz; Storr, Helen L.; Clemente, Maria; Fernandez-Cancio, Monica; Camats, Nuria; Ram, Nanik; Achermann, John C.; Van Veldhoven, Paul P.; Guasti, Leonardo; Braslavsky, Debora; Guran, Tulay; Metherell, Louise A.

    2017-01-01

    Primary adrenal insufficiency is life threatening and can present alone or in combination with other comorbidities. Here, we have described a primary adrenal insufficiency syndrome and steroid-resistant nephrotic syndrome caused by loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1). SGPL1 executes the final decisive step of the sphingolipid breakdown pathway, mediating the irreversible cleavage of the lipid-signaling molecule sphingosine-1-phosphate (S1P). Mutations in other upstream components of the pathway lead to harmful accumulation of lysosomal sphingolipid species, which are associated with a series of conditions known as the sphingolipidoses. In this work, we have identified 4 different homozygous mutations, c.665G>A (p.R222Q), c.1633_1635delTTC (p.F545del), c.261+1G>A (p.S65Rfs*6), and c.7dupA (p.S3Kfs*11), in 5 families with the condition. In total, 8 patients were investigated, some of whom also manifested other features, including ichthyosis, primary hypothyroidism, neurological symptoms, and cryptorchidism. Sgpl1–/– mice recapitulated the main characteristics of the human disease with abnormal adrenal and renal morphology. Sgpl1–/– mice displayed disrupted adrenocortical zonation and defective expression of steroidogenic enzymes as well as renal histology in keeping with a glomerular phenotype. In summary, we have identified SGPL1 mutations in humans that perhaps represent a distinct multisystemic disorder of sphingolipid metabolism. PMID:28165343

  17. Obstructive sleep apnoea in Treacher Collins syndrome: prevalence, severity and cause.

    Science.gov (United States)

    Plomp, R G; Bredero-Boelhouwer, H H; Joosten, K F M; Wolvius, E B; Hoeve, H L J; Poublon, R M L; Mathijssen, I M J

    2012-06-01

    This cohort study in 35 patients (13 children) evaluates the prevalence, severity and anatomical cause of obstructive sleep apnoea syndrome (OSAS) in patients with Treacher Collins syndrome. Ambulatory polysomnography was performed cross-sectionally to determine OSAS prevalence and severity. All upper airway related surgical interventions were evaluated retrospectively. In 11 patients, sleep endoscopy, and flexible and rigid endoscopy were applied to determine the level of anatomical obstruction of the upper airway. The overall prevalence of OSAS in Treacher Collins patients was 46% (54% in children; 41% in adults). Thirty-eight upper airway related surgical interventions were performed in 17 patients. Examination of the upper airway revealed various anatomical levels of obstruction, from the nasal septum to the trachea. Most significant obstruction was found at the level of the oro/hypopharynx. OSAS in Treacher Collins patients is an important problem so all patients should be screened for OSAS by polysomnography. Endoscopy of the upper airways was helpful in determining the level of obstruction. Surgical treatment at one level will not resolve OSAS in most patients because OSAS in Treacher Collins has a multilevel origin. Non-invasive ventilation (continuous positive airway pressure or bilevel positive airway pressure) or tracheotomy should be considered as a treatment modality.

  18. Ectopic adrenocorticotropic hormone syndrome caused by neuroendocrine carcinoma of the colon.

    Science.gov (United States)

    Fujimoto, Kazuyo; Nakashima, Takatoshi; Sasaki, Kazunari; Hayashi, Kenichi; Hanafusa, Masao; Yoshida, Shiei; Myojo, Satoshi; Yoshida, Shun-Ichi; Sawai, Shigeaki; Sano, Nobuya

    A 48-year-old woman with a history of autoimmune hemolytic anemia and taking long-term corticosteroid therapy presented with a 3-month history of general fatigue, abdominal distension, and pigmentation. A computed tomography scan of the abdomen showed a tumor in the sigmoid colon and multiple metastatic nodules in the liver. A colonoscopy revealed an obstructing mass with the presence of an irregular ulcer in the sigmoid colon. Following biopsy and histopathological analysis, the patient was diagnosed with neuroendocrine carcinoma (NEC) of the colon. She received her first cycle of chemotherapy, with carboplatin and etoposide. During hospitalization, her pigmentation and hypertension worsened and hypokalemia was observed, all of which suggsted Cushing's syndrome. Her plasma adrenocorticotropic hormone (ACTH) and cortisol levels were high, and an ectopic ACTH-producing tumor was suspected. After a second chemotherapy cycle, she developed neutropenic fever and subsequently died. At autopsy, two histological types were found in the tumor: small cell carcinoma and large cell NEC. Immunohistochemical analysis revealed ACTH in the large cell NEC. This is the first reported case of an ectopic ACTH syndrome caused by NEC of the colon.

  19. Rubinstein-Taybi syndrome caused by submicroscopic deletions within 16p13. 3

    Energy Technology Data Exchange (ETDEWEB)

    Breuning, M.H.; Dauwerse, H.G.; Fugazza, G.; Saris, J.J.; Spruit, L.; Winjnen, H.; Beverstock, G.C.; Ommen, G.J.B. van (Leiden Univ. (Netherlands)); Tommerup, N. (John F. Kennedy Inst., Glostrup (Denmark) Avd. for Medisinsk Genetikk, Oslo (Norway)); Hagen, C.B. van der (John F. Kennedy Inst., Glostrup (Denmark)); Imaizumi, Kiyoshi; Kuroki, Yoshikazu (Kanagawa Children' s Medical Center, Yokohama (Japan)); Boogaard, M.J. van den; Pater, J.M. de; Hennekam, R.C.M. (Clinical Genetics Center, Utrecht (Netherlands)); Mariman, E.C.M.; Hamel, B.C.J. (University Hospital, Nijmegen (Netherlands)); Himmelbauer, H.; Frischauf, A.M. (Imperial Cancer Research Fund Laboratories, London (United Kingdom)); Stallings, R.L. (Los Alamos National Lab., NM (United States))

    1993-02-01

    The Rubinstein-Taybi syndrome (RTS) is a well-defined complex of congenital malformations characterized by facial abnormalities, broad thumbs and big toes, and mental retardation. The breakpoint of two distinct reciprocal translocations occurring in patients with a clinical diagnosis of RTS was located to the same interval on chromosome 16, between the cosmids N2 and RT1, in band 16p13.3. By using two-color fluorescence in situ hybridization, the signal from RT1 was found to be missing from one chromosome 16 in 6 of 24 patients with RTS. The parents of five of these patients did not show a deletion of RT1, indicating a de novo rearrangement. RTS is caused by submicroscopic interstitial deletions within 16p13.3 in approximately 25% of the patients. The detection of microdeletions will allow the objective confirmation of the clinical diagnosis in new patients and provides an excellent tool for the isolation of the gene causally related to the syndrome. 32 refs., 2 figs.

  20. Bannayan-Riley-Ruvalcaba syndrome: a cause of extreme macrocephaly and neurodevelopmental delay.

    LENUS (Irish Health Repository)

    Lynch, N E

    2012-02-01

    BACKGROUND: Bannayan-Riley-Ruvalcaba syndrome (BRRS) is an autosomal dominant condition characterised by macrocephaly, developmental delay and subtle cutaneous features. BRRS results from mutations in the PTEN gene. In adults, PTEN mutations cause Cowden syndrome where, in addition to the macrocephaly, there is a higher risk of tumour development. Diagnosis of BRRS is often delayed as presentation can be variable, even within families. AIMS: To identify characteristics of this condition which might facilitate early diagnosis. Prompt diagnosis not only avoids unnecessary investigations in the child but potentially identifies heterozygote parents who are at risk of tumour development. METHODS AND RESULTS: Six children with a PTEN mutation were identified. All had extreme macrocephaly. Four parents and a male sibling were found to have a PTEN mutation on subsequent testing. Affected parents had extreme macrocephaly and a history of thyroid adenoma, or breast or skin lesions. All six children had presented to medical attention before the age of 2.5 years (3\\/6 were investigated as neonates), but the median age at diagnosis was 5 years. Four of the children had multiple investigations prior to identification of a PTEN mutation. CONCLUSION: BRRS should be considered in children with extreme macrocephaly as it is the most consistent clinical feature seen, particularly where there is a family history of macrocephaly.

  1. Epidemiology of childhood Guillain-Barré syndrome as a cause of acute flaccid paralysis in Honduras: 1989-1999.

    Science.gov (United States)

    Molinero, Marco R; Varon, Daniel; Holden, Kenton R; Sladky, John T; Molina, Ida B; Cleaves, Francisco

    2003-11-01

    The objective of this study was to investigate the incidence of acute flaccid paralysis in the pediatric population of Honduras over an 11-year period, determine what percentage of acute flaccid paralysis was Guillain-Barré syndrome, and identify the epidemiologic features of Guillain-Barré syndrome. There were 546 childhood cases of acute flaccid paralysis seen between January 1989 and December 1999 at the Hospital Escuela Materno-Infantil in Tegucigalpa, Honduras. Of these cases with acute flaccid paralysis, 394 (72.2%) were diagnosed with Guillain-Barré syndrome. Our incidence of Guillain-Barré syndrome in the Honduran pediatric population (1.37/100,000 per year) is higher than that shown in other studies. There was a significantly higher incidence of Guillain-Barré syndrome in younger children (ages 1-4 years), a significant preponderance of cases from rural areas, and a mild predominance in boys but a typical clinical presentation. The Honduran pediatric Guillain-Barré syndrome population had an increased mortality rate. Guillain-Barré syndrome has become the leading cause of childhood paralysis in Honduras. A better understanding of the population at highest risk and opportunities for earlier intervention with more effective therapeutic modalities may permit reducing the mortality among Honduran children who develop Guillain-Barré syndrome.

  2. Vascular disease modeling using induced pluripotent stem cells: Focus in Hutchinson-Gilford Progeria Syndrome.

    Science.gov (United States)

    Pitrez, P R; Rosa, S C; Praça, C; Ferreira, L

    2016-05-06

    Induced pluripotent stem cells (iPSCs) represent today an invaluable tool to create disease cell models for modeling and drug screening. Several lines of iPSCs have been generated in the last 7 years that changed the paradigm for studying diseases and the discovery of new drugs to treat them. In this article we focus our attention to vascular diseases in particular Hutchinson-Gilford Progeria Syndrome (HGPS), a devastating premature aging disease caused by a mutation in the lamin A gene. In general, patients die because of myocardial infarction or stroke. Because the patients are fragile the isolation of a particular type of cells is very difficult. Therefore in the last 5 years, researchers have used cells derived from iPSCs to model aspects of the HGPS and to screen libraries of chemicals to retard or treat the disease.

  3. Pediatric Hereditary Angioedema as a Cause of Acute Compartment Syndrome of the Hand and Forearm: A Case Report.

    Science.gov (United States)

    Venditto, Chelsea; Jager, Zachary; LoGiudice, John; Matloub, Hani

    2017-05-01

    Compartment syndrome of the upper extremity is a surgical emergency that, when left untreated, can have dire consequences. Its causes are numerous, one of which is the uncommon entity hereditary angioedema, an autosomal dominant disease resulting in edema in a variety of potential locations, including the extremities. This is only the second time hereditary angioedema has been mentioned in the literature as a cause of compartment syndrome. We present a case of hereditary angioedema leading to hand and forearm compartment syndrome in a 13-year-old pediatric patient. Diagnosis of hereditary angioedema was made by our Rheumatology colleagues with physical exam and a thorough history, and confirmed by laboratory studies. Our patient presented with compartment syndrome of the hand and forearm and underwent hand and volar forearm fasciotomies. She was subsequently worked up for hereditary angioedema with laboratory results confirming the diagnosis. She was discharged after a 5-day hospitalization with prophylactic C1-inhibitor therapy. Hereditary angioedema is a rare but known cause of compartment syndrome of the upper extremity, and must be considered when patients present with compartment syndrome of unknown etiology. This disease can be diagnosed by laboratory studies and symptoms can be controlled with medical therapy.

  4. Stent Implantation for Superior Vena Cava Syndrome of Malignant Cause.

    Science.gov (United States)

    Büstgens, Felix A; Loose, Reinhard; Ficker, Joachim H; Wucherer, Michael; Uder, Michael; Adamus, Ralf

    2017-02-02

    Purpose The purpose of this paper is the retrospective analysis of endovascular therapy for the treatment of superior vena cava syndrome (SVCS) of malignant cause. This study focuses on the effectiveness of the therapy regarding the duration of remission, symptom control and practicability. Materials and Methods From January 2003 to November 2012, therapeutic implantation of one or more stents was performed in 141 patients suffering from SVCS. The medical history was retrospectively researched using digitalized patient files. If those were incomplete, secondary research was conducted using the cancer registry of the General Hospital Nuremberg, the cancer registry of the tumor center at Friedrich-Alexander-University Erlangen-Nuremberg (FAU) or information given by physicians in private practice. This data was collected using Microsoft Office Excel(®) and statistically analyzed using IBM SPSS Statistics 22(®). Results 168 stents were implanted in 141 patients (median age: 64.6 years; range: 36 - 84), 86 being male and 55 being female. In 121 patients, SVCS was caused by lung cancer (85.8 %), in 9 patients by mediastinal metastasis of an extrathoracic carcinoma (6.4 %), in 3 patients by mesothelioma of the pleura (2.1 %) and in 1 patient by Hodgkin's disease (0.7 %). There was no histological diagnosis in 7 cases (4.9 %). The primary intervention was successful in 138 patients (97.9 %). Immediate thrombosis in the stent occurred in the remaining 3 cases. Recurrence of SVCS was observed in 22 patients (15.6 %), including 5 early and 17 late occlusions. Stent dislocation or breakage was not observed. As expected, the survival after implantation was poor. The median survival was 101 days, and the median occlusion-free survival was 80 days. Conclusion The symptomatic therapy of SVCS with endovascular stents is effective and safe. Despite effective symptom control and a low rate of recurrence, the patients' prognosis is poor. Key Points

  5. Initially unrecognised lunate dislocation as a cause of carpal tunnel syndrome

    Science.gov (United States)

    Ott, Florian; Mattiassich, Georg; Kaulfersch, Christian; Ortmaier, Reinhold

    2013-01-01

    A patient was admitted reporting tingling pain and numbness in the right hand. Neurological examination—including nerve conduction studies—diagnosed carpal tunnel syndrome. Operative carpal tunnel release was performed without complications. Four months postoperatively the otherwise healthy patient presented again due to persistent complaints, although preoperative symptoms had improved. On this occasion, the patient reported loss of strength accompanied by rigidity in the wrist. Clinical examination showed some swelling adjacent to the operation wound. A postoperative ganglion cyst was suspected and a conservative treatment option—splinting the wrist—was chosen. Four weeks later the patient presented again with further swelling and increasing rigidity of the wrist. Surgical intervention was planned. Preoperative plain radiographs of the wrist revealed chronic palmar dislocation of the lunate to be the cause of the symptoms in our patient. Radiological signs of scapholunate advanced collapse arthritis (SLAC wrist) were also observed. PMID:23513027

  6. Upstream SLC2A1 translation initiation causes GLUT1 deficiency syndrome.

    Science.gov (United States)

    Willemsen, Michèl A; Vissers, Lisenka Elm; Verbeek, Marcel M; van Bon, Bregje W; Geuer, Sinje; Gilissen, Christian; Klepper, Joerg; Kwint, Michael P; Leen, Wilhelmina G; Pennings, Maartje; Wevers, Ron A; Veltman, Joris A; Kamsteeg, Erik-Jan

    2017-06-01

    Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder with a complex phenotypic spectrum but simple biomarkers in cerebrospinal fluid. The disorder is caused by impaired glucose transport into the brain resulting from variants in SCL2A1. In 10% of GLUT1DS patients, a genetic diagnosis can not be made. Using whole-genome sequencing, we identified a de novo 5'-UTR variant in SLC2A1, generating a novel translation initiation codon, severely compromising SLC2A1 function. This finding expands our understanding of the disease mechanisms underlying GLUT1DS and encourages further in-depth analysis of SLC2A1 non-coding regions in patients without variants in the coding region.

  7. Endomyocardial fibrosis as a cause of Budd-Chiari syndrome and fatal pulmonary embolism.

    Science.gov (United States)

    Bestetti, Reinaldo B; Silva, Carolina M P D C; Ardito, Sabrina Q; Theodoropoulos, Tatiana A D; Cury, Patrícia M; Corbucci, Hélio A R

    2010-01-01

    A 24-year-old-man had right-sided heart failure of 3 months' duration. A Doppler echocardiogram revealed atrium and right ventricular enlargement, obliteration of the right ventricular apex, and a mass with an echolucent center measuring 20x21 mm in the right ventricular outlet. He died of pulmonary embolism. At autopsy, a huge organized thrombus obliterating the right ventricular apex passing through the tricuspid valve to the right atrium and then extending to the inferior vena cava up to the suprahepatic veins was seen. Histologically, an intense fibrotic thickening of the endomyocardium extending into the myocardium was observed. Cardiac thrombosis associated with endomyocardial fibrosis should be added to the list of causes of Budd-Chiari syndrome.

  8. Effective Radiotherapy Cured Cauda Equina Syndrome Caused by Remitted Intracranial Germinoma Depositing

    Directory of Open Access Journals (Sweden)

    Ying-Chun Lu

    2012-10-01

    Full Text Available Cauda equina syndrome (CES in children is very rare and can permanently disable. A remitted intracranial germinoma depositing on the spinal cord, leading to CES, has never been reported. We discuss the case of a 10-year-old girl who presented with sudden ataxia, low back pain, sensory deficits of the left lower extremity, and difficulty urinating and defecating 7 months after totally remitted intracranial germinoma postintracranial surgery and cranial irradiation. Magnetic resonance imaging (MRI of the brain and spine showed multiple intradural extramedullary homogeneous masses from the cervical to lumbar levels, compressing the conus medullaris and cauda equina. After emergent craniospinal irradiation, the patient's neurologic symptoms dramatically subsided. A remitted intracranial germinoma depositing on her spinal cord could be the cause of CES. Early identification and a proper craniospinal irradiation may halt the progression of symptoms.

  9. Bite-related and septic syndromes caused by cats and dogs.

    Science.gov (United States)

    Oehler, Richard L; Velez, Ana P; Mizrachi, Michelle; Lamarche, Jorge; Gompf, Sandra

    2009-07-01

    Bite infections can contain a mix of anaerobes and aerobes from the patient's skin and the animal's oral cavity, including species of Pasteurella, Streptococcus, Fusobacterium, and Capnocytophaga. Domestic cat and dog bite wounds can produce substantial morbidity and often require specialised care techniques and specific antibiotic therapy. Bite wounds can be complicated by sepsis. Disseminated infections, particularly those caused by Capnocytophaga canimorsus and Pasteurella multocida, can lead to septic shock, meningitis, endocarditis, and other severe sequelae. An emerging syndrome in veterinary and human medicine is meticillin-resistant Staphylococcus aureus (MRSA) infections shared between pets and human handlers, particularly community-acquired MRSA disease involving the USA300 clone. Skin, soft-tissue, and surgical infections are the most common. MRSA-associated infections in pets are typically acquired from their owners and can potentially cycle between pets and their human acquaintances.

  10. Nephrocalcinosis (Enamel Renal Syndrome) Caused by Autosomal Recessive FAM20A Mutations

    Science.gov (United States)

    Jaureguiberry, Graciana; De la Dure-Molla, Muriel; Parry, David; Quentric, Mickael; Himmerkus, Nina; Koike, Toshiyasu; Poulter, James; Klootwijk, Enriko; Robinette, Steven L.; Howie, Alexander J.; Patel, Vaksha; Figueres, Marie-Lucile; Stanescu, Horia C.; Issler, Naomi; Nicholson, Jeremy K.; Bockenhauer, Detlef; Laing, Christopher; Walsh, Stephen B.; McCredie, David A.; Povey, Sue; Asselin, Audrey; Picard, Arnaud; Coulomb, Aurore; Medlar, Alan J.; Bailleul-Forestier, Isabelle; Verloes, Alain; Le Caignec, Cedric; Roussey, Gwenaelle; Guiol, Julien; Isidor, Bertrand; Logan, Clare; Shore, Roger; Johnson, Colin; Inglehearn, Christopher; Al-Bahlani, Suhaila; Schmittbuhl, Matthieu; Clauss, François; Huckert, Mathilde; Laugel, Virginie; Ginglinger, Emmanuelle; Pajarola, Sandra; Spartà, Giuseppina; Bartholdi, Deborah; Rauch, Anita; Addor, Marie-Claude; Yamaguti, Paulo M.; Safatle, Heloisa P.; Acevedo, Ana Carolina; Martelli-Júnior, Hercílio; dos Santos Netos, Pedro E.; Coletta, Ricardo D.; Gruessel, Sandra; Sandmann, Carolin; Ruehmann, Denise; Langman, Craig B.; Scheinman, Steven J.; Ozdemir-Ozenen, Didem; Hart, Thomas C.; Hart, P. Suzanne; Neugebauer, Ute; Schlatter, Eberhard; Houillier, Pascal; Gahl, William A.; Vikkula, Miikka; Bloch-Zupan, Agnès; Bleich, Markus; Kitagawa, Hiroshi; Unwin, Robert J.; Mighell, Alan; Berdal, Ariane; Kleta, Robert

    2013-01-01

    Background/Aims Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood. Methods We investigated 25 patients from 16 families with unexplained nephrocalcinosis and characteristic dental defects (amelogenesis imperfecta, gingival hyperplasia, impaired tooth eruption). To identify the causative gene, we performed genome-wide linkage analysis, exome capture, next-generation sequencing, and Sanger sequencing. Results All patients had bi-allelic FAM20A mutations segregating with the disease; 20 different mutations were identified. Conclusions This au-tosomal recessive disorder, also known as enamel renal syndrome, of FAM20A causes nephrocalcinosis and amelogenesis imperfecta. We speculate that all individuals with biallelic FAM20A mutations will eventually show nephrocalcinosis. PMID:23434854

  11. Drug-Induced Hypersensitivity Syndrome Caused by Carbamazepine Used for the Treatment of Trigeminal Neuralgia

    Directory of Open Access Journals (Sweden)

    Yuko Ono

    2016-01-01

    Full Text Available An 88-year-old man was diagnosed with trigeminal neuralgia, and treatment of carbamazepine 200 mg/day was initiated. About 6 weeks later, the patient developed a skin rash accompanied by fever. He was admitted to hospital and diagnosed with drug-induced hypersensitivity syndrome (DIHS caused by carbamazepine. Oral carbamazepine treatment was stopped, but blood tests showed acute liver and acute renal failure. Drug-induced lymphocyte stimulation test (DLST for carbamazepine, human herpes virus-6 (HHV-6 IgG, and CMV-HRP were negative. Oral prednisolone therapy was begun 18 days later. The titer of HHV-6 IgG antibodies was then detected (640 times. Following treatment, liver and renal function improved and the erythema disappeared.

  12. Cushing syndrome

    Science.gov (United States)

    Hypercortisolism; Cortisol excess; Glucocorticoid excess - Cushing syndrome ... The most common cause of Cushing syndrome is taking too much ... exogenous Cushing syndrome . Prednisone, dexamethasone, and ...

  13. Recent Advances in Cerebellar Ischemic Stroke Syndromes Causing Vertigo and Hearing Loss.

    Science.gov (United States)

    Kim, Hyun-Ah; Yi, Hyon-Ah; Lee, Hyung

    2016-12-01

    Cerebellar ischemic stroke is one of the common causes of vascular vertigo. It usually accompanies other neurological symptoms or signs, but a small infarct in the cerebellum can present with vertigo without other localizing symptoms. Approximately 11 % of the patients with isolated cerebellar infarction simulated acute peripheral vestibulopathy, and most patients had an infarct in the territory of the medial branch of the posterior inferior cerebellar artery (PICA). A head impulse test can differentiate acute isolated vertigo associated with PICA territory cerebellar infarction from more benign disorders involving the inner ear. Acute hearing loss (AHL) of a vascular cause is mostly associated with cerebellar infarction in the territory of the anterior inferior cerebellar artery (AICA), but PICA territory cerebellar infarction rarely causes AHL. To date, at least eight subgroups of AICA territory infarction have been identified according to the pattern of neurotological presentations, among which the most common pattern of audiovestibular dysfunction is the combined loss of auditory and vestibular functions. Sometimes acute isolated audiovestibular loss can be the initial symptom of impending posterior circulation ischemic stroke (particularly within the territory of the AICA). Audiovestibular loss from cerebellar infarction has a good long-term outcome than previously thought. Approximately half of patients with superior cerebellar artery territory (SCA) cerebellar infarction experienced true vertigo, suggesting that the vertigo and nystagmus in the SCA territory cerebellar infarctions are more common than previously thought. In this article, recent findings on clinical features of vertigo and hearing loss from cerebellar ischemic stroke syndrome are summarized.

  14. Structural and functional analyses of disease-causing missense mutations in Bloom syndrome protein.

    Science.gov (United States)

    Guo, Rong-Bing; Rigolet, Pascal; Ren, Hua; Zhang, Bo; Zhang, Xing-Dong; Dou, Shuo-Xing; Wang, Peng-Ye; Amor-Gueret, Mounira; Xi, Xu Guang

    2007-01-01

    Bloom syndrome (BS) is an autosomal recessive disorder characterized by genomic instability and the early development of many types of cancer. Missense mutations have been identified in the BLM gene (encoding a RecQ helicase) in affected individuals, but the molecular mechanism and the structural basis of the effects of these mutations remain to be elucidated. We analysed five disease-causing missense mutations that are localized in the BLM helicase core region: Q672R, I841T, C878R, G891E and C901Y. The disease-causing mutants had low ATPase and helicase activities but their ATP binding abilities were normal, except for Q672, whose ATP binding activity was lower than that of the intact BLM helicase. Mutants C878R, mapping near motif IV, and G891E and C901Y, mapping in motif IV, displayed severe DNA-binding defects. We used molecular modelling to analyse these mutations. Our work provides insights into the molecular basis of BLM pathology, and reveals structural elements implicated in coupling DNA binding to ATP hydrolysis and DNA unwinding. Our findings will help to explain the mechanism underlying BLM catalysis and interpreting new BLM causing mutations identified in the future.

  15. Sudden infant death syndrome caused by cardiac arrhythmias: only a matter of genes encoding ion channels?

    Science.gov (United States)

    Sarquella-Brugada, Georgia; Campuzano, Oscar; Cesar, Sergi; Iglesias, Anna; Fernandez, Anna; Brugada, Josep; Brugada, Ramon

    2016-03-01

    Sudden infant death syndrome is the unexpected demise of a child younger than 1 year of age which remains unexplained after a complete autopsy investigation. Usually, it occurs during sleep, in males, and during the first 12 weeks of life. The pathophysiological mechanism underlying the death is unknown, and the lethal episode is considered multifactorial. However, in cases without a conclusive post-mortem diagnosis, suspicious of cardiac arrhythmias may also be considered as a cause of death, especially in families suffering from any cardiac disease associated with sudden cardiac death. Here, we review current understanding of sudden infant death, focusing on genetic causes leading to lethal cardiac arrhythmias, considering both genes encoding ion channels as well as structural proteins due to recent association of channelopathies and desmosomal genes. We support a comprehensive analysis of all genes associated with sudden cardiac death in families suffering of infant death. It allows the identification of the most plausible cause of death but also of family members at risk, providing cardiologists with essential data to adopt therapeutic preventive measures in families affected with this lethal entity.

  16. Infectious Mimicry Complicates Diagnosis in Hemophagocytic Syndrome Caused by Anaplastic Large-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Michael J. Peluso

    2012-01-01

    Full Text Available Hemophagocytic syndrome (HPS arises secondary to genetic, rheumatologic, neoplastic, and infectious causes. We discuss a patient whose presentation was consistent with systemic infection but was discovered to have HPS of unknown etiology. The presenting symptoms, as well as unremarkable malignancy and rheumatologic workups, led to the pursuit of an infectious cause, but the patient was ultimately discovered to have an occult anaplastic large-cell lymphoma (ALCL. This case demonstrates the diagnostic challenges that result from infectious mimicry in the context of HPS—first, in distinguishing noninfectious HPS from the systemic inflammation that can result from a widespread infectious process, second, in the identification of the precipitating cause of HPS. While evidence of these challenges has been suggested by the limited literature on HPS and ALCL, our case illustrates the diagnostic dilemma that arises when tissue biopsy does not quickly reveal an etiology. It is important that all physicians be aware that HPS can mimic infection and be prepared to redirect the workup when an infectious etiology for HPS cannot be identified.

  17. Autosomal-Dominant Multiple Pterygium Syndrome Is Caused by Mutations in MYH3.

    Science.gov (United States)

    Chong, Jessica X; Burrage, Lindsay C; Beck, Anita E; Marvin, Colby T; McMillin, Margaret J; Shively, Kathryn M; Harrell, Tanya M; Buckingham, Kati J; Bacino, Carlos A; Jain, Mahim; Alanay, Yasemin; Berry, Susan A; Carey, John C; Gibbs, Richard A; Lee, Brendan H; Krakow, Deborah; Shendure, Jay; Nickerson, Deborah A; Bamshad, Michael J

    2015-05-01

    Multiple pterygium syndrome (MPS) is a phenotypically and genetically heterogeneous group of rare Mendelian conditions characterized by multiple pterygia, scoliosis, and congenital contractures of the limbs. MPS typically segregates as an autosomal-recessive disorder, but rare instances of autosomal-dominant transmission have been reported. Whereas several mutations causing recessive MPS have been identified, the genetic basis of dominant MPS remains unknown. We identified four families affected by dominantly transmitted MPS characterized by pterygia, camptodactyly of the hands, vertebral fusions, and scoliosis. Exome sequencing identified predicted protein-altering mutations in embryonic myosin heavy chain (MYH3) in three families. MYH3 mutations underlie distal arthrogryposis types 1, 2A, and 2B, but all mutations reported to date occur in the head and neck domains. In contrast, two of the mutations found to cause MPS in this study occurred in the tail domain. The phenotypic overlap among persons with MPS, coupled with physical findings distinct from other conditions caused by mutations in MYH3, suggests that the developmental mechanism underlying MPS differs from that of other conditions and/or that certain functions of embryonic myosin might be perturbed by disruption of specific residues and/or domains. Moreover, the vertebral fusions in persons with MPS, coupled with evidence of MYH3 expression in bone, suggest that embryonic myosin plays a role in skeletal development.

  18. De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome.

    Science.gov (United States)

    Burrage, Lindsay C; Charng, Wu-Lin; Eldomery, Mohammad K; Willer, Jason R; Davis, Erica E; Lugtenberg, Dorien; Zhu, Wenmiao; Leduc, Magalie S; Akdemir, Zeynep C; Azamian, Mahshid; Zapata, Gladys; Hernandez, Patricia P; Schoots, Jeroen; de Munnik, Sonja A; Roepman, Ronald; Pearring, Jillian N; Jhangiani, Shalini; Katsanis, Nicholas; Vissers, Lisenka E L M; Brunner, Han G; Beaudet, Arthur L; Rosenfeld, Jill A; Muzny, Donna M; Gibbs, Richard A; Eng, Christine M; Xia, Fan; Lalani, Seema R; Lupski, James R; Bongers, Ernie M H F; Yang, Yaping

    2015-12-03

    Meier-Gorlin syndrome (MGS) is a genetically heterogeneous primordial dwarfism syndrome known to be caused by biallelic loss-of-function mutations in one of five genes encoding pre-replication complex proteins: ORC1, ORC4, ORC6, CDT1, and CDC6. Mutations in these genes cause disruption of the origin of DNA replication initiation. To date, only an autosomal-recessive inheritance pattern has been described in individuals with this disorder, with a molecular etiology established in about three-fourths of cases. Here, we report three subjects with MGS and de novo heterozygous mutations in the 5' end of GMNN, encoding the DNA replication inhibitor geminin. We identified two truncating mutations in exon 2 (the 1(st) coding exon), c.16A>T (p.Lys6(∗)) and c.35_38delTCAA (p.Ile12Lysfs(∗)4), and one missense mutation, c.50A>G (p.Lys17Arg), affecting the second-to-last nucleotide of exon 2 and possibly RNA splicing. Geminin is present during the S, G2, and M phases of the cell cycle and is degraded during the metaphase-anaphase transition by the anaphase-promoting complex (APC), which recognizes the destruction box sequence near the 5' end of the geminin protein. All three GMNN mutations identified alter sites 5' to residue Met28 of the protein, which is located within the destruction box. We present data supporting a gain-of-function mechanism, in which the GMNN mutations result in proteins lacking the destruction box and hence increased protein stability and prolonged inhibition of replication leading to autosomal-dominant MGS.

  19. Pyridoxine for prevention of hand-foot syndrome caused by chemotherapy: a systematic review.

    Directory of Open Access Journals (Sweden)

    Min Chen

    Full Text Available BACKGROUND: Hand-foot syndrome (HFS is a relatively frequent dermatologic toxic reaction to certain anti-cancer chemotherapies. The syndrome can evolve into a distressing condition that limits function and affects quality of life. Pyridoxine (vitamin B6 has been used empirically for the prevention of HFS caused by anti-cancer therapy. However, evidence of its efficacy remains controversial. METHODOLOGY//PRINCIPAL FINDINGS: Systematic literature searches were conducted on the Cochrane Library, PUBMED, EMBASE, LILACS, CBM, CNKI, VIP, WANFANG and the U.S. ClinicalTrials.gov website. We included all related randomized controlled trials (RCTs irrespective of language. Reviewers from different professions independently assessed all potential studies and extracted data. Subgroup analysis was planned according to dose of pyridoxine. 5 RCTs involving 607 patients were contributed to the meta-analysis. No significant differences were found between patients receiving pyridoxine and placebo for prevention of incidence of HFS and grade 2 or worse HFS (relative risk (RR 0.96, 95%confidence interval (CI 0.86-1.06; RR0.95, 95%CI 0.73-1.24, respectively. Similarly, no significant improvement in quality of life was detected among patients. However, significant difference was found for prevention of grade 2 or worse HFS with pyridoxine 400 mg daily compared to 200 mg (RR0.55, 95%CI 0.33-0.92. CONCLUSIONS/SIGNIFICANCE: There is inadequate evidence to make any recommendation about using pyridoxine for prevention of HFS caused by chemotherapy. However, pyridoxine 400 mg may have some efficacy. Further studies of large sample sizes are needed to evaluate the efficacy and safety of pyridoxine, especially at high dose, in comparison with placebo.

  20. The molecular basis of variable phenotypic severity among common missense mutations causing Rett syndrome.

    Science.gov (United States)

    Brown, Kyla; Selfridge, Jim; Lagger, Sabine; Connelly, John; De Sousa, Dina; Kerr, Alastair; Webb, Shaun; Guy, Jacky; Merusi, Cara; Koerner, Martha V; Bird, Adrian

    2016-02-01

    Rett syndrome is caused by mutations in the X-linked MECP2 gene, which encodes a chromosomal protein that binds to methylated DNA. Mouse models mirror the human disorder and therefore allow investigation of phenotypes at a molecular level. We describe an Mecp2 allelic series representing the three most common missense Rett syndrome (RTT) mutations, including first reports of Mecp2[R133C] and Mecp2[T158M] knock-in mice, in addition to Mecp2[R306C] mutant mice. Together these three alleles comprise ∼25% of all RTT mutations in humans, but they vary significantly in average severity. This spectrum is mimicked in the mouse models; R133C being least severe, T158M most severe and R306C of intermediate severity. Both R133C and T158M mutations cause compound phenotypes at the molecular level, combining compromised DNA binding with reduced stability, the destabilizing effect of T158M being more severe. Our findings contradict the hypothesis that the R133C mutation exclusively abolishes binding to hydroxymethylated DNA, as interactions with DNA containing methyl-CG, methyl-CA and hydroxymethyl-CA are all reduced in vivo. We find that MeCP2[T158M] is significantly less stable than MeCP2[R133C], which may account for the divergent clinical impact of the mutations. Overall, this allelic series recapitulates human RTT severity, reveals compound molecular aetiologies and provides a valuable resource in the search for personalized therapeutic interventions.

  1. FAM20A mutations can cause enamel-renal syndrome (ERS.

    Directory of Open Access Journals (Sweden)

    Shih-Kai Wang

    Full Text Available Enamel-renal syndrome (ERS is an autosomal recessive disorder characterized by severe enamel hypoplasia, failed tooth eruption, intrapulpal calcifications, enlarged gingiva, and nephrocalcinosis. Recently, mutations in FAM20A were reported to cause amelogenesis imperfecta and gingival fibromatosis syndrome (AIGFS, which closely resembles ERS except for the renal calcifications. We characterized three families with AIGFS and identified, in each case, recessive FAM20A mutations: family 1 (c.992G>A; g.63853G>A; p.Gly331Asp, family 2 (c.720-2A>G; g.62232A>G; p.Gln241_Arg271del, and family 3 (c.406C>T; g.50213C>T; p.Arg136* and c.1432C>T; g.68284C>T; p.Arg478*. Significantly, a kidney ultrasound of the family 2 proband revealed nephrocalcinosis, revising the diagnosis from AIGFS to ERS. By characterizing teeth extracted from the family 3 proband, we demonstrated that FAM20A(-/- molars lacked true enamel, showed extensive crown and root resorption, hypercementosis, and partial replacement of resorbed mineral with bone or coalesced mineral spheres. Supported by the observation of severe ectopic calcifications in the kidneys of Fam20a null mice, we conclude that FAM20A, which has a kinase homology domain and localizes to the Golgi, is a putative Golgi kinase that plays a significant role in the regulation of biomineralization processes, and that mutations in FAM20A cause both AIGFS and ERS.

  2. Shaken baby syndrome: re-examination of diffuse axonal injury as cause of death.

    Science.gov (United States)

    Oehmichen, Manfred; Schleiss, Daniela; Pedal, Ingo; Saternus, Klaus-Steffen; Gerling, Ivana; Meissner, Christoph

    2008-09-01

    The discussion surrounding shaken baby syndrome (SBS) arose from the lack of evidence implicating diffuse axonal injury (DAI) as a cause of death. It was assumed instead that injury to the cervical cord, medulla, and nerve roots played a causal role. The present pathomorphological study examines 18 selected infants (<1-year-old) whose deaths were highly suspicious for SBS, exhibiting the classical SBS triad of acute subdural hemorrhage (SDH), retinal bleeding, and encephalopathy. Gross autopsy and microscopic findings of these infants were compared with those of 19 victims of sudden infant death syndrome (SIDS; control group 1) and of 14 infants who died of disease or injuries/violence not involving the head, neck or eyes (control group 2). Symptoms of mechanical impact to the head were evident in seven of the SBS infants, but in none of the control infants. DAI was not detected in either the SBS or control cases. Localized axonal injury (AI) was regularly present in the brains of the SBS infants surviving longer than 1.5-3.0 h, but only occasionally in the craniocervical junction and within the nerve roots of the upper cervical cord; it was never present in the medulla. Epidural hemorrhage of the cervical cord was seen in four of the ten examined SBS cases, but in none of the control cases. Based on the absence of DAI in the brain and of signs of generalized cervical cord or nerve root injuries, we conclude that the cause of death in the SBS victims was a global cerebral ischemia secondary to SDH, focal vasospasm, trauma-induced transitory respiratory and/or circulatory failure.

  3. Reversible operculum syndrome caused by progressive epilepsia partialis continua in a child with left hemimegalencephaly.

    Science.gov (United States)

    Fusco, L; Vigevano, F

    1991-01-01

    In a child with left hemimegalencephaly and seizures, a reversible operculum syndrome developed when continuous epileptic discharges spread from the left hemisphere to the contralateral central regions. The operculum syndrome lasted for three months until left hemispherectomy was performed. Soon after surgery the seizures and the operculum syndrome resolved. The operculum syndrome is a facio-pharyngo-glosso-masticatory diplegia usually due to structural lesions in both opercular regions. The reversibility of the syndrome in the reported case demonstrates that the operculum syndrome is sometimes functional rather than lesional. Images PMID:1908890

  4. Cervical neuro-muscular syndrome: discovery of a new disease group caused by abnormalities in the cervical muscles.

    Science.gov (United States)

    Matsui, Takayoshi; Ii, Kunio; Hojo, Shuntaro; Sano, Keiji

    2012-01-01

    Our previous study of whiplash injury found that abnormalities in the cervical muscles cause autonomic dystonia. Further research has found that abnormalities in the cervical muscles cause headache, chronic fatigue syndrome, vertigo, and dizziness. We named this group of diseases cervical neuro-muscular syndrome. Patients treated within a 2-year period from April 1, 2002 to March 31, 2004 reported good outcomes in 83.8% for headache, 88.4% for vertigo and dizziness, 84.5% for chronic fatigue syndrome, 88.0% for autonomic dystonia, and 83.7% for whiplash-associated disorder. A large number of outpatients present with general malaise, including many general physical complaints without identifiable cause. We propose that treatment of the cervical muscle is effective for general malaise.

  5. Pilot Study: Colostomy and Urine Collection Protocol for Investigating Potential Inciting Causes of Hen Diuresis Syndrome.

    Science.gov (United States)

    Jones, Kelli; Turner, Bradley; Brandão, João; Hubbard, Sue Ann; Magee, Danny; Baughman, Brittany; Wills, Robert; Tully, Thomas

    2015-06-01

    Hen diuresis syndrome has emerged over the past 5 yr as a significant cause of mortality in the U.S. broiler breeder industry. The condition affects hens in production and is characterized by transient muscle weakness in the vent region, transient diuresis, and often urate deposits on the skin below the vent. Affected hens are often seen straining to lay an egg, which suggests oviduct contraction is also impaired. Related hen mortality, often reaching 1% or more a week, is believed to be primarily the result of male aggression of the vent region (Turner et al., "Investigating Causes of Excessive Urate Production in Broiler Breeder Hens Associated with Peritonitis and Cannibalism Mortality," Oral Presentation at The American Association of Avian Pathologists Annual Meeting, p. 139, 2010). The exact association between the cause of mortality and this syndrome is unknown, but it may be the consequence of transient partial to full oviduct prolapse, which predisposes or stimulates cannibalism and aggression. Based on unpublished work done prior to this study (Turner et al., ibid.), the evidence suggests the underlying problem is metabolic. We feel that urine collection and analysis is an essential component to understanding this condition. This study serves as a pilot study for future investigations that attempt to identify the nature and cause of the metabolic disturbance through paired urine and serum collection and analysis. For the purpose of this study, a small sample of 10 affected and 10 unaffected birds was used for sample collection. In order to collect pure urine, the birds were surgically colostomized. Colostomy did prove to be a useful means of collecting urine free of feces, and for the purposes of our study it yielded adequate urine samples for analysis. There were statistically relevant urine values observed. Affected birds had a higher presence of blood in the urine, a lower uric acid excretion rate (mg/hr), higher concentration (mEq/L) of urine Na+, and

  6. Mechanisms of cardiovascular disease in accelerated aging syndromes.

    Science.gov (United States)

    Capell, Brian C; Collins, Francis S; Nabel, Elizabeth G

    2007-07-06

    In the past several years, remarkable progress has been made in the understanding of the mechanisms of premature aging. These rare, genetic conditions offer valuable insights into the normal aging process and the complex biology of cardiovascular disease. Many of these advances have been made in the most dramatic of these disorders, Hutchinson-Gilford progeria syndrome. Although characterized by features of normal aging such as alopecia, skin wrinkling, and osteoporosis, patients with Hutchinson-Gilford progeria syndrome are affected by accelerated, premature arteriosclerotic disease that leads to heart attacks and strokes at a mean age of 13 years. In this review, we highlight recent advances in the biology of premature aging uncovered in Hutchinson-Gilford progeria syndrome and other accelerated aging syndromes, advances that provide insight into the mechanisms of cardiovascular diseases ranging from atherosclerosis to arrhythmias.

  7. Experimental infection of bats with Geomyces destructans causes white-nose syndrome

    Science.gov (United States)

    Lorch, J.M.; Meteyer, C.U.; Behr, M.J.; Boyles, J.G.; Cryan, P.M.; Hicks, A.C.; Ballmann, A.E.; Coleman, J.T.H.; Redell, D.N.; Reeder, D.M.; Blehert, D.S.

    2011-01-01

    White-nose syndrome (WNS) has caused recent catastrophic declines among multiple species of bats in eastern North America. The disease's name derives from a visually apparent white growth of the newly discovered fungus Geomyces destructans on the skin (including the muzzle) of hibernating bats. Colonization of skin by this fungus is associated with characteristic cutaneous lesions that are the only consistent pathological finding related to WNS. However, the role of G. destructans in WNS remains controversial because evidence to implicate the fungus as the primary cause of this disease is lacking. The debate is fuelled, in part, by the assumption that fungal infections in mammals are most commonly associated with immune system dysfunction. Additionally, the recent discovery that G. destructans commonly colonizes the skin of bats of Europe, where no unusual bat mortality events have been reported, has generated further speculation that the fungus is an opportunistic pathogen and that other unidentified factors are the primary cause of WNS. Here we demonstrate that exposure of healthy little brown bats (Myotis lucifugus) to pure cultures of G. destructans causes WNS. Live G. destructans was subsequently cultured from diseased bats, successfully fulfilling established criteria for the determination of G. destructans as a primary pathogen. We also confirmed that WNS can be transmitted from infected bats to healthy bats through direct contact. Our results provide the first direct evidence that G. destructans is the causal agent of WNS and that the recent emergence of WNS in North America may represent translocation of the fungus to a region with a naive population of animals. Demonstration of causality is an instrumental step in elucidating the pathogenesis and epidemiology of WNS and in guiding management actions to preserve bat populations against the novel threat posed by this devastating infectious disease. ?? 2011 Macmillan Publishers Limited. All rights reserved.

  8. Catatonia in Down syndrome; a treatable cause of regression

    Directory of Open Access Journals (Sweden)

    Ghaziuddin N

    2015-04-01

    Full Text Available Neera Ghaziuddin,1 Armin Nassiri,2 Judith H Miles3 1Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, 2Community Psychiatry, San Jose, California, 3Thompson Center for Autism and Neurodevelopmental Disorders and Department of Child Health, University of Missouri, Columbia, Missouri, USA Objective: The main aim of this case series report is to alert physicians to the occurrence of catatonia in Down syndrome (DS. A second aim is to stimulate the study of regression in DS and of catatonia. A subset of individuals with DS is noted to experience unexplained regression in behavior, mood, activities of daily living, motor activities, and intellectual functioning during adolescence or young adulthood. Depression, early onset Alzheimer’s, or just “the Down syndrome” are often blamed after general medical causes have been ruled out. Clinicians are generally unaware that catatonia, which can cause these symptoms, may occur in DS.Study design: Four DS adolescents who experienced regression are reported. Laboratory tests intended to rule out causes of motor and cognitive regression were within normal limits. Based on the presence of multiple motor disturbances (slowing and/or increased motor activity, grimacing, posturing, the individuals were diagnosed with unspecified catatonia and treated with anti-catatonic treatments (benzodiazepines and electroconvulsive therapy [ECT].Results: All four cases were treated with a benzodiazepine combined with ECT and recovered their baseline functioning.Conclusion: We suspect catatonia is a common cause of unexplained deterioration in adolescents and young adults with DS. Moreover, pediatricians and others who care for individuals with DS are generally unfamiliar with the catatonia diagnosis outside schizophrenia, resulting in misdiagnosis and years of morbidity. Alerting physicians to catatonia in DS is essential to prompt diagnosis, appropriate treatment, and identification of the frequency

  9. Mutations in the pre-replication complex cause Meier-Gorlin syndrome

    NARCIS (Netherlands)

    Bicknell, L.S.; Bongers, M.H.F.; Leitch, A.; Brown, S.; Schoots, J.; Harley, M.E.; Aftimos, S.; Al-Aama, J.Y.; Bober, M.; Brown, P.A.; Bokhoven, J.H.L.M. van; Dean, J.; Edrees, A.Y.; Feingold, M.; Fryer, A.; Hoefsloot, L.H.; Kau, N.; Knoers, N.V.A.M.; Mackenzie, J.; Opitz, J.M.; Sarda, P.; Ross, A.; Temple, I.K.; Toutain, A.; Wise, C.A.; Wright, M.; Jackson, A.P.

    2011-01-01

    Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears(1)(3). Both pre- and post-natal growth are impaired in this disorder, and although microcephaly is often evid

  10. Mutations in the TGF-beta repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm

    NARCIS (Netherlands)

    Doyle, A.J.; Doyle, J.J.; Bessling, S.L.; Maragh, S.; Lindsay, M.E.; Schepers, D.; Gillis, E.; Mortier, G.; Homfray, T.; Sauls, K.; Norris, R.A.; Huso, N.D.; Leahy, D.; Mohr, D.W.; Caulfield, M.J.; Scott, A.F.; Destree, A.; Hennekam, R.C.; Arn, P.H.; Curry, C.J.; Laer, L. van; McCallion, A.S.; Loeys, B.L.; Dietz, H.C.

    2012-01-01

    Elevated transforming growth factor (TGF)-beta signaling has been implicated in the pathogenesis of syndromic presentations of aortic aneurysm, including Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). However, the location and character of many of the causal mutations in LDS intuitively imply

  11. Mutations in ROGDI Cause Kohlschütter-Tönz Syndrome.

    Science.gov (United States)

    Schossig, Anna; Wolf, Nicole I; Fischer, Christine; Fischer, Maria; Stocker, Gernot; Pabinger, Stephan; Dander, Andreas; Steiner, Bernhard; Tönz, Otmar; Kotzot, Dieter; Haberlandt, Edda; Amberger, Albert; Burwinkel, Barbara; Wimmer, Katharina; Fauth, Christine; Grond-Ginsbach, Caspar; Koch, Martin J; Deichmann, Annette; von Kalle, Christof; Bartram, Claus R; Kohlschütter, Alfried; Trajanoski, Zlatko; Zschocke, Johannes

    2012-04-06

    Kohlschütter-Tönz syndrome (KTS) is an autosomal-recessive disease characterized by the combination of epilepsy, psychomotor regression, and amelogenesis imperfecta. The molecular basis has not yet been elucidated. Here, we report that KTS is caused by mutations in ROGDI. Using a combination of autozygosity mapping and exome sequencing, we identified a homozygous frameshift deletion, c.229_230del (p.Leu77Alafs(∗)64), in ROGDI in two affected individuals from a consanguineous family. Molecular studies in two additional KTS-affected individuals from two unrelated Austrian and Swiss families revealed homozygosity for nonsense mutation c.286C>T (p.Gln96(∗)) and compound heterozygosity for the splice-site mutations c.531+5G>C and c.532-2A>T in ROGDI, respectively. The latter mutation was also found to be heterozygous in the mother of the Swiss affected individual in whom KTS was reported for the first time in 1974. ROGDI is highly expressed throughout the brain and other organs, but its function is largely unknown. Possible interactions with DISC1, a protein involved in diverse cytoskeletal functions, have been suggested. Our finding that ROGDI mutations cause KTS indicates that the protein product of this gene plays an important role in neuronal development as well as amelogenesis. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  12. Duck egg-drop syndrome caused by BYD virus, a new Tembusu-related flavivirus.

    Directory of Open Access Journals (Sweden)

    Jingliang Su

    Full Text Available Since April 2010, a severe outbreak of duck viral infection, with egg drop, feed uptake decline and ovary-oviduct disease, has spread around the major duck-producing regions in China. A new virus, named BYD virus, was isolated in different areas, and a similar disease was reproduced in healthy egg-producing ducks, infecting with the isolated virus. The virus was re-isolated from the affected ducks and replicated well in primary duck embryo fibroblasts and Vero cells, causing the cytopathic effect. The virus was identified as an enveloped positive-stranded RNA virus with a size of approximately 55 nm in diameter. Genomic sequencing of the isolated virus revealed that it is closely related to Tembusu virus (a mosquito-borne Ntaya group flavivirus, with 87-91% nucleotide identity of the partial E (envelope proteins to that of Tembusu virus and 72% of the entire genome coding sequence with Bagaza virus, the most closely related flavivirus with an entirely sequenced genome. Collectively our systematic studies fulfill Koch's postulates, and therefore, the causative agent of the duck egg drop syndrome occurring in China is a new flavivirus. Flavivirus is an emerging and re-emerging zoonotic pathogen and BYD virus that causes severe egg-drop, could be disastrous for the duck industry. More importantly its public health concerns should also be evaluated, and its epidemiology should be closely watched due to the zoonotic nature of flaviviruses.

  13. Duck egg-drop syndrome caused by BYD virus, a new Tembusu-related flavivirus.

    Science.gov (United States)

    Su, Jingliang; Li, Shuang; Hu, Xudong; Yu, Xiuling; Wang, Yongyue; Liu, Peipei; Lu, Xishan; Zhang, Guozhong; Hu, Xueying; Liu, Di; Li, Xiaoxia; Su, Wenliang; Lu, Hao; Mok, Ngai Shing; Wang, Peiyi; Wang, Ming; Tian, Kegong; Gao, George F

    2011-03-24

    Since April 2010, a severe outbreak of duck viral infection, with egg drop, feed uptake decline and ovary-oviduct disease, has spread around the major duck-producing regions in China. A new virus, named BYD virus, was isolated in different areas, and a similar disease was reproduced in healthy egg-producing ducks, infecting with the isolated virus. The virus was re-isolated from the affected ducks and replicated well in primary duck embryo fibroblasts and Vero cells, causing the cytopathic effect. The virus was identified as an enveloped positive-stranded RNA virus with a size of approximately 55 nm in diameter. Genomic sequencing of the isolated virus revealed that it is closely related to Tembusu virus (a mosquito-borne Ntaya group flavivirus), with 87-91% nucleotide identity of the partial E (envelope) proteins to that of Tembusu virus and 72% of the entire genome coding sequence with Bagaza virus, the most closely related flavivirus with an entirely sequenced genome. Collectively our systematic studies fulfill Koch's postulates, and therefore, the causative agent of the duck egg drop syndrome occurring in China is a new flavivirus. Flavivirus is an emerging and re-emerging zoonotic pathogen and BYD virus that causes severe egg-drop, could be disastrous for the duck industry. More importantly its public health concerns should also be evaluated, and its epidemiology should be closely watched due to the zoonotic nature of flaviviruses.

  14. A new mutation site in the AIRE gene causes autoimmune polyendocrine syndrome type 1.

    Science.gov (United States)

    Zhu, Wufei; Hu, Zhen; Liao, Xiangyu; Chen, Xing; Huang, Wenrong; Zhong, Yu; Zeng, Zhaoyang

    2017-05-24

    Autoimmune polyendocrine syndrome type 1 (APS-1, OMIM 2403000) is a rare autosomal recessive disease that is caused by autoimmune regulator (AIRE). The main symptoms of APS-1 are chronic mucocutaneous candidiasis, autoimmune adrenocortical insufficiency (Addison's disease) and hypoparathyroidism. We collected APS-1 cases and analysed them. The AIRE genes of the patient and his family members were sequenced to identify whether the APS-1 patient had an AIRE mutation. We discovered a mutation site (c.206A>C) that had never before been reported in the AIRE gene located in exon 2 of the AIRE gene. This homogyzous mutation caused a substitution of the 69th amino acid of the AIRE protein from glutamine to proline (p.Q69P). A yeast two-hybrid assay, which was used to analyse the homodimerization properties of the mutant AIRE protein, showed that the mutant AIRE protein could not interact with the normal AIRE protein. Flow cytometry and RT-qPCR analyses indicated that the new mutation site could decrease the expression levels of the AIRE, glutamic acid decarboxylase 65 (GAD65) and tryptophan hydroxylase-1 (TPH1) proteins to affect central immune tolerance. In conclusion, our research has shown that the new mutation site (c.206A>C) may influence the homodimerization and expression levels and other aspects of the AIRE protein. It may also impact the expression levels of tissue-restricted antigens (TRAs), leading to a series of autoimmune diseases.

  15. First Report of a Single Exon Deletion in TCOF1 Causing Treacher Collins Syndrome.

    Science.gov (United States)

    Beygo, J; Buiting, K; Seland, S; Lüdecke, H-J; Hehr, U; Lich, C; Prager, B; Lohmann, D R; Wieczorek, D

    2012-01-01

    Treacher Collins syndrome (TCS) is a rare craniofacial disorder characterized by facial anomalies and ear defects. TCS is caused by mutations in the TCOF1 gene and follows autosomal dominant inheritance. Recently, mutations in the POLR1D and POLR1C genes have also been identified to cause TCS. However, in a subset of patients no causative mutation could be found yet. Inter- and intrafamilial phenotypic variability is high as is the variety of mainly family-specific mutations identified throughout TCOF1. No obvious correlation between pheno- and genotype could be observed. The majority of described point mutations, small insertions and deletions comprising only a few nucleotides within TCOF1 lead to a premature termination codon. We investigated a cohort of 112 patients with a tentative clinical diagnosis of TCS by multiplex ligation-dependent probe amplification (MLPA) to search for larger deletions not detectable with other methods used. All patients were selected after negative screening for mutations in TCOF1, POLR1D and POLR1C. In 1 patient with an unequivocal clinical diagnosis of TCS, we identified a 3.367 kb deletion. This deletion abolishes exon 3 and is the first described single exon deletion within TCOF1. On RNA level we observed loss of this exon which supposedly leads to haploinsufficiency of TREACLE, the nucleolar phosphoprotein encoded by TCOF1.

  16. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes.

    Science.gov (United States)

    Schubert, Julian; Siekierska, Aleksandra; Langlois, Mélanie; May, Patrick; Huneau, Clément; Becker, Felicitas; Muhle, Hiltrud; Suls, Arvid; Lemke, Johannes R; de Kovel, Carolien G F; Thiele, Holger; Konrad, Kathryn; Kawalia, Amit; Toliat, Mohammad R; Sander, Thomas; Rüschendorf, Franz; Caliebe, Almuth; Nagel, Inga; Kohl, Bernard; Kecskés, Angela; Jacmin, Maxime; Hardies, Katia; Weckhuysen, Sarah; Riesch, Erik; Dorn, Thomas; Brilstra, Eva H; Baulac, Stephanie; Møller, Rikke S; Hjalgrim, Helle; Koeleman, Bobby P C; Jurkat-Rott, Karin; Lehman-Horn, Frank; Roach, Jared C; Glusman, Gustavo; Hood, Leroy; Galas, David J; Martin, Benoit; de Witte, Peter A M; Biskup, Saskia; De Jonghe, Peter; Helbig, Ingo; Balling, Rudi; Nürnberg, Peter; Crawford, Alexander D; Esguerra, Camila V; Weber, Yvonne G; Lerche, Holger

    2014-12-01

    Febrile seizures affect 2-4% of all children and have a strong genetic component. Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B, that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature. Wild-type human syntaxin-1B but not a mutated protein rescued the effects of stx1b knockdown in zebrafish. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes.

  17. Mutations in ROGDI Cause Kohlschütter-Tönz Syndrome

    Science.gov (United States)

    Schossig, Anna; Wolf, Nicole I.; Fischer, Christine; Fischer, Maria; Stocker, Gernot; Pabinger, Stephan; Dander, Andreas; Steiner, Bernhard; Tönz, Otmar; Kotzot, Dieter; Haberlandt, Edda; Amberger, Albert; Burwinkel, Barbara; Wimmer, Katharina; Fauth, Christine; Grond-Ginsbach, Caspar; Koch, Martin J.; Deichmann, Annette; von Kalle, Christof; Bartram, Claus R.; Kohlschütter, Alfried; Trajanoski, Zlatko; Zschocke, Johannes

    2012-01-01

    Kohlschütter-Tönz syndrome (KTS) is an autosomal-recessive disease characterized by the combination of epilepsy, psychomotor regression, and amelogenesis imperfecta. The molecular basis has not yet been elucidated. Here, we report that KTS is caused by mutations in ROGDI. Using a combination of autozygosity mapping and exome sequencing, we identified a homozygous frameshift deletion, c.229_230del (p.Leu77Alafs∗64), in ROGDI in two affected individuals from a consanguineous family. Molecular studies in two additional KTS-affected individuals from two unrelated Austrian and Swiss families revealed homozygosity for nonsense mutation c.286C>T (p.Gln96∗) and compound heterozygosity for the splice-site mutations c.531+5G>C and c.532-2A>T in ROGDI, respectively. The latter mutation was also found to be heterozygous in the mother of the Swiss affected individual in whom KTS was reported for the first time in 1974. ROGDI is highly expressed throughout the brain and other organs, but its function is largely unknown. Possible interactions with DISC1, a protein involved in diverse cytoskeletal functions, have been suggested. Our finding that ROGDI mutations cause KTS indicates that the protein product of this gene plays an important role in neuronal development as well as amelogenesis. PMID:22424600

  18. Mobile Right Colon Syndrome: Obscure Cause of Lower Right Abdominal Pain

    Directory of Open Access Journals (Sweden)

    Bains

    2016-06-01

    Full Text Available Context The mobile right colon is a developmental aberration. During the development and rotation of the gut, the cecum and ascending colon are the last to take their final position and fuse with the posterior abdominal wall. Evidence Acquisition Though a mobile right colon may be present in 20% - 30% of the population but causes symptoms in very few. The patients present intermittent colicky right lower quadrant abdominal pain with associated abdominal distention and symptomatic relief after passing flatus or having a bowel movement. Results Non fixation along with heavy load of the right colon drags the cecum and ascending colon down and leads to stasis, obstruction or volvulus. The diagnosis of this entity is very difficult as radiological studies are not conclusive. Conclusions The mobile colon syndrome should be considered in the differential diagnosis of right lower quadrant pain from obscure causes. A proper detailed history is a must to consider this as differential diagnosis. Laparoscopy offers diagnostic and therapeutic treatment. Colopexy provides dramatic relief in carefully selected patients.

  19. A Turkish family with Clouston syndrome caused by G11R mutation in GJB6

    Directory of Open Access Journals (Sweden)

    Zafer Yüksel

    2015-06-01

    Full Text Available Clouston Syndrome (CS is an ectodermal dyplasia characterized by nail dystrophy and hair defects and inherited in an autosomal dominant trait (OMIM #129500. It is caused by the mutations in GJB6 gene which is encoding connexin 30 (Cx30, a member of connexin family and included in the structure of gap junctions serving in intercellular interactions. In the present paper, a 30-year-old mother and her 3-year-old daughter diagnosed as CS. Seven more family members were also diagnosed as CS compatible with autosomal dominant trait. The disease causing heterozygous mutation c.31G>A (p.G11R was found by Sanger sequencing in exon 5 of GJB6. The latter mutation had been reported in several different populations yet it is reported for the first time in a Turkish family. Additionally, it is suggested that the history of cardiac conduction problems such as cardiac arrest and sinus bradycardia might be related with mutant Cx30.

  20. Glutamatergic transmission aberration: a major cause of behavioral deficits in a murine model of Down's syndrome.

    Science.gov (United States)

    Kaur, Gurjinder; Sharma, Ajay; Xu, Wenjin; Gerum, Scott; Alldred, Melissa J; Subbanna, Shivakumar; Basavarajappa, Balapal S; Pawlik, Monika; Ohno, Masuo; Ginsberg, Stephen D; Wilson, Donald A; Guilfoyle, David N; Levy, Efrat

    2014-04-09

    Trisomy 21, or Down's syndrome (DS), is the most common genetic cause of intellectual disability. Altered neurotransmission in the brains of DS patients leads to hippocampus-dependent learning and memory deficiency. Although genetic mouse models have provided important insights into the genes and mechanisms responsible for DS-specific changes, the molecular mechanisms leading to memory deficits are not clear. We investigated whether the segmental trisomy model of DS, Ts[Rb(12.1716)]2Cje (Ts2), exhibits hippocampal glutamatergic transmission abnormalities and whether these alterations cause behavioral deficits. Behavioral assays demonstrated that Ts2 mice display a deficit in nest building behavior, a measure of hippocampus-dependent nonlearned behavior, as well as dysfunctional hippocampus-dependent spatial memory tested in the object-placement and the Y-maze spontaneous alternation tasks. Magnetic resonance spectra measured in the hippocampi revealed a significantly lower glutamate concentration in Ts2 as compared with normal disomic (2N) littermates. The glutamate deficit accompanied hippocampal NMDA receptor1 (NMDA-R1) mRNA and protein expression level downregulation in Ts2 compared with 2N mice. In concert with these alterations, paired-pulse analyses suggested enhanced synaptic inhibition and/or lack of facilitation in the dentate gyrus of Ts2 compared with 2N mice. Ts2 mice also exhibited disrupted synaptic plasticity in slice recordings of the hippocampal CA1 region. Collectively, these findings imply that deficits in glutamate and NMDA-R1 may be responsible for impairments in synaptic plasticity in the hippocampus associated with behavioral dysfunctions in Ts2 mice. Thus, these findings suggest that glutamatergic deficits have a significant role in causing intellectual disabilities in DS.

  1. Throw caution to the wind: is refeeding syndrome really a cause of death in acute care?

    Science.gov (United States)

    Matthews, K L; Capra, S M; Palmer, M A

    2017-08-16

    Refeeding syndrome (RFS), a life-threatening medical condition, is commonly associated with acute or chronic starvation. While the prevalence of patients at risk of RFS in hospital reportedly ranges from 0 to 80%, the prevalence and types of patients who die as a result of RFS is unknown. We aimed to measure the prevalence rate and examine the case histories of patients who passed away with RFS listed as a cause of death. Patients were eligible for inclusion provided their death occurred within a Queensland hospital. Medical charts were reviewed, for medical, clinical and nutrition histories with results presented using descriptive statistics. Across 18 years (1997-2015) and ~260000 hospital deaths, five individuals (4F, 74 (37-87)yrs) were identified. No patient had a past or present diagnosis, such as anorexia nervosa, that would classify them as at high risk for RFS. RFS was not listed as the primary cause of death for any patient. No individual consumed >3400 kJ per day. Limited consensus was observed in the signs and symptoms used to diagnose RFS, although all patients experienced low levels of potassium, phosphate and/or magnesium. Eighty percent of electrolytes improved before death. RFS was a rare underlying cause of death, despite reported high prevalence rates of risk. Patient groups usually considered to be at high risk were not identified, suggesting a level of imprecision with the interpretation of criteria used to identify RFS risk. More detailed research is warranted to assist in the identification of those distinctly at risk of RFS.European Journal of Clinical Nutrition advance online publication, 16 August 2017; doi:10.1038/ejcn.2017.124.

  2. Cauda equina syndrome caused by epidural pneumorrhachis: treatment with percutaneous computed tomography-guided translaminar trephination.

    Science.gov (United States)

    Paik, Nam Chull; Lim, Chun Soo; Jang, Ho Suk

    2013-04-01

    A case report and review of the literature. To present a rare case, and its treatment, of cauda equina syndrome (CES) caused by epidural pneumorrhachis after repeated caudal epidural injections. Pneumorrhachis is defined as the presence of air in the epidural or subarachnoid space. Epidural pneumorrhachis is usually asymptomatic and managed conservatively, but rare cases of lumbar radiculopathy resulting from epidural air have been reported. To the best of our knowledge, there has been no previous report of CES caused by epidural air. A 63-year-old male presented with recent aggravation of a low backache, with pain radiating to both lower limbs. He also complained of newly developed numbness in the buttocks, groins, and perineum, and difficulty with urination and defecation, after repeated caudal epidural injections during a 3-week period. Computed tomography and magnetic resonance imaging revealed epidural pneumorrhachis compressing the lumbar dural sac at the L2-L3 and L3-L4 levels. The patient's symptoms persisted despite 3 days of oxygen inhalation therapy. Attempted needle aspiration of the epidural air was unsuccessful and percutaneous computed tomography-guided translaminar trephination was performed. The day after trephination, the patient's lower extremity motor strength began to improve; sphincter dysfunction began to resolve on the second day. During 8 weeks, his pain resolved and he gradually regained sensation. Two years later, the patient was free of symptoms or signs of CES. Epidural pneumorrhachis may cause dural sac compression, thus worsening a patient's previous symptoms and possibly eliciting new problems such as CES. Conservative treatment should be the first-line approach, but surgery is often necessary when the problem remains unsolved. Percutaneous computed tomography-guided translaminar trephination may be an alternative to surgical decompression of the epidural space in selected patients.

  3. A Frame-Shift Mutation in CAV1 Is Associated with a Severe Neonatal Progeroid and Lipodystrophy Syndrome.

    Science.gov (United States)

    Schrauwen, Isabelle; Szelinger, Szabolcs; Siniard, Ashley L; Kurdoglu, Ahmet; Corneveaux, Jason J; Malenica, Ivana; Richholt, Ryan; Van Camp, Guy; De Both, Matt; Swaminathan, Shanker; Turk, Mari; Ramsey, Keri; Craig, David W; Narayanan, Vinodh; Huentelman, Matthew J

    2015-01-01

    A 3-year-old female patient presenting with an unknown syndrome of a neonatal progeroid appearance, lipodystrophy, pulmonary hypertension, cutis marmorata, feeding disorder and failure to thrive was investigated by whole-genome sequencing. This revealed a de novo, heterozygous, frame-shift mutation in the Caveolin1 gene (CAV1) (p.Phe160X). Mutations in CAV1, encoding the main component of the caveolae in plasma membranes, cause Berardinelli-Seip congenital lipodystrophy type 3 (BSCL). Although BSCL is recessive, heterozygous carriers either show a reduced phenotype of partial lipodystrophy, pulmonary hypertension, or no phenotype. To investigate the pathogenic mechanisms underlying this syndrome in more depth, we performed next generation RNA sequencing of peripheral blood, which showed several dysregulated pathways in the patient that might be related to the phenotypic progeroid features (apoptosis, DNA repair/replication, mitochondrial). Secondly, we found a significant down-regulation of known Cav1 interaction partners, verifying the dysfunction of CAV1. Other known progeroid genes and lipodystrophy genes were also dysregulated. Next, western blotting of lysates of cultured fibroblasts showed that the patient shows a significantly decreased expression of wild-type CAV1 protein, demonstrating a loss-of-function mutation, though her phenotype is more severe that other heterozygotes with similar mutations. This phenotypic variety could be explained by differences in genetic background. Indications for this are supported by additional rare variants we found in AGPAT2 and LPIN1 lipodystrophy genes. CAV1, AGPAT2 and LPIN1 all play an important role in triacylglycerol (TAG) biosynthesis in adipose tissue, and the defective function in different parts of this pathway, though not all to the same extend, could contribute to a more severe lipoatrophic phenotype in this patient. In conclusion, we report, for the first time, an association of CAV1 dysfunction with a syndrome

  4. Progeria (Hutchison - Gilford syndrome in siblings: In an autosomal recessive pattern of inheritance

    Directory of Open Access Journals (Sweden)

    Raghu Tanjore

    2001-09-01

    Full Text Available Progeria is an autosomal dominant, premature aging syndrome. Six and three year old female siblings had sclcrodermatous changes over the extremities, alopecia, beaked nose, prominent veins and bird-like facies. Radiological features were consistent with features of progeria. The present case highlights rarity of progeria in siblings with a possible autosomal recessive pattern.

  5. Physical and functional interactions between Werner syndrome helicase and mismatch-repair initiation factors

    DEFF Research Database (Denmark)

    Saydam, Nurten; Kanagaraj, Radhakrishnan; Dietschy, Tobias;

    2007-01-01

    Werner syndrome (WS) is a severe recessive disorder characterized by premature aging, cancer predisposition and genomic instability. The gene mutated in WS encodes a bi-functional enzyme called WRN that acts as a RecQ-type DNA helicase and a 3'-5' exonuclease, but its exact role in DNA metabolism...

  6. Progeria (Hutchison-Gilford syndrome) in siblings: in an autosomal recessive pattern of inheritance.

    Science.gov (United States)

    Raghu, T Y; Venkatesulu, G A; Kantharaj, G R; Suresh, T; Veeresh, V; Hanumanthappa, Y

    2001-01-01

    Progeria is an autosomal dominant, premature aging syndrome. Six and three year old female siblings had sclerodermatous changes over the extremities, alopecia, beaked nose, prominent veins and bird-like facies. Radiological features were consistent with features of progeria. The present case highlights rarity of progeria in siblings with a possible autosomal recessive pattern.

  7. Accelerated aging syndromes, are they relevant to normal human aging?

    Science.gov (United States)

    Dreesen, Oliver; Stewart, Colin L

    2011-09-01

    Hutchinson-Gilford Progeria (HGPS) and Werner syndromes are diseases that clinically resemble some aspects of accelerated aging. HGPS is caused by mutations in theLMNA gene resulting in post-translational processing defects that trigger Progeria in children. Werner syndrome, arising from mutations in the WRN helicase gene, causes premature aging in young adults. What are the molecular mechanism(s) underlying these disorders and what aspects of the diseases resemble physiological human aging? Much of what we know stems from the study of patient derived fibroblasts with both mutations resulting in increased DNA damage, primarily at telomeres. However, in vivo patients with Werner's develop arteriosclerosis, among other pathologies. In HGPS patients, including iPS derived cells from HGPS patients, as well as some mouse models for Progeria, vascular smooth muscle (VSM) appears to be among the most severely affected tissues. Defective Lamin processing, associated with DNA damage, is present in VSM from old individuals, indicating processing defects may be a factor in normal aging. Whether persistent DNA damage, particularly at telomeres, is the root cause for these pathologies remains to be established, since not all progeroid Lmna mutations result in DNA damage and genome instability.

  8. Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syndrome.

    NARCIS (Netherlands)

    Ruiz-Perez, V.L.; Tompson, S.W.; Blair, H.J.; Espinoza-Valdez, C.; Lapunzina, P.; Silva, E.O.; Hamel, B.C.J.; Gibbs, J.L.; Young, I.D.; Wright, M.J.; Goodship, J.A.

    2003-01-01

    Ellis-van Creveld syndrome (EvC) is an autosomal recessive skeletal dysplasia. Elsewhere, we described mutations in EVC in patients with this condition (Ruiz-Perez et al. 2000). We now report that mutations in EVC2 also cause EvC. These two genes lie in a head-to-head configuration that is conserved

  9. Clinical features and molecular genetic analysis of a boy with Prader-Willi syndrome caused by an imprinting defect

    DEFF Research Database (Denmark)

    Schulze, A; Hansen, Claus; Baekgaard, P;

    1997-01-01

    Prader-Willi syndrome (PWS) is a neuroendocrine disorder caused by a non-functioning paternally derived gene(s) within the chromosome region 15q11-q13. Most cases result from microscopically visible deletions of paternal origin, or maternal uniparental disomy of chromosome 15. In both instances...

  10. Novel TK2 mutations as a cause of delayed muscle maturation in mtDNA depletion syndrome.

    Science.gov (United States)

    Termglinchan, Thanes; Hisamatsu, Seito; Ohmori, Junko; Suzumura, Hiroshi; Sumitomo, Noriko; Imataka, George; Arisaka, Osamu; Murakami, Nobuyuki; Minami, Narihiro; Akihiko, Ishiyama; Sasaki, Masayuki; Goto, Yuichi; Noguchi, Satoru; Nonaka, Ikuya; Mitsuhashi, Satomi; Nishino, Ichizo

    2016-10-01

    Recessive mutations in TK2 cause a severe mitochondrial DNA depletion syndrome (MDS),(1) characterized by severe myopathy from early infancy. Recent reports have suggested a wider clinical spectrum including encephalomyopathic form.(1,2) We report a patient with infantile-onset fatal encephalomyopathy presenting with extreme muscle fiber immaturity.

  11. Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome.

    NARCIS (Netherlands)

    Koolen, D.A.; Kramer, J.M.; Neveling, K.; Nillesen, W.M.; Moore-Barton, H.L.; Elmslie, F.V.; Toutain, A.; Amiel, J.; Malan, V.; Tsai, A.C.; Cheung, S.W.; Gilissen, C.F.H.A.; Verwiel, E.T.P.; Martens, Sarah; Feuth, T.; Bongers, M.H.F.; Vries, P.F. de; Scheffer, H.; Vissers, L.E.L.M.; Brouwer, A.P.M. de; Brunner, H.G.; Veltman, J.A.; Schenck, A.; Yntema, H.G.; Vries, B.B. de

    2012-01-01

    We show that haploinsufficiency of KANSL1 is sufficient to cause the 17q21.31 microdeletion syndrome, a multisystem disorder characterized by intellectual disability, hypotonia and distinctive facial features. The KANSL1 protein is an evolutionarily conserved regulator of the chromatin modifier KAT8

  12. Compound heterozygosity for severe and hypomorphic NDUFS2 mutations cause non-syndromic LHON-like optic neuropathy

    NARCIS (Netherlands)

    Gerber, S.; Ding, M.G.; Gerard, X.; Zwicker, K.; Zanlonghi, X.; Rio, M. del; Serre, V.; Hanein, S.; Munnich, A.; Rotig, A.; Bianchi, L.; Amati-Bonneau, P.; Elpeleg, O.; Kaplan, J.; Brandt, U.; Rozet, J.M.

    2017-01-01

    BACKGROUND: Non-syndromic hereditary optic neuropathy (HON) has been ascribed to mutations in mitochondrial fusion/fission dynamics genes, nuclear and mitochondrial DNA-encoded respiratory enzyme genes or nuclear genes of poorly known mitochondrial function. However, the disease causing gene remains

  13. Lacrimal punctum occlusion in the treatment of severe keratoconjunctivitis sicca caused by Sjogren syndrome - A uniocular evaluation

    NARCIS (Netherlands)

    Mansour, Khaled; Leonhardt, Carolien J.; Kalk, Wouter W.; Bootsma, Hendrika; Bruin, Klaas J.; Blanksma, Lieuwe J.

    Purpose: A controlled uniocular study to evaluate the short-term efficacy of lacrimal punctum occlusion in the treatment of severe dry eye caused by Sjogren syndrome. Methods: Uniocular punctum occlusion by punctum plug in the upper and lower puncta in 1 eye was performed in 20 patients with severe

  14. Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.

    Science.gov (United States)

    Zhang, Weiqi; Li, Jingyi; Suzuki, Keiichiro; Qu, Jing; Wang, Ping; Zhou, Junzhi; Liu, Xiaomeng; Ren, Ruotong; Xu, Xiuling; Ocampo, Alejandro; Yuan, Tingting; Yang, Jiping; Li, Ying; Shi, Liang; Guan, Dee; Pan, Huize; Duan, Shunlei; Ding, Zhichao; Li, Mo; Yi, Fei; Bai, Ruijun; Wang, Yayu; Chen, Chang; Yang, Fuquan; Li, Xiaoyu; Wang, Zimei; Aizawa, Emi; Goebl, April; Soligalla, Rupa Devi; Reddy, Pradeep; Esteban, Concepcion Rodriguez; Tang, Fuchou; Liu, Guang-Hui; Belmonte, Juan Carlos Izpisua

    2015-06-05

    Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina-heterochromatin anchoring protein LAP2β. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.

  15. Acute encephalopathy associated with hemolytic uremic syndrome caused by Escherichia coli O157: H7 and rotavirus infection.

    Science.gov (United States)

    Imataka, G; Wake, K; Suzuki, M; Yamanouchi, H; Arisaka, O

    2015-05-01

    We reported a case of a 22-months child with hemolytic uremic syndrome associated with encephalopathy. As the cause of this case, the involvements of verotoxin 1 and 2 caused by O157: the H7 strain of the enterohemorrhagic Escherichia coli and rotavirus were presumed. We administered brain hypothermic therapy and steroid pulse therapy in the intensive care unit, but we were not able to save his life and the child died on the 6th day from the onset.

  16. Protein causes hyperinsulinemia: a Chinese patient with hyperinsulinism/hyperammonaemia syndrome due to a glutamate dehydrogenase gene mutation

    Institute of Scientific and Technical Information of China (English)

    CHEN Shi; XIAO Xin-hua; DIAO Cheng-ming; TONG An-li; WANG Ou; QIU Zheng-qing; YU Kang; WANG Tong

    2010-01-01

    @@ Glucose is derived from three sources: intestinal absorption, glycogenolysis, and gluconeogenesis. Hypoglycemia in child is often attributed to depletion of glycogen stores. However, recently, congenital hyperinsulinism becomes an important cause of hypoglycaemia in early infancy. Mutations in the genes encoding SUR1 and KIR6.2 are the most frequent genetic causes of hyperinsulinism followed by mutations in the glutamate dehydrogenase (GDH) gene which encodes hyperinsulinism/hyperammonaemia (HI/HA) syndrome.

  17. Refining the Diagnosis of Congenital Nephrotic Syndrome on Long-term Stored Tissue: c.1097G>A (p.(Arg366His)) WT1 Mutation Causing Denys Drash Syndrome

    NARCIS (Netherlands)

    Hillen, L.M.; Kamsteeg, E.J.; Schoots, J.; Tiebosch, A.T.; Speel, E.J.; Roemen, G.M.; Peutz-Koostra, C.J.; Stumpel, C.T.

    2016-01-01

    Congenital nephrotic syndrome (CNS) caused by a mutation in the Wilms tumor 1 suppressor gene (WT1) is part of Denys Drash Syndrome or Frasier syndrome. In the framework of genetic counseling, the diagnosis of CNS can be refined with gene mutation studies on long-term stored formalin-fixed paraffin-

  18. 22q13.3 Deletion Syndrome: An Underdiagnosed Cause of Mental Retardation

    Directory of Open Access Journals (Sweden)

    ilknur Erol

    2015-03-01

    Full Text Available Phelan-McDermid syndrome, also known as 22q13.3 deletion syndrome, is characterized by global developmental delay, absent or delayed speech, generalized hypotonia, and minor physical anomalies. The deletion typically involves the terminal band 22q13.3 and has been associated with both familial and de-novo translocations. We report the case of an 11-year-old Turkish girl with 22q13.3 deletion syndrome presenting with repeated seizures during the course of a rubella infection. We also review the clinical features of 22q13.3 deletion syndrome and emphasize the importance of considering a rare microdeletion syndrome for idiopathic mental retardation when results of a routine karyotype analysis are normal. To the best of our knowledge, this is the first reported case of a Turkish patient with isolated 22q13.3 deletion syndrome. [Cukurova Med J 2015; 40(1.000: 169-173

  19. Cellular defects caused by hypomorphic variants of the Bloom syndrome helicase gene BLM

    OpenAIRE

    Shastri, Vivek M.; Schmidt, Kristina H.

    2015-01-01

    Abstract Background Bloom syndrome is an autosomal recessive disorder characterized by extraordinary cancer incidence early in life and an average life expectancy of ~27 years. Premature stop codons in BLM , which encodes a DNA helicase that functions in DNA double‐strand‐break repair, make up the vast majority of Bloom syndrome mutations, with only 13 single amino acid changes identified in the syndrome. Sequencing projects have identified nearly one hundred single nucleotide variants in BLM...

  20. De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

    DEFF Research Database (Denmark)

    Hoischen, Alexander; van Bon, Bregje W M; Rodríguez-Santiago, Benjamín;

    2011-01-01

    Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which...... is required for maintenance of both activation and silencing of Hox genes. In total, 7 out of 13 subjects with a Bohring-Opitz phenotype had de novo ASXL1 mutations, suggesting that the syndrome is genetically heterogeneous....

  1. Kabuki syndrome as a cause of non-immune fetal hydrops/ascites.

    Science.gov (United States)

    Long, Ashleigh; Sinkovskaya, Elena S; Edmondson, Andrew C; Zackai, Elaine; Schrier Vergano, Samantha A

    2016-12-01

    Kabuki syndrome (MIM 147920) is a well-described, multiple congenital anomaly syndrome characterized by growth and developmental delay, cardiac, renal, and vertebral anomalies, as well as persistent fetal finger pads and distinct facial features. Facies are characterized by long palpebral fissures with eversion of lateral third of the lower eyelid, resembling the "Kabuki make-up" theatre genre after which the syndrome is named. Kabuki syndrome is estimated to affect 1/32,000 births, with 55-80% of patients showing nonsense or frameshift mutations in the KMT2D (MLL2) gene, which encodes a histone transferase located on chromosome 12q. Additionally, owing to the heterogeneous nature of Kabuki syndrome, a smaller number of diagnosed patients have been identified with mutations or deletions in KDM6A (a component of the same transcriptional complex as KMT2D) with no mutations in KMT2D, or as those diagnosed with Kabuki syndrome and without alterations in either KMT2D or KDM6A. Diagnosis of the syndrome in newborns and infants is difficult, as the facial features are not as evident as in toddler- or childhood. There are no known "tell-tale" signs of Kabuki syndrome prenatally, and there are no reports of common, specific findings in fetuses that might suggest the diagnosis. We present here two infants who presented with prenatal hydrops/ascites, who were subsequently diagnosed with Kabuki syndrome. Although relatively non-specific, we suggest that Kabuki syndrome be added to the list of genetic syndromes that are suspected in cases of prenatal hydrops, review the molecular etiology of Kabuki syndrome, and broaden the phenotype of this well-described disorder. © 2016 Wiley Periodicals, Inc.

  2. Saethre-Chotzen syndrome : cranofacial anomalies caused by genetic changes in the TWIST gene

    OpenAIRE

    2004-01-01

    textabstractIn this thesis, one of the most frequently occurring and most variable craniosynostosis syndromes was investigated; Saethre-Chotzen syndrome. Craniosynostosis is the premature obliteration of cranial sutures in the developing embryo. It can also occur in the first few months of life. Saethre-Chotzen syndrome is, besides craniosynostosis, characterized by specific facial and limb abnormalities, of which the most frequently reported are ptosis, prominent crus helicis, cutaneous synd...

  3. Pearson's syndrome: a rare cause of non-immune hydrops fetalis

    Institute of Scientific and Technical Information of China (English)

    李澤荷; 林青雲; 李志偉; 鄺毅山; 司徒紹昌

    2003-01-01

    @@ Pearson's syndrome, or Pearson's marrow-pancreas syndrome, was first described in 1979 in four unrelated children.1 It is characterized by refractory sideroblastic anaemia with vacuolization of marrow progenitor cells, and exocrine pancreatic dysfunction. Its progressive nature, multisystem involvement and metabolic disturbances led to the subsequent identification of a unique mitochondrial DNA deletion in most affected patients.2 Despite the relentless clinical course, the majority of the patients with Pearson ' s syndrome present insidiously. Life-threatening presentation at birth is extremely rare. We report a case of Pearson ' s syndrome presenting with severe hydrops fetalis.

  4. [Proteus syndrome: Case report of bladder vascular malformation causing massive hematuria].

    Science.gov (United States)

    Abbo, O; Bouali, O; Galinier, P; Moscovici, J

    2012-02-01

    Proteus syndrome is a rare, sporadic disorder consisting of disproportionate overgrowth of multiple tissues, vascular malformations, and connective tissue or epidermal nevi. Due to mosaic pattern of distribution, the phenotypes are variable and diverse. Vascular malformations are part of the major criteria used to define and diagnose this syndrome. It can involve the gastrointestinal tract, spleen, or the urinary tract but bladder malformations are rare. We report here a case of bladder vascular malformation in a 12-year-old boy known to have Proteus syndrome and review the literature on bladder malformations or tumors in this syndrome. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  5. Deleterious Mutations in the Zinc-Finger 469 Gene Cause Brittle Cornea Syndrome

    Science.gov (United States)

    Abu, Almogit; Frydman, Moshe; Marek, Dina; Pras, Eran; Nir, Uri; Reznik-Wolf, Haike; Pras, Elon

    2008-01-01

    Brittle cornea syndrome (BCS) is an autosomal-recessive disorder characterized by a thin cornea that tends to perforate, causing progressive visual loss and blindness. Additional systemic symptoms such as joint hypermotility, hyperlaxity of the skin, and kyphoscoliosis place BCS among the connective-tissue disorders. Previously, we assigned the disease gene to a 4.7 Mb interval on chromosome 16q24. In order to clone the BCS gene, we first narrowed the disease locus to a 2.8 Mb interval and systematically sequenced genes expressed in connective tissue in this chromosomal segment. We have identified two frameshift mutations in the Zinc-Finger 469 gene (ZNF469). In five unrelated patients of Tunisian Jewish ancestry, we found a 1 bp deletion at position 5943 (5943 delA), and in an inbred Palestinian family we detected a single-nucleotide deletion at position 9527 (9527 delG). The function of ZNF469 is unknown. However, a 30% homology to a number of collagens suggests that it could act as a transcription factor involved in the synthesis and/or organization of collagen fibers. PMID:18452888

  6. A case of familial paraganglioma syndrome type 4 caused by a mutation in the SDHB gene.

    Science.gov (United States)

    Drucker, Aaron M; Houlden, Robyn L

    2006-12-01

    A 40-year-old man was referred to our clinic with recurrent paragangliomas. He had undergone resection of a paraganglioma superior to the right adrenal gland at 19 years of age, resection of two para-aortic paragangliomas at 39 years of age, and resection of a paraganglioma in the interatrial septum at 40 years. The patient's mother had died at age 39 years of metastases from a carotid body tumor. MRI and CT scanning, 131I-labeled metaiodobenzylguanidine scanning, and genetic testing for a mutation in the succinate dehydrogenase complex, subunit B gene. Familial paraganglioma syndrome type 4 caused by a mutation in the succinate dehydrogenase complex, subunit B gene. The patient underwent two surgical procedures in our clinic. The first was to remove two para-aortic paragangliomas, and the second to remove a paraganglioma that involved both atria. The patient is at high risk for malignant disease and should undergo an annual monitoring program that consists of physical examination and measurement of his blood pressure and levels of urinary catecholamines and metanephrines. If these procedures suggest a recurrence of paraganglioma, 123I-labeled metaiodobenzylguanidine scanning should be performed. As he might develop nonfunctional tumors, however, he should also undergo CT scanning, MRI scanning, or both, of the neck, thorax, abdomen, and pelvis every 6-12 months. Genetic testing has been offered to family members.

  7. Computer vision syndrome: a review of ocular causes and potential treatments.

    Science.gov (United States)

    Rosenfield, Mark

    2011-09-01

    Computer vision syndrome (CVS) is the combination of eye and vision problems associated with the use of computers. In modern western society the use of computers for both vocational and avocational activities is almost universal. However, CVS may have a significant impact not only on visual comfort but also occupational productivity since between 64% and 90% of computer users experience visual symptoms which may include eyestrain, headaches, ocular discomfort, dry eye, diplopia and blurred vision either at near or when looking into the distance after prolonged computer use. This paper reviews the principal ocular causes for this condition, namely oculomotor anomalies and dry eye. Accommodation and vergence responses to electronic screens appear to be similar to those found when viewing printed materials, whereas the prevalence of dry eye symptoms is greater during computer operation. The latter is probably due to a decrease in blink rate and blink amplitude, as well as increased corneal exposure resulting from the monitor frequently being positioned in primary gaze. However, the efficacy of proposed treatments to reduce symptoms of CVS is unproven. A better understanding of the physiology underlying CVS is critical to allow more accurate diagnosis and treatment. This will enable practitioners to optimize visual comfort and efficiency during computer operation.

  8. Dumping syndrome: an unusual cause of severe hyperinsulinemic hypoglycemia in neurologically impaired children with gastrostomy.

    Science.gov (United States)

    Bizzarri, C; Cervoni, M; Crea, F; Cutrera, R; Schiavino, A; Schiaffini, R; Cappa, M

    2011-02-01

    This paper describes severe hyperinsulinemic hypoglycemia during bolus enteral feeding in two neurologically impaired children. Both children were affected by dysphagia with swallowing difficulties; caloric intake was inadequate. For these reasons, percutaneous endoscopic gastrostomy had been positioned during the first months of life. In one patient due to persisting vomiting, after a few months, a gastrojejunal tube (PEG-J) was inserted. Hypoglycemia was revealed by routine blood tests, without evidence of specific symptoms. Continuous subcutaneous glucose monitoring showed wide glucose excursions, ranging from hypoglycemia to hyperglycemia. Extremely high levels of insulin were detected at the time of hypoglycemia. A diagnosis of dumping syndrome (DS) was suspected in both children. In the child with PEG, the tip of the gastrostomy catheter was found to be lying in the bulbus duodeni. Once this had been pulled back, hypoglycemic episodes disappeared. The child with PEG-J needed continuous enteral feeding to reach a normal glucose balance. DS is a relatively common complication in children with gastrostomy, but extremely irregular glucose levels, ranging from hypoglycemia to hyperglycemia, and increased insulin secretion had not been previously demonstrated. The incidence of DS is probably underestimated in children receiving enteral feeding for neurological impairment. In these patients intensive monitoring of blood glucose levels should be performed to calibrate meals. Repeated underestimated hypoglycemic episodes could worsen neurological damage and cause a deterioration in clinical conditions.

  9. Stevens–Johnson syndrome/toxic epidermal necrolysis caused by cefadroxil in a cat

    Directory of Open Access Journals (Sweden)

    Roberta Sartori

    2016-06-01

    Full Text Available Case summary A 5-year-old, spayed female, indoor-only domestic shorthair cat was referred with an acute history of multifocal cutaneous and mucocutaneous erosive-ulcerative lesions and skin detachment. The lesions occurred on the seventh day of therapy with cefadroxil. Erosive-ulcerative and occasionally crusted lesions were apparent on the medial and lateral canthus of both eyes, ventral neck, abdomen, perivulvar region, periungual skin and medial aspect of the front and hindlimbs. Diffuse and severe exfoliation was present on the dorsum and tail base and in both external ear canals. The cat was also dehydrated, tachycardic and febrile. Histopathological examination revealed extensive epidermal ulceration, interface dermatitis with vacuolar degeneration, apoptosis at multiple epidermal levels and basal, suprabasal and spinous dermoepidermal detachment. The histopathological diagnosis was consistent with Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN. The recently reported Algorithm of Drug Causality in Epidermal Necrolysis (ALDEN, currently used in human medicine, was applied and a score of +6 was calculated; this supported the view that SJS/TEN in this cat was very likely to be associated with cefadroxil administration. Relevance and novel information This clinical communication reports cefadroxil as a very probable cause of SJS/TEN in a cat; the ALDEN was applied in this case and supported diagnosis.

  10. MASA syndrome is caused by mutations in the neural cell adhesion gene, L1CAM

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, C.E.; Wang, Y.; Schroer, R.J.; Stevenson, R.E. [Greenwood Genetic Center, SC (United States)

    1994-09-01

    The MASA syndrome is a recessive X-linked disorder characterized by Mental retardation, Adducted thumbs, Shuffling gait and Aphasia. Recently we found that MASA in one family was likely caused by a point mutation in exon 6 of the L1CAM gene. This gene has also been shown to be involved in X-linked hydrocephalus (HSAS). We have screened 60 patients with either sporadic HSAS or MASA as well as two additional families with MASA. For the screening, we initially utilized 3 cDNA probes for the L1CAM gene. In one of the MASA families, K8310, two affected males were found to have an altered BglII band. The band was present in their carrier mother but not in their normal brothers. This band was detected by the entire cDNA probe as well as the cDNA probe for 3{prime} end of the gene. Analysis of the L1CAM sequence indicated the altered BglII site is distal to the exon 28 but proximal to the punative poly A signal site. It is hypothesized that this point mutation alters the stability of the L1CAM mRNA. This is being tested using cell lines established from the two affected males.

  11. A functional alternative splicing mutation in AIRE gene causes autoimmune polyendocrine syndrome type 1.

    Science.gov (United States)

    Zhang, Junyu; Liu, Hongbin; Liu, Zhiyuan; Liao, Yong; Guo, Luo; Wang, Honglian; He, Lin; Zhang, Xiaodong; Xing, Qinghe

    2013-01-01

    Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare autosomal recessive disease defined by the presence of two of the three conditions: mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease. Loss-of-function mutations of the autoimmune regulator (AIRE) gene have been linked to APS-1. Here we report mutational analysis and functional characterization of an AIRE mutation in a consanguineous Chinese family with APS-1. All exons of the AIRE gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. We identified a homozygous missense AIRE mutation c.463G>A (p.Gly155Ser) in two siblings with different clinical features of APS-1. In silico splice-site prediction and minigene analysis were carried out to study the potential pathological consequence. Minigene splicing analysis and subsequent cDNA sequencing revealed that the AIRE mutation potentially compromised the recognition of the splice donor of intron 3, causing alternative pre-mRNA splicing by intron 3 retention. Furthermore, the aberrant AIRE transcript was identified in a heterozygous carrier of the c.463G>A mutation. The aberrant intron 3-retaining transcript generated a truncated protein (p.G155fsX203) containing the first 154 AIRE amino acids and followed by 48 aberrant amino acids. Therefore, our study represents the first functional characterization of the alternatively spliced AIRE mutation that may explain the pathogenetic role in APS-1.

  12. Excessive heart rate response to orthostatic stress in postural tachycardia syndrome is not caused by anxiety.

    Science.gov (United States)

    Masuki, Shizue; Eisenach, John H; Johnson, Christopher P; Dietz, Niki M; Benrud-Larson, Lisa M; Schrage, William G; Curry, Timothy B; Sandroni, Paola; Low, Phillip A; Joyner, Michael J

    2007-03-01

    Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) without hypotension during orthostasis. The relationship between the tachycardia and anxiety is uncertain. Therefore, we tested whether the HR response to orthostatic stress in POTS is primarily related to psychological factors. POTS patients (n = 14) and healthy controls (n = 10) underwent graded venous pooling with lower body negative pressure (LBNP) to -40 mmHg while wearing deflated antishock trousers. "Sham" venous pooling was performed by 1) trouser inflation to 5 mmHg during LBNP and 2) vacuum pump activation without LBNP. HR responses to mental stress were also measured in both groups, and a questionnaire was used to measure psychological parameters. During LBNP, HR in POTS patients increased 39 +/- 5 beats/min vs. 19 +/- 3 beats/min in control subjects at -40 mmHg (P inflation markedly blunted the HR responses in the patients (9 +/- 2 beats/min) and controls (2 +/- 1 beats/min), and there was no HR increase during vacuum application without LBNP in either group. HR responses during mental stress were not different in the patients and controls (18 +/- 2 vs. 19 +/- 1 beats/min; P > 0.6). Anxiety, somatic vigilance, and catastrophic cognitions were significantly higher in the patients (P 0.1). These results suggest that the HR response to orthostatic stress in POTS patients is not caused by anxiety but that it is a physiological response that maintains arterial pressure during venous pooling.

  13. Severe hyponatremia caused by nab-paclitaxel-induced syndrome of inappropriate antidiuretic hormone secretion

    Science.gov (United States)

    Neuzillet, Cindy; Babai, Samy; Kempf, Emmanuelle; Pujol, Géraldine; Rousseau, Benoît; Le-Louët, Hervé; Christophe Tournigand

    2016-01-01

    Abstract Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing. Most patients have advanced disease at diagnosis and therapeutic options in this setting are limited. Gemcitabine plus nab-paclitaxel regimen was demonstrated to increase survival compared with gemcitabine monotherapy and is therefore indicated as first-line therapy in patients with metastatic PDAC and performance status Eastern Cooperative Oncology Group (ECOG) 0-2. The safety profile of gemcitabine and nab-paclitaxel combination includes neutropenia, fatigue, and neuropathy as most common adverse events of grade 3 or higher. No case of severe hyponatremia associated with the use of nab-paclitaxel for the treatment of PDAC has been reported to date. We report the case of a 72-year-old Caucasian man with a metastatic PDAC treated with gemcitabine and nab-paclitaxel regimen, who presented with a severe hyponatremia (grade 4) caused by a documented syndrome of inappropriate antidiuretic hormone secretion (SIADH). This SIADH was attributed to nab-paclitaxel after a rigorous imputability analysis, including a rechallenge procedure with dose reduction. After dose and schedule adjustment, nab-paclitaxel was pursued without recurrence of severe hyponatremia and with maintained efficacy. Hyponatremia is a rare but potentially severe complication of nab-paclitaxel therapy that medical oncologists and gastroenterologists should be aware of. Nab-paclitaxel-induced hyponatremia is manageable upon dose and schedule adaptation, and should not contraindicate careful nab-paclitaxel reintroduction. This is of particular interest for a disease in which the therapeutic options are limited. PMID:27368013

  14. Acute liver failure caused by drug-induced hypersensitivity syndrome associated with hyperferritinemia

    Institute of Scientific and Technical Information of China (English)

    Masayuki Miyazaki; Masatake Tanaka; Akihiro Ueda; Tsuyoshi Yoshimoto; Masaki Kato; Makoto Nakamuta; Kazuhiro Kotoh; Ryoichi Takayanagi

    2011-01-01

    Drug-induced hypersensitivity syndrome (DIHS) is a se-vere reaction usually characterized by fever, rash, and multiorgan failure, occurring 2-6 wk after drug introduction.It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release. A 54-year-old woman was diagnosed with rheumatic arthritis and initiated salazosulfapyridine by mouth. About 10 d later, she had a high fever, skin rash and liver dysfunction. She was admitted to hospital and diagnosed with a drug eruption. She was treated with oral prednisolone 30 mg/d; however, she developed high fever again and her blood tests showed acute liver failure and cytopenia associated with hyperferritinemia. She was diagnosed with acute liver failure and hemophagocytosis caused by DIHS. She was transferred to the Department of Medicine and Bioregulatory Science, Kyushu University, where she was treated with arterial steroid injection therapy. Following this treatment, her liver function improved and serum ferritin immediately decreased. We hypothesized that an immune-mediated reaction in DIHS may have generated over-activation of macrophages and T-lymphocytes, followed by a cytokine storm that affected various organs. The measurement of serum ferritin might be a useful marker of the severity of DIHS.

  15. Identification and expression analysis of a novel intragenic EFNB1 mutation causing craniofrontonasal syndrome

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    Oscar F. Chacon-Camacho

    2014-12-01

    Full Text Available Craniofrontonasal syndrome (CFNS is an X-linked disorder caused by mutations in the EFNB1 gene and characterized by distinctive craniofacial and digital malformations. In contrast with most X-linked traits, female patients with CFNS display a more severe phenotype than males. In this report, the clinical, molecular and RNA expression analyses of a female subject with CFNS are described. A novel c.445_449delGAGGG deletion in exon 3 of EFNB1 was demonstrated in this patient. To assess the effect of this novel mutation at the transcript level, the expression of EFNB1 mRNA was studied by quantitative RT-PCR. To our knowledge, this is the first time that an EFNB1 transcript carrying a truncating mutation in exon 3 is demonstrated to undergo degradation by nonsense-mediated mRNA decay. Our results expand the mutational spectrum of CFNS and add to the functional consequences of truncating EFNB1 mutations.

  16. A CHRNE frameshift mutation causes congenital myasthenic syndrome in young Jack Russell Terriers.

    Science.gov (United States)

    Rinz, Caitlin J; Lennon, Vanda A; James, Fiona; Thoreson, James B; Tsai, Kate L; Starr-Moss, Alison N; Humphries, H Dale; Guo, Ling T; Palmer, Anthony C; Clark, Leigh Anne; Shelton, G Diane

    2015-12-01

    Congenital myasthenic syndromes (CMSs) are a group of rare genetic disorders of the neuromuscular junction resulting in structural or functional causes of fatigable weakness that usually begins early in life. Mutations in pre-synaptic, synaptic and post-synaptic proteins have been demonstrated in human cases, with more than half involving aberrations in nicotinic acetylcholine receptor (AChR) subunits. CMS was first recognized in dogs in 1974 as an autosomal recessive trait in Jack Russell Terriers (JRTs). A deficiency of junctional AChRs was demonstrated. Here we characterize a CMS in 2 contemporary cases of JRT littermates with classic clinical and electromyographic findings, and immunochemical confirmation of an approximately 90% reduction in AChR protein content. Loci encoding the 5 AChR subunits were evaluated using microsatellite markers, and CHRNB1 and CHRNE were identified as candidate genes. Sequences of the splice sites and exons of both genes revealed a single base insertion in exon 7 of CHRNE that predicts a frameshift mutation and a premature stop codon. We further demonstrated this pathogenic mutation in CHRNE in archival tissues from unrelated JRTs studied 34 years ago.

  17. Temperature-dependent growth of Geomyces destructans, the fungus that causes bat white-nose syndrome

    Science.gov (United States)

    Verant, Michelle L.; Boyles, Justin G.; Waldrep, William; Wibbelt, Gudrun; Blehert, David S.

    2012-01-01

    White-nose syndrome (WNS) is an emergent disease estimated to have killed over five million North American bats. Caused by the psychrophilic fungus Geomyces destructans, WNS specifically affects bats during hibernation. We describe temperature-dependent growth performance and morphology for six independent isolates of G. destructans from North America and Europe. Thermal performance curves for all isolates displayed an intermediate peak with rapid decline in performance above the peak. Optimal temperatures for growth were between 12.5 and 15.8°C, and the upper critical temperature for growth was between 19.0 and 19.8°C. Growth rates varied across isolates, irrespective of geographic origin, and above 12°C all isolates displayed atypical morphology that may have implications for proliferation of the fungus. This study demonstrates that small variations in temperature, consistent with those inherent of bat hibernacula, affect growth performance and physiology of G. destructans, which may influence temperature-dependent progression and severity of WNS in wild bats.

  18. Narcissistic vulnerability is a common cause for depression in patients with Gilles de la Tourette syndrome.

    Science.gov (United States)

    Trillini, Morounke O; Müller-Vahl, Kirsten R

    2015-12-15

    The aim of this study was to assess for the first time different dimensions of narcissistic self-regulation in a large cohort of adult patients with Gilles de la Tourette syndrome (GTS) (n=50). From preliminary studies it is suggested that narcissistic personality trait and disorder, respectively, are relatively uncommon and occur in only 6-10% of GTS patients. In this study we used the Narcissism Inventory (NI), a 163-items questionnaire that measures four different dimensions of narcissism. The main result was that the prevalence of narcissism strongly depends on the subtype of narcissism: while the vulnerable narcissism ("threatened self" and "hypochondriac self") was common, the "classic narcissistic self" (grandiose narcissism) was rare. From our data an association between comorbid depression and increased values of the "threatened self" and comorbid OCD with increased values of the "hypochondriac self" is suggested. Narcissism correlated positively with the personality domain neuroticism and had a significantly negative impact on patients' quality of life. Therefore it can be speculated that vulnerable narcissism is - among several others - one cause for depression in patients with GTS. These findings may open new psychotherapeutic perspectives in the treatment of depression in patients with GTS.

  19. Hepatic sinusoidal obstruction syndrome caused by herbal medicine: CT and MRI features

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Hua; Lou, Hai Yan [Dept. of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China); Wang, Yi Xiang J. [Dept. of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China); Xu, Xiao Jun; Zhang, Min Ming [Dept. of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China)

    2014-04-15

    To describe the CT and MRI features of hepatic sinusoidal obstruction syndrome (HSOS) caused by herbal medicine Gynura segetum. The CT and MRI features of 16 consecutive Gynura segetum induced HSOS cases (12 men, 4 women) were analyzed. Eight patients had CT; three patients had MRI, and the remaining five patients had both CT and MRI examinations. Based on their clinical presentations and outcomes, the patients were classified into three categories: mild, moderate, and severe. The severity of the disease was also evaluated radiologically based on the abnormal hepatic patchy enhancement in post-contrast CT or MRI images. Ascites, patchy liver enhancement, and main right hepatic vein narrowing or occlusion were present in all 16 cases. Hepatomegaly and gallbladder wall thickening were present in 14 cases (87.5%, 14/16). Periportal high intensity on T2-weighted images was present in 6 cases (75%, 6/8). Normal liver parenchymal enhancement surrounding the main hepatic vein forming a clover-like sign was observed in 4 cases (25%, 4/16). The extent of patchy liver enhancement was statistically associated with clinical severity classification (kappa = 0.565). Ascites, patchy liver enhancement, and the main hepatic veins narrowing were the most frequent signs of herbal medicine induced HSOS. The grade of abnormal patchy liver enhancement was associated with the clinical severity.

  20. Mutations in SNRPB, encoding components of the core splicing machinery, cause cerebro-costo-mandibular syndrome.

    Science.gov (United States)

    Bacrot, Séverine; Doyard, Mathilde; Huber, Céline; Alibeu, Olivier; Feldhahn, Niklas; Lehalle, Daphné; Lacombe, Didier; Marlin, Sandrine; Nitschke, Patrick; Petit, Florence; Vazquez, Marie-Paule; Munnich, Arnold; Cormier-Daire, Valérie

    2015-02-01

    Cerebro-costo-mandibular syndrome (CCMS) is a developmental disorder characterized by the association of Pierre Robin sequence and posterior rib defects. Exome sequencing and Sanger sequencing in five unrelated CCMS patients revealed five heterozygous variants in the small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) gene. This gene includes three transcripts, namely transcripts 1 and 2, encoding components of the core spliceosomal machinery (SmB' and SmB) and transcript 3 undergoing nonsense-mediated mRNA decay. All variants were located in the premature termination codon (PTC)-introducing alternative exon of transcript 3. Quantitative RT-PCR analysis revealed a significant increase in transcript 3 levels in leukocytes of CCMS individuals compared to controls. We conclude that CCMS is due to heterozygous mutations in SNRPB, enhancing inclusion of a SNRPB PTC-introducing alternative exon, and show that this developmental disease is caused by defects in the splicing machinery. Our finding confirms the report of SNRPB mutations in CCMS patients by Lynch et al. (2014) and further extends the clinical and molecular observations.

  1. LRPPRC mutations cause a phenotypically distinct form of Leigh syndrome with cytochrome c oxidase deficiency.

    Science.gov (United States)

    Debray, François-Guillaume; Morin, Charles; Janvier, Annie; Villeneuve, Josée; Maranda, Bruno; Laframboise, Rachel; Lacroix, Jacques; Decarie, Jean-Claude; Robitaille, Yves; Lambert, Marie; Robinson, Brian H; Mitchell, Grant A

    2011-03-01

    The natural history of all known patients with French-Canadian Leigh disease (Saguenay-Lac-St-Jean cytochrome c oxidase deficiency, MIM220111, SLSJ-COX), the largest known cohort of patients with a genetically homogeneous, nuclear encoded congenital lactic acidosis, was studied. 55 of 56 patients were homozygous for the A354V mutation in LRPPRC. One was a genetic compound (A354V/C1277Xdel8). Clinical features included developmental delay, failure to thrive, characteristic facial appearance and, in 90% of patients, acute crises that have not previously been detailed, either metabolic (fulminant lactic acidosis) and/or neurological (Leigh syndrome and/or stroke-like episodes). Survival ranged from 5 days to >30 years. 46/56 patients (82%) died, at a median age of 1.6 years. Of 73 crises, 38 (52%) were fatal. The immediate causes of death were multiple organ failure and/or Leigh disease. Major predictors of mortality during crises (pgenetic and/or environmental factors can influence outcome.

  2. A functional alternative splicing mutation in AIRE gene causes autoimmune polyendocrine syndrome type 1.

    Directory of Open Access Journals (Sweden)

    Junyu Zhang

    Full Text Available Autoimmune polyendocrine syndrome type 1 (APS-1 is a rare autosomal recessive disease defined by the presence of two of the three conditions: mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease. Loss-of-function mutations of the autoimmune regulator (AIRE gene have been linked to APS-1. Here we report mutational analysis and functional characterization of an AIRE mutation in a consanguineous Chinese family with APS-1. All exons of the AIRE gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. We identified a homozygous missense AIRE mutation c.463G>A (p.Gly155Ser in two siblings with different clinical features of APS-1. In silico splice-site prediction and minigene analysis were carried out to study the potential pathological consequence. Minigene splicing analysis and subsequent cDNA sequencing revealed that the AIRE mutation potentially compromised the recognition of the splice donor of intron 3, causing alternative pre-mRNA splicing by intron 3 retention. Furthermore, the aberrant AIRE transcript was identified in a heterozygous carrier of the c.463G>A mutation. The aberrant intron 3-retaining transcript generated a truncated protein (p.G155fsX203 containing the first 154 AIRE amino acids and followed by 48 aberrant amino acids. Therefore, our study represents the first functional characterization of the alternatively spliced AIRE mutation that may explain the pathogenetic role in APS-1.

  3. Exploration of hydroxymethylation in Kagami-Ogata syndrome caused by hypermethylation of imprinting control regions.

    Science.gov (United States)

    Matsubara, Keiko; Kagami, Masayo; Nakabayashi, Kazuhiko; Hata, Kenichiro; Fukami, Maki; Ogata, Tsutomu; Yamazawa, Kazuki

    2015-01-01

    5-Hydroxymethylcytosine (5hmC), converted from 5-methylcytosine (5mC) by ten-eleven translocation (Tet) enzymes, has recently drawn attention as the "sixth base" of DNA since it is considered an intermediate of the demethylation pathway. Nonetheless, it remains to be addressed how 5hmC is linked to the development of human imprinting disorders. In this regard, conventional bisulfite (BS) treatment is unable to differentiate 5hmC from 5mC. It is thus hypothesized that BS conversion-derived "hypermethylation" at imprinting control regions (ICRs), which may cause imprinting disorders, would in fact be attributable to excessively increased levels of 5hmC as well as 5mC. To test this hypothesis, we applied the newly developed oxidative BS (oxBS) treatment to detect 5hmC in blood samples from Kagami-Ogata syndrome (KOS14) patients caused by an epimutation (hypermethylation) of two differentially methylated regions (DMRs) functioning as ICRs, namely, IG-DMR and MEG3-DMR. oxBS with pyrosequencing revealed that there were few amounts of 5hmC at the hypermethylated IG-DMR and MEG3-DMR in blood samples from KOS14 patients. oxBS with genome-wide methylation array demonstrated that global levels of 5hmC were very low with similar distribution patterns in blood samples from KOS14 patients and normal controls. We also confirmed the presence of large amounts of 5hmC in the brain sample from a normal control. 5hmC is not a major component in abnormally hypermethylated ICRs or at a global level, at least in blood from KOS14 patients. As the brain sample contained large amounts of 5hmC, the neural tissues of KOS14 patients are promising candidates for analysis in elucidating the role of 5hmC in the neurodevelopmental context.

  4. Bronchopulmonary Carcinoids causing Cushing Syndrome: Results from a Multicentric Study Suggesting a More Aggressive Behavior.

    Science.gov (United States)

    Lococo, Filippo; Margaritora, Stefano; Cardillo, Giuseppe; Filosso, Perluigi; Novellis, Pierluigi; Rapicetta, Cristian; Carleo, Francesco; Bora, Giulia; Cesario, Alfredo; Stefani, Alessandro; Rossi, Giulio; Paci, Massimiliano

    2016-03-01

    Cushing syndrome (CS) caused by bronchopulmonary carcinoids (BCs) is a very rare entity. The aim of this study was to revisit the features of a multicenter clinical series to identify significant prognostic factors. From January 2002 to December 2013, the clinical and pathological data of 23 patients (treated in five different institutions) were retrospectively reviewed. Survival analysis was performed to explore the relative weight of potential prognostic factors. Median age and male/female ratio were 48 years and 14/9, respectively. Most (> 80%) of the patients presented with CS-related symptoms at diagnosis. Tumor location was peripheral in 13 patients (57%) and central in 10 (43%). All patients but two (treated with chemotherapy) underwent surgical resection with curative intent. Definitive cyto/histology was indicative of typical carcinoid (TC) in 16 cases (70%) and atypical carcinoid (AC) in 7 cases (30%). A complete remission of CS was obtained in 16 cases (70%). Lymph nodal involvement was detected in 11 cases (48%), with N2 disease occurring in 7 (∼ 30% of all cases). Four patients (22%) experienced a relapse of the disease after radical surgery. Overall 5-year survival (long-term survival, LTS) was 60%, better in TCs when compared with AC (LTS: 66 v s. 48%, p = 0.28). Log-rank analysis identified ECOG performance status, cTNM and cN staging, pTNM and pN staging, persistence of CS and relapses (local p = 0.006; distant p = 0.001) as significant prognostic factors in this cohort of patients. BCs causing CS are characterized by a high rate of lymph-nodal involvement, a suboptimal prognosis (5-year survival = 60%, 66% in TCs) and a remarkable risk of relapse even after radical resection. Advanced stage, lymph-nodal involvement and the persisting of the CS after treatment correlate with a poor prognosis. Georg Thieme Verlag KG Stuttgart · New York.

  5. The Genome Sequence of the Fungal Pathogen Fusarium virguliforme That Causes Sudden Death Syndrome in Soybean

    Science.gov (United States)

    Srivastava, Subodh K.; Huang, Xiaoqiu; Brar, Hargeet K.; Fakhoury, Ahmad M.; Bluhm, Burton H.; Bhattacharyya, Madan K.

    2014-01-01

    Fusarium virguliforme causes sudden death syndrome (SDS) of soybean, a disease of serious concern throughout most of the soybean producing regions of the world. Despite the global importance, little is known about the pathogenesis mechanisms of F. virguliforme. Thus, we applied Next-Generation DNA Sequencing to reveal the draft F. virguliforme genome sequence and identified putative pathogenicity genes to facilitate discovering the mechanisms used by the pathogen to cause this disease. Methodology/Principal Findings We have generated the draft genome sequence of F. virguliforme by conducting whole-genome shotgun sequencing on a 454 GS-FLX Titanium sequencer. Initially, single-end reads of a 400-bp shotgun library were assembled using the PCAP program. Paired end sequences from 3 and 20 Kb DNA fragments and approximately 100 Kb inserts of 1,400 BAC clones were used to generate the assembled genome. The assembled genome sequence was 51 Mb. The N50 scaffold number was 11 with an N50 Scaffold length of 1,263 Kb. The AUGUSTUS gene prediction program predicted 14,845 putative genes, which were annotated with Pfam and GO databases. Gene distributions were uniform in all but one of the major scaffolds. Phylogenic analyses revealed that F. virguliforme was closely related to the pea pathogen, Nectria haematococca. Of the 14,845 F. virguliforme genes, 11,043 were conserved among five Fusarium species: F. virguliforme, F. graminearum, F. verticillioides, F. oxysporum and N. haematococca; and 1,332 F. virguliforme-specific genes, which may include pathogenicity genes. Additionally, searches for candidate F. virguliforme pathogenicity genes using gene sequences of the pathogen-host interaction database identified 358 genes. Conclusions The F. virguliforme genome sequence and putative pathogenicity genes presented here will facilitate identification of pathogenicity mechanisms involved in SDS development. Together, these resources will expedite our efforts towards discovering

  6. Dysfunction of intraflagellar transport-A causes hyperphagia-induced obesity and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Damon T. Jacobs

    2016-07-01

    Full Text Available Primary cilia extend from the plasma membrane of most vertebrate cells and mediate signaling pathways. Ciliary dysfunction underlies ciliopathies, which are genetic syndromes that manifest multiple clinical features, including renal cystic disease and obesity. THM1 (also termed TTC21B or IFT139 encodes a component of the intraflagellar transport-A complex and mutations in THM1 have been identified in 5% of individuals with ciliopathies. Consistent with this, deletion of murine Thm1 during late embryonic development results in cystic kidney disease. Here, we report that deletion of murine Thm1 during adulthood results in obesity, diabetes, hypertension and fatty liver disease, with gender differences in susceptibility to weight gain and metabolic dysfunction. Pair-feeding of Thm1 conditional knock-out mice relative to control littermates prevented the obesity and related disorders, indicating that hyperphagia caused the obese phenotype. Thm1 ablation resulted in increased localization of adenylyl cyclase III in primary cilia that were shortened, with bulbous distal tips on neurons of the hypothalamic arcuate nucleus, an integrative center for signals that regulate feeding and activity. In pre-obese Thm1 conditional knock-out mice, expression of anorexogenic pro-opiomelanocortin (Pomc was decreased by 50% in the arcuate nucleus, which likely caused the hyperphagia. Fasting of Thm1 conditional knock-out mice did not alter Pomc nor orexogenic agouti-related neuropeptide (Agrp expression, suggesting impaired sensing of changes in peripheral signals. Together, these data indicate that the Thm1-mutant ciliary defect diminishes sensitivity to feeding signals, which alters appetite regulation and leads to hyperphagia, obesity and metabolic disease.

  7. Dysfunction of intraflagellar transport-A causes hyperphagia-induced obesity and metabolic syndrome.

    Science.gov (United States)

    Jacobs, Damon T; Silva, Luciane M; Allard, Bailey A; Schonfeld, Michael P; Chatterjee, Anindita; Talbott, George C; Beier, David R; Tran, Pamela V

    2016-07-01

    Primary cilia extend from the plasma membrane of most vertebrate cells and mediate signaling pathways. Ciliary dysfunction underlies ciliopathies, which are genetic syndromes that manifest multiple clinical features, including renal cystic disease and obesity. THM1 (also termed TTC21B or IFT139) encodes a component of the intraflagellar transport-A complex and mutations in THM1 have been identified in 5% of individuals with ciliopathies. Consistent with this, deletion of murine Thm1 during late embryonic development results in cystic kidney disease. Here, we report that deletion of murine Thm1 during adulthood results in obesity, diabetes, hypertension and fatty liver disease, with gender differences in susceptibility to weight gain and metabolic dysfunction. Pair-feeding of Thm1 conditional knock-out mice relative to control littermates prevented the obesity and related disorders, indicating that hyperphagia caused the obese phenotype. Thm1 ablation resulted in increased localization of adenylyl cyclase III in primary cilia that were shortened, with bulbous distal tips on neurons of the hypothalamic arcuate nucleus, an integrative center for signals that regulate feeding and activity. In pre-obese Thm1 conditional knock-out mice, expression of anorexogenic pro-opiomelanocortin (Pomc) was decreased by 50% in the arcuate nucleus, which likely caused the hyperphagia. Fasting of Thm1 conditional knock-out mice did not alter Pomc nor orexogenic agouti-related neuropeptide (Agrp) expression, suggesting impaired sensing of changes in peripheral signals. Together, these data indicate that the Thm1-mutant ciliary defect diminishes sensitivity to feeding signals, which alters appetite regulation and leads to hyperphagia, obesity and metabolic disease.

  8. A Turkish family with Sjögren-Larsson syndrome caused by a novel ALDH3A2 mutation

    Directory of Open Access Journals (Sweden)

    Faruk Incecik

    2013-01-01

    Full Text Available Sjögren-Larsson syndrome (SLS is an inherited neurocutaneous disorder caused by mutations in the aldehyde dehydrogenase family 3 member A2 (ALDH3A2 gene that encodes fatty aldehyde dehydrogenase. Affected patients display ichthyosis, mental retardation, and spastic diplegia. More than 70 mutations in ALDH3A2 have been discovered in SLS patients. We diagnosed two brothers age of 12 and 20 years with characteristic features of this rare syndrome. Magnetic resonance imaging showed demyelinating disease in both of them. We described a novel homozygous, c. 835 T > A (p.Y279N mutation in exon 6 in two patients.

  9. Unusual cause for recurrent Cushing syndrome and its diagnosis by computed tomography and NP-59 radiocholesterol scanning

    Energy Technology Data Exchange (ETDEWEB)

    Harris, R.D.; Herwig, K.R. (Univ. of California, Irvine, Orange (USA))

    1990-09-01

    Cushing syndrome can recur following an adrenalectomy. One of the primary causes is recurrence of adrenal carcinoma either locally or from metastases. Hyperplasia and hyperfunction of adrenal remnants may also occur if there is pituitary stimulation. We have a patient in whom recurrent Cushing syndrome developed from small nonmalignant deposits of adrenal tissue in the perirenal adipose tissue following adrenalectomy of a benign adenoma. These deposits were identifiable by computed tomography. A false-negative NP-59 iodocholesterol scan was instructive in pointing out some problems in the interpretation of this type of scan for adrenal tissue.

  10. Concurrent nephrotic syndrome and acute renal failure caused by chronic lymphocytic leukemia (CLL): a case report and literature review.

    Science.gov (United States)

    Dou, Xianrui; Hu, Haitang; Ju, Yongle; Liu, Yongdong; Kang, Kaifu; Zhou, Shufeng; Chen, Wenfang

    2011-10-13

    Kidney injury associated with lymphocytic leukemia (CLL) is typically caused by direct tumor infiltration which occasionally results in acute renal failure. Glomerular involvement presenting as proteinuria or even nephrotic syndrome is exceptionally rare. Here we report a case of 54-year-old male CLL patient with nephrotic syndrome and renal failure. The lymph node biopsy confirmed that the patients had CLL with remarkable immunoglobulin light chain amyloid deposition. The renal biopsy demonstrated the concurrence of AL amyloidosis and neoplastic infiltration. Combined treatment of fludarabine, cyclophosphamide and rituximab resulted in remission of CLL, as well as the renal disfunction and nephrotic syndrome, without recurrence during a 12-month follow-up. To our knowledge, this is the first case of CLL patient showing the nephrotic syndrome and acute renal failure caused by AL amyloidosis and neoplastic infiltration. Though AL amyloidosis caused by plasma cell dyscrasia usually responses poorly to chemotherapy, this patient exhibited a satisfactory clinical outcome due to successful inhibition of the production of amylodogenic light chains by combined chemotherapy.

  11. Bovine Neonatal Pancytopenia: is this alloimmune syndrome caused by vaccine-induced alloreactive antibodies?

    Science.gov (United States)

    Bastian, Max; Holsteg, Mark; Hanke-Robinson, Heidrun; Duchow, Karin; Cussler, Klaus

    2011-07-18

    Bovine Neonatal Pancytopenia (BNP) is a new emerging disease observed since 2007 in Germany and neighbouring countries. The syndrome affects newborn calves and is characterized by pancytopenia, severe bleeding and high lethality. So far, a causative role of infectious or toxic agents has been ruled out. Instead, the syndrome is induced after ingestion of colostrum, the first milk that supplies the calf with maternal antibodies. In analogy to similar diseases in humans it has therefore been postulated that BNP is caused by alloreactive, maternal antibodies. There is a striking association between BNP and a previous vaccination of the respective dams with a particular vaccine against Bovine Virus Diarrhoea (BVD). This association has led to a suspension of the marketing authorisation for the vaccine, by the European Commission. The current study investigates the role of this vaccine in the pathogenesis of BNP. By flow cytometry we were able to demonstrate that sera of BNP dams (dams that gave birth to a BNP calf) harbour alloreactive antibodies binding to surface antigens on bovine leukocytes. A significantly weaker alloreactivity was observed with sera of non-BNP dams that have been vaccinated with the same vaccine but delivered healthy calves. No binding was seen with non-BVD-vaccinated control cows and animals that were vaccinated with other inactivated BVD vaccines so far not associated with BNP. The binding is functionally relevant, because opsonization of bovine leukocytes with alloantibodies led to an elevated cytophagocytosis by bovine macrophages. To test whether the vaccine induces alloreactive antibodies two strategies were employed: Guinea pigs were vaccinated with a panel of commercially available BVD-vaccines. Only the incriminated vaccine induced antibodies binding surface antigens on bovine leukocytes. Additionally, two calves were repeatedly vaccinated with the suspected vaccine and the development of alloreactivity was monitored. In dependence of

  12. Clinical and radiographic features of Hutchinson-Gilford progeria syndrome: A case report.

    Science.gov (United States)

    Alves, Daniel Berretta; Silva, Juliana Melo; Menezes, Tatiany Oliveira; Cavaleiro, Rosely Santos; Tuji, Fabrício Mesquita; Lopes, Marcio Ajudarte; Zaia, Alexandre Augusto; Coletta, Ricardo Della

    2014-03-16

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare dysmorphic syndrome characterized by several features of premature aging with clinical involvement of the skin, bones, and cardiovascular system. HGPS has an estimated incidence of one in four million to one in eight million births. The main clinical features of HGPS include short stature, craniofacial dimorphism, alopecia, bone fragility, and cardiovascular disorders. The most frequent cause of death is myocardial infarction at a mean age of 13 years old. Dental manifestations include delayed development and eruption of teeth, discoloration, crowding and rotation of teeth, and displaced teeth. Cone beam computed tomography images revealed the absence of the sphenoid, frontal, and maxillary sinus, flattening of the condyles and glenoid fossa, and bilateral hypoplasia of the mandibular condyles. The disease is caused by mutations in lamin A/C (LMNA). Here, we present a case report of an 11-year-old boy with classical features of HGPS, which was caused by a de novo germ-line mutation (C1824T, G608G) in exon 11 of the LMNA gene. Some uncommon HGPS-associated features in our patient, such as alterations in the facial sinuses and hypoplasia of the condyles, contributed to the expansion of the phenotypic spectrum of this syndrome from a dentomaxillofacial perspective.

  13. A new mutation causing autosomal dominant periodic fever syndrome in a Danish family

    DEFF Research Database (Denmark)

    Weyhreter, Heike; Schwartz, Marianne; Kristensen, Tim D

    2003-01-01

    We describe four members in a family of 8 individuals over 3 generations with the autosomal dominant inherited periodic fever syndrome tumor necrosis factor receptor-associated periodic syndrome (TRAPS). The patients had recurrent episodes of fever, abdominal pain, arthritis, and rash. We examined...

  14. A Novel MAPT Mutation Causing Corticobasal Syndrome Led by Progressive Apraxia of Speech.

    Science.gov (United States)

    Marshall, Charles R; Guerreiro, Rita; Thust, Steffi; Fletcher, Phillip; Rohrer, Jonathan D; Fox, Nick C

    2015-01-01

    The authors describe a case of corticobasal syndrome led by progressive apraxia of speech, associated with a novel mutation in exon 10 of the MAPT gene. Genetic bases for progressive apraxia of speech and corticobasal syndrome are only rarely described, and have not been described in conjunction.

  15. Compound heterozygosity for mutations in LMNA causes a progeria syndrome without prelamin A accumulation.

    NARCIS (Netherlands)

    Verstraeten, V.L.; Broers, J.L.; Steensel, M.A.M. van; Zinn-Justin, S.; Ramaekers, F.C.S.; Steijlen, P.M.; Kamps, M.; Kuijpers, H.J.; Merckx, D.; Smeets, H.J.M.; Hennekam, R.C.M.; Marcelis, C.L.M.; Wijngaard, A. van de

    2006-01-01

    LMNA-associated progeroid syndromes have been reported with both recessive and dominant inheritance. We report a 2-year-old boy with an apparently typical Hutchinson-Gilford progeria syndrome (HGPS) due to compound heterozygous missense mutations (p.T528M and p.M540T) in LMNA. Both mutations affect

  16. Compound heterozygosity for mutations in LMNA causes a progeria syndrome without prelamin A accumulation.

    NARCIS (Netherlands)

    Verstraeten, V.L.; Broers, J.L.; Steensel, M.A.M. van; Zinn-Justin, S.; Ramaekers, F.C.S.; Steijlen, P.M.; Kamps, M.; Kuijpers, H.J.; Merckx, D.; Smeets, H.J.M.; Hennekam, R.C.M.; Marcelis, C.L.M.; Wijngaard, A. van de

    2006-01-01

    LMNA-associated progeroid syndromes have been reported with both recessive and dominant inheritance. We report a 2-year-old boy with an apparently typical Hutchinson-Gilford progeria syndrome (HGPS) due to compound heterozygous missense mutations (p.T528M and p.M540T) in LMNA. Both mutations affect

  17. De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

    DEFF Research Database (Denmark)

    Hoischen, Alexander; van Bon, Bregje W M; Rodríguez-Santiago, Benjamín;

    2011-01-01

    Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which...

  18. A new mutation causing autosomal dominant periodic fever syndrome in a Danish family

    DEFF Research Database (Denmark)

    Weyhreter, Heike; Schwartz, Marianne; Kristensen, Tim D;

    2003-01-01

    We describe four members in a family of 8 individuals over 3 generations with the autosomal dominant inherited periodic fever syndrome tumor necrosis factor receptor-associated periodic syndrome (TRAPS). The patients had recurrent episodes of fever, abdominal pain, arthritis, and rash. We examine...

  19. Moyamoya disease associated with asymptomatic mosaic Turner syndrome: a rare cause of hemorrhagic stroke.

    Science.gov (United States)

    Manjila, Sunil; Miller, Benjamin R; Rao-Frisch, Anitha; Otvos, Balint; Mitchell, Anna; Bambakidis, Nicholas C; De Georgia, Michael A

    2014-01-01

    Moyamoya disease is a rare cerebrovascular anomaly involving the intracranial carotid arteries that can present clinically with either ischemic or hemorrhagic disease. Moyamoya syndrome, indistinguishable from moyamoya disease at presentation, is associated with multiple clinical conditions including neurofibromatosis type 1, autoimmune disease, prior radiation therapy, Down syndrome, and Turner syndrome. We present the first reported case of an adult patient with previously unrecognized mosaic Turner syndrome with acute subarachnoid and intracerebral hemorrhage as the initial manifestation of moyamoya syndrome. A 52-year-old woman was admitted with a subarachnoid hemorrhage with associated flame-shaped intracerebral hemorrhage in the left frontal lobe. Physical examination revealed short stature, pectus excavatum, small fingers, micrognathia, and mild facial dysmorphism. Cerebral angiography showed features consistent with bilateral moyamoya disease, aberrant intrathoracic vessels, and an unruptured 4-mm right superior hypophyseal aneurysm. Genetic analysis confirmed a diagnosis of mosaic Turner syndrome. Our case report is the first documented presentation of adult moyamoya syndrome with subarachnoid and intracerebral hemorrhage as the initial presentation of mosaic Turner syndrome. It illustrates the utility of genetic evaluation in patients with cerebrovascular disease and dysmorphism.

  20. Saethre-Chotzen syndrome : cranofacial anomalies caused by genetic changes in the TWIST gene

    NARCIS (Netherlands)

    I.M. de Heer (Marieke)

    2004-01-01

    textabstractIn this thesis, one of the most frequently occurring and most variable craniosynostosis syndromes was investigated; Saethre-Chotzen syndrome. Craniosynostosis is the premature obliteration of cranial sutures in the developing embryo. It can also occur in the first few months of life. Sae

  1. Partial duplications of the ATRX gene cause the ATR-X syndrome.

    Science.gov (United States)

    Thienpont, Bernard; de Ravel, Thomy; Van Esch, Hilde; Van Schoubroeck, Dominique; Moerman, Philippe; Vermeesch, Joris Robert; Fryns, Jean-Pierre; Froyen, Guy; Lacoste, Caroline; Badens, Catherine; Devriendt, Koen

    2007-10-01

    ATR-X syndrome is a rare syndromic X-linked mental retardation disorder. We report that some of the patients suspected of ATR-X carry large intragenic duplications in the ATRX gene, leading to an absence of ATRX mRNA and of the protein. These findings underscore the need for including quantitative analyses to mutation analysis of the ATRX gene.

  2. Antiphospholipid Syndrome with Antiβ2glicoprotein-1 Antibodies as the Cause of Recurrent Tibial Vein Thrombosis in SAPHO syndrome.

    Science.gov (United States)

    Przepiera-Będzak, Hanna; Brzosko, Marek

    2016-12-01

    thrombosis in this syndrome, but the patient with multiple venous thrombosis presented in his case report was negative for aCL antibodies; however, he was not tested for anti-β2G-1 antibodies. There was a paper demonstrating increased level of aCL antibodies in 5 of 12 patients with SAPHO syndrome (11). In our observations of 17 patients with SAPHO syndrome, only 1 had increased level of aCL antibodies without symptoms of thrombosis (12). That patient was negative for aCL antibodies, aPT antibodies, aPS antibodies, and antiphosphatidylserine antibodies, but she was positive twice for anti-β2G-1 antibodies. The presence of anti-β2G-1antibodies may be caused by an infectious agent, but in our case bacteria culture of the discharge from pustules was negative. One year after the first episode of deep vein thrombosis, our patient met the criteria of antiphospholipid syndrome. We conclude that antiphospholipid syndrome, especially the presence of anti-β2G-1 antibodies, could be the cause of increased risk of vein thrombosis in SAPHO syndrome.

  3. Resolution of life-threatening dysphagia caused by caudal occipital malformation syndrome following foramen magnum decompressive surgery.

    Science.gov (United States)

    Graham, K J; Black, A P; Brain, P H

    2012-08-01

    A Cavalier King Charles Spaniel was presented with acute onset, life-threatening dysphagia suspected to be secondary to medulla oblongata compression caused by caudal occipital malformation syndrome. The patient required urgent tracheostomy tube placement to remain stable and was subsequently cured of the presenting neurological deficits by foramen magnum decompressive surgery. Neurogenic dysphagia is a relatively common presenting sign in human Chiari malformation syndromes, but has not been described as a major clinical sign in veterinary patients. Caudal occipital malformation syndrome should be included in the differential diagnosis list for susceptible breeds presenting with dysphagia. Early recognition favours expeditious surgical intervention and a positive outcome in human patients, and this may also be the case in veterinary patients. © 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.

  4. Differentiating cause-of-death terminology for deaths coded as sudden infant death syndrome, accidental suffocation, and unknown cause: an investigation using US death certificates, 2003-2004.

    Science.gov (United States)

    Kim, Shin Y; Shapiro-Mendoza, Carrie K; Chu, Susan Y; Camperlengo, Lena T; Anderson, Robert N

    2012-03-01

    We compared written text on infant death certificates for deaths coded as sudden infant death syndrome (R95), unknown cause (R99), and accidental suffocation (W75). Using US mortality files supplemented with the death certifiers' written text for all infant deaths with International Classification of Diseases (ICD)-10 assigned codes R95, R99, and W75, we formed cause-of-death subcategories from common themes identified from the written text. Among all infant deaths in 2003-2004, the underlying cause of death was listed as R99 for 2128 deaths, R95 for 4408 deaths, and W75 for 931 deaths. Among the postneonatal deaths, the differences in subcategories varied between assigned ICD-10 codes: for R99-coded deaths, 45.8% were categorized as "Unknown" and 48.6% as "Pending"; for R95-coded deaths, 67.7% were categorized as "sudden infant death syndrome (SIDS)"; and for W75-coded deaths, 76.4% were categorized as "Suffocation." Examination of the written text on the death certificates demonstrates variability in the assigned ICD-10 codes which could have an important effect on the estimates of SIDS cases in the United States.

  5. NAA10 mutation causing a novel intellectual disability syndrome with Long QT due to N-terminal acetyltransferase impairment

    Science.gov (United States)

    Casey, Jillian P.; Støve, Svein I.; McGorrian, Catherine; Galvin, Joseph; Blenski, Marina; Dunne, Aimee; Ennis, Sean; Brett, Francesca; King, Mary D.; Arnesen, Thomas; Lynch, Sally Ann

    2015-01-01

    We report two brothers from a non-consanguineous Irish family presenting with a novel syndrome characterised by intellectual disability, facial dysmorphism, scoliosis and long QT. Their mother has a milder phenotype including long QT. X-linked inheritance was suspected. Whole exome sequencing identified a novel missense variant (c.128 A > C; p.Tyr43Ser) in NAA10 (X chromosome) as the cause of the family’s disorder. Sanger sequencing confirmed that the mutation arose de novo in the carrier mother. NAA10 encodes the catalytic subunit of the major human N-terminal acetylation complex NatA. In vitro assays for the p.Tyr43Ser mutant enzyme showed a significant decrease in catalytic activity and reduced stability compared to wild-type Naa10 protein. NAA10 has previously been associated with Ogden syndrome, Lenz microphthalmia syndrome and non-syndromic developmental delay. Our findings expand the clinical spectrum of NAA10 and suggest that the proposed correlation between mutant Naa10 enzyme activity and phenotype severity is more complex than anticipated; the p.Tyr43Ser mutant enzyme has less catalytic activity than the p.Ser37Pro mutant associated with lethal Ogden syndrome but results in a milder phenotype. Importantly, we highlight the need for cardiac assessment in males and females with NAA10 variants as both patients and carriers can have long QT. PMID:26522270

  6. Angelman syndrome caused by deletion: a genotype-phenotype correlation determined by breakpoint.

    Science.gov (United States)

    Valente, Kette D; Varela, Monica Castro; Koiffmann, Celia Priszkulnik; Andrade, Joaquina Queiroz; Grossmann, Rosi; Kok, Fernando; Marques-Dias, Maria Joaquina

    2013-07-01

    Deletion of the chromosome 15q11-q13, the most common genetic mechanism associated with Angelman syndrome (AS), is highly associated with a severe phenotype. However, deletion is not a genetically homogeneous group as it is composed by two main groups: Class I with breakpoints at BP1 (proximal) and BP3 (distal) and Class II present breakpoints at BP2 (proximal) and BP3 (distal). In this study, we aimed to evaluate the impact of the breakpoint on the electroclinical profile. We evaluated 16 patients with AS caused by 15q11-13 deletion (6 were Class I; 10 were Class II). We characterized epilepsy features by clinical history obtained from parents and caretakers with a pre-standard questionnaire. These data were corroborated by medical records, contact with previous physicians, and video-EEG monitoring. Suggestive EEG patterns for AS were classified according to the classical description of Boyd et al. (1988). AS patients with BP1-BP3 deletion had significantly more daily and disabling seizures than AS patients with BP1-BP2 deletion. They also presented a significant higher frequency of status epilepticus and epilepsy aggravated by fever. Need for polytherapy was significantly more frequent in BP1-BP3 patients. EEG features were similar in both groups. This study shows a significant correlation between the two deletion classes and AS clinical, but not the electrographic phenotype. Epilepsy is more severe and refractory to treatment in patients with larger deletions. Deletion is not a homogeneous group and knowledge on the breakpoint may have a clinical implication and represent an important factor in parental counseling. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. A comprehensive review on experimental and clinical findings in intermediate syndrome caused by organophosphate poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Abdollahi, Mohammad, E-mail: mohammad.abdollahi@utoronto.ca; Karami-Mohajeri, Somayyeh

    2012-02-01

    Acute organophosphate (OP) intoxication is important because of its high morbidity and mortality and occurrence of muscular paralysis associated by inhibition of acetylcholinesterase (AChE) activity at the neuromuscular junction. Cholinergic crisis, intermediate syndrome (IMS), and OP-induced delayed neuropathy (OPIDN) are the evidences that can be observed in OP intoxication. The main cause of morbidity due to OP poisoning is IMS that occurs 24–96 h after poisoning. Mechanisms underlying the IMS are not fully known. Although the electrophysiological aspects of delayed neuropathy are best characterized, the IMS remain very little studied. The aim of this study was to revisit current knowledge related to OP and the IMS. For this purpose, a systematic review without date limitation was performed. A total of 599 relevant articles were found and reviewed. Data were categorized according to experimental and clinical studies. Occurrences of persistent AChE inhibition, electromyography changes, muscle cell injury, and oxidative stress are the most important pieces of evidence for involvement of IMS in OP toxicity. Delayed AChE inhibition, muscle necrosis, down regulation or desensitization of postsynaptic ACh receptors, failure of postsynaptic ACh release, and oxidative stress-related myopathy are involved in IMS. Toxicokinetic factors, such as a high lipid-solubility, duration of AChE inhibition and metabolite excretion, evolution of alterations on repetitive nerve stimulation (RNS), type and frequency of muscle lesions can estimate the probability of the IMS. Plasma AChE of less than 200 units is a predictor and the 30 Hz RNS decremental response could be a useful marker for the IMS.

  8. Obstructive sleep apnoea syndrome as a cause of road traffic accidents.

    Science.gov (United States)

    Aguiar, M; Valença, J; Felizardo, M; Caeiro, F; Moreira, S; Staats, R; Bugalho de Almeida, A A

    2009-01-01

    Several studies have demonstrated that obstructive sleep apnoea syndrome (OSAS) patients have a higher rate of road traffic accidents. Our study aimed to analyse any differences in OSAS patients between those who reported having had road traffic accidents and/or near misses and those who did not. We studied 163 patients with OSAS (apnoea- hypopnoea index (AHI)>10/h) diagnosed using nocturnal polysomnography (NPSG), all drivers, 18.4% of whom drove for a living. Patients were asked at their first clinical interview to self-report road traffic accidents and/or near misses over the past 3 years which had been caused by abnormal daytime drowsiness. This allowed patients to be divided into two groups, those who had had road traffic accidents and/or near misses and those who had not. Both were compared as to age, body mass index (BMI), Epworth Sleepiness Scale (ESS), daytime PaO2 and PaCO2, Functional Outcomes of Sleep Questionnaire (FOSQ) test and NPSG data. This latter was total sleep time (TTS), sleep efficiency, sleep stages, arousal index (ARI), AHI, minimal and average SaO2, % of time with SaO2 TDAH) (T test). Group I (no road traffic accidents) No=89 patients; group II (road traffic accidents) No=74 patients. Age (years) was 57.6+/-11.8 vs. 54.7+/-10.9 (ns); male gender, 75% vs. 78.4%; ESS, 12.3+/-5.4 vs. 17.6+/-4.3 (pTDAH (minutes), 98.5+/-63.7 vs. 133.3+/-83.2 (p=0,005). In our experience patients who had road traffic accidents and/or near misses had a more severe OSAS, with higher AHI, excessive daytime sleepiness and lower quality of life.

  9. Quantitative and sensitive detection of GNAS mutations causing mccune-albright syndrome with next generation sequencing.

    Science.gov (United States)

    Narumi, Satoshi; Matsuo, Kumihiro; Ishii, Tomohiro; Tanahashi, Yusuke; Hasegawa, Tomonobu

    2013-01-01

    Somatic activating GNAS mutations cause McCune-Albright syndrome (MAS). Owing to low mutation abundance, mutant-specific enrichment procedures, such as the peptide nucleic acid (PNA) method, are required to detect mutations in peripheral blood. Next generation sequencing (NGS) can analyze millions of PCR amplicons independently, thus it is expected to detect low-abundance GNAS mutations quantitatively. In the present study, we aimed to develop an NGS-based method to detect low-abundance somatic GNAS mutations. PCR amplicons encompassing exons 8 and 9 of GNAS, in which most activating mutations occur, were sequenced on the MiSeq instrument. As expected, our NGS-based method could sequence the GNAS locus with very high read depth (approximately 100,000) and low error rate. A serial dilution study with use of cloned mutant and wildtype DNA samples showed a linear correlation between dilution and measured mutation abundance, indicating the reliability of quantification of the mutation. Using the serially diluted samples, the detection limits of three mutation detection methods (the PNA method, NGS, and combinatory use of PNA and NGS [PNA-NGS]) were determined. The lowest detectable mutation abundance was 1% for the PNA method, 0.03% for NGS and 0.01% for PNA-NGS. Finally, we analyzed 16 MAS patient-derived leukocytic DNA samples with the three methods, and compared the mutation detection rate of them. Mutation detection rate of the PNA method, NGS and PNA-NGS in 16 patient-derived peripheral blood samples were 56%, 63% and 75%, respectively. In conclusion, NGS can detect somatic activating GNAS mutations quantitatively and sensitively from peripheral blood samples. At present, the PNA-NGS method is likely the most sensitive method to detect low-abundance GNAS mutation.

  10. Quantitative and sensitive detection of GNAS mutations causing mccune-albright syndrome with next generation sequencing.

    Directory of Open Access Journals (Sweden)

    Satoshi Narumi

    Full Text Available Somatic activating GNAS mutations cause McCune-Albright syndrome (MAS. Owing to low mutation abundance, mutant-specific enrichment procedures, such as the peptide nucleic acid (PNA method, are required to detect mutations in peripheral blood. Next generation sequencing (NGS can analyze millions of PCR amplicons independently, thus it is expected to detect low-abundance GNAS mutations quantitatively. In the present study, we aimed to develop an NGS-based method to detect low-abundance somatic GNAS mutations. PCR amplicons encompassing exons 8 and 9 of GNAS, in which most activating mutations occur, were sequenced on the MiSeq instrument. As expected, our NGS-based method could sequence the GNAS locus with very high read depth (approximately 100,000 and low error rate. A serial dilution study with use of cloned mutant and wildtype DNA samples showed a linear correlation between dilution and measured mutation abundance, indicating the reliability of quantification of the mutation. Using the serially diluted samples, the detection limits of three mutation detection methods (the PNA method, NGS, and combinatory use of PNA and NGS [PNA-NGS] were determined. The lowest detectable mutation abundance was 1% for the PNA method, 0.03% for NGS and 0.01% for PNA-NGS. Finally, we analyzed 16 MAS patient-derived leukocytic DNA samples with the three methods, and compared the mutation detection rate of them. Mutation detection rate of the PNA method, NGS and PNA-NGS in 16 patient-derived peripheral blood samples were 56%, 63% and 75%, respectively. In conclusion, NGS can detect somatic activating GNAS mutations quantitatively and sensitively from peripheral blood samples. At present, the PNA-NGS method is likely the most sensitive method to detect low-abundance GNAS mutation.

  11. A Novel Homozygous Mutation in FOXC1 Causes Axenfeld Rieger Syndrome with Congenital Glaucoma.

    Directory of Open Access Journals (Sweden)

    Shazia Micheal

    Full Text Available Anterior segment dysgenesis (ASD disorders are a group of clinically and genetically heterogeneous phenotypes in which frequently cornea, iris, and lens are affected. This study aimed to identify novel mutations in PAX6, PITX2 and FOXC1 in families with anterior segment dysgenesis disorders.We studied 14 Pakistani and one Mexican family with Axenfeld Rieger syndrome (ARS; n = 10 or aniridia (n = 5. All affected and unaffected family members underwent full ophthalmologic and general examinations. Total genomic DNA was isolated from peripheral blood. PCR and Sanger sequencing were performed for the exons and intron-exon boundaries of the FOXC1, PAX6, and PITX2 genes.Mutations were identified in five of the 15 probands; four variants were novel and one variant was described previously. A novel de novo variant (c.225C>A; p.Tyr75* was identified in the PAX6 gene in two unrelated probands with aniridia. In addition, a known variant (c.649C>T; p.Arg217* in PAX6 segregated in a family with aniridia. In the FOXC1 gene, a novel heterozygous variant (c.454T>C; p.Trp152Arg segregated with the disease in a Mexican family with ARS. A novel homozygous variant (c.92_100del; p.Ala31_Ala33del in the FOXC1 gene segregated in a Pakistani family with ARS and congenital glaucoma.Our study expands the mutation spectrum of the PAX6 and FOXC1 genes in individuals with anterior segment dysgenesis disorders. In addition, our study suggests that FOXC1 mutations, besides typical autosomal dominant ARS, can also cause ARS with congenital glaucoma through an autosomal recessive inheritance pattern. Our results thus expand the disease spectrum of FOXC1, and may lead to a better understanding of the role of FOXC1 in development.

  12. Carpal tunnel syndrome caused by a giant cell tumour of the flexor tendon sheath.

    Science.gov (United States)

    Meek, Marcel F; Sheikh, Zahid A; Quinton, David N

    2014-02-01

    A 76-year-old woman developed right carpal tunnel syndrome after being conservatively treated for tenosynovitis of the flexor tendons with associated mild carpal tunnel syndrome. A magnetic resonance imaging scan showed a tumour in the carpal tunnel. Re-exploration showed that the median nerve was being compressed by a giant cell tumour of the flexor tendon sheaths. Appropriate imaging is advised in patients with additional findings (such as swelling) or in patients with secondary carpal tunnel syndrome and incomplete response to conservative treatment, to exclude a space-occupying lesion.

  13. Cerebral salt wasting syndrome in brain injury patients: a potential cause of hyponatremia.

    Science.gov (United States)

    Zafonte, R D; Mann, N R

    1997-05-01

    Hyponatremia is a common neuromedical problem seen in survivors of central nervous system injury. The etiology of this hyponatremia is often diagnosed as syndrome of inappropriate diuretic hormone (SIADH). Fluid restriction is usually the first line of treatment. However, this can exacerbate vasospasm and produce resultant ischemia. Cerebral salt wasting is a syndrome of renal sodium loss that may occur commonly after central nervous system injury, yet remains unrecognized. Treatment of cerebral salt wasting consists of hydration and salt replacement. This article uses a case report to discuss the importance of recognition of this syndrome, and treatment concerns are reviewed.

  14. Cockayne syndrome group B protein promotes mitochondrial DNA stability by supporting the DNA repair association with the mitochondrial membrane

    DEFF Research Database (Denmark)

    Aamann, Maria Diget; Sorensen, Martin M; Hvitby, Christina Poulsen;

    2010-01-01

    Cockayne syndrome (CS) is a human premature aging disorder associated with severe developmental deficiencies and neurodegeneration, and phenotypically it resembles some mitochondrial DNA (mtDNA) diseases. Most patients belong to complementation group B, and the CS group B (CSB) protein plays a role...

  15. Metabolic syndrome in Russian adults: associated factors and mortality from cardiovascular diseases and all causes

    Directory of Open Access Journals (Sweden)

    Grjibovski Andrej M

    2010-09-01

    Full Text Available Abstract Background Metabolic syndrome (MetS is a cluster of four major obesity-related risk factors for cardiovascular disease (CVD. Russia has one of the highest CVD mortality in the world, but its association with MetS remains unknown. Also little is known about factors associated with MetS and its components in Russia. Methods Data on 3555 adults aged 18-90 years were collected in a cross-sectional study in 2000. MetS was defined by the International Diabetes Federation (IDF and National Cholesterol Education Program (NCEP criteria. Sex-specific associations between the IDF-defined MetS, its components, and life-style, socio-economic factors and laboratory indicators, were analysed using multivariable Poisson regression. Vital status of the study participants was identified by July 2009. Sex-specific associations between MetS and stroke, Coronary Heart Disease (CHD, CVD and all-cause death, were studied by Poisson regression adjusted for age, smoking, alcohol and history of CVDs. Results After adjustment for all studied factors except BMI, age, serum GGT, C-reactive protein and AST-to-ALT ratio were associated with MetS in both genders. Additionally, MetS was associated with sedentary lifestyle in women and with smoking in men. In the same regression model drinking alcohol 2-4 times a month and consumption of five or more alcohol units at one occasion in men, and drinking alcohol 5 times or more a month in women were inversely associated with MetS. After a 9-year follow-up, MetS was associated with higher risk of death from stroke (RR = 3.76, 95% CI:1.35-10.46 and from either stroke or myocardial infarction (MI, RR = 2.87, 95% CI:1.32-6.23 in men. No associations between MetS and any of the studied causes of death were observed in women. Conclusion Factors associated with MetS in both genders were age, GGT, C-reactive protein, and AST-to-ALT ratio. Moderate frequency of alcohol consumption and binge drinking in men and higher leisure time

  16. POLD1 Germline Mutations in Patients Initially Diagnosed with Werner Syndrome.

    Science.gov (United States)

    Lessel, Davor; Hisama, Fuki M; Szakszon, Katalin; Saha, Bidisha; Sanjuanelo, Alexander Barrios; Salbert, Bonnie A; Steele, Pamela D; Baldwin, Jennifer; Brown, W Ted; Piussan, Charles; Plauchu, Henri; Szilvássy, Judit; Horkay, Edit; Högel, Josef; Martin, George M; Herr, Alan J; Oshima, Junko; Kubisch, Christian

    2015-11-01

    Segmental progeroid syndromes are rare, heterogeneous disorders characterized by signs of premature aging affecting more than one tissue or organ. A prototypic example is the Werner syndrome (WS), caused by biallelic germline mutations in the Werner helicase gene (WRN). While heterozygous lamin A/C (LMNA) mutations are found in a few nonclassical cases of WS, another 10%-15% of patients initially diagnosed with WS do not have mutations in WRN or LMNA. Germline POLD1 mutations were recently reported in five patients with another segmental progeroid disorder: mandibular hypoplasia, deafness, progeroid features syndrome. Here, we describe eight additional patients with heterozygous POLD1 mutations, thereby substantially expanding the characterization of this new example of segmental progeroid disorders. First, we identified POLD1 mutations in patients initially diagnosed with WS. Second, we describe POLD1 mutation carriers without clinically relevant hearing impairment or mandibular underdevelopment, both previously thought to represent obligate diagnostic features. These patients also exhibit a lower incidence of metabolic abnormalities and joint contractures. Third, we document postnatal short stature and premature greying/loss of hair in POLD1 mutation carriers. We conclude that POLD1 germline mutations can result in a variably expressed and probably underdiagnosed segmental progeroid syndrome.

  17. Takotsubo Syndrome as a Cause of False Acute Abdomen in the Early Postoperative Period After Bariatric Surgery-a Report of Two Cases.

    Science.gov (United States)

    Viegas, Fabio; Viegas, Carla; França, Enio; Kleuser, Klaus; de Barros, Fernando

    2016-10-01

    Takotsubo syndrome, also known as broken-heart syndrome, stress-induced cardiomyopathy or transient apical ballooning syndrome, is a transient disorder characterized by segmental left ventricular failure in the absence of obstructive coronary artery disease. Most cases of Takotsubo syndrome are caused by acute stress that leads to a sudden, temporary weakening of the cardiac musculature. This stress triggers a rise in circulating catecholamine levels that results in acute ventricular dysfunction. In this report, we describe two cases of Takotsubo syndrome in the early postoperative period after bariatric surgery.

  18. Transgene silencing of the Hutchinson-Gilford progeria syndrome mutation results in a reversible bone phenotype, whereas resveratrol treatment does not show overall beneficial effects

    DEFF Research Database (Denmark)

    Strandgren, Charlotte; Nasser, Hasina Abdul; McKenna, Tomás

    2015-01-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder that is most commonly caused by a de novo point mutation in exon 11 of the LMNA gene, c.1824C>T, which results in an increased production of a truncated form of lamin A known as progerin. In this study, we used a mouse...... model to study the possibility of recovering from HGPS bone disease upon silencing of the HGPS mutation, and the potential benefits from treatment with resveratrol. We show that complete silencing of the transgenic expression of progerin normalized bone morphology and mineralization already after 7...... weeks. The improvements included lower frequencies of rib fractures and callus formation, an increased number of osteocytes in remodeled bone, and normalized dentinogenesis. The beneficial effects from resveratrol treatment were less significant and to a large extent similar to mice treated with sucrose...

  19. Acute calcifying tendonitis--an unusual cause of carpal tunnel syndrome.

    Science.gov (United States)

    Din, R; Giannikas, K; El-Hadidi, M

    2001-03-01

    We report a rare case of acute calcifying tendinitis resulting in acute carpal tunnel syndrome. Acute medical staff should be aware of this condition and the importance of early referral to avoid long term median nerve neuropathy.

  20. Symmetrical corticobasal syndrome caused by a novel c.314dup progranulin mutation

    NARCIS (Netherlands)

    E.G.P. Dopper (Elise); H. Seelaar (Harro); W.Z. Chiu (Wang Zheng); I. de Koning (Inge); R. van Minkelen (Rick); M.C. Baker (Matthew); A.J.M. Rozemuller (Annemieke); R. Rademakers (Rosa); J.C. van Swieten (John)

    2011-01-01

    textabstractCorticobasal syndrome (CBS) is characterised by asymmetrical parkinsonism and cognitive impairment. The underlying pathology varies between corticobasal degeneration, progressive supranuclear palsy, Alzheimer's disease, Creutzfeldt-Jakob disease and frontotemporal lobar degeneration