[Molecular updates on Usher syndrome].

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Roux, A-F

2005-01-01

Usher syndrome (USH) is an autosomal recessive disorder characterized by the association of sensorineural hearing loss and retinitis pigmentosa (RP). Usher syndrome is both clinically and genetically heterogeneous. Three clinical subtypes are defined with respect to vestibular dysfunction and the degree of hearing loss. Type I (USH1) patients have profound hearing loss and vestibular dysfunction from birth. Type II (USH2) is the most frequent and patients tend to have less severe hearing impairment and normal vestibular response. Type III (USH3) is characterized by a progressive loss of hearing and is found more frequently among Finnish patients. Recently, major breakthroughs have been made in the molecular genetics of Usher syndrome as a number of chromosomal loci and causative genes have been identified in each clinical subtype. Twelve loci are known and the corresponding genes have been cloned for six of them. Although their functions are not always clearly established, a common role is emerging for the proteins identified within each subtype. As a result, each subtype could emanate from defects affecting distinct cellular mechanisms.

Noonan syndrome-causing genes: Molecular update and an assessment of the mutation rate

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Ihssane El Bouchikhi

2016-12-01

Full Text Available Noonan syndrome is a common autosomal dominant disorder characterized by short stature, congenital heart disease and facial dysmorphia with an incidence of 1/1000 to 2500 live births. Up to now, several genes have been proven to be involved in the disturbance of the transduction signal through the RAS-MAP Kinase pathway and the manifestation of Noonan syndrome. The first gene described was PTPN11, followed by SOS1, RAF1, KRAS, BRAF, NRAS, MAP2K1, and RIT1, and recently SOS2, LZTR1, and A2ML1, among others. Progressively, the physiopathology and molecular etiology of most signs of Noonan syndrome have been demonstrated, and inheritance patterns as well as genetic counseling have been established. In this review, we summarize the data concerning clinical features frequently observed in Noonan syndrome, and then, we describe the molecular etiology as well as the physiopathology of most Noonan syndrome-causing genes. In the second part of this review, we assess the mutational rate of Noonan syndrome-causing genes reported up to now in most screening studies. This review should give clinicians as well as geneticists a full view of the molecular aspects of Noonan syndrome and the authentic prevalence of the mutational events of its causing-genes. It will also facilitate laying the groundwork for future molecular diagnosis research, and the development of novel treatment strategies.

Molecular Pathogenesis of Familial Wolff-Parkinson-White Syndrome.

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Licht, Miyamotoa

2018-01-01

Familial Wolff-Parkinson-White (WPW) syndrome is an autosomal dominant inherited disease and consists of a small percentage of WPW syndrome which exhibits ventricular pre-excitation by development of accessory atrioventricular pathway. A series of mutations in PRKAG2 gene encoding gamma2 subunit of 5'AMP-activated protein kinase (AMPK) has been identified as the cause of familial WPW syndrome. AMPK is one of the most important metabolic regulators of carbohydrates and lipids in many types of tissues including cardiac and skeletal muscles. Patients and animals with the mutation in PRKAG2 gene exhibit aberrant atrioventricular conduction associated with cardiac glycogen overload. Recent studies have revealed "novel" significance of canonical pathways leading to glycogen synthesis and provided us profound insights into molecular mechanism of the regulation of glycogen metabolism by AMPK. This review focuses on the molecular basis of the pathogenesis of cardiac abnormality due to PRKAG2 mutation and will provide current overviews of the mechanism of glycogen regulation by AMPK. J. Med. Invest. 65:1-8, February, 2018.

Congenital heart disease and genetic syndromes: new insights into molecular mechanisms.

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Calcagni, Giulio; Unolt, Marta; Digilio, Maria Cristina; Baban, Anwar; Versacci, Paolo; Tartaglia, Marco; Baldini, Antonio; Marino, Bruno

2017-09-01

Advances in genetics allowed a better definition of the role of specific genetic background in the etiology of syndromic congenital heart defects (CHDs). The identification of a number of disease genes responsible for different syndromes have led to the identification of several transcriptional regulators and signaling transducers and modulators that are critical for heart morphogenesis. Understanding the genetic background of syndromic CHDs allowed a better characterization of the genetic basis of non-syndromic CHDs. In this sense, the well-known association of typical CHDs in Down syndrome, 22q11.2 microdeletion and Noonan syndrome represent paradigms as chromosomal aneuploidy, chromosomal microdeletion and intragenic mutation, respectively. Area covered: For each syndrome the anatomical features, distinctive cardiac phenotype and molecular mechanisms are discussed. Moreover, the authors include recent genetic findings that may shed light on some aspects of still unclear molecular mechanisms of these syndromes. Expert commentary: Further investigations are needed to enhance the translational approach in the field of genetics of CHDs. When there is a well-established definition of genotype-phenotype (reverse medicine) and genotype-prognosis (predictive and personalized medicine) correlations, hopefully preventive medicine will make its way in this field. Subsequently a reduction will be achieved in the morbidity and mortality of children with CHDs.

Molecular characterization of a novel X-linked syndrome involving developmental delay and deafness.

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Hildebrand, Michael S; de Silva, Michelle G; Tan, Tiong Yang; Rose, Elizabeth; Nishimura, Carla; Tolmachova, Tanya; Hulett, Joanne M; White, Susan M; Silver, Jeremy; Bahlo, Melanie; Smith, Richard J H; Dahl, Hans-Henrik M

2007-11-01

X-linked syndromes associated with developmental delay and sensorineural hearing loss (SNHL) have been characterized at the molecular level, including Mohr-Tranebjaerg syndrome and Norrie disease. In this study we report on a novel X-linked recessive, congenital syndrome in a family with developmental delay and SNHL that maps to a locus associated with mental retardation (MR) for which no causative gene has been identified. The X-linked recessive inheritance and congenital nature of the syndrome was confirmed by detailed clinical investigation and the family history. Linkage mapping of the X-chromosome was conducted to ascertain the disease locus and candidate genes were screened by direct sequencing and STRP analysis. The recessive syndrome was mapped to Xp11.3-q21.32 and a deletion was identified in a regulatory region upstream of the POU3F4 gene in affected family members. Since mutations in POU3F4 cause deafness at the DFN3 locus, the deletion is the likely cause of the SNHL in this family. The choroideremia (CHM) gene was also screened and a novel missense change was identified. The alteration changes the serine residue at position 89 in the Rab escort 1 protein (REP-1) to a cysteine (S89C). Prenylation of Rab proteins was investigated in patients and the location of REP-1 expression in the brain determined. However, subsequent analysis revealed that this change in CHM was polymorphic having no effect on REP-1 function. Although the causative gene at the MR locus in this family has not been identified, there are a number of genes involved in syndromic and nonsyndromic forms of MR that are potential candidates. Copyright 2007 Wiley-Liss, Inc.

Cugini's syndrome: its clinical history and diagnosis

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Laura Gasbarrone

2013-09-01

Full Text Available INTRODUCTION: This article deals with the description and diagnosis of a new nosographic syndrome, which received the eponym of "Cugini's syndrome" by the name of the Author who discovered its clinical picture. This syndrome is characterized by the binomial: "minimal target organ damage associated to monitoring prehypertension". CLINICAL HISTORY AND DIAGNOSIS: Between the years 1997 and 2002, the Author published a series of investigations regarding some office normotensives who inexplicably showed incipient signs of target organ damage (TOD. Investigated via ambulatory (A blood (B pressure (P monitoring (M, these subjects were surprisingly found not to be hypertensive. Neverthless, the office normotensives with TOD exibited the daily mean level of their systolic (S and diastolic (D BP (DML SBP/DBP significantly more elevated as compared to true normotensives. Because of these ABPM findings, the Author realized that the investigated subjects were false normotensives whose TOD was associated with a monitoring prehypertension (ABPM-diagnosable prehypertension alias monitoring prehypertension alias masked prehypertension. The year after the last Cugini's investigation, the INC-7 Reports introduced the term: "prehypertension" in its classification of arterial hypertension, as an office sphygmomanometric condition in between office normotension and office hypertension. The ABPM cut-off upper limits for a differential diagnosis between monitoring normotension, prehypertension and hypertension are reported, as calculated by the Author in its collection of ABPMs. The eponym of "Cugini's syndrome" was assigned in 2007 and confirmed in 2009. CONCLUSIVE REMARKS: The monitoring prehypertension is a further condition of discrepancy between office sphygmomanometry and ABPM, as per a masked prehypertension, whose diagnosis has to be immediately diagnosed, for preventing the onset of a TOD. There are reported the present investigations dealing with the possible

[When history meets molecular medicine: molecular history of human tuberculosis].

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Ottini, Laura; Falchetti, Mario

2010-01-01

Tuberculosis represents one of the humankind's most socially devastating diseases. Despite a long history of medical research and the development of effective therapies, this disease remains a global health danger even in the 21st century. Tuberculosis may cause death but infected people with effective immunity may remain healthy for years, suggesting long-term host-pathogen co-existence. Because of its antiquity, a supposed association with human settlements and the tendency to leave typical lesions on skeletal and mummified remains, tuberculosis has been the object of intensive multidisciplinary studies, including paleo-pathological research. During the past 10 years molecular paleo-pathology developed as a new scientific discipline allowing the study of ancient pathogens by direct detection of their DNA. In this work, we reviewed evidences for tuberculosis in ancient human remains, current methods for identifying ancient mycobacterial DNA and explored current theories of Mycobacterium tuberculosis evolution and their implications in the global development of tuberculosis looking into the past and present at the same time.

[Noonan syndrome can be diagnosed clinically and through molecular genetic analyses].

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Henningsen, Marie Krab; Jelsig, Anne Marie; Andersen, Helle; Brusgaard, Klaus; Ousager, Lilian Bomme; Hertz, Jens Michael

2015-08-03

Noonan syndrome is part of the group of RASopathies caused by germ line mutations in genes involved in the RAS/MAPK pathway. There is substantial phenotypic overlap among the RASopathies. Diagnosis of Noonan syndrome is often based on clinical features including dysmorphic facial features, short stature and congenital heart disease. Rapid advances in sequencing technology have made molecular genetic analyses a helpful tool in diagnosing and distinguishing Noonan syndrome from other RASopathies.

Congenital heart defects in molecularly proven Kabuki syndrome patients.

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Digilio, Maria Cristina; Gnazzo, Maria; Lepri, Francesca; Dentici, Maria Lisa; Pisaneschi, Elisa; Baban, Anwar; Passarelli, Chiara; Capolino, Rossella; Angioni, Adriano; Novelli, Antonio; Marino, Bruno; Dallapiccola, Bruno

2017-11-01

The prevalence of congenital heart defects (CHD) in Kabuki syndrome ranges from 28% to 80%. Between January 2012 and December 2015, 28 patients had a molecularly proven diagnosis of Kabuki syndrome. Pathogenic variants in KMT2D (MLL2) were detected in 27 patients, and in KDM6A gene in one. CHD was diagnosed in 19/27 (70%) patients with KMT2D (MLL2) variant, while the single patient with KDM6A change had a normal heart. The anatomic types among patients with CHD included aortic coarctation (4/19 = 21%) alone or associated with an additional CHD, bicuspid aortic valve (4/19 = 21%) alone or associated with an additional CHD, perimembranous subaortic ventricular septal defect (3/19 = 16%), atrial septal defect ostium secundum type (3/19 = 16%), conotruncal heart defects (3/19 = 16%). Additional CHDs diagnosed in single patients included aortic dilatation with mitral anomaly and hypoplastic left heart syndrome. We also reviewed CHDs in patients with a molecular diagnosis of Kabuki syndrome reported in the literature. In conclusion, a CHD is detected in 70% of patients with KMT2D (MLL2) pathogenic variants, most commonly left-sided obstructive lesions, including multiple left-sided obstructions similar to those observed in the spectrum of the Shone complex, and septal defects. Clinical management of Kabuki syndrome should include echocardiogram at the time of diagnosis, with particular attention to left-sided obstructive lesions and mitral anomalies, and annual monitoring for aortic arch dilatation. © 2017 Wiley Periodicals, Inc.

Three molecular pathways model colorectal carcinogenesis in Lynch syndrome.

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Ahadova, Aysel; Gallon, Richard; Gebert, Johannes; Ballhausen, Alexej; Endris, Volker; Kirchner, Martina; Stenzinger, Albrecht; Burn, John; von Knebel Doeberitz, Magnus; Bläker, Hendrik; Kloor, Matthias

2018-07-01

Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes. MMR deficiency has long been regarded as a secondary event in the pathogenesis of Lynch syndrome colorectal cancers. Recently, this concept has been challenged by the discovery of MMR-deficient crypt foci in the normal mucosa. We aimed to reconstruct colorectal carcinogenesis in Lynch syndrome by collecting molecular and histology evidence from Lynch syndrome adenomas and carcinomas. We determined the frequency of MMR deficiency in adenomas from Lynch syndrome mutation carriers by immunohistochemistry and by systematic literature analysis. To trace back the pathways of pathogenesis, histological growth patterns and mutational signatures were analyzed in Lynch syndrome colorectal cancers. Literature and immunohistochemistry analysis demonstrated MMR deficiency in 491 (76.7%) out of 640 adenomas (95% CI: 73.3% to 79.8%) from Lynch syndrome mutation carriers. Histologically normal MMR-deficient crypts were found directly adjacent to dysplastic adenoma tissue, proving their role as tumor precursors in Lynch syndrome. Accordingly, mutation signature analysis in Lynch colorectal cancers revealed that KRAS and APC mutations commonly occur after the onset of MMR deficiency. Tumors lacking evidence of polypous growth frequently presented with CTNNB1 and TP53 mutations. Our findings demonstrate that Lynch syndrome colorectal cancers can develop through three pathways, with MMR deficiency commonly representing an early and possibly initiating event. This underlines that targeting MMR-deficient cells by chemoprevention or vaccines against MMR deficiency-induced frameshift peptide neoantigens holds promise for tumor prevention in Lynch syndrome. © 2018 UICC.

[Economy class syndrome].

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Morio, Hiroshi

2003-10-01

Economy class syndrome is venous thromboembolism following air travel. This syndrome was firstly reported in 1946, and many cases have been reported since 1990s. Low air pressure and low humidity in the aircraft cabin may contribute to the mechanism of this syndrome. Risk factors for venous thrombosis in the plane were old age, small height, obesity, hormonal therapy, malignancy, smoking, pregnancy or recent parturition, recent trauma or operation, chronic disease and history of venous thrombosis. In Japan, the feminine gender is also risk factor though reason was not well known. For prophylaxis, adequate fluid intake and leg exercise are recommended to all passengers. For passengers with high risk, prophylactic measures such as compression stockings, aspirin or low molecular weight heparin should be considered.

Targeted next generation sequencing for molecular diagnosis of Usher syndrome.

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Aparisi, María J; Aller, Elena; Fuster-García, Carla; García-García, Gema; Rodrigo, Regina; Vázquez-Manrique, Rafael P; Blanco-Kelly, Fiona; Ayuso, Carmen; Roux, Anne-Françoise; Jaijo, Teresa; Millán, José M

2014-11-18

Usher syndrome is an autosomal recessive disease that associates sensorineural hearing loss, retinitis pigmentosa and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous. To date, 10 genes have been associated with the disease, making its molecular diagnosis based on Sanger sequencing, expensive and time-consuming. Consequently, the aim of the present study was to develop a molecular diagnostics method for Usher syndrome, based on targeted next generation sequencing. A custom HaloPlex panel for Illumina platforms was designed to capture all exons of the 10 known causative Usher syndrome genes (MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2, USH2A, GPR98, DFNB31 and CLRN1), the two Usher syndrome-related genes (HARS and PDZD7) and the two candidate genes VEZT and MYO15A. A cohort of 44 patients suffering from Usher syndrome was selected for this study. This cohort was divided into two groups: a test group of 11 patients with known mutations and another group of 33 patients with unknown mutations. Forty USH patients were successfully sequenced, 8 USH patients from the test group and 32 patients from the group composed of USH patients without genetic diagnosis. We were able to detect biallelic mutations in one USH gene in 22 out of 32 USH patients (68.75%) and to identify 79.7% of the expected mutated alleles. Fifty-three different mutations were detected. These mutations included 21 missense, 8 nonsense, 9 frameshifts, 9 intronic mutations and 6 large rearrangements. Targeted next generation sequencing allowed us to detect both point mutations and large rearrangements in a single experiment, minimizing the economic cost of the study, increasing the detection ratio of the genetic cause of the disease and improving the genetic diagnosis of Usher syndrome patients.

Clinicopathologic, Immunohistochemical, and Molecular Features of Histiocytoid Sweet Syndrome.

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Alegría-Landa, Victoria; Rodríguez-Pinilla, Socorro María; Santos-Briz, Angel; Rodríguez-Peralto, José Luis; Alegre, Victor; Cerroni, Lorenzo; Kutzner, Heinz; Requena, Luis

2017-07-01

Histiocytoid Sweet syndrome is a rare histopathologic variant of Sweet syndrome. The nature of the histiocytoid infiltrate has generated considerable controversy in the literature. The main goal of this study was to conduct a comprehensive overview of the immunohistochemical phenotype of the infiltrate in histiocytoid Sweet syndrome. We also analyze whether this variant of Sweet syndrome is more frequently associated with hematologic malignancies than classic Sweet syndrome. This is a retrospective case series study of the clinicopathologic, immunohistochemical, and molecular features of 33 patients with a clinicopathologic diagnosis of histiocytoid Sweet syndrome was conducted in the dermatology departments of 5 university hospitals and a private laboratory of dermatopathology. The clinical, histopathological, immunohistochemical, and follow-up features of 33 patients with histiocytoid Sweet syndrome were analyzed. In some cases, cytogenetic studies of the dermal infiltrate were also performed. We compare our findings with those of the literature. The dermal infiltrate from the 33 study patients (20 female; median age, 49 years; age range, 5-93 years; and 13 male; median age, 42 years; age range, 4-76 years) was mainly composed of myeloperoxidase-positive immature myelomonocytic cells with histiocytoid morphology. No cytogenetic anomalies were found in the infiltrate except in 1 case in which neoplastic cells of chronic myelogenous leukemia were intermingled with the cells of histiocytoid Sweet syndrome. Authentic histiocytes were also found in most cases, with a mature immunoprofile, but they appeared to be a minor component of the infiltrate. Histiocytoid Sweet syndrome was not more frequently related with hematologic malignancies than classic neutrophilic Sweet syndrome. The dermal infiltrate of cutaneous lesions of histiocytoid Sweet syndrome is composed mostly of immature cells of myeloid lineage. This infiltrate should not be interpreted as leukemia cutis.

Nance-Horan syndrome: a contiguous gene syndrome involving deletion of the amelogenin gene? A case report and molecular analysis.

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Franco, E; Hodgson, S; Lench, N; Roberts, G J

1995-03-01

A case of Nance-Horan syndrome in a male is presented, with some features of the condition in his carrier mother and her mother. It is proposed that Nance-Horan syndrome might be a contiguous gene syndrome mapping to chromosome Xp21.2-p22.3. The proband had congenital cataract microphthalmia and dental abnormalities including screwdriver shaped incisors and evidence of enamel pitting hypoplasia. The region Xp21.2-p22.3 also contains the tooth enamel protein gene, amelogenin (AMGX). Using molecular genetic techniques, we have shown that there is no evidence that the AMGX gene is deleted in this case of the Nance-Horan syndrome.

Churg-Strauss vasculitis and idiopathic hypereosinophyl syndrome: role of molecular biology in the differential diagnosis of hypereosinophyl syndrome

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A. d'Ascanio

2011-09-01

Full Text Available Objective: Hypereosinophilic syndromes are a heterogeneous group of uncommon disorders characterized by the presence of marked peripheral blood eosinophilia, tissue eosinophilia, or both, resulting in a wide variety of clinical manifestations, often without an identifiable cause. Churg-Strauss syndrome is a systemic vasculitis characterized by prominent peripheral eosinophilia, asthma and systemic involvement. The presence of mild to severe eosinophilia and systemic involvement raise the search of many trigger factor that need to be ruled out. Distinguishing CSS from idiopathic hypereosinophilic syndrome may be particularly challenging, especially in ANCA negative patients. Methods: The aim of the present study was to present a small case series of patients referred to a Rheumatology Unit for mild to severe eosinophilia and signs and symptoms of systemic involvement and to outline the clinical significance of molecular biology in the work-up of hypereosinophilia. Results: Eleven patients with moderate to severe peripheral eosinophylia, were referred to our Unit from 1996 to 2007. Female to male ratio was 7/4, mean age 40.54 (range 22-75. Three out of eleven patients resulted positive for molecular biology. The diagnosis of idiopathic hypereosinophylia was confirmed in one out of three on the basis of the clinical picture and bone marrow biopsy. Conclusions: Molecular biology may be useful in the screening and in the follow-up of a new hypereosinophylic patient.

Dissecting molecular stress networks: identifying nodes of divergence between life-history phenotypes.

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Schwartz, Tonia S; Bronikowski, Anne M

2013-02-01

The complex molecular network that underlies physiological stress response is comprised of nodes (proteins, metabolites, mRNAs, etc.) whose connections span cells, tissues and organs. Variable nodes are points in the network upon which natural selection may act. Thus, identifying variable nodes will reveal how this molecular stress network may evolve among populations in different habitats and how it might impact life-history evolution. Here, we use physiological and genetic assays to test whether laboratory-born juveniles from natural populations of garter snakes (Thamnophis elegans), which have diverged in their life-history phenotypes, vary concomitantly at candidate nodes of the stress response network, (i) under unstressed conditions and (ii) in response to an induced stress. We found that two common measures of stress (plasma corticosterone and liver gene expression of heat shock proteins) increased under stress in both life-history phenotypes. In contrast, the phenotypes diverged at four nodes both under unstressed conditions and in response to stress: circulating levels of reactive oxygen species (superoxide, H(2)O(2)); liver gene expression of GPX1 and erythrocyte DNA damage. Additionally, allele frequencies for SOD2 diverge from neutral markers, suggesting diversifying selection on SOD2 alleles. This study supports the hypothesis that these life-history phenotypes have diverged at the molecular level in how they respond to stress, particularly in nodes regulating oxidative stress. Furthermore, the differences between the life-history phenotypes were more pronounced in females. We discuss the responses to stress in the context of the associated life-history phenotype and the evolutionary pressures thought to be responsible for divergence between the phenotypes. © 2012 Blackwell Publishing Ltd.

Medial tibial stress syndrome can be diagnosed reliably using history and physical examination

NARCIS (Netherlands)

Winters, M.; Bakker, E. W. P.; Moen, M. H.; Barten, C. C.; Teeuwen, R.; Weir, A.

2017-01-01

The majority of sporting injuries are clinically diagnosed using history and physical examination as the cornerstone. There are no studies supporting the reliability of making a clinical diagnosis of medial tibial stress syndrome (MTSS). Our aim was to assess if MTSS can be diagnosed reliably, using

Overlap of PIV syndrome, VACTERL and Pallister-Hall syndrome: clinical and molecular analysis.

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Killoran, C E; Abbott, M; McKusick, V A; Biesecker, L G

2000-07-01

The polydactyly, imperforate anus, vertebral anomalies syndrome (PIV, OMIM 174100) was determined as a distinct syndrome by Say and Gerald in 1968 (Say B, Gerald PS. Lancet 1968: 2: 688). We noted that the features of PIV overlap with the VATER association and Pallister-Hall syndrome (PHS, OMIM 146510), which includes polydactyly, (central or postaxial), shortened fingers, hypoplastic nails, renal anomalies, imperforate anus, and hypothalamic hamartoma. Truncation mutations in GL13, a zinc finger transcription factor gene, have been shown to cause PHS. We performed a molecular evaluation on a patient diagnosed with PIV, whose mother, grandfather, and maternal aunt had similar malformations. We sequenced the GLI3 gene in the patient to determine if she had a mutation. The patient was found to have a deletion in nucleotides 2188-2207 causing a frameshift mutation that predicts a truncated protein product of the gene. Later clinical studies demonstrated that the patient also has a hypothalamic hamartoma, a finding in PHS. We concluded that this family had atypical PHS and not PIV. This result has prompted us to re-evaluate the PIV literature to see if PIV is a valid entity. Based on these data and our examination of the literature, we conclude that PIV is not a valid diagnostic entity. We conclude that patients diagnosed with PIV should be reclassified as having VACTERL, or PHS, or another syndrome with overlapping malformations.

The Importance of the Family History in Caring for Families With Long QT Syndrome and Dilated Cardiomyopathy

NARCIS (Netherlands)

Ruiter, J.S.; Berkenbosch-Nieuwhof, K.; van den Berg, M.P.; van Dijk, R.; Middel, B.; van Tintelen, J.P.

In potentially inherited cardiac diseases, the family history is of great importance. We looked at the way cardiologists take a family history in patients with idiopathic dilated cardiomyopathy (DCM) or long QT syndrome (LQTS) and whether this led to screening of relatives or other follow-up. We

Hyperactivity: nature of the syndrome and its natural history.

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Aman, M G

1984-03-01

The composition of hyperactivity as a syndrome is discussed from a historical perspective, and the principal events leading to the recent emphasis on attentional characteristics of hyperactive children are summarized. Some of the major challenges to the legitimacy of hyperactivity as a valid syndrome are set forth, and after critical examination of the most influential work, it is concluded that hyperactivity has not been disproved. This is followed by a survey of the large follow-up literature dealing with the natural history of children diagnosed as hyperactive. It is noted that the manifestations of the syndrome appear to change with age but there is little indication that problems simply remit with maturity. The evidence indicates that hyperactivity, as diagnosed in the past, is often a serious disorder with long-term and far-reaching consequences for the children and their families. Multivariate studies are also discussed, as they have important implications for differential outcome. Different symptoms such as aggression, overactivity, and learning disability appear to contain unique information about current and future status, and therefore it appears useful to retain these distinctions rather than view such children as part of an undifferentiated group. It is unknown whether the recent guidelines for diagnosing Attention Deficit Disorder with Hyperactivity will alter or refine the outlook for children so identified, but this is an active area of research at present.

Colorectal choriocarcinoma in a patient with probable Lynch syndrome

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Viktor Hendrik Koelzer

2016-11-01

Full Text Available Background: Personalized therapy of colorectal cancer (CRC is influenced by morphological, molecular and host-related factors. Here we report the comprehensive clinicopathological and molecular analysis of a pure extra-gestational colorectal choriocarcinoma in a patient with probable Lynch syndrome.Case presentation: A 61 year old female with history of gastric cancer at age 36 presented with a transmurally invasive tumor of the right hemicolon and liver metastasis. A right hemicolectomy was performed. Histopathological analysis showed a mixed trophoblastic and syncytiotrophoblastic differentiation, consistent with choriocarcinoma. Disease progression was rapid under oxaliplatin, capecitabine, irinotecan (XELOXIRI and bevacizumab. Molecular phenotyping identified loss of the mismatch-repair (MMR protein PMS2, microsatellite instability, a lack of MLH1 promoter methylation and lack of of BRAF mutation suggestive of Lynch-Syndrome. Targeted next generation sequencing revealed an Ataxia Telangiectasia Mutated (ATM p.P604S missense mutation. A bleomycin, etoposide and cisplatin (BEP treatment protocol targeting germ-cell neoplasia lead to disease remission and prolonged survival of 34 months.Conclusions: Comprehensive immunohistochemical and genetic testing is essential to identify uncommon cancers possibly related to Lynch syndrome. For rare tumors, personalized therapeutic approaches should take both molecular and morphological information into account.Key words: Colorectal cancer, choriocarcinoma, histopathology, prognostic factors, Lynch syndrome, microsatellite instability, ataxia telangiectasia mutated, molecular pathology, next generation sequencing, personalized medicine

History, genetics, and strategies for cancer prevention in Lynch syndrome.

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Kastrinos, Fay; Stoffel, Elena M

2014-05-01

Colorectal cancer (CRC) is the most common gastrointestinal malignancy and the third cause of cancer death in men and women in the United States. The majority of CRC cases diagnosed annually are due to sporadic events, but up to 6% are attributed to known monogenic disorders that confer a markedly increased risk for the development of CRC and multiple extracolonic malignancies. Lynch syndrome is the most common inherited CRC syndrome and is associated with mutations in DNA mismatch repair genes, mainly MLH1 and MSH2 but also MSH6, PMS2, and EPCAM. Although the risk of CRC and endometrial cancer may approach near 75% and 50%, respectively, in gene mutation carriers, the identification of these individuals and at-risk family members through predictive genetic testing provides opportunities for cancer prevention including specialized cancer screening, intensified surveillance, and/or prophylactic surgeries. This article will provide a review of the major advances in risk assessment, molecular genetics, DNA mutational analyses, and cancer prevention and management made since Lynch syndrome was first described 100 years ago. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

[Wolfram syndrome: clinical and genetic analysis in two sisters].

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Conart, J-B; Maalouf, T; Jonveaux, P; Guerci, B; Angioi, K

2011-10-01

Wolfram syndrome is a severe genetic disorder defined by the association of diabetes mellitus, optic atrophy, deafness, and diabetes insipidus. Two sisters complained of progressive visual loss. Fundus examination evidenced optic atrophy. Their past medical history revealed diabetes mellitus and deafness since childhood. The association of these symptoms made the diagnosis of Wolfram syndrome possible. It was confirmed by molecular analysis, which evidenced composite WFS1 heterozygous mutations inherited from both their mother and father. Ophthalmologists should be aware of the possibility of Wolfram syndrome when diagnosing optic atrophy in diabetic children. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Gastric tumours in hereditary cancer syndromes: clinical features, molecular biology and strategies for prevention.

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Sereno, María; Aguayo, Cristina; Guillén Ponce, Carmen; Gómez-Raposo, César; Zambrana, Francisco; Gómez-López, Miriam; Casado, Enrique

2011-09-01

Gastric cancer is the major cause of cancer-related deaths worldwide. The majority of them are classified as sporadic, whereas the remaining 10% exhibit familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the most important condition that leads to hereditary gastric cancer. However, other hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and hereditary breast and ovarian cancer, entail a higher risk compared to the general population for developing this kind of neoplasia. In this review, we describe briefly the most important aspects related to clinical features, molecular biology and strategies for prevention in hereditary gastric associated to different cancer syndromes.

Avoiding pitfalls in molecular genetic testing: case studies of high-resolution array comparative genomic hybridization testing in the definitive diagnosis of Mowat-Wilson syndrome.

Science.gov (United States)

Kluk, Michael Joseph; An, Yu; James, Philip; Coulter, David; Harris, David; Wu, Bai-Lin; Shen, Yiping

2011-05-01

The molecular testing options available for the diagnosis of genetic disorders are numerous and include a variety of different assay platforms. The consultative input of molecular pathologists and cytogeneticists, working closely with the ordering clinicians, is often important for definitive diagnosis. Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology. Initial molecular testing in both cases was negative, but the application of high-resolution array comparative genomic hybridization technology lead to definitive diagnosis in both cases. We summarize the clinical findings and molecular testing in each case, discuss the differential diagnoses, and review the clinical and pathological findings of Mowat-Wilson syndrome. This report highlights the importance for those involved in molecular testing to know the nature of the underlying genetic abnormalities associated with the suspected diagnosis, to recognize the limitations of each testing platform, and to persistently pursue repeat testing using high-resolution technologies when indicated. This concept is applicable to both germline and somatic molecular genetic testing. Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Natural history of the classical form of primary growth hormone (GH) resistance (Laron syndrome).

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Laron, Z

1999-04-01

A description of the clinical, biochemical and endocrinological features of the classical form of the syndrome of primary growth hormone (GH) resistance (Laron syndrome) is presented including the progressive changes during follow-up from infancy into adulthood. The main diagnostic features are: severe growth retardation, acromicria, small gonads and genitalia, and obesity. Serum GH levels are elevated and insulin-like growth factor-I (IGF-I) values are low and do not rise upon stimulation by exogenous hGH. The pathogenesis of this syndrome is due to various molecular defects from exon deletion to nonsense, frameshift, splice and missense mutations in the GH receptor (GH-R) gene or in its post-receptor pathways.

Next generation sequencing for molecular confirmation of hereditary sudden cardiac death syndromes.

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Márquez, Manlio F; Cruz-Robles, David; Ines-Real, Selene; Vargas-Alarcón, Gilberto; Cárdenas, Manuel

2015-01-01

Hereditary sudden cardiac death syndromes comprise a wide range of diseases resulting from alteration in cardiac ion channels. Genes involved in these syndromes represent diverse mutations that cause the altered encoding of the diverse proteins constituting these channels, thus affecting directly the currents of the corresponding ions. In the present article we will briefly review how to arrive to a clinical diagnosis and we will present the results of molecular genetic studies made in Mexican subjects attending the SCD Syndromes Clinic of the National Institute of Cardiology of Mexico City. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Some aspects of molecular diagnostics in Lynch syndrome

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Kurzawski Grzegorz

2006-12-01

Full Text Available Abstract This manuscript is composed of five parts which summarize five publications in succession. Essentially, they are concerned with molecular diagnostics of Lynch syndrome and are based on studies in 238 families. The finding that young age at diagnosis is the key feature in patients with MSH2 and MLH1 mutations (Part 1 has helped to define simple criteria for the preliminary diagnosis of this syndrome. A cheaper method for the detection of mutations has been developed (Part 2 and applied to study the types of mutations and their prevalence in Poland (Part 3 and the Baltic States (Part 4. A specific feature of these mutations, i.e. presence of recurrent mutations in the majority of affected families with mutations, has suggested the feasibility of effective diagnostics with a single test disclosing all of them. An attempt to reveal other causes of familial aggregation of colorectal cancer has ruled out any association with C insertion in the NOD2 gene (Part 5.

Natural history of Wolff-Parkinson-White syndrome diagnosed in childhood.

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Cain, Nicole; Irving, Claire; Webber, Steven; Beerman, Lee; Arora, Gaurav

2013-10-01

Wolff-Parkinson-White (WPW) syndrome carries a risk for symptomatic arrhythmias and sudden death. The aim of this study was to examine the natural history of patients with Wolff-Parkinson-White syndrome diagnosed in childhood followed longitudinally at a single institution. The study population consisted of 446 patients. The median age of diagnosis was 7 years, and 61% were male. Associated heart disease was present in 40 patients (9%). Modes of presentation included supraventricular tachycardia (38%), palpitations (22%), chest pain (5%), syncope (4%), atrial fibrillation (0.4%), sudden death (0.2%), and incidental findings (26%); data were unavailable in 4%. During the study period, a total of 243 patients (54%) had supraventricular tachycardia, and 7 patients (1.6%) had atrial fibrillation. Of patients who presented at ≤3 months of age, 35% had resolution of manifest preexcitation compared with 5.8% who presented at >3 months of age (p Wolff-Parkinson-White syndrome diagnosed in childhood, 64% had symptoms at presentation, and an additional 20% developed symptoms during follow-up. There were 6 sudden deaths (1.3%), with an overall incidence of 1.1 per 1,000 patient-years in patients with structurally normal hearts and 27 per 1,000 patient-years in patients with associated heart disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Primary Molecular Disorders and Secondary Biological Adaptations in Bartter Syndrome

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Deschênes, Georges; Fila, Marc

2011-01-01

Bartter syndrome is a hereditary disorder that has been characterized by the association of hypokalemia, alkalosis, and the hypertrophy of the juxtaglomerular complex with secondary hyperaldosteronism and normal blood pressure. By contrast, the genetic causes of Bartter syndrome primarily affect molecular structures directly involved in the sodium reabsorption at the level of the Henle loop. The ensuing urinary sodium wasting and chronic sodium depletion are responsible for the contraction of the extracellular volume, the activation of the renin-aldosterone axis, the secretion of prostaglandins, and the biological adaptations of downstream tubular segments, meaning the distal convoluted tubule and the collecting duct. These secondary biological adaptations lead to hypokalemia and alkalosis, illustrating a close integration of the solutes regulation in the tubular structures. PMID:21941653

Primary Molecular Disorders and Secondary Biological Adaptations in Bartter Syndrome

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Georges Deschênes

2011-01-01

Full Text Available Bartter syndrome is a hereditary disorder that has been characterized by the association of hypokalemia, alkalosis, and the hypertrophy of the juxtaglomerular complex with secondary hyperaldosteronism and normal blood pressure. By contrast, the genetic causes of Bartter syndrome primarily affect molecular structures directly involved in the sodium reabsorption at the level of the Henle loop. The ensuing urinary sodium wasting and chronic sodium depletion are responsible for the contraction of the extracellular volume, the activation of the renin-aldosterone axis, the secretion of prostaglandins, and the biological adaptations of downstream tubular segments, meaning the distal convoluted tubule and the collecting duct. These secondary biological adaptations lead to hypokalemia and alkalosis, illustrating a close integration of the solutes regulation in the tubular structures.

Diabetes risk in women with gestational diabetes mellitus and a history of polycystic ovary syndrome: a retrospective cohort study.

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Bond, R; Pace, R; Rahme, E; Dasgupta, K

2017-12-01

To investigate whether polycystic ovary syndrome further increases postpartum diabetes risk in women with gestational diabetes mellitus and to explore relationships between polycystic ovary syndrome and incident diabetes in women who do not develop gestational diabetes. This retrospective cohort study (Quebec Physician Services Claims; Hospitalization Discharge Databases; Birth and Death registries) included 34 686 women with gestational diabetes during pregnancy (live birth), matched 1:1 to women without gestational diabetes by age group, year of delivery and health region. Diagnostic codes were used to define polycystic ovary syndrome and incident diabetes. Cox regression models were used to examine associations between polycystic ovary syndrome and incident diabetes. Polycystic ovary syndrome was present in 1.5% of women with gestational diabetes and 1.2% of women without gestational diabetes. There were more younger mothers and mothers who were not of white European ancestry among those with polycystic ovary syndrome. Those with polycystic ovary syndrome more often had a comorbidity and a lower proportion had a previous pregnancy. Polycystic ovary syndrome was associated with incident diabetes (hazard ratio 1.52; 95% CI 1.27, 1.82) among women with gestational diabetes. No conclusive associations between polycystic ovary syndrome and diabetes were identified (hazard ratio 0.94; 95% CI 0.39, 2.27) in women without gestational diabetes. In women with gestational diabetes, polycystic ovary syndrome confers additional risk for incident diabetes postpartum. In women without gestational diabetes, an association between PCOS and incident diabetes was not observed. Given the already elevated risk of diabetes in women with a history of gestational diabetes, a history of both polycystic ovary syndrome and gestational diabetes signal a critical need for diabetes surveillance and prevention. © 2017 Diabetes UK.

A further case of a Prader-Willi syndrome phenotype in a patient with Angelman syndrome molecular defect

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De Molfetta Greice Andreotti

2002-01-01

Full Text Available Angelman syndrome (AS and Prader-Willi syndrome (PWS are distinct human neurogenetic disorders; however, a clinical overlap between AS and PWS has been identified. We report on a further case of a patient showing the PWS phenotype with the AS molecular defect. Despite the PWS phenotype, the DNA methylation analysis of SNRPN revealed an AS pattern. Cytogenetic and FISH analysis showed normal chromosomes 15 and microsatellite analysis showed heterozygous loci inside and outside the 15q11-13 region. The presence of these atypical cases could be more frequent than previously expected and we reinforce that the DNA methylation analysis is important for the correct diagnosis of severe mental deficiency, congenital hypotonia and obesity.

The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives

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Bosch Annet M

2012-10-01

Full Text Available Abstract The Brown-Vialetto-Van Laere syndrome is a rare neurological disorder which may present at all ages with sensorineural deafness, bulbar palsy and respiratory compromise. Fazio-Londe syndrome is considered to be the same disease entity. Recently it was demonstrated that in some patients the disease is caused by mutations in the SLC52A3 gene which encodes the intestinal (hRFT2 riboflavin transporter. In these patients riboflavin deficiency is the cause of the BVVL/FL syndrome and supplementation of riboflavin proved a life saving treatment. Mutations in the SLC52A2 gene and the SLC52A1 (GPR172B gene, coding for human riboflavin transporters hRFT3 and hRFT1 have been associated with the BVVL syndrome as well. We performed a review of the literature, with emphasis on the natural history and the effects of treatment in these patients. A total of 35 publications were traced reporting on the clinical presentation of 74 patients who presented before age 18. The most prevalent symptoms were bulbar palsy, hearing loss, facial weakness and respiratory compromise. Death was reported in 28 of the 61 untreated patients, with a very low survival in patients presenting before age 4. All 13 patients who were treated with riboflavin survived, with a strong clinical improvement after days to months of treatment in eight patients. Three patients demonstrated a stable clinical course and treatment was stopped early in two patients. Abnormalities in plasma flavin levels and/or plasma acylcarnitine profiles were observed in some but not in all patients, and also patients with normal plasma flavin levels and acylcarnitine profiles demonstrated a striking clinical improvement on riboflavin supplementation. It is now clear that proper diagnosis requires mutation analysis of all three transporter genes and treatment should be started immediately without first awaiting results of molecular analysis. Clinical improvement may be rapid or gradual over a period of

Rett syndrome diagnostic criteria: lessons from the Natural History Study.

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Percy, Alan K; Neul, Jeffrey L; Glaze, Daniel G; Motil, Kathleen J; Skinner, Steven A; Khwaja, Omar; Lee, Hye-Seung; Lane, Jane B; Barrish, Judy O; Annese, Fran; McNair, Lauren; Graham, Joy; Barnes, Katherine

2010-12-01

Analysis of 819 participants enrolled in the Rett syndrome (RTT) Natural History Study validates recently revised diagnostic criteria. 765 females fulfilled 2002 consensus criteria for classic (653/85.4%) or variant (112/14.6%) RTT. All participants classified as classic RTT fulfilled each revised main criterion; supportive criteria were not uniformly present. All variant RTT participants met at least 3 of 6 main criteria in the 2002, 2 of 4 main criteria in the current format, and 5 of 11 supportive criteria in both. This analysis underscores the critical role of main criteria for classic RTT; variant RTT requires both main and supportive criteria.

[Long QT syndrome. History, genetics, clinical symptoms, causes and therapy].

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Krönauer, T; Friederich, P

2015-08-01

The long QT syndrome is caused by a change in cardiac repolarization due to functional ion channel defects. A differentiation is made between a congenital (cLQTS) and an acquired (aLQTS) form of the disease. The disease results in the name-giving prolongation of the QT interval in the electrocardiogram and represents a predisposition for cardiac arrhythmia and sudden cardiac death. This article summarizes the current knowledge on the history, pathophysiology, clinical symptoms and therapy of cLQTS and aLQTS. This knowledge of pathophysiological features of the symptoms allows the underlying anesthesiological approach for individualized perioperative concepts for patients suffering from LQTS to be derived.

[Familial Wolfram syndrome].

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Bessahraoui, M; Paquis, V; Rouzier, C; Bouziane-Nedjadi, K; Naceur, M; Niar, S; Zennaki, A; Boudraa, G; Touhami, M

2014-11-01

Wolfram syndrome (WS) is a rare autosomal recessive progressive neurodegenerative disorder, and it is mainly characterized by the presence of diabetes mellitus and optic atrophy. Other symptoms such as diabetes insipidus, deafness, and psychiatric disorders are less frequent. The WFS1 gene, responsible for the disease and encoding for a transmembrane protein called wolframin, was localized in 1998 on chromosome 4p16. In this report, we present a familial observation of Wolfram syndrome (parents and three children). The propositus was a 6-year-old girl with diabetes mellitus and progressive visual loss. Her family history showed a brother with diabetes mellitus, optic atrophy, and deafness since childhood and a sister with diabetes mellitus, optic atrophy, and bilateral hydronephrosis. Thus, association of these familial and personal symptoms is highly suggestive of Wolfram syndrome. The diagnosis was confirmed by molecular analysis (biology), which showed the presence of WFS1 homozygous mutations c.1113G>A (p.Trp371*) in the three siblings and a heterozygote mutation in the parents. Our observation has demonstrated that pediatricians should be aware of the possibility of Wolfram syndrome when diagnosing optic atrophy in diabetic children. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Relationship between Metabolic Syndrome and History of Cervical Cancer among a US National Population.

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Penaranda, Eribeth K; Shokar, Navkiran; Ortiz, Melchor

2013-01-01

The metabolic changes present in the metabolic syndrome (MetS) have been associated with increased risk of pancreatic and colon cancers; however, there is little information about the association between MetS and cervical cancer risk. We performed a case-control study using data from the National Health and Nutrition Examination Survey (NHANES) between 1999-2010. We identified women 21 years of age and older, of which an estimated 585,924 (2.3% of the sample) self-reported a history of cervical cancer (cases). About half (48.6%) of cases and 33.2% of controls met criteria for MetS. Logistic regression analysis showed increased odds of history of cervical cancer among women with MetS (OR = 1.9; 95% CI 1.06, 3.42; P value ≤ 0.05) for the risk of history of cervical cancer among women with MetS while adjusting for other known risk factors (high number of lifetime sexual partners, multiparty, history of hormonal contraceptive use, and history of smoking) (AOR = 1.82; 95% CI 1.02, 3.26; P value ≤ 0.05). In this US surveyed population we found increased odds of history of cervical cancer among subjects with MetS.

Adrenal Surgery for Cushing's Syndrome: An Update.

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Di Dalmazi, Guido; Reincke, Martin

2018-06-01

Recent advances in the molecular pathogenesis and the natural history of Cushing's syndrome have improved the understanding of the management of this disease. The long-term efficacy of several cortisol-lowering medical treatments is currently under evaluation. However, adrenalectomy is a safe option for the treatment of patients affected by Cushing's syndrome. Unilateral adrenalectomy is the gold standard for treatment of adrenocortical adenomas associated with hypercortisolism. Bilateral adrenalectomy has been widely used in the past as definitive treatment of bilateral macronodular hyperplasia and persistent or recurrent Cushing's disease. The indication and the potential applications of this technique have been recently critically analyzed. Copyright © 2018 Elsevier Inc. All rights reserved.

Usher syndrome (sensorineural deafness and retinitis pigmentosa): pathogenesis, molecular diagnosis and therapeutic approaches.

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Bonnet, Crystel; El-Amraoui, Aziz

2012-02-01

Usher syndrome (USH) is the most prevalent cause of hereditary deafness-blindness in humans. In this review, we pinpoint new insights regarding the molecular mechanisms defective in this syndrome, its molecular diagnosis and prospective therapies. Animal models wherein USH proteins were targeted at different maturation stages of the auditory hair cells have been engineered, shedding new light on the development and functioning of the hair bundle, the sound receptive structure. Improved protocols and guidelines for early molecular diagnosis of USH (USH genotyping microarrays, otochips and complete Sanger sequencing of the 366 coding exons of identified USH genes) have been developed. Approaches to alleviate or cure hearing and visual impairments have been initiated, leading to various degrees of functional rescuing. Whereas the mechanisms underlying hearing impairment in USH patients are being unraveled, showing in particular that USH1 proteins are involved in the shaping of the hair bundle and the functioning of the mechanoelectrical transduction machinery, the mechanisms underlying the retinal defects are still unclear. Efforts to improve clinical diagnosis have been successful. Yet, despite some encouraging results, further development of therapeutic approaches is necessary to ultimately treat this dual sensory defect.

Molecular medicine of fragile X syndrome: based on known molecular mechanisms.

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Luo, Shi-Yu; Wu, Ling-Qian; Duan, Ran-Hui

2016-02-01

Extensive research on fragile X mental retardation gene knockout mice and mutant Drosophila models has largely expanded our knowledge on mechanism-based treatment of fragile X syndrome (FXS). In light of these findings, several clinical trials are now underway for therapeutic translation to humans. Electronic literature searches were conducted using the PubMed database and ClinicalTrials.gov. The search terms included "fragile X syndrome", "FXS and medication", "FXS and therapeutics" and "FXS and treatment". Based on the publications identified in this search, we reviewed the neuroanatomical abnormalities in FXS patients and the potential pathogenic mechanisms to monitor the progress of FXS research, from basic studies to clinical trials. The pathological mechanisms of FXS were categorized on the basis of neuroanatomy, synaptic structure, synaptic transmission and fragile X mental retardation protein (FMRP) loss of function. The neuroanatomical abnormalities in FXS were described to motivate extensive research into the region-specific pathologies in the brain responsible for FXS behavioural manifestations. Mechanism-directed molecular medicines were classified according to their target pathological mechanisms, and the most recent progress in clinical trials was discussed. Current mechanism-based studies and clinical trials have greatly contributed to the development of FXS pharmacological therapeutics. Research examining the extent to which these treatments provided a rescue effect or FMRP compensation for the developmental impairments in FXS patients may help to improve the efficacy of treatments.

Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications

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Lynch, HT; Lynch, PM; Lanspa, SJ; Snyder, CL; Lynch, JF; Boland, CR

2010-01-01

More than one million patients will manifest colorectal cancer (CRC) this year of which, conservatively, approximately 3% (~30,700 cases) will have Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome. Each case belongs to a family with clinical needs that require genetic counseling, DNA testing for mismatch repair genes (most frequently MLH1 or MSH2) and screening for CRC. Colonoscopy is mandated, given CRC’s proximal occurrence (70–80% proximal to the splenic flexure). Due to its early age of onset (average 45 years of age), colonoscopy needs to start by age 25, and because of its accelerated carcinogenesis, it should be repeated every 1 to 2 years through age 40 and then annually thereafter. Should CRC occur, subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC. Because 40–60% of female patients will manifest endometrial cancer, tailored management is essential. Additional extracolonic cancers include ovary, stomach, small bowel, pancreas, hepatobiliary tract, upper uroepithelial tract, brain (Turcot variant) and sebaceous adenomas/carcinomas (Muir-Torre variant). LS explains only 10–25% of familial CRC. PMID:19659756

Clinical spectrum and molecular diagnosis of Angelman and Prader-Willi syndrome patients with an imprinting mutation

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Saitoh, S.; Cassidy, S.B.; Conroy, J.M. [Univ. of Hospitals of Cleveland, OH (United States)] [and others

1997-01-20

Recent studies have identified a new class of Prader-Willi syndrome (PWS) and Angelman syndrome (AS) patients who have biparental inheritance, but neither the typical deletion nor uniparental disomy (UPD) or translocation. However, these patients have uniparental DNA methylation throughout 15q11-q13, and thus appear to have a mutation in the imprinting process for this region. Here we describe detailed clinical findings of five AS imprinting mutation patients (three families) and two PWS imprinting mutation patients (one new family). All these patients have essentially the classical clinical phenotype for the respective syndrome, except that the incidence of microcephaly is lower in imprinting mutation AS patients than in deletion AS patients. Furthermore, imprinting mutation AS and PWS patients do not typically have hypopigmentation, which is commonly found in patients with the usual large deletion. Molecular diagnosis of these cases is initially achieved by DNA methylation analyses of the DN34/ZNF127, PW71 (D15S63), and SNRPN loci. The latter two probes have clear advantages in the simple molecular diagnostic analysis of PWS and AS patients with an imprinting mutation, as has been found for typical deletion or UPD PWS and AS cases. With the recent finding of inherited microdeletions in PWS and AS imprinting mutation families, our studies define a new class of these two syndromes. The clinical and molecular identification of these PWS and AS patients has important genetic counseling consequences. 49 refs., 4 figs., 3 tabs.

Natural History of Thyroid Function in Adults with Down Syndrome--10-Year Follow-Up Study

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Prasher, V.; Gomez, G.

2007-01-01

Background: The natural history of thyroid function in adults with Down syndrome (DS) is unknown. Method: This study investigated annual thyroid function tests in 200 adults with DS over a 10-year period. Results: Transient and persistent thyroid dysfunction was common. The 5- and 10-year incidence of definite hypothyroidism was 0.9%-1.64% and…

A Case of Bardet-Biedl Syndrome

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katayon Etemadi

2007-09-01

Full Text Available Etemadi K1, Khazaii MR2 1. MSC of Human Genetic, Molecular Medicine and Genetic department, Medical school, Hamadan University of medical sciences. 2. Assistant professor of Pediatric Urology Abstract Background: The Bardet Biedl syndrome is a heterogenous and autosomal recessive disorder. Primary features are: retinitis pigmentosa, obesity, polydactyly, mental retardation, renal abnormalities and hypogonadism. Renal failure is the major cause of death in homozygote patients, with chronic glomerolopathy that cause chronic renal disease. Secondary features are: speech disorder delay, developmental delay, polyuria, diabetes mellitus and hypertension. The diagnosis of Bardet- Biedl syndrome is established by clinical findings. Twelve genes are known to be associated with Bardet Biedl syndromes: BBS1, BBS2… BBS12. Case presentation: In this article we report a four and half year old boy that have Bardet Biedl syndrome as a result of a consanguine marriage (third degree. Conclusion: A monogenic syndrome such as Bardet Biedl has a lot of symptoms. These symptoms are out put of a mutation in locus of a recessive allel. Therefore people like to marry consanguinly have to do genetic counseling before marriage. Because analysis of family history will reduced the risk of such syndromes.

Ambras syndrome

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Sudhir Malwade

2015-01-01

Full Text Available Ambras syndrome, a form of congenital hypertrichosis lanuginosa, is extremely rare in neonates. It is characterized by typical pattern of hair distribution, dysmorphic facial features and a familial pattern of inheritance. We report a case of Ambras syndrome in a preterm neonate with history of consanguinity and positive family history.

Molecular changes preceding endometrial and ovarian cancer: a study of consecutive endometrial specimens from Lynch syndrome surveillance.

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Niskakoski, Anni; Pasanen, Annukka; Lassus, Heini; Renkonen-Sinisalo, Laura; Kaur, Sippy; Mecklin, Jukka-Pekka; Bützow, Ralf; Peltomäki, Päivi

2018-03-27

Molecular alterations preceding endometrial and ovarian cancer and the sequence of events are unknown. Consecutive specimens from lifelong surveillance for Lynch syndrome provides a natural setting to address such questions. To molecularly define the multistep gynecological tumorigenesis, DNA mismatch repair gene mutation carriers with endometrial or ovarian carcinoma or endometrial hyperplasia were identified from a nation-wide registry and endometrial biopsy specimens taken from these individuals during 20 years of screening were collected. A total of 213 endometrial and ovarian specimens from Lynch syndrome individuals and 197 histology-matched (non-serous) samples from sporadic cases were available for this investigation. The specimens were profiled for markers linked to endometrial and ovarian tumorigenesis, including ARID1A protein expression, mismatch repair status, and tumor suppressor gene promoter methylation. In Lynch syndrome-associated endometrial and ovarian carcinomas, ARID1A protein was lost in 61-100% and mismatch repair was deficient in 97-100%, compared to 0-17% and 14-44% in sporadic cases (P = 0.000). ARID1A loss appeared in complex hyperplasia and deficient mismatch repair and tumor suppressor gene promoter methylation in histologically normal endometrium. Despite quantitative differences between Lynch syndrome and sporadic cases, ARID1A expression, mismatch repair, and tumor suppressor gene promoter methylation divided endometrial samples from both patient groups into three categories of increasing abnormality, comprising normal endometrium and simple hyperplasia (I), complex hyperplasia with or without atypia (II), and endometrial cancer (III). Complex hyperplasias without vs. with atypia were molecularly indistinguishable. In conclusion, surveillance specimens from Lynch syndrome identify mismatch repair deficiency, tumor suppressor gene promoter methylation, and ARID1A loss as early changes in tumor development. Our findings are

Parent stress across molecular subtypes of children with Angelman syndrome.

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Miodrag, N; Peters, S

2015-09-01

Parenting stress has been consistently reported among parents of children with developmental disabilities. However, to date, no studies have investigated the impact of a molecular subtype of Angelman syndrome (AS) on parent stress, despite distinct phenotypic differences among subtypes. Data for 124 families of children with three subtypes of AS: class I and II deletions (n = 99), imprinting centre defects (IC defects; n = 11) and paternal uniparental disomy (UPD; n = 14) were drawn from the AS Rare Diseases Clinical Research Network (RDCRN) database and collected from five research sites across the Unites States. The AS study at the RDCRN gathered health information to understand how the syndrome develops and how to treat it. Parents completed questionnaires on their perceived psychological stress, the severity of children's aberrant behaviour and children's sleep patterns. Children's adaptive functioning and developmental levels were clinically evaluated. Child-related stress reached clinical levels for 40% of parents of children with deletions, 100% for IC defects and 64.3% for UPD. Sleep difficulties were similar and elevated across subtypes. There were no differences between molecular subtypes for overall child and parent-related stress. However, results showed greater isolation and lack of perceived parenting skills for parents of children with UPD compared with deletions. Better overall cognition for children with deletions was significantly related to more child-related stress while their poorer adaptive functioning was associated with more child-related stress. For all three groups, the severity of children's inappropriate behaviour was positively related to different aspects of stress. How parents react to stress depends, in part, on children's AS molecular subtype. Despite falling under the larger umbrella term of AS, it is important to acknowledge the unique aspects associated with children's molecular subtype. Identifying these factors can

Family history of type 2 diabetes and prevalence of metabolic syndrome in adult Asian Indians.

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Das, Mithun; Pal, Susil; Ghosh, Arnab

2012-04-01

Our objective was to test the association between familial risk of type 2 diabetes mellitus (T2DM) and the prevalence of metabolic syndrome (MS) in adult Asian Indians. A total of 448 adult (>30 years) individuals (257 males and 191 females) participated in the study. Familial risk of T2DM was classified into three groups viz., 1=both parents affected; 2=parent and/or siblings affected and 3=none or no family history for T2DM. Anthropometric measures, blood pressures, fasting blood glucose and metabolic profiles were studied using standard techniques. MS was defined accordingly. The prevalence of MS phenotypes was estimated and compared among the three familial risk strata. Individuals with a history of both parents affected from diabetes had significantly higher (Pfamily history of T2DM. Significant difference was also noticed between individuals with and without MS according to the family history of diabetes (Pfamily history of T2DM. Family history of T2DM had significant effect on individuals with MS as compared to their counterparts (individuals having no family history of T2DM). It therefore seems reasonable to argue that family history of T2DM could be useful as a predictive tool for early diagnosis and prevention of MS in Asian Indian population.

Diagnosing lynch syndrome in absence of colorectal cancer.

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Lynch, Henry T; Knezetic, Joseph; Lanspa, Stephen

2012-11-01

There are many ways in which a diagnosis of Lynch syndrome can be made, most prominent of which is family history, presence of cancer, high microsatellite instability, immunohistochemistry, and a mismatch repair germline mutation. There are at least four molecular pathways for colorectal cancer carcinogenesis: 1) adenoma-carcinoma sequence; 2) hereditary microsatellite instability; 3) serrated pathway; 4) epidermal growth factor receptor. The answer to diagnosing Lynch syndrome in the absence of colorectal cancer may be partially based upon the phenotypic characteristics of the colonic polyps should they be identified at colonoscopy, specifically their phenotypic characteristics of location, size, histology, number, and age of polyp onset.

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease

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Wei-Ming Xu

2018-01-01

Full Text Available Background: Ischemic heart disease (IHD has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated.Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures.Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules. These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620 and Renin-angiotensin system (hsa04614, with the molecular functions of angiotensin maturation (GO:0002003 and response to bacterium (GO:0009617, which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO and published biomedical literatures.Conclusion: A network medicine

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease.

Science.gov (United States)

Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

2018-01-01

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease

Science.gov (United States)

Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

2018-01-01

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine

Molecular Etiology of Hereditary Single-Side Deafness: Its Association With Pigmentary Disorders and Waardenburg Syndrome.

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Kim, Shin Hye; Kim, Ah Reum; Choi, Hyun Seok; Kim, Min Young; Chun, Eun Hi; Oh, Seung-Ha; Choi, Byung Yoon

2015-10-01

Unilateral sensorineural hearing loss (USNHL)/single-side deafness (SSD) is a frequently encountered disability in children. The etiology of a substantial portion of USNHL/SSD still remains unknown, and genetic causes have not been clearly elucidated. In this study, the authors evaluated the heritability of USNHL/SSD.The authors sequentially recruited 50 unrelated children with SSD. For an etiologic diagnosis, we performed a rigorous review on the phenotypes of family members of all children and conducted, if necessary, molecular genetic tests including targeted exome sequencing of 129 deafness genes.Among the 50 SSD children cohort, the authors identify 4 (8%) unrelated SSD probands from 4 families (SH136, SB173, SB177, and SB199) with another hearing impaired family members. Notably, all 4 probands in our cohort with a familial history of SSD also have pigmentary abnormalities such as brown freckles or premature gray hair within first degree relatives, which may indicate that genes whose products are involved with pigmentary disorder could be candidates for heritable SSD. Indeed, SH136 and SB199 turned out to segregate a mutation in MITF and PAX3, respectively, leading to a molecular diagnosis of Waardenburg syndrome (WS).We report, for the first time in the literature, a significant heritability of pediatric SSD. There is a strong association between the heritability of USNHL/SSD and the pigmentary abnormality, shedding a new light on the understanding of the molecular basis of heritable USNHL/SSD. In case of children with congenital SSD, it would be mandatory to rigorously screen pigmentary abnormalities. WS should also be included in the differential diagnosis of children with USNHL/SSD, especially in a familial form.

Comprehensive molecular diagnosis of a large cohort of Japanese retinitis pigmentosa and Usher syndrome patients by next-generation sequencing.

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Oishi, Maho; Oishi, Akio; Gotoh, Norimoto; Ogino, Ken; Higasa, Koichiro; Iida, Kei; Makiyama, Yukiko; Morooka, Satoshi; Matsuda, Fumihiko; Yoshimura, Nagahisa

2014-10-16

Retinitis pigmentosa (RP), a major cause of blindness in developed countries, has multiple causative genes; its prevalence differs by ethnicity. Usher syndrome is the most common form of syndromic RP and is accompanied by hearing impairment. Although molecular diagnosis is challenging, recent technological advances such as targeted high-throughput resequencing are efficient screening tools. We performed comprehensive molecular testing in 329 Japanese RP and Usher syndrome patients by using a custom capture panel that covered the coding exons and exon/intron boundaries of all 193 known inherited eye disease genes combined with Illumina HiSequation 2500. Candidate variants were screened using systematic data analyses, and their potential pathogenicity was assessed according to the frequency of the variants in normal populations, in silico prediction tools, and compatibility with known phenotypes or inheritance patterns. Molecular diagnoses were made in 115/317 RP patients (36.3%) and 6/12 Usher syndrome patients (50%). We identified 104 distinct mutations, including 66 novel mutations. EYS, USH2A, and RHO were common causative genes. In particular, mutations in EYS accounted for 15.0% of the autosomal recessive/simplex RP patients or 10.7% of the entire RP cohort. Among the 189 previously reported mutations detected in the current study, 55 (29.1%) were found commonly in Japanese or other public databases and were excluded from molecular diagnoses. By screening a large cohort of patients, this study catalogued the genetic variations involved in RP and Usher syndrome in a Japanese population and highlighted the different distribution of causative genes among populations. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Williams syndrome

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Williams-Beuren syndrome ... Williams syndrome is caused by not having a copy of several genes. It may be passed down in families. ... history of the condition. However, people with Williams syndrome have a 50% chance of passing the disorder ...

Familial occurrence of pigment dispersion syndrome.

Science.gov (United States)

Bovell, A M; Damji, K F; Dohadwala, A A; Hodge, W G; Allingham, R R

2001-02-01

Pigment dispersion syndrome affects up to 4% of the white population. It is characterized by the presence of transillumination defects, Krukenberg's spindle and dense trabecular meshwork pigmentation. Open-angle glaucoma will develop in as many as 50% of affected patients. In this study we describe the familial occurrence of pigment dispersion syndrome in six North American pedigrees and the phenotypic characteristics with respect to pigment dispersion syndrome and glaucoma. Probands with pigment dispersion syndrome were identified in glaucoma clinics at university eye centres in Ottawa and Durham, NC. Families with two or more affected members were evaluated. All willing members in each family underwent a thorough clinical examination and were classified as affected with pigment dispersion syndrome, suspect or unaffected. The previous medical records were reviewed to obtain the past medical and ocular history, including risk factors for glaucoma. All six families are white. Three families show at least two generations of affected members. Of the 43 subjects examined 58% were women. All 14 affected members showed moderate to heavy trabecular meshwork pigmentation and either Krukenberg's spindle or transillumination defects. The affected members were also considerably more myopic (mean spherical equivalent for the right eye -4.72 dioptres) than the suspect group or the unaffected group (mean spherical equivalent -0.79 D and +1.19 D respectively) (p pigment dispersion syndrome. Our ultimate goal is to identify the gene(s) that causes this disorder in order to clarify its molecular etiology and pathophysiology. This may give rise to a molecular classification of the disease as well as provide the foundation for genetic testing and new treatment approaches.

Chromosomal fragility syndrome and family history of radiosensitivity as indicators for radiotherapy dose modification

International Nuclear Information System (INIS)

Alsbeih, Ghazi; Story, Michael D.; Maor, Moshe H.; Geara, Fady B.; Brock, William A.

2003-01-01

Beside a few known radiosensitive syndromes, a patient's reaction to radiotherapy is difficult to predict. In this report we describe the management of a pediatric cancer patient presented with a family history of radiosensitivity and cancer proneness. Laboratory investigations revealed a chromosomal fragility syndrome and an increased cellular radiosensitivity in vitro. AT gene sequencing revealed no mutations. The patient was treated with reduced radiation doses to avoid the presumed increased risks of toxicity to normal tissues. The patient tolerated well the treatment with no significant acute or late radiation sequelae. Five years later, the patient remains both disease and complications free. While an accurate laboratory test for radiosensitivity is still lacking, assessments of chromosomal fragility, cell survival and clinical medicine will continue to be useful for a small number of patients

Facial palsy in Melkersson-Rosenthal syndrome and Bell's palsy: familial history and recurrence tendency.

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Sun, Baochun; Zhou, Chengyong; Han, Zeli

2015-02-01

The aim of this study was to compare genetic predilection and recurrence tendency between facial palsy in Melkersson-Rosenthal syndrome (MRS) and Bell's palsy We carried out an investigation on patients with facial palsy in MRS and those with Bell's palsy who visited the outpatient department in our hospital between February 2009 and February 2013. They were asked about familial history and whether it was the first episode, with the results recorded and compared. There were 16 patients with facial palsy in MRS and 860 patients with Bell's palsy involved in the study. Familial history was positive in 5 of 16 patients (31.3%) with facial palsy in MRS and 56 of 860 patients (6.5%) with Bell's palsy (P palsy in MRS and 88 of 860 cases (10.2%) with Bell's palsy had a history of facial palsy in the past (P Bell's palsy, facial palsy in MRS has an obvious genetic predilection and recurrence tendency. © The Author(s) 2014.

The familial hyperchylomicronemia syndrome: New insights into underlying genetic defects

Energy Technology Data Exchange (ETDEWEB)

Santamarina-Fojo, S.; Brewer, H.B. (National Inst. of Health, Bethesda, MD (United States))

1991-02-20

This case history reports the diagnosis of familial hyperchylomicronemia, a rare genetic syndrome inherited as an autosomal recessive trait. It is characterized by severe fasting hypertriglyceridemia and massive accumulations of chylomicrons in plasma. The two major molecular defects in the disease are a deficiency of lipoprotein lipase or of apo C-II. The location of the mutations in the human apolipoprotein (apo) C-II gene are identified.

Family history of cancer predicts endometrial cancer risk independently of Lynch Syndrome: Implications for genetic counselling.

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Johnatty, Sharon E; Tan, Yen Y; Buchanan, Daniel D; Bowman, Michael; Walters, Rhiannon J; Obermair, Andreas; Quinn, Michael A; Blomfield, Penelope B; Brand, Alison; Leung, Yee; Oehler, Martin K; Kirk, Judy A; O'Mara, Tracy A; Webb, Penelope M; Spurdle, Amanda B

2017-11-01

To determine endometrial cancer (EC) risk according to family cancer history, including assessment by degree of relatedness, type of and age at cancer diagnosis of relatives. Self-reported family cancer history was available for 1353 EC patients and 628 controls. Logistic regression was used to quantify the association between EC and cancer diagnosis in ≥1 first or second degree relative, and to assess whether level of risk differed by degree of relationship and/or relative's age at diagnosis. Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression. Report of EC in ≥1 first- or second-degree relative was associated with significantly increased risk of EC (P=3.8×10 -7 ), independent of lifestyle risk factors. There was a trend in increasing EC risk with closer relatedness and younger age at EC diagnosis in relatives (P Trend =4.43×10 -6 ), and with increasing numbers of Lynch cancers in relatives (P Trend ≤0.0001). EC risk associated with family history did not differ by proband tumor MMR status, or histological subtype. Reported EC in first- or second-degree relatives remained associated with EC risk after conservative correction for potential misreported family history (OR 2.0; 95% CI, 1.24-3.37, P=0.004). The strongest predictor of EC risk was closer relatedness and younger EC diagnosis age in ≥1 relative. Associations remained significant irrespective of proband MMR status, and after excluding MMR pathogenic variant carriers, indicating that Lynch syndrome genes do not fully explain familial EC risk. Copyright © 2017 Elsevier Inc. All rights reserved.

Novel Implications in Molecular Diagnosis of Lynch Syndrome

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Raffaella Liccardo

2017-01-01

Full Text Available About 10% of total colorectal cancers are associated with known Mendelian inheritance, as Familial Adenomatous Polyposis (FAP and Lynch syndrome (LS. In these cancer types the clinical manifestations of disease are due to mutations in high-risk alleles, with a penetrance at least of 70%. The LS is associated with germline mutations in the DNA mismatch repair (MMR genes. However, the mutation detection analysis of these genes does not always provide informative results for genetic counseling of LS patients. Very often, the molecular analysis reveals the presence of variants of unknown significance (VUSs whose interpretation is not easy and requires the combination of different analytical strategies to get a proper assessment of their pathogenicity. In some cases, these VUSs may make a more substantial overall contribution to cancer risk than the well-assessed severe Mendelian variants. Moreover, it could also be possible that the simultaneous presence of these genetic variants in several MMR genes that behave as low risk alleles might contribute in a cooperative manner to increase the risk of hereditary cancer. In this paper, through a review of the recent literature, we have speculated a novel inheritance model in the Lynch syndrome; this could pave the way toward new diagnostic perspectives.

Molecular dynamics of Middle East Respiratory Syndrome Coronavirus (MERS CoV) fusion heptad repeat trimers

KAUST Repository

Kandeel, Mahmoud; Al-Taher, Abdulla; Li, Huifang; Schwingenschlö gl, Udo; Alnazawi, Mohamed

2018-01-01

Structural studies related to Middle East Respiratory Syndrome Coronavirus (MERS CoV) infection process are so limited. In this study, molecular dynamics (MD) simulation was carried out to unravel changes in the MERS CoV heptad repeat domains (HRs

Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome

OpenAIRE

Burkhart, Keith K.; Abernethy, Darrell; Jackson, David

2015-01-01

Drug features that are associated with Stevens-Johnson syndrome (SJS) have not been fully characterized. A molecular target analysis of the drugs associated with SJS in the FDA Adverse Event Reporting System (FAERS) may contribute to mechanistic insights into SJS pathophysiology. The publicly available version of FAERS was analyzed to identify disproportionality among the molecular targets, metabolizing enzymes, and transporters for drugs associated with SJS. The FAERS in-house version was al...

A Molecular Neurobiological Approach to Understanding the Aetiology of Chronic Fatigue Syndrome (Myalgic Encephalomyelitis or Systemic Exertion Intolerance Disease) with Treatment Implications.

Science.gov (United States)

Monro, Jean A; Puri, Basant K

2018-02-06

Currently, a psychologically based model is widely held to be the basis for the aetiology and treatment of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME)/systemic exertion intolerance disease (SEID). However, an alternative, molecular neurobiological approach is possible and in this paper evidence demonstrating a biological aetiology for CFS/ME/SEID is adduced from a study of the history of the disease and a consideration of the role of the following in this disease: nitric oxide and peroxynitrite, oxidative and nitrosative stress, the blood-brain barrier and intestinal permeability, cytokines and infections, metabolism, structural and chemical brain changes, neurophysiological changes and calcium ion mobilisation. Evidence is also detailed for biologically based potential therapeutic options, including: nutritional supplementation, for example in order to downregulate the nitric oxide-peroxynitrite cycle to prevent its perpetuation; antiviral therapy; and monoclonal antibody treatment. It is concluded that there is strong evidence of a molecular neurobiological aetiology, and so it is suggested that biologically based therapeutic interventions should constitute a focus for future research into CFS/ME/SEID.

Evaluation of white spot syndrome virus variable DNA loci as molecular markers of virus spread at intermediate spatiotemporal scales

NARCIS (Netherlands)

Bui Thi Minh Dieu,; Marks, H.; Zwart, M.P.; Vlak, J.M.

2010-01-01

Variable genomic loci have been employed in a number of molecular epidemiology studies of white spot syndrome virus (WSSV), but it is unknown which loci are suitable molecular markers for determining WSSV spread on different spatiotemporal scales. Although previous work suggests that multiple

Non-alcoholic Korsakoff syndrome in psychiatric patients with a history of undiagnosed Wernicke's encephalopathy.

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Nikolakaros, Georgios; Ilonen, Tuula; Kurki, Timo; Paju, Janina; Papageorgiou, Sokratis G; Vataja, Risto

2016-11-15

Wernicke's encephalopathy is often undiagnosed, particularly in non-alcoholics. There are very few reports of non-alcoholic patients diagnosed with Korsakoff syndrome in the absence of a prior diagnosis of Wernicke's encephalopathy and no studies of diffusion tensor imaging in non-alcoholic Korsakoff syndrome. We report on three non-alcoholic psychiatric patients (all women) with long-term non-progressive memory impairment that developed after malnutrition accompanied by at least one of the three Wernicke's encephalopathy manifestations: ocular abnormalities, ataxia or unsteadiness, and an altered mental state or mild memory impairment. In neuropsychological examination, all patients had memory impairment, including intrusions. One patient had mild cerebellar vermis atrophy in MRI taken after the second episode of Wernicke's encephalopathy. The same patient had mild hypometabolism in the lateral cortex of the temporal lobes. Another patient had mild symmetrical atrophy and hypometabolism of the superior frontal lobes. Two patients were examined with diffusion tensor imaging. Reduced fractional anisotropy values were found in the corona radiata in two patients, and the uncinate fasciculus and the inferior longitudinal fasciculus in one patient. Our results suggest that non-alcoholic Korsakoff syndrome is underdiagnosed. Psychiatric patients with long-term memory impairment may have Korsakoff syndrome and, therefore, they should be evaluated for a history of previously undiagnosed Wernicke's encephalopathy. Copyright © 2016 Elsevier B.V. All rights reserved.

Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

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Ritch Robert

2004-06-01

Full Text Available Abstract Background Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. Methods We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. Results Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1 probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. Conclusions Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss.

Clinical and molecular analyses of Beckwith-Wiedemann syndrome: Comparison between spontaneous conception and assisted reproduction techniques.

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Tenorio, Jair; Romanelli, Valeria; Martin-Trujillo, Alex; Fernández, García-Moya; Segovia, Mabel; Perandones, Claudia; Pérez Jurado, Luis A; Esteller, Manel; Fraga, Mario; Arias, Pedro; Gordo, Gema; Dapía, Irene; Mena, Rocío; Palomares, María; Pérez de Nanclares, Guiomar; Nevado, Julián; García-Miñaur, Sixto; Santos-Simarro, Fernando; Martinez-Glez, Víctor; Vallespín, Elena; Monk, David; Lapunzina, Pablo

2016-10-01

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome characterized by an excessive prenatal and postnatal growth, macrosomia, macroglossia, and hemihyperplasia. The molecular basis of this syndrome is complex and heterogeneous, involving genes located at 11p15.5. BWS is correlated with assisted reproductive techniques. BWS in individuals born following assisted reproductive techniques has been found to occur four to nine times higher compared to children with to BWS born after spontaneous conception. Here, we report a series of 187 patients with to BWS born either after assisted reproductive techniques or conceived naturally. Eighty-eight percent of BWS patients born via assisted reproductive techniques had hypomethylation of KCNQ1OT1:TSS-DMR in comparison with 49% for patients with BWS conceived naturally. None of the patients with BWS born via assisted reproductive techniques had hypermethylation of H19/IGF2:IG-DMR, neither CDKN1 C mutations nor patUPD11. We did not find differences in the frequency of multi-locus imprinting disturbances between groups. Patients with BWS born via assisted reproductive techniques had an increased frequency of advanced bone age, congenital heart disease, and decreased frequency of earlobe anomalies but these differences may be explained by the different molecular background compared to those with BWS and spontaneous fertilization. We conclude there is a correlation of the molecular etiology of BWS with the type of conception. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Evolutionary and molecular analysis of the emergent severe fever with thrombocytopenia syndrome virus.

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Lam, Tommy Tsan-Yuk; Liu, Wei; Bowden, Thomas A; Cui, Ning; Zhuang, Lu; Liu, Kun; Zhang, Yao-Yun; Cao, Wu-Chun; Pybus, Oliver G

2013-03-01

In 2009, a novel Bunyavirus, called severe fever with thrombocytopenia syndrome virus (SFTSV) was identified in the vicinity of Huaiyangshan, China. Clinical symptoms of this zoonotic virus included severe fever, thrombocytopenia, and leukocytopenia, with a mortality rate of ~10%. By the end of 2011 the disease associated with this pathogen had been reported from eleven Chinese provinces and human-to-human transmission suspected. However, current understanding of the evolution and molecular epidemiology of SFTSV before and after its identification is limited. To address this we undertake phylogenetic, evolutionary and structural analyses of all available SFTSV genetic sequences, including a new SFTSV complete genome isolated from a patient from Henan in 2011. Our discovery of a mosaic L segment sequence, which is descended from two major circulating lineages of SFTSV in China, represents the first evidence that homologous recombination plays a role in SFTSV evolution. Selection analyses indicate that negative selection is predominant in SFTSV genes, yet differences in selective forces among genes are consistent between Phlebovirus species. Further analysis reveals structural conservation between SFTSV and Rift Valley fever virus in the residues of their nucleocapsids that are responsible for oligomerisation and RNA-binding, suggesting the viruses share similar modes of higher-order assembly. We reconstruct the epidemic history of SFTSV using molecular clock and coalescent-based methods, revealing that the extant SFTSV lineages originated 50-150 years ago, and that the viral population experienced a recent growth phase that concurs with and extends the earliest serological reports of SFTSV infection. Taken together, our combined structural and phylogenetic analyses shed light into the evolutionary behaviour of SFTSV in the context of other, better-known, pathogenic Phleboviruses. Copyright © 2012 Elsevier B.V. All rights reserved.

Efficacy of syndromic management measured as symptomatic improvement in females with vaginal discharge syndrome.

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Chauhan, Vidyalaxmi; Shah, Maitri C; Patel, Sangita V; Marfatia, Yogesh S; Zalavadiya, Dhara

2016-01-01

In spite of a few shortcomings such as over diagnosis and over treatment, syndromic management is a recommended practice in India for sexually transmitted infections (STIs). This study tries to find out the efficacy of syndromic management measured as symptomatic improvement in females with vaginal discharge syndrome. The objective of the study is to find out the effectiveness of syndromic management in terms of symptomatic improvement among females with vaginal discharge syndrome. A longitudinal study was conducted in Gynecology Department of Tertiary Care Hospital including 180 symptomatic females having vaginal discharge syndrome. Demographic profile, presenting complaints, menstrual history, obstetric history, partner history, and contraceptive history were noted. This was followed by clinical examination and specimen collection for laboratory tests and blood tests to find out type of STI including viral STI such as human immunodeficiency virus (HIV), herpes simplex virus (HSV), and hepatitis B surface antigen (HBsAg). Treatment was given according to syndromic management on the same day. All the participants were asked to come for follow-up after 15 days and their improvement in symptoms was noted as complete improvement, some improvement or no improvement on a five point scale. 63.9% cases showed complete improvement, while 36.1% showed some improvement. None of the patients was without any improvement. Vaginal discharge syndrome was most common between 20 and 30 years (43.4%), and 67.8% of symptomatic females with vaginal discharge syndrome belonged to the lower socioeconomic group. HSV infection was the most common (15%) associated viral infection with vaginal discharge syndrome, while hepatitis B infection was the least common (0.5%). HIV was reactive in 2.8% cases only. Syndromic management was found to be effective in relieving symptoms in most of the cases of vaginal discharge syndrome.

Endocrine neoplasms in familial syndromes of hyperparathyroidism.

Science.gov (United States)

Li, Yulong; Simonds, William F

2016-06-01

Familial syndromes of hyperparathyroidism, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and the hyperparathyroidism-jaw tumor (HPT-JT), comprise 2-5% of primary hyperparathyroidism cases. Familial syndromes of hyperparathyroidism are also associated with a range of endocrine and nonendocrine tumors, including potential malignancies. Complications of the associated neoplasms are the major causes of morbidities and mortalities in these familial syndromes, e.g., parathyroid carcinoma in HPT-JT syndrome; thymic, bronchial, and enteropancreatic neuroendocrine tumors in MEN1; and medullary thyroid cancer and pheochromocytoma in MEN2A. Because of the different underlying mechanisms of neoplasia, these familial tumors may have different characteristics compared with their sporadic counterparts. Large-scale clinical trials are frequently lacking due to the rarity of these diseases. With technological advances and the development of new medications, the natural history, diagnosis, and management of these syndromes are also evolving. In this article, we summarize the recent knowledge on endocrine neoplasms in three familial hyperparathyroidism syndromes, with an emphasis on disease characteristics, molecular pathogenesis, recent developments in biochemical and radiological evaluation, and expert opinions on surgical and medical therapies. Because these familial hyperparathyroidism syndromes are associated with a wide variety of tumors in different organs, this review is focused on those endocrine neoplasms with malignant potential. © 2016 Society for Endocrinology.

Sheldon-Hall syndrome

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Bamshad Michael J

2009-03-01

Full Text Available Abstract Sheldon-Hall syndrome (SHS is a rare multiple congenital contracture syndrome characterized by contractures of the distal joints of the limbs, triangular face, downslanting palpebral fissures, small mouth, and high arched palate. Epidemiological data for the prevalence of SHS are not available, but less than 100 cases have been reported in the literature. Other common clinical features of SHS include prominent nasolabial folds, high arched palate, attached earlobes, mild cervical webbing, short stature, severe camptodactyly, ulnar deviation, and vertical talus and/or talipes equinovarus. Typically, the contractures are most severe at birth and non-progressive. SHS is inherited in an autosomal dominant pattern but about half the cases are sporadic. Mutations in either MYH3, TNNI2, or TNNT3 have been found in about 50% of cases. These genes encode proteins of the contractile apparatus of fast twitch skeletal muscle fibers. The diagnosis of SHS is based on clinical criteria. Mutation analysis is useful to distinguish SHS from arthrogryposis syndromes with similar features (e.g. distal arthrogryposis 1 and Freeman-Sheldon syndrome. Prenatal diagnosis by ultrasonography is feasible at 18–24 weeks of gestation. If the family history is positive and the mutation is known in the family, prenatal molecular genetic diagnosis is possible. There is no specific therapy for SHS. However, patients benefit from early intervention with occupational and physical therapy, serial casting, and/or surgery. Life expectancy and cognitive abilities are normal.

Metabolic syndrome and parental history of cardiovascular disease in young adults in urban Ghana.

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Yeboah, Kwame; Dodam, Kennedy Konlan; Affrim, Patrick Kormla; Adu-Gyamfi, Linda; Bado, Anormah Rashid; Owusu Mensah, Richard N A; Adjei, Afua Bontu; Gyan, Ben

2017-08-03

Metabolic syndrome (MetS) in young adults poses significant cardiovascular diseases (CVD) risk for later years. Parental history of CVDs is known to affect the prevalence of CVD risk in adulthood. In sub-Saharan Africa, the burden of MetS in young adults and its relationship with parental CVDs is largely unknown. We studied the gender-specific prevalence of MetS and its association with parental history of diabetes, hypertension and CVDs in young adults resident in urban Ghana. In a cross-sectional design, 364 young adults aged 20-30 years were randomly recruited from students of University of Ghana. A structured questionnaire was used to collect data on demography, lifestyle, medical and parental medical history. Anthropometric indices and blood pressures were measured. Fasting blood samples were collected to measure plasma levels of glucose, lipid profile, urea and creatinine. MetS was defined according to the Joint Scientific Statement criteria. The prevalence of MetS was 12.4%, higher in females than male participants (18.4% vs 5.7, p = 0.019). Female participants had higher levels of all the components of MetS than the male participants. Compared to participants with no history of parental CVDs, participants with parental CVDs had a higher proportion of abdominal obesity. A positive history of parental CVDs was associated with increase in odds of MetS [OR (95% CI): 1.23 (1.12-3.04), p = 0.037]. In our study population, there is relatively high prevalence of MetS; higher in females compared to male participants. Parental history of CVDs was associated with MetS.

Evolutionary and molecular analysis of the emergent severe fever with thrombocytopenia syndrome virus

OpenAIRE

Lam, Tommy Tsan-Yuk; Liu, Wei; Bowden, Thomas A.; Cui, Ning; Zhuang, Lu; Liu, Kun; Zhang, Yao-Yun; Cao, Wu-Chun; Pybus, Oliver G.

2013-01-01

In 2009, a novel Bunyavirus, called severe fever with thrombocytopenia syndrome virus (SFTSV) was identified in the vicinity of Huaiyangshan, China. Clinical symptoms of this zoonotic virus included severe fever, thrombocytopenia, and leukocytopenia, with a mortality rate of ?10%. By the end of 2011 the disease associated with this pathogen had been reported from eleven Chinese provinces and human-to-human transmission suspected. However, current understanding of the evolution and molecular e...

Aortic Disease in the Young: Genetic Aneurysm Syndromes, Connective Tissue Disorders, and Familial Aortic Aneurysms and Dissections

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Marcelo Cury

2013-01-01

Full Text Available There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS, Ehlers-Danlos syndrome (EDS, Loeys-Dietz syndrome (LDS, familial thoracic aortic aneurysms and dissections (TAAD, bicuspid aortic valve disease (BAV, and autosomal dominant polycystic kidney disease (ADPKD. In the absence of familial history and other clinical findings, the proportion of thoracic and abdominal aortic aneurysms and dissections resulting from a genetic predisposition is still unknown. In this study, we propose the review of the current genetic knowledge in the aortic disease, observing, in the results that the causative genes and molecular pathways involved in the pathophysiology of aortic aneurysm disease remain undiscovered and continue to be an area of intensive research.

Risk factors of diabetes in North Indians with metabolic syndrome.

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Pratyush, Daliparthy D; Tiwari, Shalbha; Singh, Saurabh; Singh, Surya K

2016-01-01

Metabolic syndrome progresses to diabetes and determinants of this progression like hyperinsulinemia, hypertriglyceridemia and genetic factors have been speculative. The present study was aimed at quantifying the insulin resistance and influence of family history of diabetes in subjects with metabolic syndrome developing prediabetes and diabetes. Consecutive subjects attending the endocrine clinic were evaluated for metabolic syndrome as per definition of International Diabetes Federation, 2005. The family history of diabetes in their first degree relatives was ascertained and Homeostasis model assessment of Insulin resistance (HOMA-IR), Homeostasis model assessment for beta cell function (HOMA-B) and Quantitative insulin sensitivity check index (QUICKI) were calculated in 163 subjects enrolled. HOMA-IR was higher (pmetabolic syndrome+prediabetes or diabetes compared to metabolic syndrome with normal glucose tolerance. HOMA-B was lower and prevalence of prediabetes and diabetes was higher in metabolic syndrome subjects with family history of diabetes than in those without such family history (pmetabolic syndrome having prediabetes and diabetes had more severe insulin resistance than those with metabolic syndrome only. Beta cell dysfunction was remarkable and prevalence of prediabetes was high in metabolic syndrome subjects with family history of diabetes. Both the severity of the insulin resistance and family history of diabetes are therefore proposed to be determinants of diminished Beta cell function leading to diabetes in metabolic syndrome. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Higher molecular weight dissolved organic nitrogen turnover as affected by soil management history

DEFF Research Database (Denmark)

Lønne Enggrob, Kirsten

of different management histories on the turnover of high Mw DON. Further, we distinguished between several classes of high Mw DON, i.e., 1-10 kDa and >10 kDa. 3. Materials and methods With the use of micro-lysimeters, the turnover of triple-labeled (15N, 14C and 13C) high Mw DON was studied in a sandy soil......High molecular weight dissolved organic nitrogen turnover as affected by soil management history *Kirsten Lønne Enggrob,1 Lars Elsgaard,1 and Jim Rasmussen1 1Aarhus University, Dept. of Agroecology, Foulum, Denmark 1. Introduction Dissolved organic nitrogen (DON) play an important role in soil N...... are presented for 14CO2 evolution during 14 days of incubation. 4. Results and conclusion Results showed that the turnover rate of high Mw DON was dependent on both the Mw size of DON and on the soil liming history. Evidence showing where in the DON Mw sizes the bottleneck lies will be presented....

Complex regional pain syndromes (CRPS type 1 validating case histories

Directory of Open Access Journals (Sweden)

P. Berger

2003-01-01

Full Text Available The treatment of patients with complex regional pain syndrome (CRPS type 1 is challenging and unpredictable as the condition presents with vascular and neuropathic symptoms after nil or even minor injury to a peripheral nerve. The condition is one of a pain and motor dysfunction. The pathophysiology is not well understood and the relief of symptoms may change from being sympathetically mediated to sympathetically independent during  the course of the disease. At any stage physiotherapy has been advocated as the corner stone and most important aspect of treatment in the rehabilitation of these individuals but unfortunately it has been difficult to execute when pain is exacerbated due to allodynia (unbearable to touch or move and hyperalgesia. Best results have been obtained if the patients are recognised and treated in the early or acute phase and it has been found that through careful assessment and analysis these patients can be recognised by previous events that have occurred in their initial case history. The treatment in the acute stage with physiotherapy modalities such as electrical stimulation and acupuncture will produce an early cessation of the symptoms and prevention of the disease developing into the fully blown CRPS type 1 with irreversible and possibly atrophic consequences. Case histories have been presented that illustrate these important aspects and demonstrate  the value of early and the appropriate physiotherapy that may be more successful than other pharmacological and physical interventions in this disease.

Defining Moments in MMWR History: Toxic-Shock Syndrome -- 1980

Centers for Disease Control (CDC) Podcasts

In the late 1970s and early 1980s, an outbreak of a disease called Toxic Shock Syndrome made healthy women sick. CDC's disease detectives helped unravel the link between Toxic Shock Syndrome and high-absorbency tampons. MMWR was the first scientific publication to break the news of these cases. In this podcast, Dr. Kathy Shands, former chief of CDC's Toxic Shock Syndrome Task Force, recalls her experience working with state epidemiologists to identify the link between toxic shock syndrome and tampon use.

Muscle stiffness of posterior lower leg in runners with a history of medial tibial stress syndrome.

Science.gov (United States)

Saeki, J; Nakamura, M; Nakao, S; Fujita, K; Yanase, K; Ichihashi, N

2018-01-01

Previous history of medial tibial stress syndrome (MTSS) is a risk factor for MTSS relapse, which suggests that there might be some physical factors that are related to MTSS development in runners with a history of MTSS. The relationship between MTSS and muscle stiffness can be assessed in a cross-sectional study that measures muscle stiffness in subjects with a history of MTSS, who do not have pain at the time of measurement, and in those without a history of MTSS. The purpose of this study was to compare the shear elastic modulus, which is an index of muscle stiffness, of all posterior lower leg muscles of subjects with a history of MTSS and those with no history and investigate which muscles could be related to MTSS. Twenty-four male collegiate runners (age, 20.0±1.7 years; height, 172.7±4.8 cm; weight, 57.3±3.7 kg) participated in this study; 14 had a history of MTSS, and 10 did not. The shear elastic moduli of the lateral gastrocnemius, medial gastrocnemius, soleus, peroneus longus, peroneus brevis, flexor hallucis longus, flexor digitorum longus, and tibialis posterior were measured using shear wave elastography. The shear elastic moduli of the flexor digitorum longus and tibialis posterior were significantly higher in subjects with a history of MTSS than in those with no history. However, there was no significant difference in the shear elastic moduli of other muscles. The results of this study suggest that flexor digitorum longus and tibialis posterior stiffness could be related to MTSS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparative study between clinical history and polysomnogram in the obstructive sleep apnea/ hypopnea syndrome.

Science.gov (United States)

Gondim, Lys Maria Allenstein; Matumoto, Luciana Matshie; Melo Júnior, Marco Antônio Cezário de; Bittencourt, Sérgio; Ribeiro, Ulisses José

2007-01-01

Recognizing sleep-disordered breathing is on the rise every year. Manifestations, such as snoring, that were earlier considered mere inconvenients are now acquiring greater importance concerning life quality and social impact. To compare the clinical history to polysomnogram (PSG) results in the Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS). 125 patients were analyzed, in a retrospective study. Specific questionnaires, avaliations of Body Mass Index and Epworth Scale were carried out. Among the patients, 75 were males and 50 were females. The main symptom was snoring. 46% had normal PSG, 30% had light OSAHS, 15% moderate and 9% severe OSAHS and it was not observed a correlation between clinical data and PSG results. Concerning clinical symptoms, only insomnia has shown relevance when univariably analyzed in normal and light OSAHS patients (plosing its importance when analyzed together with other factors. the clinical history, per se, is not sufficient to define OSAHS' diagnosis or it's severity.

Medical history and the onset of complex regional pain syndrome (CRPS).

Science.gov (United States)

de Mos, M; Huygen, F J P M; Dieleman, J P; Koopman, J S H A; Stricker, B H Ch; Sturkenboom, M C J M

2008-10-15

Knowledge concerning the medical history prior to the onset of complex regional pain syndrome (CRPS) might provide insight into its risk factors and potential underlying disease mechanisms. To evaluate prior to CRPS medical conditions, a case-control study was conducted in the Integrated Primary Care Information (IPCI) project, a general practice (GP) database in the Netherlands. CRPS patients were identified from the records and validated through examination by the investigator (IASP criteria) or through specialist confirmation. Cases were matched to controls on age, gender and injury type. All diagnoses prior to the index date were assessed by manual review of the medical records. Some pre-specified medical conditions were studied for their association with CRPS, whereas all other diagnoses, grouped by pathogenesis, were tested in a hypothesis-generating approach. Of the identified 259 CRPS patients, 186 cases (697 controls) were included, based on validation by the investigator during a visit (102 of 134 visited patients) or on specialist confirmation (84 of 125 unvisited patients). A medical history of migraine (OR: 2.43, 95% CI: 1.18-5.02) and osteoporosis (OR: 2.44, 95% CI: 1.17-5.14) was associated with CRPS. In a recent history (1-year before CRPS), cases had more menstrual cycle-related problems (OR: 2.60, 95% CI: 1.16-5.83) and neuropathies (OR: 5.7; 95% CI: 1.8-18.7). In a sensitivity analysis, including only visited cases, asthma (OR: 3.0; 95% CI: 1.3-6.9) and CRPS were related. Psychological factors were not associated with CRPS onset. Because of the hypothesis-generating character of this study, the findings should be confirmed by other studies.

Marfan syndrome: clinical diagnosis and management.

Science.gov (United States)

Dean, John C S

2007-07-01

Marfan syndrome is a multisystem connective tissue disorder usually associated with mutation in fibrillin, and occasionally with mutation in TGFBR1 or 2. The clinical diagnosis is made using the Ghent nosology, which will unequivocally diagnose or exclude Marfan syndrome in 86% of cases. Use of a care pathway can help implementation of the nosology in the clinic. The penetrance of some features is age dependent, so the nosology must be used with caution in children. Molecular testing may be helpful in this context. The nosology cannot be used in families with isolated aortic dissection, or with related conditions such as Loeys-Dietz syndrome, although it may help identify families for further diagnostic evaluation because they do not fulfill the nosology, despite a history of aneurysm. Prophylactic medical (eg beta-blockade) and surgical intervention is important in reducing the cardiovascular complications of Marfan syndrome. Musculoskeletal symptoms are common, although the pathophysiology is less clear--for example, the correlation between dural ectasia and back pain is uncertain. Symptoms in other systems require specialist review such as ophthalmology assessment of refractive errors and ectopia lentis. Pregnancy is a time of increased cardiovascular risk for women with Marfan syndrome, particularly if the aortic root exceeds 4 cm at the start of pregnancy. High-intensity static exercise should be discouraged although low-moderate intensity dynamic exercise may be beneficial. The diagnosis and management of Marfan syndrome requires a multidisciplinary team approach, in view of its multisystem effects and phenotypic variability.

Male patients with partial androgen insensitivity syndrome

DEFF Research Database (Denmark)

Hellmann, Philip; Christiansen, Peter; Johannsen, Trine Holm

2012-01-01

To describe the natural history of phenotype, growth and gonadal function in patients with partial androgen insensitivity syndrome.......To describe the natural history of phenotype, growth and gonadal function in patients with partial androgen insensitivity syndrome....

Behavioural mediators of genetic life-history trade-offs: a test of the pace-of-life syndrome hypothesis in field crickets.

Science.gov (United States)

Santostefano, Francesca; Wilson, Alastair J; Niemelä, Petri T; Dingemanse, Niels J

2017-10-11

The pace-of-life syndrome (POLS) hypothesis predicts associations between life history and 'risky' behaviours. Individuals with 'fast' lifestyles should develop faster, reproduce earlier, exhibit more risk-prone behaviours, and die sooner than those with 'slow' lifestyles. While support for POLS has been equivocal to date, studies have relied on individual-level (phenotypic) patterns in which genetic trade-offs may be masked by environmental effects on phenotypes. We estimated genetic correlations between life history (development, lifespan, size) and risky behaviours (exploration, aggression) in a pedigreed population of Mediterranean field crickets ( Gryllus bimaculatus ). Path analyses showed that behaviours mediated some genetic relationships between life history traits, though not those involved in trade-offs. Thus, while specific predictions of POLS theory were not supported, genetic integration of behaviour and life history was present. This implies a major role for risky behaviours in life history evolution. © 2017 The Author(s).

Glioblastoma, a brief review of history, molecular genetics, animal models and novel therapeutic strategies.

Science.gov (United States)

Agnihotri, Sameer; Burrell, Kelly E; Wolf, Amparo; Jalali, Sharzhad; Hawkins, Cynthia; Rutka, James T; Zadeh, Gelareh

2013-02-01

Glioblastoma (GBM) is the most common and lethal primary brain tumor. Over the past few years tremendous genomic and proteomic characterization along with robust animal models of GBM have provided invaluable data that show that "GBM", although histologically indistinguishable from one another, are comprised of molecularly heterogenous diseases. In addition, robust pre-clinical models and a better understanding of the core pathways disrupted in GBM are providing a renewed optimism for novel strategies targeting these devastating tumors. Here, we summarize a brief history of the disease, our current molecular knowledge, lessons from animal models and emerging concepts of angiogenesis, invasion, and metabolism in GBM that may lend themselves to therapeutic targeting.

Molecular profile of the Lynch Syndrome in the Republic of Macedonia

Directory of Open Access Journals (Sweden)

Marija Hiljadnikova-Bajro

2012-12-01

Full Text Available The most frequent type of hereditary colorectal cancer, the one occurring in the setting of the Lynch syndrome (LS is considered a phenotypic manifestation of a germline defect in the mismatch repair mechanism i.e. in the MLH1, MSH2, MSH6 or PMS2 gene. Aiming towards establishment of a standardized protocol involving molecular analyses for diagnosis of this syndrome and developing a unique national register of families with hereditary colorectal cancer syndromes in the Republic of Macedonia, we began a prospective study to reveal the genetic defects among Macedonian patients with colorectal cancer (CRC and identifying families with hereditary CRC. A total of 53 patients fulfilling the revised Bethesda criteria for MSI-genetic testing were compared to 350 patients with sporadic CRC. The results reveal significant differences in age at diagnosis (p=0.03, involvement of microsatellite instability (pG nonsense mutation with a possible founder effect in the Macedonian population, the MLH1 ex.3-12 deletion, as well as the c.244A>G mutation, IVS14- 19A>G and IVS4+65A>C changes in MLH1 without confirmed pathological significance. The observed high frequency (87.5% of the Ile219Val (c.655A>G variant in MLH1 among the LS suspects prompts further analyses to evaluate its involvement in the development of hereditary CRC by itself or as a risk modifying factor among the patients from the Republic of Macedonia.

Ellis-van Creveld syndrome: its history.

Science.gov (United States)

Muensterer, Oliver J; Berdon, Walter; McManus, Chris; Oestreich, Alan; Lachman, Ralph S; Cohen, M Michael; Done, Stephen

2013-08-01

The story of Ellis-van Creveld syndrome is one of serendipity. By chance, Simon van Creveld and Richard Ellis purportedly met on a train and combined their independently encountered patients with short stature, dental anomalies and polydactyly into one landmark publication in 1940. They included a patient used in work published previously by Rustin McIntosh without naming McIntosh as a coauthor. This patient was followed radiologically by Caffey for nearly two decades. In 1964, Victor McKusick felt compelled to investigate a brief report in an obscure pharmaceutical journal on an unusual geographic cluster of short-statured Amish patients in Pennsylvania. This review highlights the lives of the individuals involved in the discovery of Ellis-van Creveld syndrome in their historic context.

[Jerusalem syndrome - a case report].

Science.gov (United States)

Poleszczyk, Anna; Swiecicki, Łukasz

2013-01-01

The aim of the paper was to present the case of a patient who developed acute psychotic symptoms on her visit to Jerusalem. The analysis of the clinical case and medical history. The presented 62-year-old women with a history of previous psychiatric disorder arrived with her husband to Jerusalem as a part of organised touristic group. She developed acute psychotic reaction through some stages characteristic for the third type of Jerusalem syndrome. Symptoms resolved completely soon after returning to Poland and admission to the hospital where an antipsychotic treatment was performed. Despite the rare occurrence of this phenomenon, it is worth noting that we can divide Jerusalem syndrome into three types depending on its clinical course, patient's history of previous psychiatric disorders and this division has some clinical implications. This syndrome can be also considered in the context of some factors connected with travelling in general which may be responsible for psychiatric disturbances occurring among travelers. The course of psychiatric disturbances in the presented patient resembled the third type of Jerusalem syndrome despite her past psychiatric history and probably travelling caused her decompensations. In clinical practice we have to remember that in case of the patients with a known psychiatric history, clinical evaluation may be useful before travelling. In previously healthy patients developing the third type of the Jerusalem syndrome early intervention and separation from Jerusalem and its holy places and their contact with family are crucial for soon recovery.

Chemical and molecular factors in irritable bowel syndrome: current knowledge, challenges, and unanswered questions.

Science.gov (United States)

Camilleri, Michael; Oduyebo, Ibironke; Halawi, Houssam

2016-11-01

Several chemical and molecular factors in the intestine are reported to be altered and to have a potentially significant role in irritable bowel syndrome (IBS), particularly in IBS with diarrhea. These include bile acids; short-chain fatty acids; mucosal barrier proteins; mast cell products such as histamine, proteases, and tryptase; enteroendocrine cell products; and mucosal mRNAs, proteins, and microRNAs. This article reviews the current knowledge and unanswered questions in the pathobiology of the chemical and molecular factors in IBS. Evidence continues to point to significant roles in pathogenesis of these chemical and molecular mechanisms, which may therefore constitute potential targets for future research and therapy. However, it is still necessary to address the interaction between these factors in the gut and to appraise how they may influence hypervigilance in the central nervous system in patients with IBS. Copyright © 2016 the American Physiological Society.

Defining Moments in MMWR History: Toxic-Shock Syndrome -- 1980

Centers for Disease Control (CDC) Podcasts

2017-11-03

In the late 1970s and early 1980s, an outbreak of a disease called Toxic Shock Syndrome made healthy women sick. CDC’s disease detectives helped unravel the link between Toxic Shock Syndrome and high-absorbency tampons. MMWR was the first scientific publication to break the news of these cases. In this podcast, Dr. Kathy Shands, former chief of CDC’s Toxic Shock Syndrome Task Force, recalls her experience working with state epidemiologists to identify the link between toxic shock syndrome and tampon use.  Created: 11/3/2017 by MMWR.   Date Released: 11/3/2017.

Homozygous deletion in MYL9 expands the molecular basis of megacystis-microcolon-intestinal hypoperistalsis syndrome.

Science.gov (United States)

Moreno, Carolina Araujo; Sobreira, Nara; Pugh, Elizabeth; Zhang, Peng; Steel, Gary; Torres, Fábio Rossi; Cavalcanti, Denise Pontes

2018-05-01

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a severe disease characterized by functional obstruction in the urinary and gastrointestinal tract. The molecular basis of this condition started to be defined recently, and the genes related to the syndrome (ACTG2-heterozygous variant in sporadic cases; and MYH11 (myosin heavy chain 11), LMOD1 (leiomodin 1) and MYLK (myosin light chain (MLC) kinase)-autosomal recessive inheritance), encode proteins involved in the smooth muscle contraction, supporting a myopathic basis for the disease. In the present article, we described a family with two affected siblings with MMIHS born to consanguineous parents and the molecular investigation performed to define the genetic etiology. Previous whole exome sequencing of the affected child and parents did not identify a candidate gene for the disease in this family, but now we present a reanalysis of the data that led to the identification of a homozygous deletion encompassing the last exon of MYL9 (myosin regulatory light chain 9) in the affected individual. MYL9 gene encodes a regulatory myosin MLC and the phosphorylation of this protein is a crucial step in the contraction process of smooth muscle cell. Despite the absence of human or animal phenotype related to MYL9, a cause-effect relationship between MYL9 and the MMIHS seems biologically plausible. The present study reveals a strong candidate gene for autosomal recessive forms of MMIHS, expanding the molecular basis of this disease and reinforces the myopathic basis of this condition.

PPAR? population shift produces disease-related changes in molecular networks associated with metabolic syndrome

OpenAIRE

Jurkowski, W; Roomp, K; Crespo, I; Schneider, J G; del Sol, A

2011-01-01

Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation and has an important role in metabolic syndrome. Phosphorylation of the receptor's ligand-binding domain at serine 273 has been shown to change the expression of a large number of genes implicated in obesity. The difference in gene expression seen when comparing wild-type phosphorylated with mutant non-phosphorylated PPARγ may have important consequences for the cellular molecular network,...

Lynch syndrome-related small intestinal adenocarcinomas.

Science.gov (United States)

Jun, Sun-Young; Lee, Eui-Jin; Kim, Mi-Ju; Chun, Sung Min; Bae, Young Kyung; Hong, Soon Uk; Choi, Jene; Kim, Joon Mee; Jang, Kee-Taek; Kim, Jung Yeon; Kim, Gwang Il; Jung, Soo Jin; Yoon, Ghilsuk; Hong, Seung-Mo

2017-03-28

Lynch syndrome is an autosomal-dominant disorder caused by defective DNA mismatch repair (MMR) genes and is associated with increased risk of malignancies in multiple organs. Small-intestinal adenocarcinomas are common initial manifestations of Lynch syndrome. To define the incidence and characteristics of Lynch syndrome-related small-intestinal adenocarcinomas, meticulous familial and clinical histories were obtained from 195 patients with small-intestinal adenocarcinoma, and MMR protein immunohistochemistry, microsatellite instability, MLH1 methylation, and germline mutational analyses were performed. Lynch syndrome was confirmed in eight patients (4%), all of whom had synchronous/metachronous malignancies without noticeable familial histories. Small-intestinal adenocarcinomas were the first clinical manifestation in 37% (3/8) of Lynch syndrome patients, and second malignancies developed within 5 years in 63% (5/8). The patients with accompanying Lynch syndrome were younger (≤50 years; P=0.04) and more likely to have mucinous adenocarcinomas (P=0.003), and tended to survive longer (P=0.11) than those with sporadic cases. A meticulous patient history taking, MMR protein immunolabeling, and germline MMR gene mutational analysis are important for the diagnosis of Lynch syndrome-related small-intestinal adenocarcinomas. Identifying Lynch syndrome in patients with small-intestinal adenocarcinoma can be beneficial for the early detection and treatment of additional Lynch syndrome-related cancers, especially in patients who are young or have mucinous adenocarcinomas.

The chequered history of the antiphospholipid syndrome.

Science.gov (United States)

Jayakody Arachchillage, Deepa; Greaves, Mike

2014-06-01

Consideration of the chronology of advances in medical knowledge can provide useful insights into the pathogenesis, diagnosis and treatment of diseases. The antiphospholipid syndrome is an enigmatic disorder and this is reinforced by the misleading associated terminology, the adoption of which results directly from early discoveries relating to the condition. Thus the target antigen of the causative autoantibodies in antiphospholipid syndrome does not reside on phospholipid, and the frequently associated lupus anticoagulant is not restricted to subjects with systemic lupus erythematosus and, paradoxically, despite causing prolongation of clotting times in vitro it is associated with a pronounced tendency to thrombosis. Recognition of the antiphospholipid syndrome has its origins in the identification of subjects with so-called biological false-positive serological reactions for syphilis in the middle years of the last century. Since that time there have been considerable advances in our understanding of the pathogenesis of the disease and the clinical manifestations and associations, improved diagnostic accuracy and an evolving evidence base for optimal therapy. However many gaps in our knowledge remain. © 2014 John Wiley & Sons Ltd.

Molecular defects of the growth hormone receptor gene, including a new mutation, in Laron syndrome patients in Israel: relationship between defects and ethnic groups.

Science.gov (United States)

Shevah, Orit; Rubinstein, Menachem; Laron, Zvi

2004-10-01

Laron Syndrome, first described in Israel, is a form of dwarfism similar to isolated growth hormone deficiency caused by molecular defects in the GH receptor gene. To characterize the molecular defects of the GH-R in Laron syndrome patients followed in our clinic. Of the 63 patients in the cohort, we investigated 31 patients and 32 relatives belonging to several ethnic origins. Molecular analysis of the GH-R gene was performed using the single strand conformation polymorphism and DNA sequencing techniques. Eleven molecular defects including a novel mutation were found. Twenty-two patients carried mutations in the extracellular domain, one in the transmembrane domain, and 3 siblings with typical Laron syndrome presented a normal GH-R. Of interest are, on one hand, different mutations within the same ethnic groups: W-15X and 5, 6 exon deletion in Jewish-Iraqis, and E180 splice and 5, 6 exon deletion in Jewish-Moroccans; and on the other hand, identical findings in patients from distinct regions: the 785-1 G to T mutation in an Israeli-Druze and a Peruvian patient. A polymorphism in exon 6, Gly168Gly, was found in 15 probands. One typical Laron patient from Greece was heterozygous for R43X in exon 4 and heterozygous for Gly168Gly. In addition, a novel mutation in exon 5: substitution of T to G replacing tyrosine 86 for aspartic acid (Y86D) is described. This study demonstrates: a) an increased focal incidence of Laron syndrome in different ethnic groups from our area with a high incidence of consanguinity; and b) a relationship between molecular defects of the GH-R, ethnic group and geographic area.

A multicenter study on Leigh syndrome

DEFF Research Database (Denmark)

Sofou, Kalliopi; De Coo, Irenaeus F M; Isohanni, Pirjo

2014-01-01

BACKGROUND: Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural...... history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients. METHODS: This is a retrospective study of patients with Leigh syndrome...... to thrive, brainstem lesions on neuroimaging and intensive care treatment were significantly associated with poorer survival. CONCLUSIONS: This is a multicenter study performed in a large cohort of patients with Leigh syndrome. Our data help define the natural history of Leigh syndrome and identify novel...

Malignant Tregs express low molecular splice forms of FOXP3 in Sézary syndrome

DEFF Research Database (Denmark)

Krejsgaard, T; Gjerdrum, L M; Ralfkiaer, E

2008-01-01

Sézary syndrome (SS) is an aggressive variant of cutaneous T-cell lymphoma. During disease progression, immunodeficiency develops; however, the underlying molecular and cellular mechanisms are not fully understood. Here, we study the regulatory T cell (Treg) function and the expression of FOXP3...... in SS. We demonstrate that malignant T cells in 8 of 15 patients stain positive with an anti-FOXP3 antibody. Western blotting analysis shows expression of two low molecular splice forms of FOXP3, but not of wild-type (wt) FOXP3. The malignant T cells produce interleukin-10 and TGF-beta and suppress...... the growth of non-malignant T cells. The Treg phenotype and the production of suppressive cytokines are driven by aberrant activation of Jak3 independent of the FOXP3 splice forms. In contrast to wt FOXP3, the low molecular splice forms of FOXP3 have no inhibitory effect on nuclear factor-kappaB (NF...

Evidence for an agitated-aggressive syndrome in early-onset psychosis correlated with antisocial personality disorder, forensic history, and substance use disorder.

Science.gov (United States)

Huber, Christian G; Hochstrasser, Lisa; Meister, Klara; Schimmelmann, Benno G; Lambert, Martin

2016-08-01

Agitation, aggression, and violence are increased in psychotic disorders. Additionally, an earlier age at onset may be associated with aggressive behavior. However, the relationship of age at onset, an agitated-aggressive syndrome as measured with the Positive And Negative Syndrome Scale for Schizophrenia - Excited Component (PANSS-EC), and its potential correlates in first-episode psychosis (FEP) has not been studied. This study assessed the association between age at onset, an agitated-aggressive syndrome, and its potential correlates in a prospective sample of 52 FEP patients with early-onset and adult-onset followed up for 12months. Twenty-six patients conformed to the criteria of early-onset psychosis. Early age at onset was associated with antisocial personality disorder (p=0.004; φc=0.39), a history of legal involvement (p=0.005; φc=0.39), and higher rates of lifetime substance use disorder (SUD; p=0.002; φc=0.42). Early-onset patients had significantly higher PANSS-EC scores over the course of observation (F(1,44.4)=5.39; p=0.025; d=0.656), but no significant group differences emerged for the remaining PANSS subscores. PANSS-EC scores were correlated positively with antisocial personality disorder and forensic history at 6weeks, 3months, 6months, and 12months, and with lifetime substance use disorder at 3months and 6months. Patients with early onset psychosis may have increased levels of agitation/aggressiveness, and, more likely, antisocial personality disorder, forensic history, and lifetime substance use disorder. These variables were linked to suicidality, aggressiveness, and involuntary treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

In-hospital management and outcomes of acute coronary syndromes in relation to prior history of heart failure.

Science.gov (United States)

Zhang, Hanfei; Goodman, Shaun G; Yan, Raymond T; Steg, Ph Gabriel; Kornder, Jan M; Gyenes, Gabor T; Grondin, Francois R; Brieger, David; DeYoung, J Paul; Gallo, Richard; Yan, Andrew T

2016-06-01

The prognostic significance of prior heart failure in acute coronary syndromes has not been well studied. Accordingly, we evaluated the baseline characteristics, management patterns and clinical outcomes in patients with acute coronary syndromes who had prior heart failure. The study population consisted of acute coronary syndrome patients in the Global Registry of Acute Coronary Events, expanded Global Registry of Acute Coronary Events and Canadian Registry of Acute Coronary Events between 1999 and 2008. Of the 13,937 eligible patients (mean age 66±13 years, 33% female and 28.3% with ST-elevation myocardial infarction), 1498 (10.7%) patients had a history of heart failure. Those with prior heart failure tended to be older, female and had lower systolic blood pressure, higher Killip class and creatinine on presentation. Prior heart failure was also associated with significantly worse left ventricular systolic function and lower rates of cardiac catheterization and coronary revascularization. The group with previous heart failure had significantly higher rates of acute decompensated heart failure, cardiogenic shock, myocardial (re)infarction and mortality in hospital. In multivariable analysis, prior heart failure remained an independent predictor of in-hospital mortality (odds ratio 1.48, 95% confidence interval 1.08-2.03, p=0.015). Prior heart failure was associated with high risk features on presentation and adverse outcomes including higher adjusted in-hospital mortality in acute coronary syndrome patients. However, acute coronary syndrome patients with prior heart failure were less likely to receive evidence-based therapies, suggesting potential opportunities to target more intensive treatment to improve their outcome. © The European Society of Cardiology 2015.

From playfulness and self-centredness via grand expectations to normalisation: a psychoanalytical rereading of the history of molecular genetics.

Science.gov (United States)

Zwart, H A E

2013-11-01

In this paper, I will reread the history of molecular genetics from a psychoanalytical angle, analysing it as a case history. Building on the developmental theories of Freud and his followers, I will distinguish four stages, namely: (1) oedipal childhood, notably the epoch of model building (1943-1953); (2) the latency period, with a focus on the development of basic skills (1953-1989); (3) adolescence, exemplified by the Human Genome Project, with its fierce conflicts, great expectations and grandiose claims (1989-2003) and (4) adulthood (2003-present) during which revolutionary research areas such as molecular biology and genomics have achieved a certain level of normalcy--have evolved into a normal science. I will indicate how a psychoanalytical assessment conducted in this manner may help us to interpret and address some of the key normative issues that have been raised with regard to molecular genetics over the years, such as 'relevance', 'responsible innovation' and 'promise management'.

Congenital hypoventilation syndrome and Hirschsprung's disease - Haddad syndrome: A neonatal case presentation.

Science.gov (United States)

Jaiyeola, P; El-Metwally, D; Viscardi, R; Greene, C; Woo, H

2015-01-01

Congenital central hypoventilation syndrome (CCHS) is an uncommon cause of apnea in the newborn characterized by the occurrence of apnea predominantly during sleep. Haddad syndrome is CCHS with Hirschsprung's disease. We report a newborn with Haddad syndrome that had a family history of spinal muscular atrophy and discuss aspects of CCHS and important considerations in the evaluation of apnea in the term newborn.

Hantavirus Pulmonary Syndrome (HPS)

Science.gov (United States)

... to Yosemite FAQ: Non-U.S. Visitors to Yosemite History of HPS Related Links Prevent Rodent Infestations Cleaning Up After Rodents Diseases From Rodent Hantavirus Pulmonary Syndrome (HPS) Recommend on Facebook Tweet Share Compartir Hantavirus Pulmonary Syndrome (HPS) is ...

West syndrome in a patient with Schinzel-Giedion syndrome.

Science.gov (United States)

Miyake, Fuyu; Kuroda, Yukiko; Naruto, Takuya; Ohashi, Ikuko; Takano, Kyoko; Kurosawa, Kenji

2015-06-01

Schinzel-Giedion syndrome is a rare recognizable malformation syndrome defined by characteristic facial features, profound developmental delay, severe growth failure, and multiple congenital anomalies. The causative gene of Schinzel-Giedion syndrome, SETBP1, has been identified, but limited cases have been confirmed by molecular analysis. We present a 9-month-old girl affected by West syndrome with Schinzel-Giedion syndrome. Congenital severe hydronephrosis, typical facial features, and multiple anomalies suggested a clinical diagnosis of Schinzel-Giedion syndrome. Hypsarrhythmia occurred at 7 months of age and was temporarily controlled by adrenocorticotropic hormone (ACTH) therapy during 5 weeks. SETBP1 mutational analysis showed the presence of a recurrent mutation, p.Ile871Thr. The implications in management of Schinzel-Giedion syndrome are discussed. © The Author(s) 2014.

Application of whole-exome sequencing to unravel the molecular basis of undiagnosed syndromic congenital neutropenia with intellectual disability.

Science.gov (United States)

Gauthier-Vasserot, Alexandra; Thauvin-Robinet, Christel; Bruel, Ange-Line; Duffourd, Yannis; St-Onge, Judith; Jouan, Thibaud; Rivière, Jean-Baptiste; Heron, Delphine; Donadieu, Jean; Bellanné-Chantelot, Christine; Briandet, Claire; Huet, Frédéric; Kuentz, Paul; Lehalle, Daphné; Duplomb-Jego, Laurence; Gautier, Elodie; Maystadt, Isabelle; Pinson, Lucile; Amram, Daniel; El Chehadeh, Salima; Melki, Judith; Julia, Sophia; Faivre, Laurence; Thevenon, Julien

2017-01-01

Neutropenia can be qualified as congenital when of neonatal onset or when associated with extra-hematopoietic manifestations. Overall, 30% of patients with congenital neutropenia (CN) remain without a molecular diagnosis after a multidisciplinary consultation and tedious diagnostic strategy. In the rare situations when neutropenia is identified and associated with intellectual disability (ID), there are few diagnostic hypotheses to test. This retrospective multicenter study reports on a clinically heterogeneous cohort of 10 unrelated patients with CN associated with ID and no molecular diagnosis prior to whole-exome sequencing (WES). WES provided a diagnostic yield of 40% (4/10). The results suggested that in many cases neutropenia and syndromic manifestations could not be assigned to the same molecular alteration. Three sub-groups of patients were highlighted: (i) severe, symptomatic chronic neutropenia, detected early in life, and related to a known mutation in the CN spectrum (ELANE); (ii) mild to moderate benign intermittent neutropenia, detected later, and associated with mutations in genes implicated in neurodevelopmental disorders (CHD2, HUWE1); and (iii) moderate to severe intermittent neutropenia as a probably undiagnosed feature of a newly reported syndrome (KAT6A). Unlike KAT6A, which seems to be associated with a syndromic form of CN, the other reported mutations may not explain the entire clinical picture. Although targeted gene sequencing can be discussed for the primary diagnosis of severe CN, we suggest that performing WES for the diagnosis of disorders associating CN with ID will not only provide the etiological diagnosis but will also pave the way towards personalized care and follow-up. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Molecular genetics of experimental hypertension and the metabolic syndrome: from gene pathways to new therapies

Czech Academy of Sciences Publication Activity Database

Pravenec, Michal; Kurtz, T. W.

2007-01-01

Roč. 49, č. 5 (2007), s. 941-952 ISSN 0194-911X R&D Projects: GA MZd(CZ) NR8545; GA ČR(CZ) GA301/04/0390; GA ČR(CZ) GA301/06/0028 Grant - others:The Howard Hughes Institute(US) HHMI55005624 Institutional research plan: CEZ:AV0Z50110509 Keywords : SHR * CD36 * metabolic syndrome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.194, year: 2007

A Concise History of Asperger Syndrome: the short reign of a troublesome diagnosis

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Bernardo eBarahona-Correa

2016-01-01

Full Text Available First described in 1944 by Hans Asperger, it was not before 1994 that Asperger Syndrome (AS was included in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders, only to disappear in the Manual’s 5th edition in 2013. During its brief existence as a diagnostic entity, AS aroused immense interest and controversy. Similar to patients with autism, AS patients show deficits in social interaction, inappropriate communication skills, and interest restriction, but also display a rich variety of subtle clinical characteristics that for many distinguish AS from autism. However, difficulties operationalising diagnostic criteria and differentiating AS from autism ultimately led to its merging into the unifying category of Autistic Spectrum Disorders. Here we briefly review the short history of this fascinating condition.

Supernumerary teeth in non-syndromic patients

International Nuclear Information System (INIS)

Mali, Santosh; Karjodkar, Freny Rashmiraj; Sontakke, Subodh; Sansare, Kaustubh

2012-01-01

Hyperdontia or supernumerary teeth without associated syndrome is a rare phenomenon, as supernumerary teeth are usually associated with cleft lip and palate or other syndromes such as Gardner's syndrome, cleidocranial dysplasia, and so on. Five patients with supernumerary teeth visited our department. They had no familial history or other pathology, certain treatment protocols was modified due to the presence of supernumerary teeth. Non-syndromic supernumerary teeth, if asymptomatic, need to have periodical radiographic observation. If they showed no variation as they impacted in the jaw, careful examination is necessary because they may develop into pathological status such as dentigerous cysts. The importance of a precise clinical history and radiographic examination for patients with multiple supernumerary teeth should be emphasized.

Korsakoff's syndrome is preventable

NARCIS (Netherlands)

Oudman, Erik; Wijnia, Jan W.

2014-01-01

Wernicke-Korsakoff syndrome (WKS) is a life-threatening neuropsychiatric disorder caused by thiamine (vitamin B1) deficiency. Wernicke-Korsakoff syndrome is associated with mammillary body edema and small vessel ischemia. Many patients who develop WKS have a history of serious alcoholism and

A classical Ehlers-Danlos syndrome family with incomplete presentation diagnosed by molecular testing.

Science.gov (United States)

Colombi, Marina; Dordoni, Chiara; Cinquina, Valeria; Venturini, Marina; Ritelli, Marco

2018-01-01

The 2017 EDS revised nosology indicates that minimal criteria suggestive for classical Ehlers-Danlos syndrome (cEDS) are skin hyperextensibility plus atrophic scarring together with either generalized joint hypermobility (gJHM) and/or at least three minor criteria that include cutaneous features and gJHM complications. Confirmatory molecular testing is obligatory to reach a final diagnosis. Although the large majority of the patients presents with these clinical features, some do not and might remain undiagnosed or misdiagnosed. Here we describe a family with 2 affected members, a 23-year-old proposita and her 51-year-old mother, who presented subtle cutaneous signs, including a variable degree of skin hyperextensibility without extensive widened atrophic scars that apparently better fitted with the overlapping hypermobile EDS. The proposita also presented gastrointestinal symptoms secondary to aberrant mast cells mediators release, making the clinical picture even more puzzling. Both patients were diagnosed by molecular testing that revealed a COL5A1 splice mutation. This report highlights the relevance of molecular analysis in patients presenting rather mild signs of EDS, especially in familial cases, and the importance of clinical expertise to make such a diagnosis. Copyright © 2017. Published by Elsevier Masson SAS.

Genetics Home Reference: Sotos syndrome

Science.gov (United States)

... gene are the primary cause of Sotos syndrome , accounting for up to 90 percent of cases. Other ... Sotos syndrome cases occur in people with no history of the disorder in their family. Most of ...

Concurrent Van der Woude syndrome and Turner syndrome: A case report.

Science.gov (United States)

Los, Evan; Baines, Hayley; Guttmann-Bauman, Ines

2017-01-01

Most cases of Van der Woude syndrome are caused by a mutation to interferon regulatory factor 6 on chromosome 1. Turner syndrome is caused by complete or partial absence of the second sex chromosome in girls. We describe a unique case of the two syndromes occurring concurrently though apparently independently in a girl with Van der Woude syndrome diagnosed at birth and Turner syndrome at 14 years 9 months. Short stature was initially misattributed to Van der Woude syndrome and pituitary insufficiency associated with clefts before correctly diagnosing Turner syndrome. We discuss the prevalence of delayed diagnosis of Turner syndrome, the rarity of reports of concurrent autosomal chromosome mutation and sex chromosome deletion, as well as the need to consider the diagnosis of Turner syndrome in all girls with short stature regardless of prior medical history.

Evolutionary history of genus Macrobrachium inferred from mitochondrial markers: a molecular clock approach.

Science.gov (United States)

Jose, Deepak; Harikrishnan, Mahadevan

2018-04-17

Caridea, an infraorder of shrimps coming under Pleocyemata was first reported from the oceans before 417 million years followed by their radiation recorded during the Permian period. Hitherto, about 3877 extant caridean species were accounted within which one quarter constitute freshwater species. Freshwater prawns of genus Macrobrachium (Infraorder Caridea; Family Palaemonidae), with more than 240 species are inhabitants of diverse aquatic habitats like coastal lagoons, lakes, tropical streams, ponds and rivers. Previous studies on Macrobrachium relied on the highly variable morphological characters which were insufficient for accurate diagnosis of natural species groups. Present study focuses on the utility of molecular markers (viz. COI and 16S rRNA) for resolving the evolutionary history of genus Macrobrachium using a combination of phylogeny and timescale components. It is for the first time a molecular clock approach had been carried out towards genus Macrobrachium in a broad aspect with the incorporation of congeners inhabiting diverse geographical realms including endemic species M. striatum from South West coast of India. Molecular results obtained revealed the phylogenetic relationships between congeners of genus Macrobrachium at intra/inter-continental level along with the corresponding evolutionary time estimates.

Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype.

Science.gov (United States)

de Heredia, Miguel López; Clèries, Ramón; Nunes, Virginia

2013-07-01

Wolfram syndrome is a degenerative, recessive rare disease with an onset in childhood. It is caused by mutations in WFS1 or CISD2 genes. More than 200 different variations in WFS1 have been described in patients with Wolfram syndrome, which complicates the establishment of clear genotype-phenotype correlation. The purpose of this study was to elucidate the role of WFS1 mutations and update the natural history of the disease. This study analyzed clinical and genetic data of 412 patients with Wolfram syndrome published in the last 15 years. (i) 15% of published patients do not fulfill the current -inclusion criterion; (ii) genotypic prevalence differences may exist among countries; (iii) diabetes mellitus and optic atrophy might not be the first two clinical features in some patients; (iv) mutations are nonuniformly distributed in WFS1; (v) age at onset of diabetes mellitus, hearing defects, and diabetes insipidus may depend on the patient's genotypic class; and (vi) disease progression rate might depend on genotypic class. New genotype-phenotype correlations were established, disease progression rate for the general population and for the genotypic classes has been calculated, and new diagnostic criteria have been proposed. The conclusions raised could be important for patient management and counseling as well as for the development of treatments for Wolfram syndrome.

A Molecular Diagnostic Test for Persistent Müllerian Duct Syndrome in Miniature Schnauzer Dogs

OpenAIRE

Pujar, S.; Meyers-Wallen, V.N.

2009-01-01

In persistent Müllerian duct syndrome (PMDS), Müllerian ducts fail to regress in males during sexual differentiation. In the canine miniature schnauzer model, PMDS is caused by a C to T transition in exon 3 of the Müllerian inhibiting substance type II receptor (MISRII), which introduces a DdeI restriction site. Here we report a molecular diagnostic test for PMDS in the miniature schnauzer to identify affected dogs and carriers. As our test results suggest that the mutation is identical by de...

Medulloblastoma: Molecular Genetics and Animal Models

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Corey Raffel

2004-07-01

Full Text Available Medulloblastoma is a primary brain tumor found in the cerebellum of children. The tumor occurs in association with two inherited cancer syndromes: Turcot syndrome and Gorlin syndrome. Insights into the molecular biology of the tumor have come from looking at alterations in the genes altered in these syndromes, PTC and APC, respectively. Murine models of medulloblastoma have been constructed based on these alterations. Additional murine models that, while mimicking the appearance of the human tumor, seem unrelated to the human tumor's molecular alterations have been made. In this review, the clinical picture, origin, molecular biology, murine models of medulloblastoma are discussed. Although a great deal has been discovered about this tumor, the genetic alterations responsible for tumor development in a majority of patients have yet to be described.

Conservation of nucleotide sequences for molecular diagnosis of Middle East respiratory syndrome coronavirus, 2015

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Yuki Furuse

2015-11-01

Full Text Available Infection due to the Middle East respiratory syndrome coronavirus (MERS-CoV is widespread. The present study was performed to assess the protocols used for the molecular diagnosis of MERS-CoV by analyzing the nucleotide sequences of viruses detected between 2012 and 2015, including sequences from the large outbreak in eastern Asia in 2015. Although the diagnostic protocols were established only 2 years ago, mismatches between the sequences of primers/probes and viruses were found for several of the assays. Such mismatches could lead to a lower sensitivity of the assay, thereby leading to false-negative diagnosis. A slight modification in the primer design is suggested. Protocols for the molecular diagnosis of viral infections should be reviewed regularly after they are established, particularly for viruses that pose a great threat to public health such as MERS-CoV.

Noonan Syndrome: An Underestimated Cause of Severe to Profound Sensorineural Hearing Impairment. Which Clues to Suspect the Diagnosis?

Science.gov (United States)

Ziegler, Alban; Loundon, Natalie; Jonard, Laurence; Cavé, Hélène; Baujat, Geneviève; Gherbi, Souad; Couloigner, Vincent; Marlin, Sandrine

2017-09-01

To highlight Noonan syndrome as a clinically recognizable cause of severe to profound sensorineural hearing impairment. New clinical cases and review. Patients evaluated for etiological diagnosis by a medical geneticist in a reference center for hearing impairment. Five patients presenting with confirmed Noonan syndrome and profound sensorineural hearing impairment. Diagnostic and review of the literature. Five patients presented with profound sensorineural hearing impairment and molecularly confirmed Noonan syndrome. Sensorineural hearing impairment has been progressive for three patients. Cardiac echography identified pulmonary stenosis in two patients and was normal for the three other patients. Short stature was found in two patients. Mild intellectual disability was found in one patient. Inconspicuous clinical features as facial dysmorphism, cryptorchidism, or easy bruising were of peculiar interest to reach the diagnosis of Noonan syndrome. Profound sensorineural hearing impairment can be the main feature of Noonan syndrome. Associated features are highly variable; thus, detailed medical history and careful physical examination are mandatory to consider the diagnosis in case of a sensorineural hearing impairment.

Churg-Strauss syndrome masquerading as an acute coronary syndrome.

Science.gov (United States)

Triantafyllis, Andreas S; Sakadakis, Eleftherios A; Papafilippaki, Argyro; Katsimbri, Pelagia; Panou, Fotios; Anastasiou-Nana, Maria; Lekakis, Ioannis

2015-02-01

Churg-Strauss Syndrome (CSS) is a rare vasculitis with multiorgan involvement. Cardiac manifestations are common causing serious complications. We report a case of CSS masquerading as a non-ST elevation myocardial infarction with heart failure. CSS should be considered in the differential diagnosis of an acute coronary syndrome(ACS)with normal coronary arteries when history of asthma, peripheral eosinophilia and multisystemic involvement is present.

History of mechanical ventilation may affect respiratory mechanics evolution in acute respiratory distress syndrome.

Science.gov (United States)

Koutsoukou, Antonia; Perraki, Helen; Orfanos, Stylianos E; Koulouris, Nikolaos G; Tromaropoulos, Andreas; Sotiropoulou, Christina; Roussos, Charis

2009-12-01

The aim of this study was to investigate the effect of mechanical ventilation (MV) before acute respiratory distress syndrome (ARDS) on subsequent evolution of respiratory mechanics and blood gases in protectively ventilated patients with ARDS. Nineteen patients with ARDS were stratified into 2 groups according to ARDS onset relative to the onset of MV: In group A (n = 11), MV was applied at the onset of ARDS; in group B (n = 8), MV had been initiated before ARDS. Respiratory mechanics and arterial blood gas were assessed in early (protectively ventilated patients with ARDS, late alteration of respiratory mechanics occurs more commonly in patients who have been ventilated before ARDS onset, suggesting that the history of MV affects the subsequent progress of ARDS even when using protective ventilation.

The Marfan syndrome genetics

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Galina Pungerčič

2005-05-01

Full Text Available Background: The Marfan syndrome is an autosomal dominant heritable disorder of connective tissue. It is caused by mutations in the fibrillin-1 gene encoding glycoprotein fibrillin-1, a component of microfibrils of extracellular matrix. Patients with Marfan syndrome show wide spectra of clinical signs, primarily on skeletal, cardiovascular and ocular organ systems. Cardiovascular complications (especially aortic aneurysm and aortic dissection are the most common cause of mortality of Marfan syndrome patients. Discovering genotype-phenotype correlations is complicated because of the large number of mutations reported as well as clinical heterogeneity among individuals with the same mutation. Despite the progress in the knowledge of the molecular nature of Marfan syndrome the diagnosis is still based mainly on the clinical features in the different body systems.Conclusions: Early identification of patient with Marfan syndrome is of considerable importance because of appropriate treatment that can greatly improve life expectancy. Unfortunately, despite the improvement of diagnostic methods, medical and surgical therapy, the mortality due to undiagnosed Marfan syndrome is still high. The present article reviews the molecular genetic studies of Marfan syndrome since the discovery of the mutations in the fibrillin-1 gene.

Women with double primary cancers of the colorectum and endometrium: do they have Lynch syndrome?

Science.gov (United States)

Song, Taejong; Kim, Min Kyu; Lee, Yoo-Young; Choi, Chel Hun; Kim, Tae-Joong; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

2016-04-01

The aim of this study was to determine the clinical characteristics of women with double primary cancers of the colorectum and endometrium and assess the probability of Lynch syndrome. We identified 15 women with paraffin-embedded blocks available who were diagnosed, treated and followed for double primary colorectal and endometrial cancers at in a single institution between 1994 and 2014. If there was a family history that met the revised Amsterdam criteria for Lynch syndrome, the woman was considered to have 'clinically defined Lynch syndrome'. If immunohistochemical (IHC) loss of expression of mismatch repair genes (MLH1, MSH2, MSH6, or PMS2) or high microsatellite instability (MSI) was demonstrated in molecular testing, the case was considered 'suspected Lynch syndrome'. The incidence of clinically defined Lynch syndrome according to the revised Amsterdam criteria was 66% (8 of 15). All 8 of the women clinically diagnosed with Lynch syndrome had either abnormal IHC loss or MSI-high, indicating a suspected Lynch syndrome. Furthermore, 27% (4 of 15) experienced second primary colorectal cancer or other Lynch syndrome-related cancers. Overall, 66% (10 of 15) met the criteria for clinically defined Lynch syndrome or suspected Lynch syndrome. Based on our findings, a large percentage (66%) of women with double primary cancers of the colorectum and endometrium are likely to be diagnosed with Lynch syndrome. Copyright © 2015. Published by Elsevier Ireland Ltd.

Supernumerary teeth in non-syndromic patients

Energy Technology Data Exchange (ETDEWEB)

Mali, Santosh; Karjodkar, Freny Rashmiraj; Sontakke, Subodh; Sansare, Kaustubh [Nair Hospital Dental College, Maharashtra (India)

2012-03-15

Hyperdontia or supernumerary teeth without associated syndrome is a rare phenomenon, as supernumerary teeth are usually associated with cleft lip and palate or other syndromes such as Gardner's syndrome, cleidocranial dysplasia, and so on. Five patients with supernumerary teeth visited our department. They had no familial history or other pathology, certain treatment protocols was modified due to the presence of supernumerary teeth. Non-syndromic supernumerary teeth, if asymptomatic, need to have periodical radiographic observation. If they showed no variation as they impacted in the jaw, careful examination is necessary because they may develop into pathological status such as dentigerous cysts. The importance of a precise clinical history and radiographic examination for patients with multiple supernumerary teeth should be emphasized.

Natural history of seminiferous tubule degeneration in Klinefelter syndrome

DEFF Research Database (Denmark)

Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa

2006-01-01

Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatic......Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates...... summarize current knowledge on the development of the classical endocrinological and histological features of 47,XXY males from fetus to adulthood and review the literature concerning the degeneration of the seminiferous tubules in this syndrome....

Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome

NARCIS (Netherlands)

Narumi, Yoko; Aoki, Yoko; Niihori, Tetsuya; Neri, Giovanni; Cave, Helene; Verloes, Alain; Nava, Caroline; Kavamura, Maria Ines; Okamoto, Nobuhiko; Kurosawa, Kenji; Hennekam, Raoul C. M.; Wilson, Louise C.; Gillessen-Kaesbach, Gabriele; Wieczorek, Dagmar; Lapunzina, Pablo; Ohashi, Hirofumi; Makita, Yoshio; Kondo, Ikuko; Tsuchiya, Shigeru; Ito, Etsuro; Sameshima, Kiyoko; Kato, Kumi; Kure, Shigeo; Matsubara, Yokhi

2007-01-01

Cardio-facio-cutaneous (CFC) syndrome is a multiple congenital anomaly/mental retardation syndrome characterized by heart defects, a distinctive facial appearance, ectodermal abnormalities and mental retardation. Clinically, it overlaps with both Noonan syndrome and Costello syndrome, which are

Ankle and toe muscle strength characteristics in runners with a history of medial tibial stress syndrome.

Science.gov (United States)

Saeki, Junya; Nakamura, Masatoshi; Nakao, Sayaka; Fujita, Kosuke; Yanase, Ko; Morishita, Katsuyuki; Ichihashi, Noriaki

2017-01-01

A high proportion of flexor digitorum longus attachment is found at the posteromedial border of the tibia, which is the most common location of medial tibial stress syndrome (MTSS). Therefore, plantar flexion strength of the lesser toes could be related to MTSS; however, the relationship between MTSS and muscle strength of the hallux and lesser toes is not yet evaluated due to the lack of quantitative methods. This study investigated the muscle strength characteristics in runners with a history of MTSS by using a newly developed device to measure the muscle strength of the hallux, lesser toes, and ankle. This study comprised 27 collegiate male runner participants (20.0 ± 1.6 years, 172.1 ± 5.1 cm, 57.5 ± 4.0 kg). Maximal voluntary isometric contraction (MVIC) torque of the plantar flexion, dorsiflexion, inversion, and eversion of the ankle were measured by using an electric dynamometer. MVIC torque of the 1st metatarsophalangeal joint (MTPJ) and 2nd-5th MTPJ were measured by using a custom-made torque-measuring device. MVIC torques were compared between runners with and without a history of MTSS. MVIC torque of the 1st MTPJ plantar flexion was significantly higher in runners with a history of MTSS than in those without it. In contrast, there were no significant differences in the MVIC torque values of the 2nd-5th MTPJ plantar flexion and each MVIC torque of the ankle between runners with and without a history of MTSS. A history of MTSS increased the isometric FHL strength.

The importance of the family history in caring for families with long QT syndrome and dilated cardiomyopathy.

Science.gov (United States)

Ruiter, Jolien S; Berkenbosch-Nieuwhof, Karin; van den Berg, Maarten P; van Dijk, Rene; Middel, Berrie; van Tintelen, J Peter

2010-03-01

In potentially inherited cardiac diseases, the family history is of great importance. We looked at the way cardiologists take a family history in patients with idiopathic dilated cardiomyopathy (DCM) or long QT syndrome (LQTS) and whether this led to screening of relatives or other follow-up. We performed retrospective cross-sectional analyses of adult index patients with DCM or LQTS in a general hospital (GH) or a University Medical Center (UMC). We identified 82 index patients with DCM (34 GH; 48 UMC) and 20 with LQTS (all UMC) between 1996 and 2005. Mean follow-up was 58 months. A family history was recorded in 90% of both LQTS and DCM patients most of the cases restricted to first-degree family members. The genetic aspects, counseling and screening of family members was discussed significantly more often with LQTS than DCM patients (all P family members, DNA analysis and referral) was performed significantly more often in LQTS than DCM patients. Cardiologists in the UMC referred DCM index patients for genetic counseling more often than those in the GH (25% vs. 6%; P familial. Since early recognition and treatment may reduce morbidity and mortality we recommend cardiologists take a more thorough family history and always consider referring to a clinical genetics department in such index patients. (c) 2010 Wiley-Liss, Inc.

Autosomal dominant syndrome resembling Coffin-Siris syndrome.

Science.gov (United States)

Flynn, Maureen A; Milunsky, Jeff M

2006-06-15

Coffin-Siris syndrome is a multiple congenital anomaly/mental retardation syndrome with phenotypic variability [OMIM 135900]. The diagnosis is based solely on clinical findings, as there is currently no molecular, biochemical, or cytogenetic analysis available to confirm a diagnosis. Although typically described as an autosomal recessive disorder, autosomal dominant inheritance has also been infrequently reported. We describe a mother and her two daughters who all have features that resemble Coffin-Siris syndrome. However, this is not a completely convincing diagnosis given that hypertelorism is not a feature of Coffin-Siris syndrome and the family is relatively mildly affected. Yet, this family provides further evidence of an autosomal dominant mode of inheritance for a likely variant of Coffin-Siris syndrome (at least in some families). In addition, Sibling 1 had premature thelarche. She is the second reported individual within the spectrum of Coffin-Siris syndrome to have premature thelarche, indicating that it may be a rare clinical feature. Copyright 2006 Wiley-Liss, Inc.

Medial tibial stress syndrome can be diagnosed reliably using history and physical examination.

Science.gov (United States)

Winters, M; Bakker, E W P; Moen, M H; Barten, C C; Teeuwen, R; Weir, A

2017-02-08

The majority of sporting injuries are clinically diagnosed using history and physical examination as the cornerstone. There are no studies supporting the reliability of making a clinical diagnosis of medial tibial stress syndrome (MTSS). Our aim was to assess if MTSS can be diagnosed reliably, using history and physical examination. We also investigated if clinicians were able to reliably identify concurrent lower leg injuries. A clinical reliability study was performed at multiple sports medicine sites in The Netherlands. Athletes with non-traumatic lower leg pain were assessed for having MTSS by two clinicians, who were blinded to each others' diagnoses. We calculated the prevalence, percentage of agreement, observed percentage of positive agreement (Ppos), observed percentage of negative agreement (Pneg) and Kappa-statistic with 95%CI. Forty-nine athletes participated in this study, of whom 46 completed both assessments. The prevalence of MTSS was 74%. The percentage of agreement was 96%, with Ppos and Pneg of 97% and 92%, respectively. The inter-rater reliability was almost perfect; k=0.89 (95% CI 0.74 to 1.00), phistory and physical examination, in clinical practice and research settings. We also found that concurrent lower leg injuries are common in athletes with MTSS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome

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Maki Fukami

2012-01-01

Full Text Available Aromatase excess syndrome (AEXS is a rare autosomal dominant disorder characterized by gynecomastia. This condition is caused by overexpression of CYP19A1 encoding aromatase, and three types of cryptic genomic rearrangement around CYP19A1, that is, duplications, deletions, and inversions, have been identified in AEXS. Duplications appear to have caused CYP19A1 overexpression because of an increased number of physiological promoters, whereas deletions and inversions would have induced wide CYP19A1 expression due to the formation of chimeric genes consisting of a noncoding exon(s of a neighboring gene and CYP19A1 coding exons. Genotype-phenotype analysis implies that phenotypic severity of AEXS is primarily determined by the expression pattern of CYP19A1 and the chimeric genes and by the structural property of the fused exons with a promoter function (i.e., the presence or the absence of a natural translation start codon. These results provide novel information about molecular mechanisms of human genetic disorders and biological function of estrogens.

[Poland's syndrome].

Science.gov (United States)

Slezak, R; Sasiadek, M

2000-08-01

Poland's syndrome consists of the variable clinical features, but always includes unilateral aplasia of the chest wall muscles and ipsilateral anomalies of upper extremity. The incidence of Poland's syndrome, reported by different authors ranges from 1:10,000 to 1:100,000 and is observed more frequently in males than in females with the right side of the body affected more often than the left. The etiology of this syndrome is still discussed. However most of described cases were sporadic, rare familial incidence of Poland's syndrome were also presented. Therefore different etiologic factors of the Poland's syndrome are taken into account: genetic, vascular compromise during early stages of embriogenesis but also teratogenic effect of environmental xenobiotics (e.g. cigarette smoking by pregnant women). The authors present also the case of 20-years old man with inherited bilateral syndactyly with the right side aplasia of major pectoralis muscle and face asymmetry. The familial history was negative in respect to the features, associated with Poland's syndrome.

The potential impact of family history of metabolic syndrome and risk of type 2 diabetes mellitus: In a highly endogamous population.

Science.gov (United States)

Bener, Abdulbari; Darwish, Sarah; Al-Hamaq, Abdulla O A; Yousafzai, Mohammad T; Nasralla, Eman A

2014-03-01

This study aims to determine the potential impact of positive family history of Metabolic Syndrome (MetS) among two generations, on developing Type 2 Diabetes Mellitus (T2DM) and the potential relation of consanguineous marriage among patients with MetS to the risk of developing T2DM among a sample of Qataris. A cross-sectional study. Primary healthcare (PHC) centers. The survey and measurement were conducted from April 2011 to December 2012 among Qatari nationals above 20 years of age. Of the 2,182 subjects, who were approached to participate in the study, 1,552 (71%) gave their consent. Face-to-face interviews were conducted using a structured questionnaire followed by anthropometric measurements and laboratory tests. Metabolic syndrome was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (ATP III) as well as International Diabetes Federation (IDF). Overall, the prevalence of MetS was 26.2% according to ATP III and 36.9% according to IDF (P family history for MetS was significantly higher in MetS patients with T2DM as compared to those without T2DM (46.7% vs. 33.8%; P = 0.009). The proportion of positive family history of MetS among fathers (35% vs. 21.9%; P = 0.005), mothers (30.5% vs. 18.8%; P = 0.008), maternal aunt (18.3% vs. 11.2%; P = 0.055), and maternal grand father (19.5% vs. 10%; P = 0.010) were significantly higher in MetS patients with T2DM as compared to the counterpart. The proportion of consanguineous marriages was almost two times higher among MetS patients with T2DM as compared to those without T2DM (80.9% vs. 41.9%; P Family history of MetS among parents, maternal aunt, maternal grandfather, and consanguineous marriages among patients of MetS are significantly associated with the development of T2DM in Qatar. These results support the necessity of earlier screening for T2DM among MetS patients with positive family history of MetS.

Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome.

Science.gov (United States)

Fung, Lawrence K; Quintin, Eve-Marie; Haas, Brian W; Reiss, Allan L

2012-04-01

The overarching goal of this review is to compare and contrast the cognitive-behavioral features of fragile X syndrome (FraX) and Williams syndrome and to review the putative neural and molecular underpinnings of these features. Information is presented in a framework that provides guiding principles for conceptualizing gene-brain-behavior associations in neurodevelopmental disorders. Abnormalities, in particular cognitive-behavioral domains with similarities in underlying neurodevelopmental correlates, occur in both FraX and Williams syndrome including aberrant frontostriatal pathways leading to executive function deficits, and magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal lobe, and postcentral gyrus abnormalities contributing to deficits in visuospatial function. Compelling cognitive-behavioral and neurodevelopmental contrasts also exist in these two disorders, for example, aberrant amygdala and fusiform cortex structure and function occurring in the context of contrasting social behavioral phenotypes, and temporal cortical and cerebellar abnormalities potentially underlying differences in language function. Abnormal dendritic development is a shared neurodevelopmental morphologic feature between FraX and Williams syndrome. Commonalities in molecular machinery and processes across FraX and Williams syndrome occur as well - microRNAs involved in translational regulation of major synaptic proteins; scaffolding proteins in excitatory synapses; and proteins involved in axonal development. Although the genetic variations leading to FraX and Williams syndrome are different, important similarities and contrasts in the phenotype, neurocircuitry, molecular machinery, and cellular processes in these two disorders allow for a unique approach to conceptualizing gene-brain-behavior links occurring in neurodevelopmental disorders.

Pfeiffer syndrome

Directory of Open Access Journals (Sweden)

Fryns Jean-Pierre

2006-06-01

Full Text Available Abstract Pfeiffer syndrome is a rare autosomal dominantly inherited disorder that associates craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly on hands and feet. Hydrocephaly may be found occasionally, along with severe ocular proptosis, ankylosed elbows, abnormal viscera, and slow development. Based on the severity of the phenotype, Pfeiffer syndrome is divided into three clinical subtypes. Type 1 "classic" Pfeiffer syndrome involves individuals with mild manifestations including brachycephaly, midface hypoplasia and finger and toe abnormalities; it is associated with normal intelligence and generally good outcome. Type 2 consists of cloverleaf skull, extreme proptosis, finger and toe abnormalities, elbow ankylosis or synostosis, developmental delay and neurological complications. Type 3 is similar to type 2 but without a cloverleaf skull. Clinical overlap between the three types may occur. Pfeiffer syndrome affects about 1 in 100,000 individuals. The disorder can be caused by mutations in the fibroblast growth factor receptor genes FGFR-1 or FGFR-2. Pfeiffer syndrome can be diagnosed prenatally by sonography showing craniosynostosis, hypertelorism with proptosis, and broad thumb, or molecularly if it concerns a recurrence and the causative mutation was found. Molecular genetic testing is important to confirm the diagnosis. Management includes multiple-staged surgery of craniosynostosis. Midfacial surgery is performed to reduce the exophthalmos and the midfacial hypoplasia.

Does family history of metabolic syndrome affect the metabolic profile phenotype in young healthy individuals?

Science.gov (United States)

Lipińska, Anna; Koczaj-Bremer, Magdalena; Jankowski, Krzysztof; Kaźmierczak, Agnieszka; Ciurzyński, Michał; Ou-Pokrzewińska, Aisha; Mikocka, Ewelina; Lewandowski, Zbigniew; Demkow, Urszula; Pruszczyk, Piotr

2014-01-01

Early identification of high-risk individuals is key for the prevention of cardiovascular disease (CVD). The aim of this study was to assess the potential impact of a family history of metabolic syndrome (fhMetS) on the risk of metabolic disorders (abnormal body mass, lipid profile, glucose metabolism, insulin resistance, and blood pressure) in healthy young individuals. We studied CVD risk factors in 90 healthy volunteers, aged 27-39 years; of these, 78 had fhMetS and 12 were without fhMetS (control group). Fasting serum lipids, glucose, and insulin levels were assayed, and anthropometric parameters and blood pressure using, an ambulatory blood pressure monitoring system, were measured. Nutritional and physical activity habits were assessed. Despite similar nutritional and physical activity habits, abnormal body mass was found in 53.2% of the fhMetS participants and 46.1% of the control participants (p = 0.54). The occurrence of obesity was 19.4% and 0%, respectively (p = 0.69). Compared to the control participants, fhMetS was associated with significantly higher total cholesterol (5.46 mmol/L vs. 4.69 mmol/L, p family history of MetS.

Molecular biology of pancreatic cancer.

Science.gov (United States)

Zavoral, Miroslav; Minarikova, Petra; Zavada, Filip; Salek, Cyril; Minarik, Marek

2011-06-28

In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syndromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

Overset Wolff-Parkinson-White-syndrom

DEFF Research Database (Denmark)

Nielsen, Trine Skov; Dalager, Søren; Larsen, Maiken Kudahl

2010-01-01

An autopsy in a 28-year-old man did not explain the cause of sudden unexpected death. However, a history of episodes with tachycardia and dizziness and a reassessed previous electrocardiogram exhibiting ventricular pre-excitation was consistent with Wolff-Parkinson-White (WPW) syndrome. In this p......An autopsy in a 28-year-old man did not explain the cause of sudden unexpected death. However, a history of episodes with tachycardia and dizziness and a reassessed previous electrocardiogram exhibiting ventricular pre-excitation was consistent with Wolff-Parkinson-White (WPW) syndrome...

Usher syndrome in Denmark

DEFF Research Database (Denmark)

Shzeena, Dad; Rendtorff, Nanna Dahl; Tranebjærg, Lisbeth

2016-01-01

BACKGROUND: Usher syndrome (USH) is a genetically heterogeneous deafness-blindness syndrome, divided into three clinical subtypes: USH1, USH2 and USH3. METHODS: Mutations in 21 out of 26 investigated Danish unrelated individuals with USH were identified, using a combination of molecular diagnostic...

Recent discoveries in the molecular genetics of Lynch syndrome.

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Boland, C Richard

2016-07-01

Lynch syndrome is the inherited predisposition to cancer caused by a germline mutation in a DNA mismatch repair gene. The consequent tumors have a characteristic microsatellite instability (MSI) phenotype. Genomic sequencing of Lynch syndrome-associated colorectal cancers (CRCs) has demonstrated that these tumors have a substantially greater number of mutations than non-MSI CRCs, and that the target mutations driving tumor behavior are also different from what occurs in sporadic tumors. There are multiple non-Lynch syndrome entities that can create clinical confusion with that disease, including the acquired methylation of MLH1, Lynch-like syndrome, and Familial CRC-Type X. Patients with Lynch syndrome-associated CRCs have a substantially better prognosis, and there is growing evidence that this is due to the generation of immunogenic frameshift peptides as a consequence of defective DNA mismatch repair, and an effective immune response to the tumor.

Understanding the molecular mechanisms of human microtia via a pig model of HOXA1 syndrome

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Ruimin Qiao

2015-06-01

Full Text Available Microtia is a congenital malformation of the outer ears. Although both genetic and environmental components have been implicated in microtia, the genetic causes of this innate disorder are poorly understood. Pigs have naturally occurring diseases comparable to those in humans, providing exceptional opportunity to dissect the molecular mechanism of human inherited diseases. Here we first demonstrated that a truncating mutation in HOXA1 causes a monogenic disorder of microtia in pigs. We further performed RNA sequencing (RNA-Seq analysis on affected and healthy pig embryos (day 14.25. We identified a list of 337 differentially expressed genes (DEGs between the normal and mutant samples, shedding light on the transcriptional network involving HOXA1. The DEGs are enriched in biological processes related to cardiovascular system and embryonic development, and neurological, renal and urological diseases. Aberrant expressions of many DEGs have been implicated in human innate deformities corresponding to microtia-associated syndromes. After applying three prioritizing algorithms, we highlighted appealing candidate genes for human microtia from the 337 DEGs. We searched for coding variants of functional significance within six candidate genes in 147 microtia-affected individuals. Of note, we identified one EVC2 non-synonymous mutation (p.Asp1174Asn as a potential disease-implicating variant for a human microtia-associated syndrome. The findings advance our understanding of the molecular mechanisms underlying human microtia, and provide an interesting example of the characterization of human disease-predisposing variants using pig models.

Nodding syndrome: origins and natural history of a longstanding epileptic disorder in sub-Saharan Africa.

Science.gov (United States)

Spencer, P S; Palmer, V S; Jilek-Aall, L

2013-06-01

Repetitive involuntary head nodding was first reported in the 1960s in the Wapogoro tribe of Tanzania. We describe the natural history of head nodding in the Wapogoro tribe, with special reference to the earliest reported dates of onset. We analyzed clinical data from 150 historical patients seen between 1960 and 1971. Head nodding with or without grand mal convulsions was present in 33/150 (∼20%) cases, was mostly familial and equally distributed by gender. Age at onset of head nodding ranged from 2-22 years (mean: ∼10 years) in the period 1934-1962. Head nodding preceded onset of grand mal convulsions by up to 12 months, and motor and psychomotor deficits indicative of brain damage developed with time. Fourteen of the 33 cases died at 13-39 years of age (mean: ∼20 years) while nineteen aged 16-28 years (mean: ∼16 years) were still alive. Historical accounts of head nodding (amesinzia kichwa, Swahili) among the Wapogoro tribe fit the August 2012 World Health Organization (WHO) case definition of probable Nodding Syndrome. Reported to have existed in this population for at least 80 years, Nodding Syndrome is a progressive seizure disorder that leads to generalized convulsions (kifafa), brain damage and death.

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

Korsakoff's syndrome: A critical review

NARCIS (Netherlands)

Arts, N.J.M.; Walvoort, S.J.W.; Kessels, R.P.C.

2017-01-01

In this review, we present a survey on Korsakoff's syndrome (KS), a residual syndrome in patients who suffered from a Wernicke encephalopathy (WE) that is predominantly characterized by global amnesia, and in more severe cases also by cognitive and behavioral dysfunction. We describe the history of

Hereditary Nonpolyposis Colorectal Cancer and Cancer Syndromes: Recent Basic and Clinical Discoveries

Directory of Open Access Journals (Sweden)

Erbao Chen

2018-01-01

Full Text Available Approximately one-third of individuals diagnosed with colorectal cancer have a family history of cancer, suggesting that CRCs may result from a heritable component. Despite the availability of current gene-identification techniques, only 5% of all CRCs emerge from well-identifiable inherited causes for predisposition, including polyposis and nonpolyposis syndromes. Hereditary nonpolyposis colorectal cancer represents a large proportion of cases, and robustly affected patients are at increased risk for early onset, synchronous, and metachronous colorectal malignancies and extracolonic malignancies. HNPCC encompasses several cancer syndromes, such as Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X, which have remarkable clinical presentations and overlapping genetic profiles that make clinical diagnosis a challenging task. Therefore, distinguishing between the HNPCC disorders is crucial for physicians as an approach to tailor different recommendations for patients and their at-risk family members according to the risks for colonic and extracolonic cancer associated with each syndrome. Identification of these potential patients through epidemiological characteristics and new genetic testing can estimate the individual risk, which informs appropriate cancer screening, surveillance, and/or treatment strategies. In the past three years, many appealing and important advances have been made in our understanding of the relationship between HNPCC and CRC-associated syndromes. The knowledge from the genetic profile of cancer syndromes and unique genotype-phenotype profiles in the different syndromes has changed our cognition. Therefore, this review presents and discusses HNPCC and several common nonpolyposis syndromes with respect to molecular phenotype, histopathologic features, and clinical presentation.

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. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Natural history of seminiferous tubule degeneration in Klinefelter syndrome

DEFF Research Database (Denmark)

Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa

2006-01-01

Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatic......Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates...

Eye Development Genes and Known Syndromes

Science.gov (United States)

Slavotinek, Anne M.

2011-01-01

Anophthalmia and microphthalmia (A/M) are significant eye defects because they can have profound effects on visual acuity. A/M is associated with non-ocular abnormalities in an estimated 33–95% of cases and around 25% of patients have an underlying genetic syndrome that is diagnosable. Syndrome recognition is important for targeted molecular genetic testing, prognosis and for counseling regarding recurrence risks. This review provides clinical and molecular information for several of the commonest syndromes associated with A/M: Anophthalmia-Esophageal-Genital syndrome, caused by SOX2 mutations, Anophthalmia and pituitary abnormalities caused by OTX2 mutations, Matthew-Wood syndrome caused by STRA6 mutations, Oculocardiafaciodental syndrome and Lenz microphthalmia caused by BCOR mutations, Microphthalmia Linear Skin pigmentation syndrome caused by HCCS mutations, Anophthalmia, pituitary abnormalities, polysyndactyly caused by BMP4 mutations and Waardenburg anophthalmia caused by mutations in SMOC1. In addition, we briefly discuss the ocular and extraocular phenotypes associated with several other important eye developmental genes, including GDF6, VSX2, RAX, SHH, SIX6 and PAX6. PMID:22005280

Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

Science.gov (United States)

Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

2016-06-01

Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

Prevalence of dry eye syndrome and Sjogren's syndrome in patients with rheumatoid arthritis.

Science.gov (United States)

Kosrirukvongs, Panida; Ngowyutagon, Panotsom; Pusuwan, Pawana; Koolvisoot, Ajchara; Nilganuwong, Surasak

2012-04-01

Rheumatoid arthritis has manifestations in various organs including ophthalmic involvement. The present study evaluates prevalence of dry eye and secondary Sjogren's syndrome using salivary scintigraphy which has not been used in previous reports. To evaluate the prevalence of secondary Sjogren's syndrome in patients with rheumatoid arthritis, including clinical characteristics and dry eye, compared with non-Sjogren's syndrome. Descriptive cross sectional study Sixty-one patients with rheumatoid arthritis were recruited at Siriraj Hospital during March 2009-September 2010 and filled in the questionnaires about dry eye for Ocular Surface Disease Index (OSDI) with a history taking of associated diseases, medications, duration of symptoms of dry eyes and dry mouth. The Schirmer I test without anesthesia, tear break-up time, rose bengal staining score, severity of keratitis and salivary scintigraphy were measured and analyzed. Prevalence of secondary Sjogren's syndrome and dry eye were 22.2% (95% CI 15.4 to 30.9) and 46.7% (95% CI 38.0 to 55.6), respectively. Dry eye interpreted from OSDI, Schirmer 1 test, tear break-up time and rose bengal staining was 16.4%, 46.7%, 82% and 3.3% respectively. Fifty-two percent of patients had a history of dry eye and dry mouth with mean duration 27.4 and 29.8 months, respectively. Superficial punctate keratitis and abnormal salivary scintigraphy were found in 58.2% and 77.8%. Duration of rheumatoid arthritis, erythrocyte sedimentation rate were not correlated with secondary Sjogren's syndrome. Dry eye from OSDI with secondary Sjogren's syndrome (33.3%) compared with non-Sjogren's syndrome (9.5%) was significant difference (p = 0.008). Adjusted odds ratio for secondary Sjogren's syndrome in OSDIL score > 25 was 13.8 (95% CI 2.6 to 73.8, p = 0.002) compared to OSDI score dry eye syndrome and secondary Sjogren's syndrome in rheumatoid arthritis was crucial for evaluation of their severity and proper management.

Molecular beam epitaxy a short history

CERN Document Server

Orton, J W

2015-01-01

This volume describes the development of molecular beam epitaxy from its origins in the 1960s through to the present day. It begins with a short historical account of other methods of crystal growth, both bulk and epitaxial, to set the subject in context, emphasising the wide range of semiconductor materials employed. This is followed by an introduction to molecular beams and their use in the Stern-Gerlach experiment and the development of the microwave MASER.

Severe obstructive sleep apnoea syndrome in an adult patient with Laron syndrome.

Science.gov (United States)

Dagan, Y; Abadi, J; Lifschitz, A; Laron, Z

2001-08-01

A 68 year old patient with Laron syndrome (primary growth hormone (GH) resistance-insensitivity due to a molecular defect of the GH receptor) and severe obstructive sleep apnoea syndrome is described. Treatment with continuous positive air pressure therapy resulted in improved nocturnal sleep, daytime alertness and cognitive functions. Copyright 2001 Harcourt Publishers Ltd.

The history of Old World camelids in the light of molecular genetics.

Science.gov (United States)

Burger, Pamela Anna

2016-06-01

Old World camels have come into the focus as sustainable livestock species, unique in their morphological and physiological characteristics and capable of providing vital products even under extreme environmental conditions. The evolutionary history of dromedary and Bactrian camels traces back to the middle Eocene (around 40 million years ago, mya), when the ancestors of Camelus emerged on the North American continent. While the genetic status of the two domestic species has long been established, the wild two-humped camel has only recently been recognized as a separate species, Camelus ferus, based on molecular genetic data. The demographic history established from genome drafts of Old World camels shows the independent development of the three species over the last 100,000 years with severe bottlenecks occurring during the last glacial period and in the recent past. Ongoing studies involve the immune system, relevant production traits, and the global population structure and domestication of Old World camels. Based on the now available whole genome drafts, specific metabolic pathways have been described shedding new light on the camels' ability to adapt to desert environments. These new data will also be at the origin for genome-wide association studies to link economically relevant phenotypes to genotypes and to conserve the diverse genetic resources in Old World camelids.

Skin symptoms in four ectodermal dysplasia syndromes including two case reports of Rapp-Hodgkin-Syndrome.

Science.gov (United States)

Knaudt, Björn; Volz, Thomas; Krug, Markus; Burgdorf, Walter; Röcken, Martin; Berneburg, Mark

2012-01-01

The skin, hair and nail changes in four distinct ectodermal dysplasia syndromes are compared and reviewed. These syndromes comprise Christ-Siemens-Touraine syndrome; ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome; ankyloblepharon-ectodermal defects-cleft lip/palate syndrome and Rapp-Hodgkin syndrome. A comprehensive overview of the dermatological signs and symptoms in these syndromes was generated from the database of the Ectodermal Dysplasia Network Germany, the clinical findings in the patients seen in our department and an extensive review of the literature. The findings included abnormalities of skin, sweating, hair and nails. These clinical findings are discussed in relation to the underlying molecular defects known to play a role in these four ectodermal dysplasia syndromes.

Cotard's delusion or syndrome?: a conceptual history.

Science.gov (United States)

Berrios, G E; Luque, R

1995-01-01

This report offers an account of the historical construction of Cotard's syndrome showing that by délire des négations the French author meant a subtype of depressive illness. Subsequent debate led first to the belief that it was just a collection of symptoms associated with agitated depression (anxious melancholia) or general paralysis, and later to the view that it might after all constitute a separate entity. At the present moment, and impervious to the fact that the French term délire means far more than "delusion," some authors use Cotard's syndrome to refer to the belief of being dead and suggest that such a delusion might have a specific brain location. From the clinical and evolutionary perspective, it is unclear why a delusion should merit, simply because of its "nihilistic" content, a special brain location or presage chronicity. It is suggested here that before neurobiologic speculation starts, efforts should be made to map out the clinical features and correlations of the délire des négations.

A molecular diagnostic test for persistent Müllerian duct syndrome in miniature schnauzer dogs.

Science.gov (United States)

Pujar, S; Meyers-Wallen, V N

2009-01-01

In persistent Müllerian duct syndrome (PMDS), Müllerian ducts fail to regress in males during sexual differentiation. In the canine miniature schnauzer model, PMDS is caused by a C to T transition in exon 3 of the Müllerian inhibiting substance type II receptor (MISRII), which introduces a DdeI restriction site. Here we report a molecular diagnostic test for PMDS in the miniature schnauzer to identify affected dogs and carriers. As our test results suggest that the mutation is identical by descent in affected dogs of this breed, the test could be used to eliminate this mutation from the miniature schnauzer breed worldwide.

C-reactive protein, high-molecular-weight adiponectin and development of metabolic syndrome in the Japanese general population: a longitudinal cohort study.

Directory of Open Access Journals (Sweden)

Yoshifumi Saisho

Full Text Available AIMS: To clarify predictive values of C-reactive protein (CRP and high-molecular-weight (HMW adiponectin for development of metabolic syndrome. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of Japanese workers who had participated in an annual health checkup in 2007 and 2011. A total of 750 subjects (558 men and 192 women, age 46±8 years who had not met the criteria of metabolic syndrome and whose CRP and HMW-adiponectin levels had been measured in 2007 were enrolled in this study. Associations between CRP, HMW-adiponectin and development of metabolic syndrome after 4 years were assessed by logistic regression analysis and their predictive values were compared by receiver operating characteristic analysis. RESULTS: Among 750 subjects, 61 (8.1% developed metabolic syndrome defined by modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III criteria and 53 (7.1% developed metabolic syndrome defined by Japan Society for the Study of Obesity (JASSO in 2011. Although CRP and HMW-adiponectin were both significantly correlated with development of metabolic syndrome, multivariate logistic regression analysis revealed that HMW-adiponectin but not CRP was associated with metabolic syndrome independently of BMI or waist circumference. Adding these biomarkers to BMI or waist circumference did not improve the predictive value for metabolic syndrome. CONCLUSION: Our findings indicate that the traditional markers of adiposity such as BMI or waist circumference remain superior markers for predicting metabolic syndrome compared to CRP, HMW-adiponectin, or the combination of both among the Japanese population.

Poland's Syndrome: A Case Report

African Journals Online (AJOL)

jen

The Poland's anomaly was first described in 1841 by Sir Alfred Poland as a syndrome presenting with absence or underdevelopment of pectoralis ... He was the second child in a family of four. There was no familial history of similar .... hypoplasia: a middle degree of Poland syndrome. Acta Radiologica 1996; 37: 759-762. 8.

Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments

Directory of Open Access Journals (Sweden)

Bas Verbruggen

2016-01-01

Full Text Available Since its emergence in the 1990s, White Spot Disease (WSD has had major economic and societal impact in the crustacean aquaculture sector. Over the years shrimp farming alone has experienced billion dollar losses through WSD. The disease is caused by the White Spot Syndrome Virus (WSSV, a large dsDNA virus and the only member of the Nimaviridae family. Susceptibility to WSSV in a wide range of crustacean hosts makes it a major risk factor in the translocation of live animals and in commodity products. Currently there are no effective treatments for this disease. Understanding the molecular basis of disease processes has contributed significantly to the treatment of many human and animal pathogens, and with a similar aim considerable efforts have been directed towards understanding host–pathogen molecular interactions for WSD. Work on the molecular mechanisms of pathogenesis in aquatic crustaceans has been restricted by a lack of sequenced and annotated genomes for host species. Nevertheless, some of the key host–pathogen interactions have been established: between viral envelope proteins and host cell receptors at initiation of infection, involvement of various immune system pathways in response to WSSV, and the roles of various host and virus miRNAs in mitigation or progression of disease. Despite these advances, many fundamental knowledge gaps remain; for example, the roles of the majority of WSSV proteins are still unknown. In this review we assess current knowledge of how WSSV infects and replicates in its host, and critique strategies for WSD treatment.

Diagnosis of a terminal deletion of 4p with duplication of Xp22.31 in a patient with findings of Opitz G/BBB syndrome and Wolf-Hirschhorn syndrome.

Science.gov (United States)

So, Joyce; Müller, Ines; Kunath, Melanie; Herrmann, Susanne; Ullmann, Reinhard; Schweiger, Susann

2008-01-01

Opitz G/BBB syndrome (OS) is a congenital midline malformation syndrome characterized by hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and cardiac defects. The X-linked form is caused by mutations in the MID1 gene, while no gene has yet been identified for the autosomal dominant form. Here, we report on a 15-year-old boy who was referred for MID1 mutation analysis with findings typical of OS, including apparent hypertelorism, hypospadias, a history of feeding difficulties, dysphagia secondary to esophageal arteria lusoria, growth retardation and developmental delay. No MID1 mutation was found, but subsequent sub-megabase resolution array CGH unexpectedly documented a 2.34 Mb terminal 4p deletion, suggesting a diagnosis of WHS, and a duplication in Xp22.31. Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving terminal chromosome 4p deletions, in particular 4p16.3. WHS is characterized by typical facial appearance ("Greek helmet facies"), mental retardation, congenital hypotonia, and growth retardation. While the severity of developmental delay in this patient supports the diagnosis of WHS rather than OS, this case illustrates the striking similarities of clinical findings in seemingly unrelated syndromes, suggesting common or interacting pathways at the molecular and pathogenetic level. This is the first report of arteria lusoria (esophageal vascular ring) in a patient with WHS. (c) 2007 Wiley-Liss, Inc.

Syndrome in question: Gorlin-Goltz syndrome.

Science.gov (United States)

Ribeiro, Pauline Lyrio; Souza, João Basílio de; Abreu, Karina Demoner de; Brezinscki, Marisa Simon; Pignaton, Christine Chambo

2016-01-01

The Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an uncommon disorder caused by a mutation in Patched, tumor suppressor gene. It is mainly characterized by numerous early onset basal cell carcinomas, odontogenic cysts of jaw and skeletal abnormalities. Due to the wide clinical spectrum, treatment and management of its modalities are not standardized and should be individualized and monitored by a multidisciplinary team. We report a typical case in a 30-year-old man with multiple basal cell carcinomas, keratotic pits of palmar creases and bifid ribs, with a history of several corrective surgeries for keratocystic odontogenic tumors, among other lesions characteristic of the syndrome.

Diagnosis in Prader-Willi syndrome.

OpenAIRE

Chu, C E; Cooke, A; Stephenson, J B; Tolmie, J L; Clarke, B; Parry-Jones, W L; Connor, J M; Donaldson, M D

1994-01-01

Thirty one patients with the putative diagnosis of Prader-Willi syndrome were reassessed clinically and by DNA analysis. Eleven patients were judged not to have Prader-Willi syndrome and 20 to have the condition. This was confirmed by DNA analysis in all but one case. The diagnosis of Prader-Willi syndrome, especially in early infancy, should be made with caution unless confirmed by molecular genetic studies.

Diagnostic yield of molecular autopsy in patients with sudden arrhythmic death syndrome using targeted exome sequencing

DEFF Research Database (Denmark)

Nunn, Laurence M; Lopes, Luis R; Syrris, Petros

2016-01-01

AIMS: The targeted genetic screening of Sudden Arrhythmic Death Syndrome (SADS) probands in a molecular autopsy has a diagnostic yield of up to 35%. Exome sequencing has the potential to improve this yield. The primary aim of this study is to examine the feasibility and diagnostic utility...... of targeted exome screening in SADS victims, utilizing familial clinical screening whenever possible. METHODS AND RESULTS: To determine the feasibility and diagnostic yield of targeted exome sequencing deoxyribonucleic acid (DNA) was isolated from 59 SADS victims (mean age 25 years, range 1-51 years...... previously published rare (0.02-0.5%) candidate mutations-a total yield of 29%. Co-segregation fully confirmed two private SCN5A Na channel mutations. Variants of unknown significance were detected in a further 34% of probands. CONCLUSION: Molecular autopsy using targeted exome sequencing has a relatively...

CHARGE and Kabuki syndromes: a phenotypic and molecular link.

Science.gov (United States)

Schulz, Yvonne; Freese, Luisa; Mänz, Johanna; Zoll, Barbara; Völter, Christiane; Brockmann, Knut; Bögershausen, Nina; Becker, Jutta; Wollnik, Bernd; Pauli, Silke

2014-08-15

CHARGE syndrome is a complex developmental disorder caused by mutations in the chromodomain helicase DNA-binding gene CHD7. Kabuki syndrome, another developmental disorder, is characterized by typical facial features in combination with developmental delay, short stature, prominent digit pads and visceral abnormalities. Mutations in the KMT2D gene, which encodes a H3K4 histone methyltransferase, are the major cause of Kabuki syndrome. Here, we report a patient, who was initially diagnosed with CHARGE syndrome based on the spectrum of inner organ malformations like choanal hypoplasia, heart defect, anal atresia, vision problems and conductive hearing impairment. While sequencing and MLPA analysis of all coding exons of CHD7 revealed no pathogenic mutation, sequence analysis of the KMT2D gene identified the heterozygous de novo nonsense mutation c.5263C > T (p.Gln1755*). Thus, our patient was diagnosed with Kabuki syndrome. By using co-immunoprecipitation, immunohistochemistry and direct yeast two hybrid assays, we could show that, like KMT2D, CHD7 interacts with members of the WAR complex, namely WDR5, ASH2L and RbBP5. We therefore propose that CHD7 and KMT2D function in the same chromatin modification machinery, thus pointing out a mechanistic connection, and presenting a probable explanation for the phenotypic overlap between Kabuki and CHARGE syndromes. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Branchio-otic syndrome caused by a genomic rearrangement: clinical findings and molecular cytogenetic studies in a patient with a pericentric inversion of chromosome 8.

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Schmidt, T; Bierhals, T; Kortüm, F; Bartels, I; Liehr, T; Burfeind, P; Shoukier, M; Frank, V; Bergmann, C; Kutsche, K

2014-01-01

Branchio-oto-renal (BOR) syndrome is an autosomal dominantly inherited developmental disorder, which is characterized by anomalies of the ears, the branchial arches and the kidneys. It is caused by mutations in the genes EYA1,SIX1 and SIX5. Genomic rearrangements of chromosome 8 affecting the EYA1 gene have also been described. Owing to this fact, methods for the identification of abnormal copy numbers such as multiplex ligation-dependent probe amplification (MLPA) have been introduced as routine laboratory techniques for molecular diagnostics of BOR syndrome. The advantages of these techniques are clear compared to standard cytogenetic and array approaches as well as Southern blot. MLPA detects deletions or duplications of a part or the entire gene of interest, but not balanced structural aberrations such as inversions and translocations. Consequently, disruption of a gene by a genomic rearrangement may escape detection by a molecular genetic analysis, although this gene interruption results in haploinsufficiency and, therefore, causes the disease. In a patient with clinical features of BOR syndrome, such as hearing loss, preauricular fistulas and facial dysmorphisms, but no renal anomalies, neither sequencing of the 3 genes linked to BOR syndrome nor array comparative genomic hybridization and MLPA were able to uncover a causative mutation. By routine cytogenetic analysis, we finally identified a pericentric inversion of chromosome 8 in the affected female. High-resolution multicolor banding confirmed the chromosome 8 inversion and narrowed down the karyotype to 46,XX,inv(8)(p22q13). By applying fluorescence in situ hybridization, we narrowed down both breakpoints on chromosome 8 and found the EYA1 gene in q13.3 to be directly disrupted. We conclude that standard karyotyping should not be neglected in the genetic diagnostics of BOR syndrome or other Mendelian disorders, particularly when molecular testing failed to detect any causative alteration in patients with

Metabolic syndrome: clinical concept and molecular basis.

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Funahashi, Tohru; Matsuzawa, Yuji

2007-01-01

The metabolic syndrome is a cluster of insulin resistance, elevated blood pressure, and atherogenic dyslipidemia and is a common basis of cardiovascular diseases (CVD). Although the precise mechanism remains to be elucidated, a practical definition is needed. A worldwide definition that considers increased waist circumference as an essential component has been settled. Visceral fat locates upstream of the liver. Free fatty acids and glycerol derived from visceral fat reach the liver and stimulate lipoprotein synthesis and gluconeogenesis, respectively. The adipose tissue produces a variety of bioactive substances conceptualized as 'adipocytokines'. Overproduction of plasminogen activator inhibitor-1 and tumor necrosis factor- seems to relate to the thrombotic and inflammatory tendency. On the other hand, adiponectin, which has antiatherogenic and antidiabetic activities, is reduced in subjects with metabolic syndrome. In Japan, the waist circumference criterion based on visceral fat accumulation has been adopted. The concept of this syndrome has been widely publicized, and health promotion programs based on the concept have commenced in various areas of the country. Such 'Adipo-Do-It' movement is an incentive to encourage physical exercise to reduce visceral fat and is a big challenge to prevent life-style-related diseases and CVD.

Chromosomal Instability and Molecular Defects in Induced Pluripotent Stem Cells from Nijmegen Breakage Syndrome Patients

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Tomer Halevy

2016-08-01

Full Text Available Nijmegen breakage syndrome (NBS results from the absence of the NBS1 protein, responsible for detection of DNA double-strand breaks (DSBs. NBS is characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. Here, we show successful reprogramming of NBS fibroblasts into induced pluripotent stem cells (NBS-iPSCs. Our data suggest a strong selection for karyotypically normal fibroblasts to go through the reprogramming process. NBS-iPSCs then acquire numerous chromosomal aberrations and show a delayed response to DSB induction. Furthermore, NBS-iPSCs display slower growth, mitotic inhibition, a reduced apoptotic response to stress, and abnormal cell-cycle-related gene expression. Importantly, NBS neural progenitor cells (NBS-NPCs show downregulation of neural developmental genes, which seems to be mediated by P53. Our results demonstrate the importance of NBS1 in early human development, shed light on the molecular mechanisms underlying this severe syndrome, and further expand our knowledge of the genomic stress cells experience during the reprogramming process.

LKB1 as the ghostwriter of crypt history

NARCIS (Netherlands)

Jansen, Marnix; Langeveld, Danielle; De Leng, Wendy W. J.; Milne, Anya N. A.; Giardiello, Francis M.; Offerhaus, G. Johan A.

Familial cancer syndromes present rare insights into malignant tumor development. The molecular background of polyp formation and the cancer prone state in Peutz-Jeghers syndrome remain enigmatic to this day. Previously, we proposed that Peutz-Jeghers polyps are not pre-malignant lesions, but an

Usher's syndrome--case report.

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Kwiecień, Sława; Sulak, Robert; Szaflik, Jerzy

2008-01-01

The aim of this study is to present a case of coincidence of sensorineural hearing loss with chronic recurrent bilateral cystoid macular oedema in a 32-year-old woman, who was admitted to the clinic for deterioration of visual acuity of four months' duration. The patient gave a history of hearing loss for 29 years. Visual field examination disclosed peripheral ring scotoma. Electrophysiological examination was performed: pattern visual evoked response was within normal limits and electroretinogram displayed diminished both photopic and scotopic response. As ophthalmoscopy demonstrated no pigment in the fundus of the eye, the findings were consisted with diagnosis of retinitis pigmentosis sine pigmento. The presence of loss of hearing indicated the necessity of performing the genetic examination for Usher's syndrome. In order to establish a final diagnosis of Usher's syndrome genetic examination must be performed, but family history is relevant. Early investigation for Usher's syndrome in children with sensorineural hearing impairment is of a great significance. The patient may develop symptoms of retinitis pigmentosa in second or even third decade of his life. The necessity of thorough investigation for detecting other systemic abnormalities should be emphasized. There is no effective treatment of this syndrome. A child with Usher's syndrome requires a comprehensive care of different medical specialties. Psychological, educational and sociological attitude is also of a great importance in the child development.

Lemierre's syndrome.

LENUS (Irish Health Repository)

O'Dwyer, D N

2012-02-01

Lemierre\\'s syndrome is a rare disease that results in an oropharyngeal infection, which precipitates an internal jugular vein thrombosis and metastatic infection. Fusobacterium necrophorum is an anaerobic Gram-negative bacillus and has been identified as the causative agent. We describe the case of a young girl whose presentation and diagnosis were confounded by a history of valvular heart disease. Infection of heart valves can produce many of the signs and symptoms associated with Lemierre\\'s syndrome. We describe the diagnosis, investigation and optimal management of this rare disorder.

[Clinical characteristics of Rett Syndrome].

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Abbes, Zeineb; Bouden, Asma; Halayem, Soumaya; Othman, Sami; Bechir Halayem, Mohamed

2011-10-01

Rett Syndrome is a neurodevelopmental disorder, one of the least commonly occurring autism spectrum disorders (ASD),affecting mainly females. To describe features and molecular specificities of Rett syndrome. To identify articles for this review, a Pubmed search was conducted using the following keywords: Rett syndrome, regression,mutation, stereotypes. This syndrome is characterized by cognitive impairment,communication dysfunction, stereotypic movement disorder, and growth failure. It is generally caused by mutations in the MECP2 gene. Rett Syndrome has a prevalence ranging from 10-20 000 females. Specific treatment is not available, but patients need a careful planning for long-term care, with multidisciplinary approaches.

Hennekam lymphangiectasia syndrome

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Lakshminarayana, G.; Mathew, A.; Rajesh, R.; Kurien, G.; Unni, V. N.

2011-01-01

Hennekam lymphangiectasia syndrome is a rare disorder comprising of intestinal and renal lymphangiectasia, dysmorphic facial appearance and mental retardation. The facial features include hypertelorism with a wide, flat nasal bridge, epicanthic folds, small mouth and small ears. We describe a case of a multigravida with bad obstetric history and characteristic facial and dental anomalies and bilateral renal lymphangiectasia. To our knowledge this is the first case of Hennekam lymphangiectasia syndrome with anodontia to be reported from India. PMID:22022089

A Review of Von Hippel-Lindau Syndrome

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Neha Varshney

2017-08-01

Full Text Available Von Hippel-Lindau syndrome (VHL is a familial neoplastic condition seen in approximately 1 in 36,000 live births. It is caused by germline mutations of the tumor suppressor gene VHL, located on the short arm of chromosome 3. While the majority of the affected individuals have a positive family history, up to 20% of cases arise from de novo mutations. VHL syndrome is characterized by the presence of benign and malignant tumors affecting the central nervous system, kidneys, adrenals, pancreas, and reproductive organs. Common manifestations include hemangioblastomas of the brain, spinal cord, and retina; pheochromocytoma and paraganglioma; renal cell carcinoma; pancreatic cysts and neuroendocrine tumors; and endolymphatic sac tumors. Diagnosis of VHL is prompted by clinical suspicion and confirmed by molecular testing. Management of VHL patients is complex and multidisciplinary. Routine genetic testing and surveillance using various diagnostic techniques are used to help monitor disease progression and implement treatment options. Despite recent advances in clinical diagnosis and management, life expectancy for VHL patients remains low at 40–52 years. This article provides an overview of the major clinical, histological, and radiological findings, as well as treatment modalities.

Biological Factors Associated with Asperger Syndrome.

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Rickarby, Geoff; And Others

1991-01-01

This paper reviews Asperger Syndrome, a form of developing autism with average intelligence, in 12 boys (ages 5 to late teens). Examination of family histories, medical history and findings, obstetric, and neonatal data found no common environmental factors and supports a brain damage hypothesis. (DB)

Lynch syndrome: still not a familiar picture

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Hes Frederik J

2008-02-01

Full Text Available Abstract Background Germ line mutations in mismatch repair genes underlie Lynch syndrome and predispose carriers for colorectal carcinoma and malignancies in many other organ systems. Case presentation A large Lynch syndrome family with 15 affected family members and involvement in 7 organs is reported. It illustrates a lack of awareness and knowledge about this hereditary tumor syndrome among doctors as well as patients. None of the described family members underwent presymptomatic screening on the basis of the family history. Conclusion Hereditary features, like young age at diagnosis, multiple tumors in multiple organs and a positive family history, should lead to timely referral of suspected cases for genetic counseling and diagnostics. For Lynch syndrome, these features can be found in the Amsterdam and Bethesda criteria. Subsequently, early identification of mutation carriers might have diminished, at least in part, the high and early morbidity and mortality observed in this family.

Xeroderma Pigmentosum with Severe Neurological Manifestations/De Sanctis–Cacchione Syndrome and a Novel XPC Mutation

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Esteban Uribe-Bojanini

2017-01-01

Full Text Available Several genetic disorders caused by defective nucleotide excision repair that affect the skin and the nervous system have been described, including Xeroderma Pigmentosum (XP, De Sanctis–Cacchione syndrome (DSC, Cockayne syndrome, and Trichothiodystrophy. Cutaneous photosensitivity with an increased risk of skin malignancy is a common feature of these disorders, but clinical manifestations commonly overlap these syndromes. Several genes have been found to be altered in these pathologies, but we lack more genotype-phenotype correlations in order to make an accurate diagnosis. Very few cases of DSC syndrome have been reported in the literature. We present a case of a 12-year-old Colombian male, with multiple skin lesions in sun-exposed areas from the age of 3 months and a history of 15 skin cancers. He also displayed severe neurologic abnormalities (intellectual disability, ataxia, altered speech, and hyperreflexia, short stature, and microcephaly, which are features associated with DSC. Genetic testing revealed a novel germline mutation in the XP-C gene (c.547A>T. This is the first case of an XP-C mutation causing De Sanctis–Cacchione syndrome. Multigene panel testing is becoming more widely available and accessible in the clinical setting and will help rapidly unveil the molecular etiology of these rare genetic disorders.

Xeroderma Pigmentosum with Severe Neurological Manifestations/De Sanctis–Cacchione Syndrome and a Novel XPC Mutation

Science.gov (United States)

Hernandez-Quiceno, Sara

2017-01-01

Several genetic disorders caused by defective nucleotide excision repair that affect the skin and the nervous system have been described, including Xeroderma Pigmentosum (XP), De Sanctis–Cacchione syndrome (DSC), Cockayne syndrome, and Trichothiodystrophy. Cutaneous photosensitivity with an increased risk of skin malignancy is a common feature of these disorders, but clinical manifestations commonly overlap these syndromes. Several genes have been found to be altered in these pathologies, but we lack more genotype-phenotype correlations in order to make an accurate diagnosis. Very few cases of DSC syndrome have been reported in the literature. We present a case of a 12-year-old Colombian male, with multiple skin lesions in sun-exposed areas from the age of 3 months and a history of 15 skin cancers. He also displayed severe neurologic abnormalities (intellectual disability, ataxia, altered speech, and hyperreflexia), short stature, and microcephaly, which are features associated with DSC. Genetic testing revealed a novel germline mutation in the XP-C gene (c.547A>T). This is the first case of an XP-C mutation causing De Sanctis–Cacchione syndrome. Multigene panel testing is becoming more widely available and accessible in the clinical setting and will help rapidly unveil the molecular etiology of these rare genetic disorders. PMID:28255305

Molecular genetics of Turner syndrome: correlation with clinical phenotype and response to growth hormone therapy.

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Tsezou, A; Hadjiathanasiou, C; Gourgiotis, D; Galla, A; Kavazarakis, E; Pasparaki, A; Kapsetaki, M; Sismani, C; Theodoridis, C; Patsalis, P C; Moschonas, N; Kitsiou, S

1999-12-01

To correlate the origin of the retained X in Turner syndrome with phenotype, pre-treatment height and response to recombinant human growth hormone (rhGH) therapy, systematic clinical assessment and molecular studies were carried out in 33 Greek children with Turner syndrome and their parents including 18 children with 45,X and 15 with X-mosaicism. Microsatellite markers on X chromosomes (DXS101 and DXS337) revealed that the intact X was paternal (Xp) in 15/30 and maternal (Xm) in 15/30 children, while 3/33 families were non-informative. No significant relationship was found between parental origin of the retained X and birth weight/length/gestational age, blepharoptosis, pterygium colli, webbed neck, low hairline, abnormal ears, lymphoedema, short 4th metacarpal, shield chest, widely spaced nipples, cubitus valgus, pigmented naevi, streak gonads, and cardiovascular/renal anomalies. With regard to the children's pre-treatment height, there was a significant correlation with maternal height and target height in both Xm and Xp groups. No differences were found between Xm and Xp groups and the improvement of growth velocity (GV) during the first and second year of rhGH administration, while for both groups GV significantly improved with rhGH by the end of the first and the second year. To our knowledge, this is the first attempt to correlate the parental origin of Turner syndrome with the response to rhGH therapy.

Diagnosis, natural history, and management in vascular Ehlers-Danlos syndrome.

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Byers, Peter H; Belmont, John; Black, James; De Backer, Julie; Frank, Michael; Jeunemaitre, Xavier; Johnson, Diana; Pepin, Melanie; Robert, Leema; Sanders, Lynn; Wheeldon, Nigel

2017-03-01

Vascular Ehlers Danlos syndrome (vEDS) is an uncommon genetic disorders characterized by arterial aneurysm, dissection and rupture, bowel rupture, and rupture of the gravid uterus. The frequency is estimated as 1/50,000-1/200,000 and results from pathogenic variants in COL3A1, which encodes the chains of type III procollagen, a major protein in vessel walls and hollow organs. Initial diagnosis depends on the recognitions of clinical features, including family history. Management is complex and requires multiple specialists who can respond to and manage the major complications. A summary of recommendations for management include: Identify causative variants in COL3A1 prior to application of diagnosis, modulate life style to minimize injury, risk of vessel/organ rupture, identify and create care team, provide individual plans for emergency care ("vascular EDS passport") with diagnosis and management plan for use when traveling, centralize management at centers of excellence (experience) when feasible, maintain blood pressure in the normal range and treat hypertension aggressively, surveillance of vascular tree by doppler ultrasound, CTA (low radiation alternatives) or MRA if feasible on an annual basis. These recommendations represent a consensus of an international group of specialists with a broad aggregate experience in the care of individuals with vascular EDS that will need to be assessed on a regular basis as new information develops. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation

Science.gov (United States)

2011-01-01

Background The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA) (OMIM 225400) is a rare inheritable connective tissue disorder characterized by a deficiency of collagen lysyl hydroxylase 1 (LH1; EC 1.14.11.4) due to mutations in PLOD1. Biochemically this results in underhydroxylation of collagen lysyl residues and, hence, an abnormal pattern of lysyl pyridinoline (LP) and hydroxylysyl pyridinoline (HP) crosslinks excreted in the urine. Clinically the disorder is characterized by hypotonia and kyphoscoliosis at birth, joint hypermobility, and skin hyperelasticity and fragility. Severe hypotonia usually leads to delay in gross motor development, whereas cognitive development is reported to be normal. Methods We describe the clinical, biochemical and molecular characterisation, as well as electron microscopy findings of skin, in 15 patients newly diagnosed with this rare type of Ehlers-Danlos syndrome. Results Age at diagnosis ranged from 5 months to 27 years, with only 1/3 of the patients been diagnosed correctly in the first year of life. A similar disease frequency was found in females and males, however a broad disease severity spectrum (intra- and interfamilial), independent of molecular background or biochemical phenotype, was observed. Kyphoscoliosis, one of the main clinical features was not present at birth in 4 patients. Importantly we also noted the occurrence of vascular rupture antenatally and postnatally, as well as developmental delay in 5 patients. Conclusion In view of these findings we propose that EDS VIA is a highly variable clinical entity, presenting with a broad clinical spectrum, which may also be associated with cognitive delay and an increased risk for vascular events. Genotype/phenotype association studies and additional molecular investigations in more extended EDS VIA populations will be necessary to further elucidate the cause of the variability of the disease severity. PMID:21699693

Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA: clinical, molecular and biochemical delineation

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Kariminejad Ariana

2011-06-01

Full Text Available Abstract Background The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA (OMIM 225400 is a rare inheritable connective tissue disorder characterized by a deficiency of collagen lysyl hydroxylase 1 (LH1; EC 1.14.11.4 due to mutations in PLOD1. Biochemically this results in underhydroxylation of collagen lysyl residues and, hence, an abnormal pattern of lysyl pyridinoline (LP and hydroxylysyl pyridinoline (HP crosslinks excreted in the urine. Clinically the disorder is characterized by hypotonia and kyphoscoliosis at birth, joint hypermobility, and skin hyperelasticity and fragility. Severe hypotonia usually leads to delay in gross motor development, whereas cognitive development is reported to be normal. Methods We describe the clinical, biochemical and molecular characterisation, as well as electron microscopy findings of skin, in 15 patients newly diagnosed with this rare type of Ehlers-Danlos syndrome. Results Age at diagnosis ranged from 5 months to 27 years, with only 1/3 of the patients been diagnosed correctly in the first year of life. A similar disease frequency was found in females and males, however a broad disease severity spectrum (intra- and interfamilial, independent of molecular background or biochemical phenotype, was observed. Kyphoscoliosis, one of the main clinical features was not present at birth in 4 patients. Importantly we also noted the occurrence of vascular rupture antenatally and postnatally, as well as developmental delay in 5 patients. Conclusion In view of these findings we propose that EDS VIA is a highly variable clinical entity, presenting with a broad clinical spectrum, which may also be associated with cognitive delay and an increased risk for vascular events. Genotype/phenotype association studies and additional molecular investigations in more extended EDS VIA populations will be necessary to further elucidate the cause of the variability of the disease severity.

Usher syndrome: molecular links of pathogenesis, proteins and pathways.

NARCIS (Netherlands)

Kremer, H.; Wijk, E. van; Marker, T.; Wolfrum, U.; Roepman, R.

2006-01-01

Usher syndrome is the most common form of deaf-blindness. The syndrome is both clinically and genetically heterogeneous, and to date, eight causative genes have been identified. The proteins encoded by these genes are part of a dynamic protein complex that is present in hair cells of the inner ear

Thermal histories of chondrules in solar nebula shocks, including the effect of molecular line cooling

Science.gov (United States)

Morris, Melissa A.

Chondrules are millimeter-sized, silicate (mostly ferromagnesian) igneous spheres found within chondritic meteorites. They are some of the oldest materials in our Solar System, having formed within a few million years of its birth. Chondrules were melted at high temperature (over 1800 K), while they were free-floating objects in the early solar nebula. Their petrology and chemistry constrain their formation, especially their thermal histories. Chondrules provide some of the most powerful constraints on conditions in the solar nebula. Models in which chondrule precursors melted by passage through solar nebula shocks are very promising, and meet most constraints on chondrule formation in broad brush. However, these models have been lacking in some of the relevant physics. Previous shock models have used incorrect approximations to the input radiation boundary condition, and the opacity of solids has been treated simply. Most important, a proper treatment of cooling due to molecular line emission has not been included. In this thesis, the shock model is significantly improved in order to determine if it remains consistent with observational constraints. The appropriate boundary condition for the input radiation and the proper method for calculation of the opacity of solids are determined, and a complete treatment of molecular line cooling due to water is included. Previous estimates of the effect of line cooling predicted chondrule cooling rates in excess of 10,000 K per hour. However, once molecular line cooling due to water was incorporated into the full shock model, it was found that line cooling has a minimal effect on the thermal histories of gas and chondrules. This behavior is attributed mostly to the thermal buffering of the gas due to hydrogen dissociation and recombination, which tends to keep the gas temperature at approximately 2000 K until the column densities of water become optically thick to line emission. Chondrule cooling rates in the range of 10

Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome.

Science.gov (United States)

Burkhart, Keith K; Abernethy, Darrell; Jackson, David

2015-06-01

Drug features that are associated with Stevens-Johnson syndrome (SJS) have not been fully characterized. A molecular target analysis of the drugs associated with SJS in the FDA Adverse Event Reporting System (FAERS) may contribute to mechanistic insights into SJS pathophysiology. The publicly available version of FAERS was analyzed to identify disproportionality among the molecular targets, metabolizing enzymes, and transporters for drugs associated with SJS. The FAERS in-house version was also analyzed for an internal comparison of the drugs most highly associated with SJS. Cyclooxygenases 1 and 2, carbonic anhydrase 2, and sodium channel 2 alpha were identified as disproportionately associated with SJS. Cytochrome P450 (CYPs) 3A4 and 2C9 are disproportionately represented as metabolizing enzymes of the drugs associated with SJS adverse event reports. Multidrug resistance protein 1 (MRP-1), organic anion transporter 1 (OAT1), and PEPT2 were also identified and are highly associated with the transport of these drugs. A detailed review of the molecular targets identifies important roles for these targets in immune response. The association with CYP metabolizing enzymes suggests that reactive metabolites and oxidative stress may have a contributory role. Drug transporters may enhance intracellular tissue concentrations and also have vital physiologic roles that impact keratinocyte proliferation and survival. Data mining FAERS may be used to hypothesize mechanisms for adverse drug events by identifying molecular targets that are highly associated with drug-induced adverse events. The information gained may contribute to systems biology disease models.

Wolfram Syndrome: Diagnosis, Management, and Treatment.

Science.gov (United States)

Urano, Fumihiko

2016-01-01

Wolfram syndrome is a rare genetic disorder characterized by juvenile-onset diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing loss, and neurodegeneration. Although there are currently no effective treatments that can delay or reverse the progression of Wolfram syndrome, the use of careful clinical monitoring and supportive care can help relieve the suffering of patients and improve their quality of life. The prognosis of this syndrome is currently poor, and many patients die prematurely with severe neurological disabilities, raising the urgency for developing novel treatments for Wolfram syndrome. In this article, we describe natural history and etiology, provide recommendations for diagnosis and clinical management, and introduce new treatments for Wolfram syndrome.

Constitutional MLH1 methylation presenting with colonic polyposis syndrome and not Lynch syndrome.

Science.gov (United States)

Kidambi, Trilokesh D; Blanco, Amie; Van Ziffle, Jessica; Terdiman, Jonathan P

2016-04-01

At least one-third of patients meeting clinical criteria for Lynch syndrome will have no germline mutation and constitutional epimutations leading to promoter methylation of MLH1 have been identified in a subset of these patients. We report the first case of constitutional MLH1 promoter methylation associated with a colonic polyposis syndrome in a 39 year-old man with a family history of colorectal cancer (CRC) and a personal history of 21 polyps identified over 8 years as well as the development of two synchronous CRCs over 16 months who was evaluated for a hereditary cancer syndrome. Immunohistochemistry (IHC) of multiple tumors showed absent MLH1 and PMS2 expression, though germline testing with Sanger sequencing and multiplex ligation-dependent probe amplification of these mismatch repair genes (MMR) genes was negative. A next generation sequencing panel of 29 genes also failed to identify a pathogenic mutation. Hypermethylation was identified in MLH1 intron 1 in tumor specimens along with buccal cells and peripheral white blood cells, confirming the diagnosis of constitutional MLH1 promoter methylation. This case highlights that constitutional MLH1 methylation should be considered in the differential diagnosis for a polyposis syndrome if IHC staining shows absent MMR gene expression.

Esthesioneuroblastoma in Maffucci's syndrome

International Nuclear Information System (INIS)

Kurian, Sobha; Crowell, Edward B.; Ertan, Esmer; Rassekh, Christopher; Ducatman, Barbara

2004-01-01

Maffucci's syndrome consists of multiple cutaneous hemangiomas, dyschondroplasia, and enchondromas with potential for malignant change. We report a case of a 33-year-old man with Maffucci's syndrome who presented with a several month history of nasal congestion, facial pain, and diminished vision in his left eye. Radiological studies showed a large soft tissue mass centered in the sinonasal area, extending bilaterally into maxillary sinuses and orbits with compression of left optic nerve. Biopsy of the mass showed esthesioneuroblastoma (olfactory neuroblastoma). Chemotherapy resulted in initial improvement, but the tumor recurred and did not respond to further treatment, resulting in his death. Sarcomatous tumors are reported in Maffucci's syndrome, but this is a rare case of a neuroendocrine tumor in a patient with Maffucci's syndrome. (orig.)

Molecular cytogenetic analysis of Inv Dup(15) chromosomes, using probes specific for the Pradar-Willi/Angelman syndrome region: Clinical implications

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Leana-Cox, J. (Univ. of Maryland School of Medicine, Baltimore, MD (United States)); Jenkins, L. (Kaiser Permanente Medical Group, San Jose, CA (United States)); Palmer, C.G.; Plattner, R. (Indiana School of Medicine, Indianapolis, IN (United States)); Sheppard, L. (Palo Verde Laboratory, Inc., Chandler, AZ (United States)); Flejter, W.L. (Univ. of Michigan, Ann Arbor, MI (United States)); Zackowski, J. (Univ. of Florida Health Science Center, Gainsville, FL (United States)); Tsien, F. (Tulane Univ. School of Medicine, New Orleans, LA (United States)); Schwartz, S. (Case Western Reserve Univ., Cleveland, OH (United States))

1994-05-01

Twenty-seven cases of inverted duplications of chromosome 15 (inv dup[15]) were investigated by FISH with two DNA probes specific for the Prader-Willi syndrome/Angelman syndrome (PWS/AS) region on proximal 15q. Sixteen of the marker chromosomes displayed two copies of each probe, while in the remaining 11 markers no hybridization was observed. A significant association was found between the presence of this region and an abnormal phenotype (P<.01). This is the largest study to date of inv dup(15) chromosomes, that uses molecular cytogenetic methods and is the first to report a significant association between the presence of a specific chromosomal region in such markers and an abnormal phenotype. 30 refs., 1 fig., 4 tabs.

Metastatic neuroendocrine tumor with initial presentation of orbital apex syndrome

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Yen-Yu Huang

2017-03-01

Full Text Available The possible etiologies of orbital apex syndrome range from inflammatory, infectious, neoplastic, iatrogenic/traumatic, to vascular processes. In patients without obvious infection or systemic cancer history, judicious use of corticosteroids is a reasonable strategy. We describe a 64-year-old man who presented with orbital apex syndrome and had progressed to total visual loss in three days after admission. Radiological imaging and pathological studies were consistent with a neuroendocrine tumor with multiple metastases. We recommend that a biopsy-proven specimen is warranted in patient with orbital apex syndrome even without a cancer history.

Clinicopathologic and Molecular Features of Colorectal Adenocarcinoma with Signet-Ring Cell Component.

Directory of Open Access Journals (Sweden)

Qing Wei

Full Text Available We performed a retrospective study to assess the clinicopathological characters, molecular alterations and multigene mutation profiles in colorectal cancer patients with signet-ring cell component.Between November 2008 and January 2015, 61 consecutive primary colorectal carcinomas with signet-ring cell component were available for pathological confirmation. RAS/BRAF status was performed by direct sequencing. 14 genes associated with hereditary cancer syndromes were analyzed by targeted gene sequencing.A slight male predominance was detected in these patients (59.0%. Colorectal carcinomas with signet-ring cell component were well distributed along the large intestine. A frequently higher TNM stage at the time of diagnosis was observed, compared with the conventional adenocarcinoma. Family history of malignant tumor was remarkable with 49.2% in 61 cases. The median OS time of stage IV patients in our study was 14 months. RAS mutations were detected in 22.2% (12/54 cases with KRAS mutations in 16.7% (9/54 cases and Nras mutations in 5.4%(3/54 cases. BRAF V600E mutation was detected in 3.7% (2/54 cases. As an exploration, we analyzed 14 genes by targeted gene sequencing. These genes were selected based on their biological role in association with hereditary cancer syndromes. 79.6% cases carried at least one pathogenic mutation. Finally, the patients were classified by the percentage of signet-ring cell. 39 (63.9% cases were composed of ≥50% signet-ring cells; 22 (36.1% cases were composed of <50% signet-ring cells. We compared clinical parameters, molecular and genetic alterations between the two groups and found no significant differences.Colorectal adenocarcinoma with signet-ring cell component is characterized by advanced stage at diagnosis with remarkable family history of malignant tumor. It is likely a negative prognostic factor and tends to affect male patients with low rates of RAS /BRAF mutation. Colorectal patients with any component of

A case of Pseudo-Bartter syndrome

International Nuclear Information System (INIS)

Yang, Ik; Choi, Bo Whan; Lee, Yul; Chung, Soo Young

1994-01-01

Pseudo-Bartter Syndrome is a rare medical disease of the kidney characterized by normal blood pressure, hypokalemic metabolic alkalosis, hyperreninemia and hyperaldosteronism with drug history of diuretics. We report US, CT and MRI findings of a patients with clinically proved Pseudo-Bartter syndrome. The patient was a 37 year old woman with a history of long term ingestion of the diuretics(furosemide) for 20 years. Renal US revealed hyperechoic renal medulla at both kidneys. The resistive index(RI), calculated from the duplex doppler waveform is 0.61. Unenhanced CT revealed faint high attenuation along the medulla. T1-weighted MRI revealed indistinct corticomedullary differentiation

A case of Pseudo-Bartter syndrome

Energy Technology Data Exchange (ETDEWEB)

Yang, Ik; Choi, Bo Whan; Lee, Yul; Chung, Soo Young [College of Medicine, Hallym University, Seoul (Korea, Republic of)

1994-10-15

Pseudo-Bartter Syndrome is a rare medical disease of the kidney characterized by normal blood pressure, hypokalemic metabolic alkalosis, hyperreninemia and hyperaldosteronism with drug history of diuretics. We report US, CT and MRI findings of a patients with clinically proved Pseudo-Bartter syndrome. The patient was a 37 year old woman with a history of long term ingestion of the diuretics(furosemide) for 20 years. Renal US revealed hyperechoic renal medulla at both kidneys. The resistive index(RI), calculated from the duplex doppler waveform is 0.61. Unenhanced CT revealed faint high attenuation along the medulla. T1-weighted MRI revealed indistinct corticomedullary differentiation.

Crohn’s Disease and the Melkersson-Rosenthal Syndrome

Directory of Open Access Journals (Sweden)

Alexandra Ilnyckyj

1999-01-01

Full Text Available A 30-year-old woman with a 10-year history of recurrent bloody diarrhea and documented colitis of the descending colon, consistent with Crohn’s disease, presented with an exacerbation of her gastrointestinal disease and an 18-month history of recurrent facial and genital swelling. Her course evolved to include severe ear pain, dysphagia and colonic dysmotility. She was diagnosed with Melkersson-Rosenthal syndrome and treated with multiple agents. The neurological aspects of her presentation are highlighted, and the Melkersson-Rosenthal syndrome is reviewed.

Metabolic syndrome in acute coronary syndrome

International Nuclear Information System (INIS)

Bhalli, M.A.; Aamir, M.; Mustafa, G.

2011-01-01

Objective: To determine the frequency of metabolic syndrome in male patients presenting with acute coronary syndrome Study design: A Descriptive study Place and duration of study: Armed Forces Institute of Cardiology and National Institute of Heart Diseases, Rawalpindi, from October 2007 to September 2008 Patients and Methods: Male patients with acute coronary syndrome (ACS) were included. Patients having angioplasty (PCI), coronary artery bypass surgery in the past and other co-morbid diseases were excluded. All patients were assessed for the presence of five components of metabolic syndrome including hypertension, HDL-Cholesterol and triglycerides, glucose intolerance and abdominal obesity. Systolic, diastolic blood pressures, waist circumference (WC) and body mass index (BMI) were measured. ECG, cardiac enzymes, fasting glucose and lipid profile were also done. Results: A total of 135 male patients of ACS were studied with a mean age of 54.26 +- 11 years. Metabolic syndrome (MS) was present in 55 (40.7%) patients. MS with all five components was documented in 4 (7.27%) while MS with four and three components was seen in 23 (41.81%) and 28 (50.90%) patients respectively. Only 24 (43.63%) patients with MS had diabetes mellitus, remaining 31(56.36%) were non diabetic. Frequencies of diabetes, hypertension and family history of CAD were significantly higher (p<0.05) in patients with metabolic syndrome as compared to patients with normal metabolic status. Conclusion: Metabolic syndrome is fairly common and important risk factor in patients of IHD. Other risk factors like smoking, dyslipidemia, hypertension and diabetes were also frequently found. Public awareness to control the risk factors can reduce the prevalence of CAD in our country. (author)

Metabolic syndrome in acute coronary syndrome

Energy Technology Data Exchange (ETDEWEB)

Bhalli, M A; Aamir, M; Mustafa, G [Combined Military Hospital, Abbottabad (Pakistan)

2011-06-15

Objective: To determine the frequency of metabolic syndrome in male patients presenting with acute coronary syndrome Study design: A Descriptive study Place and duration of study: Armed Forces Institute of Cardiology and National Institute of Heart Diseases, Rawalpindi, from October 2007 to September 2008 Patients and Methods: Male patients with acute coronary syndrome (ACS) were included. Patients having angioplasty (PCI), coronary artery bypass surgery in the past and other co-morbid diseases were excluded. All patients were assessed for the presence of five components of metabolic syndrome including hypertension, HDL-Cholesterol and triglycerides, glucose intolerance and abdominal obesity. Systolic, diastolic blood pressures, waist circumference (WC) and body mass index (BMI) were measured. ECG, cardiac enzymes, fasting glucose and lipid profile were also done. Results: A total of 135 male patients of ACS were studied with a mean age of 54.26 +- 11 years. Metabolic syndrome (MS) was present in 55 (40.7%) patients. MS with all five components was documented in 4 (7.27%) while MS with four and three components was seen in 23 (41.81%) and 28 (50.90%) patients respectively. Only 24 (43.63%) patients with MS had diabetes mellitus, remaining 31(56.36%) were non diabetic. Frequencies of diabetes, hypertension and family history of CAD were significantly higher (p<0.05) in patients with metabolic syndrome as compared to patients with normal metabolic status. Conclusion: Metabolic syndrome is fairly common and important risk factor in patients of IHD. Other risk factors like smoking, dyslipidemia, hypertension and diabetes were also frequently found. Public awareness to control the risk factors can reduce the prevalence of CAD in our country. (author)

Avoiding Pitfalls in Molecular Genetic Testing: Case Studies of High-Resolution Array Comparative Genomic Hybridization Testing in the Definitive Diagnosis of Mowat-Wilson Syndrome

OpenAIRE

Kluk, Michael Joseph; An, Yu; James, Philip; Coulter, David; Harris, David; Wu, Bai-Lin; Shen, Yiping

2011-01-01

The molecular testing options available for the diagnosis of genetic disorders are numerous and include a variety of different assay platforms. The consultative input of molecular pathologists and cytogeneticists, working closely with the ordering clinicians, is often important for definitive diagnosis. Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology. Initial molecular testing in both ca...

Molecular diagnostic testing for Klinefelter syndrome and other male sex chromosome aneuploidies

Directory of Open Access Journals (Sweden)

Hager Karl

2012-04-01

Full Text Available Abstract Background Male sex chromosome aneuploidies are underdiagnosed despite concomitant physical and behavioral manifestations. Objective To develop a non-invasive, rapid and high-throughput molecular diagnostic assay for detection of male sex chromosome aneuploidies, including 47,XXY (Klinefelter, 47,XYY, 48,XXYY and 48,XXXY syndromes. Methods The assay utilizes three XYM and four XA markers to interrogate Y:X and X:autosome ratios, respectively. The seven markers were PCR amplified using genomic DNA isolated from a cohort of 323 males with aneuploid (n = 117 and 46,XY (n = 206 karyotypes. The resulting PCR products were subjected to Pyrosequencing, a quantitative DNA sequencing method. Results Receiver operator characteristic (ROC curves were used to establish thresholds for the discrimination of aneuploid from normal samples. The XYM markers permitted the identification of 47,XXY, 48,XXXY and 47,XYY syndromes with 100% sensitivity and specificity in both purified DNA and buccal swab samples. The 48,XXYY karyotype was delineated by XA marker data from 46,XY; an X allele threshold of 43% also permitted detection of 48,XXYY with 100% sensitivity and specificity. Analysis of X chromosome-specific biallelic SNPs demonstrated that 43 of 45 individuals (96% with 48,XXYY karyotype had two distinct X chromosomes, while 2 (4% had a duplicate X, providing evidence that 48,XXYY may result from nondisjunction during early mitotic divisions of a 46,XY embryo. Conclusions Quantitative Pyrosequencing, with high-throughput potential, can detect male sex chromosome aneuploidies with 100% sensitivity.

Superior Mesenteric Artery Syndrome: An Uncommon Cause of ...

African Journals Online (AJOL)

comprehensive series of 75 patients.[1] SMA syndrome is a ... Patient had history of weight loss of about ten kilogram in the ... had past history for appendicular perforation 3 years back for ... Uncommon Cause of Abdominal Pain Mimicking.

The History of the Wolff–Parkinson–White Syndrome

Science.gov (United States)

Scheinman, Melvin M.

2012-01-01

While Drs Wolff, Parkinson, and White fully described the syndrome in 1930, prior case reports had described the essentials. Over the ensuing century this syndrome has captivated the interest of anatomists, clinical cardiologists, and cardiac surgeons. Stanley Kent described lateral muscular connections over the atrioventricular (AV) groove which he felt were the normal AV connections. The normal AV connections were, however, clearly described by His and Tawara. True right-sided AV connections were initially described by Wood et al., while Öhnell first described left free wall pathways. David Scherf is thought to be the first to describe our current understanding of the pathogenesis of the WPW syndrome in terms of a re-entrant circuit involving both the AV node–His axis as well as the accessory pathway. This hypothesis was not universally accepted, and many theories were applied to explain the clinical findings. The basics of our understanding were established by the brilliant work of Pick, Langendorf, and Katz who by using careful deductive analysis of ECGs were able to define the basic pathophysiological processes. Subsequently, Wellens and Durrer applied invasive electrical stimulation to the heart in order to confirm the pathophysiological processes. Sealy and his colleagues at Duke University Medical Center were the first to successfully surgically divide an accessory pathway and ushered in the modern era of therapy for these patients. Morady and Scheinman were the first to successfully ablate an accessory pathway (posteroseptal) using high-energy direct-current shocks. Subsequently Jackman, Kuck, Morady, and a number of groups proved the remarkable safety and efficiency of catheter ablation for pathways in all locations using radiofrequency energy. More recently, Gollob et al. first described the gene responsible for a familial form of WPW. The current ability to cure patients with WPW is due to the splendid contributions of individuals from diverse

The History of the Wolff–Parkinson–White Syndrome

Directory of Open Access Journals (Sweden)

Melvin M. Scheinman

2012-07-01

Full Text Available While Drs Wolff, Parkinson, and White fully described the syndrome in 1930, prior case reports had described the essentials. Over the ensuing century this syndrome has captivated the interest of anatomists, clinical cardiologists, and cardiac surgeons. Stanley Kent described lateral muscular connections over the atrioventricular (AV groove which he felt were the normal AV connections. The normal AV connections were, however, clearly described by His and Tawara. True right-sided AV connections were initially described by Wood et al., while Öhnell first described left free wall pathways. David Scherf is thought to be the first to describe our current understanding of the pathogenesis of the WPW syndrome in terms of a re-entrant circuit involving both the AV node–His axis as well as the accessory pathway. This hypothesis was not universally accepted, and many theories were applied to explain the clinical findings. The basics of our understanding were established by the brilliant work of Pick, Langendorf, and Katz who by using careful deductive analysis of ECGs were able to define the basic pathophysiological processes. Subsequently, Wellens and Durrer applied invasive electrical stimulation to the heart in order to confirm the pathophysiological processes. Sealy and his colleagues at Duke University Medical Center were the first to successfully surgically divide an accessory pathway and ushered in the modern era of therapy for these patients. Morady and Scheinman were the first to successfully ablate an accessory pathway (posteroseptal using high-energy direct-current shocks. Subsequently Jackman, Kuck, Morady, and a number of groups proved the remarkable safety and efficiency of catheter ablation for pathways in all locations using radiofrequency energy. More recently, Gollob et al. first described the gene responsible for a familial form of WPW. The current ability to cure patients with WPW is due to the splendid contributions of individuals

Congenital varicella syndrome

Directory of Open Access Journals (Sweden)

Atul Chaudhary

2016-01-01

Full Text Available A 7 month old female presented with localized scarring over right buttock and right leg with hypoplasia of right lower limb. Mother had history of chicken pox at tenth week of pregnancy. We confirm the diagnosis of varicella zoster syndrome clinically.

Radiographic findings in Marfan's syndrome

International Nuclear Information System (INIS)

Watanabe, Yasutaka; Tanaka, Osamu; Koyama, Shinichiro

2010-01-01

Spontaneous pneumothorax and apical bulla are included in minor criteria of the diagnosis of Marfan's syndrome. We evaluated the frequency of radiological abnormal findings of the lung in Marfan's syndrome. Lungs could be assessed with CT in 38 cases that were selected from 50 cases in Marfan's syndrome with a cardiovascular disease or the valvular disease. Eleven cases (22%) in 50 cases had the past history of spontaneous pneumothorax. Chest CT scan in 38 cases showed emphysematous bullae in 12 cases, apical scar in eight cases, centrilobular emphysema in three cases, and bronchiectasis in one case. CT manifestations of the lung in Marfan's syndrome were mainly spontaneous pneumothorax and apical bullae as were previously reported. (author)

Natural and molecular history of prolactinoma: insights from a Prlr-/- mouse model.

Science.gov (United States)

Bernard, Valérie; Villa, Chiara; Auguste, Aurélie; Lamothe, Sophie; Guillou, Anne; Martin, Agnès; Caburet, Sandrine; Young, Jacques; Veitia, Reiner A; Binart, Nadine

2018-01-19

Lactotroph adenoma, also called prolactinoma, is the most common pituitary tumor but little is known about its pathogenesis. Mouse models of prolactinoma can be useful to better understand molecular mechanisms involved in abnormal lactotroph cell proliferation and secretion. We have previously developed a prolactin receptor deficient ( Prlr -/- ) mouse, which develops prolactinoma. The present study aims to explore the natural history of prolactinoma formation in Prlr -/- mice, using hormonal, radiological, histological and molecular analyses to uncover mechanisms involved in lactotroph adenoma development. Prlr -/- females develop large secreting prolactinomas from 12 months of age, with a penetrance of 100%, mimicking human aggressive densely granulated macroprolactinoma, which is a highly secreting subtype. Mean blood PRL measurements reach 14 902 ng/mL at 24 months in Prlr -/- females while PRL levels were below 15 ng/mL in control mice ( p model in ACI rats, we pinpointed 218 concordantly differentially expressed (DE) genes involved in cell cycle, mitosis, cell adhesion molecules, dopaminergic synapse and estrogen signaling. Pathway/gene-set enrichment analyses suggest that the transcriptomic dysregulation in both models of prolactinoma might be mediated by a limited set of transcription factors (i.e., STAT5, STAT3, AhR, ESR1, BRD4, CEBPD, YAP, FOXO1) and kinases (i.e., JAK2, AKT1, BRAF, BMPR1A, CDK8, HUNK, ALK, FGFR1, ILK). Our experimental results and their bioinformatic analysis provide insights into early genomic changes in murine models of the most frequent human pituitary tumor.

LEOPARD-syndrom

DEFF Research Database (Denmark)

Hansen, Lars Kjaersgård; Risby, Kirsten; Bygum, Anette

2009-01-01

We describe a 12-year-old boy with a typical phenotype of the LEOPARD syndrome (LS). The diagnosis was confirmed in the boy and his mother, who both had a mutation in the PTPN11 gene at Thr468Met (c.1403C > T). Several other members of the maternal family are suspected also to have the LEOPARD sy...... syndrome. We discuss the clinical characteristics of LS, the need for follow-up and genetic counselling, and the molecular-genetic background as well as the relationship to the allelic disease Noonan syndrome. Udgivelsesdato: 2009-Jan-26......We describe a 12-year-old boy with a typical phenotype of the LEOPARD syndrome (LS). The diagnosis was confirmed in the boy and his mother, who both had a mutation in the PTPN11 gene at Thr468Met (c.1403C > T). Several other members of the maternal family are suspected also to have the LEOPARD...

The clinical and molecular spectrum of androgen insensitivity syndromes

Energy Technology Data Exchange (ETDEWEB)

Hiort, O.; Sinnecker, G.H.G.; Holterhus, P.M.; Nitsche, E.M.; Kruse, K. [Medical Univ. of Luebeck (Germany)

1996-05-03

Androgen insensitivity syndromes (AIS) are due to end-organ resistance to androgenic steroids in males leading to defective virilization of the external genitalia. The phenotype encompasses a wide array of genital ambiguity and may range from completely female to undervirilized but unequivocally male with infertility. This disorder is caused by mutations of the androgen receptor and is an X-linked recessive trait. We have studied 47 patients with AIS and have characterized the underlying molecular abnormality in the androgen receptor gene. Twenty patients had complete AIS and twenty-seven had partial AIS. Of the latter, 11 were of predominantly female phenotypic appearance and gender was assigned accordingly, while 16 were raised as males. Within the group of complete AIS, two patients had gross deletions within the gene, one had a small deletion, and one had an insertion. In the other patients with complete AIS, as well as all individuals with partial AIS, single nucleotide substitutions within the coding region were detected, each leading to an amino acid alteration. Seven codons were involved in more than one mutation in different cases. In addition, in one patient with spinal and bulbar muscular atrophy, an elongation of a glutamine-repeat was characterized. We conclude that mutations in the androgen receptor gene may be present throughout the whole coding region. However, our study provides evidence that several mutational hot spots exist. 18 refs., 2 figs.

IMAGe syndrome: clinical and genetic implications based on investigations in three Japanese patients.

Science.gov (United States)

Kato, Fumiko; Hamajima, Takashi; Hasegawa, Tomonobu; Amano, Naoko; Horikawa, Reiko; Nishimura, Gen; Nakashima, Shinichi; Fuke, Tomoko; Sano, Shinichirou; Fukami, Maki; Ogata, Tsutomu

2014-05-01

Arboleda et al. have recently shown that IMAGe (intra-uterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital abnormalities) syndrome is caused by gain-of-function mutations of maternally expressed gene CDKN1C on chromosome 11p15.5. However, there is no other report describing clinical findings in patients with molecularly studied IMAGe syndrome. Here, we report clinical and molecular findings in Japanese patients. We studied a 46,XX patient aged 8·5 years (case 1) and two 46,XY patients aged 16·5 and 15·0 years (cases 2 and 3). Clinical studies revealed not only IMAGe syndrome-compatible phenotypes in cases 1-3, but also hitherto undescribed findings including relative macrocephaly and apparently normal pituitary-gonadal endocrine function in cases 1-3, familial glucocorticoid deficiency (FGD)-like adrenal phenotype and the history of oligohydramnios in case 2, and arachnodactyly in case 3. Sequence analysis of CDKN1C, pyrosequencing-based methylation analysis of KvDMR1 and high-density oligonucleotide array comparative genome hybridization analysis for chromosome 11p15.5 were performed, showing an identical de novo and maternally inherited CDKN1C gain-of-function mutation (p.Asp274Asn) in cases 1 and 2, respectively, and no demonstrable abnormality in case 3. The results of cases 1 and 2 with CDKN1C mutation would argue the following: [1] relative macrocephaly is consistent with maternal expression of CDKN1C in most tissues and biparental expression of CDKN1C in the foetal brain; [2] FGD-like phenotype can result from CDKN1C mutation; and [3] genital abnormalities may primarily be ascribed to placental dysfunction. Furthermore, lack of CDKN1C mutation in case 3 implies genetic heterogeneity in IMAGe syndrome. © 2013 John Wiley & Sons Ltd.

A case of possible Kounis syndrome as a complication of scombroid syndrome

Directory of Open Access Journals (Sweden)

Stefano Rusconi

2017-11-01

Full Text Available Kounis syndrome is defined as the concurrence of acute coronary syndromes such as coronary spasm or acute myocardial infarction with conditions associated with activation of inflammatory mediators such histamine, arachidonic acid and various cytokines and chemokines. Recently, a variety of unusual etiologies have been reported, including scombroid syndrome. We present a case of a woman without previous history of cardiac diseases or cardiovascular risk factors, who presented to emergency department after the onset of flushing, asthenia, palpitations, burning sensation in the mouth having just eaten tuna. The electrocardiogram revealed a sinus tachycardia with diffuse ST segment depression. After therapy, in a short time symptoms recovered and a second electrocardiogram no longer showed any ST changes. These electrocardiographic changes observed in our case were probably due to transitory coronary vasospasm as described in type I variant of Kounis syndrome.

Phenotypical and molecular characterization of portuguese usher syndrome patients

OpenAIRE

Nunes, Jóni Luís Soares

2015-01-01

Trabalho final de mestrado integrado em Medicina (Oftalmologia), apresentado à Faculdade de Medicina da Universidade de Coimbra. Introduction: Usher syndrome (USH) is a recessive inherited disease characterized by sensorineural hearing loss (HL), visual loss due to retinitis pigmentosa (RP) and, in some cases, vestibular dysfunction. This syndrome is the most common cause that affects those two major senses, vision and hearing and encompasses three clinical sub-types (USH1, USH2 a...

Kartagener's Syndrome.

Science.gov (United States)

Dhar, D K; Ganguly, K C; Alam, S; Hossain, A; Sarker, U K; Das, B K; Haque, M J

2009-01-01

Kartagener's Syndrome or Immotile Cilia Syndrome, a variant of Primary Ciliary Dyskinesia (PCD), is a rare autosomal recessive genetic disorder caused by defect in the tiny hair like structure, the cilia lining the respiratory tract (upper and lower), sinuses, eustachian tubes, middle ear and fallopian tubes. Here electron microscopy shows abnormal arrangement of ciliary tubules and patients with Kartagener's syndrome has an absence of dynein arms at the base of the cilia. The inability of cilia to move results in inadequate clearance of bacteria from the air passages, resulting in an increased risk of infection and causing bronchiectasis. Another result of ciliary immobility is infertility. A 60 years old lady was diagnosed as a case of Kartagener's syndrome. She had history of chronic cough for 20 years, irregular fever for 20 years and occasional shortness of breath for 5 years. Relevant investigations revealed dextrocardia, situs inversus, bilateral maxillary sinusitis with non pneumatised frontal sinus and bronchiectasis. She was treated with low concentration oxygen inhalation, antibiotic, bronchodilator, chest physiotherapy including postural drainage, vitamins and other supportive treatment.

p.Ser252Trp and p.Pro253Arg mutations in FGFR2 gene causing Apert syndrome: the first clinical and molecular report of Indonesian patients

NARCIS (Netherlands)

Mundhofir, F.E.P.; Sistermans, E.A.; Faradz, S.M.H.; Hamel, B.C.J.

2013-01-01

Apert syndrome (AS) is a rare autosomal dominant disorder characterised by craniosynostosis and limb malformations, and is associated with congenital heart disease and other systemic malformations, including intellectual disability. We report two Indonesian patients with AS, in whom molecular

An Individual with Gilles de la Tourette Syndrome and Smith-Magenis Microdeletion Syndrome: Is Chromosome 17p11.2 a Candidate Region for Tourette Syndrome Putative Susceptibility Genes?

Science.gov (United States)

Shelley, B. P.; Robertson, M. M.; Turk, J.

2007-01-01

This is the first published case description in the current literature of the association of definite Gilles de la Tourette syndrome (GTS) and the Smith-Magenis syndrome (SMS), both confirmed by DSM-IV-TR criteria and molecular cytogenetic analysis, respectively. The co-occurrence of GTS, SMS and their common behavioural/neuropsychiatric…

New onset epilepsy in Prader-Willi syndrome: semiology and literature review.

Science.gov (United States)

Benson, Leslie A; Maski, Kiran P; Kothare, Sanjeev V; Bourgeois, Blaise F

2010-10-01

Prader-Willi syndrome is a chromosomal disorder caused by absence of expression of the paternal active genes in the 15q11∼q13 chromosome region; it is associated with an increased incidence of epilepsy and narcolepsy. Presented here is the case of a 2.5-year-old boy with Prader-Willi syndrome and a history of neonatal superior sagittal sinus thrombosis with new onset of atonic seizures with electrographic onset from the parasagittal region. It is postulated that microscarring from neonatal venous sinus thrombosis, history of febrile seizures, and Prader-Willi syndrome are factors predisposing him to epilepsy. The importance of video electroencephalography with electromyography electrodes is emphasized for Prader-Willi syndrome patients with drop episodes, to differentiate cataplexy from seizures. This being a novel report of a Prader-Willi syndrome patient with atonic seizures, the literature on seizure semiology among patients with Prader-Willi syndrome is reviewed. Copyright © 2010 Elsevier Inc. All rights reserved.

Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome.

Science.gov (United States)

Diamanti-Kandarakis, Evanthia; Christakou, Charikleia D; Kandaraki, Eleni; Economou, Frangiskos N

2010-02-01

Polycystic ovary syndrome (PCOS) is now recognized to be the most common endocrinopathy in women of reproductive age with a prevalence of 6.6-6.8%. PCOS, a syndrome of unknown etiology, was initially regarded as a reproductive disorder. However, in the last 15 years the role of insulin resistance (IR) has been identified as a significant contributor to the pathogenesis of PCOS, and the metabolic and cardiovascular sequelae of the syndrome have been increasingly appreciated. The coexistence and interaction of reproductive and cardiometabolic abnormalities in the context of PCOS have created a need for a modified therapeutic management of affected women. Insulin sensitizers, particularly metformin, have been introduced as a pharmaceutical option targeting not only IR, but several other aspects of the syndrome, including reproductive abnormalities. The landscape of the multifaceted actions of metformin evolves to broaden the therapeutic implications of this old drug in a new fashion for patients with PCOS. Most recently, the spectrum of metformin's targets has been expanded, and molecular studies have explored the tissue-specific mechanisms of metformin in the liver, the muscle, the endothelium, and the ovary. The use of metformin in pregnant women with PCOS comprises another scarcely explored, but promising area of research. This review attempts to cover the spectrum of metformin's cellular actions in different tissues and to summarize the current literature regarding the potential medical value of this medication in PCOS. Even if many of these actions are individually modest, they seem to be collectively sufficient to confer therapeutic benefits not only in cardiometabolic aspects but also in reproductive aspects of PCOS.

Exploding head syndrome.

Science.gov (United States)

Sharpless, Brian A

2014-12-01

Exploding head syndrome is characterized by the perception of abrupt, loud noises when going to sleep or waking up. They are usually painless, but associated with fear and distress. In spite of the fact that its characteristic symptomatology was first described approximately 150 y ago, exploding head syndrome has received relatively little empirical and clinical attention. Therefore, a comprehensive review of the scientific literature using Medline, PsycINFO, Google Scholar, and PubMed was undertaken. After first discussing the history, prevalence, and associated features, the available polysomnography data and five main etiological theories for exploding head syndrome are summarized. None of these theories has yet reached dominance in the field. Next, the various methods used to assess and treat exploding head syndrome are discussed, as well as the limited outcome data. Finally, recommendations for future measure construction, treatment options, and differential diagnosis are provided. Copyright © 2014 Elsevier Ltd. All rights reserved.

Management of moyamoya syndrome in patients with Noonan syndrome.

Science.gov (United States)

Gupta, Mihir; Choudhri, Omar A; Feroze, Abdullah H; Do, Huy M; Grant, Gerald A; Steinberg, Gary K

2016-06-01

A few isolated reports have described an association between Noonan syndrome and cerebrovascular abnormalities, including moyamoya syndrome. These reports have been limited to pediatric patients presenting with recurrent transient ischemic attacks (TIA) or headaches. Management has primarily been pharmacologic, with only one prior report of surgical revascularization to our knowledge. We report four cases of Noonan syndrome patients presenting with headaches and/or sensorimotor strokes in childhood that caused unilateral sensorimotor impairment. Cerebral angiography and MRI revealed bilateral moyamoya syndrome. All patients underwent successful bilateral extracranial-to-intracranial revascularization. The first patient was a 10-year-old girl who presented following a hemorrhagic stroke and recovered well after indirect bypass. The second patient was an adult with a history of childhood stroke whose symptoms progressed in adulthood. She underwent a direct bypass and improved, but continued to experience TIA at her 4 year follow-up. The third patient was a 7-year-old girl with headaches and a new onset TIA who failed pharmacological therapy and subsequently underwent bilateral indirect bypass. The fourth patient was a 24-year-old woman with worsening headaches and an occluded left middle cerebral artery from unilateral moyamoya syndrome. A left sided direct bypass was completed given delayed MRI perfusion with poor augmentation. To our knowledge these are the first reported surgical cases of combined Noonan and moyamoya syndrome. These cases highlight the need to recognize moyamoya syndrome in patients with Noonan syndrome. Early surgical revascularization should be pursued in order to prevent symptom progression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neck extensor muscle weakness (Dropped head syndrome) following radiotherapy

International Nuclear Information System (INIS)

Bhatia, S.; Miller, R.C.; Lachance, D.L.

2006-01-01

Background. Dropped head syndrome is an unusual condition in which the head cannot be held upright in its normal anatomic position secondary to pronounced, isolated, neck extensor muscle weakness. Case report. A case of dropped head syndrome in a female with a history of radiotherapy for Hodgkin's lymphoma and a clinical history consistent with multiple sclerosis is presented, and potential etiologies are discussed. Conclusions. Muscular atrophy and lower motor neuron injury secondary to isolated anterior horn cell injury from radiotherapy emerge as the most likely etiology. (author)

Aortic root pathology in Marfan syndrome increases the risk of migraine with aura

DEFF Research Database (Denmark)

Koppen, H; Vis, J C; Gooiker, D J

2012-01-01

To assess the lifetime prevalence of migraine in patients with Marfan syndrome (MFS) and to investigate a history of aortic root replacement (AR) as a possible risk factor.......To assess the lifetime prevalence of migraine in patients with Marfan syndrome (MFS) and to investigate a history of aortic root replacement (AR) as a possible risk factor....

A case of adrenal Cushing's syndrome with bilateral adrenal masses.

Science.gov (United States)

Guo, Ya-Wun; Hwu, Chii-Min; Won, Justin Ging-Shing; Chu, Chia-Huei; Lin, Liang-Yu

2016-01-01

A functional lesion in corticotrophin (ACTH)-independent Cushing's syndrome is difficult to distinguish from lesions of bilateral adrenal masses. Methods for distinguishing these lesions include adrenal venous sampling and (131)I-6β-iodomethyl-19-norcholesterol ((131)I-NP-59) scintigraphy. We present a case of a 29-year-old Han Chinese female patient with a history of hypercholesterolaemia and polycystic ovary syndrome. She presented with a 6month history of an 8kg body weight gain and gradual rounding of the face. Serial examinations revealed loss of circadian rhythm of cortisol, elevated urinary free-cortisol level and undetectable ACTH level (Cushing's syndrome presenting with bilateral adrenal masses. The clinical presentation of Cushing' syndrome includes symptoms and signs of fat redistribution and protein-wasting features.The diagnosis of patients with ACTH-independent Cushing's syndrome with bilateral adrenal masses is challenging for localisation of the lesion.Both adrenal venous sampling and (131)I-NP-59 scintigraphy are good methods to use in these patients with Cushing's syndrome presenting with bilateral adrenal masses.

Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone

International Nuclear Information System (INIS)

Adachi, A.; Gendelman, H.E.; Koenig, S.; Folks, T.; Willey, R.; Rabson, A.; Martin, M.A.

1986-01-01

The authors considered an infectious molecular clone of acquired immunodeficiency syndrome-associated retrovirus. Upon transfection, this clone directed the production of infectious virus particles in a wide variety of cells in addition to human T4 cells. The progeny, infectious virions, were synthesized in mouse, mink, monkey, and several human non-T cell lines, indicating the absence of any intracellular obstacle to viral RNA or protein production or assembly. During the course of these studies, a human colon carcinoma cell line, exquisitely sensitive to DNA transfection, was identified

Primary Antiphospholipid Syndrome: Unusual Presentation in a ...

African Journals Online (AJOL)

A 72 year old man with a history of TIAs and stroke with unexplained moderately raised ESR presented a year later with rapid deterioration of vision in his left eye because of central retinal vein occlusion. Primary antiphospholipid syndrome is found in patients with history of arterial or venous thromboembolism, ...

The history of neuromyelitis optica

Science.gov (United States)

2013-01-01

The discovery of a novel serum autoantibody (termed NMO-IgG or AQP4-Ab) in a subset of patients in 2004 has revived interest in neuromyelitis optica (NMO). While the history of classical multiple sclerosis has been extensively studied, only little is known about the history of NMO. In the present article, we provide a comprehensive review of the early history of this rare but intriguing syndrome. We trace the origins of the concept of NMO in the 19th century medical literature and follow its evolution throughout the 20th and into the 21st century. Finally, we discuss recent proposals to revise the concept of NMO and explain why there is indeed a need for a more systematic and descriptive nomenclature. PMID:23320783

The endemic gastropod fauna of Lake Titicaca: correlation between molecular evolution and hydrographic history.

Science.gov (United States)

Kroll, Oliver; Hershler, Robert; Albrecht, Christian; Terrazas, Edmundo M; Apaza, Roberto; Fuentealba, Carmen; Wolff, Christian; Wilke, Thomas

2012-07-01

Lake Titicaca, situated in the Altiplano high plateau, is the only ancient lake in South America. This 2- to 3-My-old (where My is million years) water body has had a complex history that included at least five major hydrological phases during the Pleistocene. It is generally assumed that these physical events helped shape the evolutionary history of the lake's biota. Herein, we study an endemic species assemblage in Lake Titicaca, composed of members of the microgastropod genus Heleobia, to determine whether the lake has functioned as a reservoir of relic species or the site of local diversification, to evaluate congruence of the regional paleohydrology and the evolutionary history of this assemblage, and to assess whether the geographic distributions of endemic lineages are hierarchical. Our phylogenetic analyses indicate that the Titicaca/Altiplano Heleobia fauna (together with few extralimital taxa) forms a species flock. A molecular clock analysis suggests that the most recent common ancestor (MRCAs) of the Altiplano taxa evolved 0.53 (0.28-0.80) My ago and the MRCAs of the Altiplano taxa and their extralimital sister group 0.92 (0.46-1.52) My ago. The endemic species of Lake Titicaca are younger than the lake itself, implying primarily intralacustrine speciation. Moreover, the timing of evolutionary branching events and the ages of two precursors of Lake Titicaca, lakes Cabana and Ballivián, is congruent. Although Lake Titicaca appears to have been the principal site of speciation for the regional Heleobia fauna, the contemporary spatial patterns of endemism have been masked by immigration and/or emigration events of local riverine taxa, which we attribute to the unstable hydrographic history of the Altiplano. Thus, a hierarchical distribution of endemism is not evident, but instead there is a single genetic break between two regional clades. We also discuss our findings in relation to studies of other regional biota and suggest that salinity tolerance was

Developing diagnostic guidelines for the acute radiation syndrome

International Nuclear Information System (INIS)

Densow, D.; Fliedner, T.M.; Kindler, H.

1996-01-01

Diagnostic guidelines seem to be promising for improving medical care. One aspect of a diagnostic guideline for the acute radiation syndrome has been tested against an extensive case history database. Subsequently, the guideline has been optimized for a small set of case histories. The improved performance has been proven by a test against the rest of the case history database

Absence of family history and phenotype-genotype correlation in pediatric Brugada syndrome: more burden to bear in clinical and genetic diagnosis.

Science.gov (United States)

Daimi, Houria; Khelil, Amel Haj; Ben Hamda, Khaldoun; Aranega, Amelia; Chibani, Jemni B E; Franco, Diego

2015-06-01

Brugada syndrome (BrS) is an autosomal-dominant genetic cardiac disorder caused in 18-30 % of the cases by SCN5A gene mutations and manifested by an atypical right bundle block pattern with ST segment elevation and T wave inversion in the right precordial leads. The syndrome is usually detected after puberty. The identification of BrS in pediatric patients is thus a rare occurrence, and most of the reported cases are unmasked after febrile episodes. Usually, having a family history of sudden death represents the first reason to perform an ECG in febrile children. However, this practice makes the sporadic cases of cardiac disease and specially the asymptomatic ones excluded from this diagnosis. Here, we report a sporadic case of a 2-month-old male patient presented with vaccination-related fever and ventricular tachycardia associated with short breathing, palpitation and cold sweating. ECG changes were consistent with type 1 BrS. SCN5A gene analysis of the proband and his family revealed a set of mutations and polymorphisms differentially distributed among family members, however, without any clear genotype-phenotype correlation. Based on our findings, we think that genetic testing should be pursued as a routine practice in symptomatic and asymptomatic pediatric cases of BrS, with or without family history of sudden cardiac death. Similarly, our study suggests that pediatrician should be encouraged to perform an ECG profiling in suspicious febrile children and quickly manage fever since it is the most important factor unmasking BrS in children.

The molecular genetics of Usher syndrome: Genetics of Usher syndrome

OpenAIRE

Ahmed, Zm; Riazuddin, S.; Riazuddin, S.; Wilcox, Er

2003-01-01

Association of sensorineural deafness and progressive retinitis pigmentosa with and without a vestibular abnormality is the hallmark of Usher syndrome and involves at least 12 loci among three different clinical subtypes. Genes identified for the more commonly inherited loci are USH2A (encoding usherin), MYO7A (encoding myosin VIIa), CDH23 (encoding cadherin 23), PCDH15 (encoding protocadherin 15), USH1C (encoding harmonin), USH3A (encoding clarin 1), and USH1G (encoding SANS). Transcripts fr...

Molecular and clinical characterization of the myopathic form of mitochondrial DNA depletion syndrome caused by mutations in the thymidine kinase (TK2) gene.

Science.gov (United States)

Chanprasert, Sirisak; Wang, Jing; Weng, Shao-Wen; Enns, Gregory M; Boué, Daniel R; Wong, Brenda L; Mendell, Jerry R; Perry, Deborah A; Sahenk, Zarife; Craigen, William J; Alcala, Francisco J Climent; Pascual, Juan M; Melancon, Serge; Zhang, Victor Wei; Scaglia, Fernando; Wong, Lee-Jun C

2013-01-01

Mitochondrial DNA (mtDNA) depletion syndromes (MDSs) are a clinically and molecularly heterogeneous group of mitochondrial cytopathies characterized by severe mtDNA copy number reduction in affected tissues. Clinically, MDSs are mainly categorized as myopathic, encephalomyopathic, hepatocerebral, or multi-systemic forms. To date, the myopathic form of MDS is mainly caused by mutations in the TK2 gene, which encodes thymidine kinase 2, the first and rate limiting step enzyme in the phosphorylation of pyrimidine nucleosides. We analyzed 9 unrelated families with 11 affected subjects exhibiting the myopathic form of MDS, by sequencing the TK2 gene. Twelve mutations including 4 novel mutations were detected in 9 families. Skeletal muscle specimens were available from 7 out of 11 subjects. Respiratory chain enzymatic activities in skeletal muscle were measured in 6 subjects, and enzymatic activities were reduced in 3 subjects. Quantitative analysis of mtDNA content in skeletal muscle was performed in 5 subjects, and marked mtDNA content reduction was observed in each. In addition, we outline the molecular and clinical characteristics of this syndrome in a total of 52 patients including those previously reported, and a total of 36 TK2 mutations are summarized. Clinically, hypotonia and proximal muscle weakness are the major phenotypes present in all subjects. In summary, our study expands the molecular and clinical spectrum associated with TK2 deficiency. © 2013.

Primary CNS lymphoma as a cause of Korsakoff syndrome.

Science.gov (United States)

Toth, Cory; Voll, Chris; Macaulay, Robert

2002-01-01

Korsakoff syndrome presents with memory dysfunction with retrograde amnesia, anterograde amnesia, limited insight into dysfunction, and confabulation. The most common etiology of Korsakoff syndrome is thiamine deficiency secondary to alcoholism. There are limited case reports of structural lesions causing Korsakoff syndrome. A 46-year-old male with a long history of alcoholism presented with a history of confusion, amnesia, and confabulation with no localizing features on neurological examination. The patient showed no clinical change with intravenous thiamine. Computed tomography of the brain revealed a heterogenous, enhancing mass lesion centered within the third ventricle, with other lesions found throughout cortical and subcortical regions. The patient was given dexamethasone i.v. without noticeable clinical improvement but with marked radiological improvement with mass reduction. Stereotactic biopsy revealed a diagnosis of primary central nervous system (CNS) lymphoma. Most patients presenting with Korsakoff syndrome have thiamine deficiency; however, mass lesions can produce an identical clinical picture. This is the first case report of a patient with primary CNS lymphoma presenting as Korsakoff syndrome.

Report from the workshop on Pallister-Hall syndrome and related phenotypes

Energy Technology Data Exchange (ETDEWEB)

Biesecker, L.G.; Kang, Seongman; Peters, K. [Johns Hopkins Univ., Baltimore, MD (United States)] [and others

1996-10-02

A one day workshop was convened on the NIH campus on March 1, 1996, in Bethesda, Maryland to discuss emerging clinical and molecular information on Pallister-Hall syndrome (PHS) and related disorders. PHS is a pleiotropic autosomal dominant disorder comprising hypothalamic hamartoma, pituitary dysfunction, central polydactyly, and visceral malformations. The goals of the meeting were to update participants in the latest clinical and research findings in the disorder, review the history and evolution of the understanding of the phenotype, determine diagnostic criteria for PHS, and make recommendations for clinical evaluation of individuals affected by PHS. These topics were addressed by several speakers and data were displayed from several of the large pedigrees of autosomal dominant PHS. 37 refs., 4 tabs.

Noonan syndrome - a new survey.

Science.gov (United States)

Tafazoli, Alireza; Eshraghi, Peyman; Koleti, Zahra Kamel; Abbaszadegan, Mohammadreza

2017-02-01

Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate. Noonan syndrome shares clinical features with other rare conditions, including LEOPARD syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair, and Costello syndrome. Germline mutations in the RAS-MAPK (mitogen-activated protein kinase) signal transduction pathway are responsible for NS and other related disorders. Noonan syndrome diagnosis is primarily based on clinical features, but molecular testing should be performed to confirm it in patients. Due to the high number of genes associated with NS and other RASopathy disorders, next-generation sequencing is the best choice for diagnostic testing. Patients with NS also have higher risk for leukemia and specific solid tumors. Age-specific guidelines for the management of NS are available.

Molecular characteristics of endometrial cancer coexisting with peritoneal malignant mesothelioma in Li-Fraumeni-like syndrome.

Science.gov (United States)

Chao, Angel; Lai, Chyong-Huey; Lee, Yun-Shien; Ueng, Shir-Hwa; Lin, Chiao-Yun; Wang, Tzu-Hao

2015-01-15

Endometrial cancer that occurs concurrently with peritoneal malignant mesothelioma (PMM) is difficult to diagnose preoperatively. A postmenopausal woman had endometrial cancer extending to the cervix, vagina and pelvic lymph nodes, and PMM in bilateral ovaries, cul-de-sac, and multiple peritoneal sites. Adjuvant therapies included chemotherapy and radiotherapy. Targeted, massively parallel DNA sequencing and molecular inversion probe microarray analysis revealed a germline TP53 mutation compatible with Li-Fraumeni-like syndrome, somatic mutations of PIK3CA in the endometrial cancer, and a somatic mutation of GNA11 and JAK3 in the PMM. Large-scale genomic amplifications and some deletions were found in the endometrial cancer. The patient has been stable for 24 months after therapy. One of her four children was also found to carry the germline TP53 mutation. Molecular characterization of the coexistent tumors not only helps us make the definite diagnosis, but also provides information to select targeted therapies if needed in the future. Identification of germline TP53 mutation further urged us to monitor future development of malignancies in this patient and encourage cancer screening in her family.

Molecular genetics in neurology.

Science.gov (United States)

Martin, J B

1993-12-01

There has been remarkable progress in the identification of mutations in genes that cause inherited neurological disorders. Abnormalities in the genes for Huntington disease, neurofibromatosis types 1 and 2, one form of familial amyotrophic lateral sclerosis, fragile X syndrome, myotonic dystrophy, Kennedy syndrome, Menkes disease, and several forms of retinitis pigmentosa have been elucidated. Rare disorders of neuronal migration such as Kallmann syndrome, Miller-Dieker syndrome, and Norrie disease have been shown to be due to specific gene defects. Several muscle disorders characterized by abnormal membrane excitability have been defined as mutations of the muscle sodium or chloride channels. These advances provide opportunity for accurate molecular diagnosis of at-risk individuals and are the harbinger of new approaches to therapy of these diseases.

Syncope as initial symptom for nephrotic syndrome: a case report

Science.gov (United States)

Wu, Xuemei; Wang, Guangliang; Feng, Jiachun

2015-01-01

Although syncope and nephrotic syndrome are frequently encountered independently in pediatric practice, syncope as the initial symptom for nephrotic syndrome is rarely observed in the pediatric age group. In this report, we present the case of 3-year-old boy with nephrotic syndrome who presented with a history of three episodes of syncope before admission. The syncope occurred after excessive fluid loss or inadequate intake of fluids and was relieved spontaneously. History taking revealed that the early morning palpebral edema, and laboratory tests showed decreased plasma protein levels and elevated serum lipid levels. Nephrotic syndrome was diagnosed, but could not be confirmed histopathologically because the patient’s parent refused consent for biopsy. The patient was managed with fluid expansion, correction of acidosis, and improvement of microcirculation to prevent recurrence of syncope, and glucocorticoids were administered to prevent disease progression. PMID:26629237

Oral mucosal manifestations in primary and secondary Sjögren syndrome and dry mouth syndrome

Directory of Open Access Journals (Sweden)

Katarzyna Błochowiak

2016-02-01

Full Text Available Introduction : One of the most important symptoms of Sjögren syndrome is xerostomia. The oral cavity deprived of saliva and its natural lubricative, protective and antibacterial properties is prone to a number of unfavourable consequences. Aim : To present the most important lesions on the oral mucosa in primary and secondary Sjögren syndrome and in dry mouth syndrome. Material and methods: The study group comprised 55 patients including 52 women and 3 men aged 20–72 years (average: 28.25 years. Results : Basing on the accepted criteria, primary Sjögren syndrome was diagnosed in 22 (40% patients, secondary Sjögren syndrome in 18 (32.7% patients, and dry mouth syndrome in 15 (27.27% patients. The physical examination and the examination of the mouth were performed and history was elicited from every patient. Conclusions : The most common pathologies appearing on the oral mucosa in primary and secondary Sjögren syndrome are angular cheilitis, cheilitis, increased lip dryness as well as non-specific ulcerations, aphthae and aphthoid conditions.

Noonan syndrome: an update on growth and development.

Science.gov (United States)

Yart, Armelle; Edouard, Thomas

2018-02-01

To provide an update on recent developments on Noonan syndrome with a special focus on endocrinology, bone, and metabolism aspects. The key issues still to be resolved and the future therapeutic perspectives will be discussed. The discovery of the molecular genetic causes of Noonan syndrome and Noonan-syndrome-related disorders has permitted us to better understand the mechanisms underlying the different symptoms of these diseases and to establish genotype-phenotype correlations (in growth patterns for example). In addition to the classical clinical hallmarks of Noonan syndrome, new important aspects include decreased fertility in men, lean phenotype with increased energy expenditure and possible impact on carbohydrate metabolism/insulin sensitivity, and impaired bone health. Further clinical studies are needed to investigate the long-term impact of these findings and their possible interconnections. Finally, the understanding of the crucial role of RAS/mitogen-activated protein kinases dysregulation in the pathophysiology of Noonan syndrome allows us to devise new therapeutic approaches. Some agents are currently undergoing clinical trials in Noonan syndrome patients. On the last 10 years, our knowledge of the molecular basis and the pathophysiology of Noonan syndrome has greatly advanced allowing us to gain insight in all the aspects of this disease and to devise new specific therapeutic strategies.

Gulf War syndrome: an emerging threat or a piece of history?

Science.gov (United States)

Greenberg, N; Wessely, S

2008-01-01

‘Gulf War syndrome’ is a phrase coined after the 1991 Gulf War to group together disparate, unexplained health symptoms in Gulf veterans. This paper examines the many hypotheses that have been put forward about the origins of the concept and gives an overview of the studies that have attempted to explain the lasting health effects associated with Gulf service. Our review finds that although in the UK there has not yet been evidence of a new Gulf War syndrome as a result of the current conflicts in Iraq and Afghanistan, there is a rise in post-conflict psychiatric disorders now being reported in the USA. We postulate that after conflicts military personnel will always face some form of post-conflict syndrome and the nature of the threats experienced is likely to dictate the form the syndrome might take. We also postulate that media reporting is likely to have influenced and to continue unhelpfully to influence the health of service personnel. PMID:22460210

Lynch syndrome-associated neoplasms

DEFF Research Database (Denmark)

Shia, Jinru; Holck, Susanne; Depetris, Giovanni

2013-01-01

It was a century ago that Warthin, a pathologist, first described the clinical condition now known as Lynch syndrome. One hundred years later, our understanding of this syndrome has advanced significantly. Much of the progress took place over the last 25 years and was marked by a series...... of interacting developments from the disciplines of clinical oncology, pathology, and molecular genetics, with each development serving to guide or enhance the next. The advancement of our understanding about the pathology of Lynch syndrome associated tumors exemplifies such intimate interplay among disciplines....... Today, accumulative knowledge has enabled surgical pathologists to detect tumors that are likely to be associated with Lynch syndrome, and the pathologist is playing an increasingly more important role in the care of these patients. The pathologist's ability is afforded primarily by information gained...

Waardenburg syndrome type 2: an orthodontic perspective.

Science.gov (United States)

Şuhani, Raluca Diana; Şuhani, Mihai Flaviu; Muntean, Alexandrina; Mesaroş, Michaela Florica; Badea, Mîndra Eugenia

2015-01-01

Waardenburg syndrome is a rare form of neurocristopathy. It is a disorder in the development of neural crest cells, caused by an altered cellular migration during the embryonic phase. That alteration causes an association of different abnormalities such as pigmentary disturbances of the hair, iris, skin, stria vascularis of the cochlea, dystopia canthorum and sensorineural hearing loss. We report a case of a 14-year-old Romanian male, with a family history of Waardenburg syndrome (mother) and Usher syndrome (father - congenitally sensorineural hearing loss and retinal degeneration). The case particularities are: the correlation between malocclusion and Waardenburg syndrome due to hypoplastic alae nasi and also factors that produced hearing loss, which could be Waardenburg syndrome, Usher syndrome or the presence of the connexin 26 (W24X) gene mutation.

Cytological and molecular studies of chromosomal radiosensitivity in Down Syndrome cells

International Nuclear Information System (INIS)

MacLaren, R.A.

1988-01-01

Molecular, cellular and cytogenetic studies were conducted to determine if altered levels of poly(ADP-ribose) polymerase, a DNA repair-related enzyme, is responsible for the reported formation of excess X-ray induced chromosome aberrations in cells derived from Down Syndrome (DS) patients. Nonstimulated lymphocytes from normal and DS subjects were pretreated with 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase, for 30 minutes before exposure to X-rays and the levels of induced chromosome aberrations were determined in mitotic cells. DS lymphocytes exhibited significantly higher frequencies of chromosome aberrations in the presence of 3-aminobenzamide that normal lymphocytes. No difference was observed in the absence of 3-aminobenzamide. Additional studies were done using normal and DS lymphoblastoid cell lines which exhibited a similar response at the DNA level as the lymphocytes. Analysis of poly(ADP-ribose) polymerase activity based on incorporation of the substrate, NAD + , into acid insoluble materials, revealed that there was no significant difference in the ability to form poly (ADP-ribose) in the DS or normal cells. 3-aminobenzamide effectively inhibited poly(ADP-ribose) polymerase in both the normal and DS cells

Bardet-Biedl syndrome and Usher syndrome.

Science.gov (United States)

Koenig, Rainer

2003-01-01

Bardet-Biedl syndrome (BBS) and Usher syndrome (USH) are the most prevalent syndromic forms of retinitis pigmentosa (RP), together they make up almost a quarter of the patients with RP. BBS is defined by the association of retinopathy, obesity, hypogonadism, renal dysfunction, postaxial polydactyly and mental retardation. This clinically complex syndrome is genetically heterogeneous with linkage to more than 6 loci, and 4 genes have been cloned so far. Recent molecular data present evidence that, in some instances, the clinical manifestation of BBS requires recessive mutations in 1 of the 6 BBS loci plus one or two additional mutations in a second BBS locus (tri- or tetra-allelic inheritance). USH is characterized by the combination of congenital or early-onset sensorineural deafness, RP, and variable degrees of vestibular dysfunction. Each of the three clinical types is genetically heterogeneous: 7 loci have been mapped for type 1, three loci for type 2, and two loci for type 3. Currently, 6 USH genes (MYO7A, USH1C, CDH23, PCDH15, USH2A, USH3) have been identified. Pathogenetically, mutations of the USH1 genes seem to result in defects of auditory and retinal sensory cells, the USH 2 phenotype is caused by defects of extracellular matrix or cell surface receptor proteins, and USH3 may be due to synaptic disturbances. The considerable contribution of syndromic forms of RP requires interdisciplinary approaches to the clinical and diagnostic management of RP patients.

ADULT VARIANT BARTTER’S SYNDROME- A CASE REPORT

Directory of Open Access Journals (Sweden)

Ishwar Sidappa Hasabi

2017-02-01

Full Text Available BACKGROUND Bartter syndrome is a group of channelopathies with different genetic origins and molecular pathophysiologies, but sharing common feature of decreased tubular transport of sodium chloride in thick ascending loop of Henle (TAL, 1 although more common in antenatal group. Classic adult variant of Bartter syndrome is a rare entity. We hereby present a rare adult variant of classic Bartter syndrome.

Epilepsy in Individuals with a History of Asperger's Syndrome

DEFF Research Database (Denmark)

Rich, Bente; Isager, Torben; Mouridsen, Svend Erik Birkebæk

2013-01-01

We performed a nationwide, register-based retrospective follow-up study of epilepsy in all people who were born between January 1, 1980 and June 29, 2006 and registered in the Danish Psychiatric Central Register with Asperger's syndrome on February 7, 2011. All 4,180 identified cases with AS (3...

[Wernicke-Korsakoff syndrome: malignant tumour as triggering factor].

Science.gov (United States)

Guisado, J; Carbonell, C; Donaire, L; De Miguel, J; Vaz, F

2001-01-01

Gastrectomy, alcoholism and malignant tumour are three predisponing risk factors for the development of Wernicke-Korsakoff syndrome. We described the clinical case of a patient with history of alcoholism that developed Wernicke-Korsakoff syndrome 30 years after undergoing gastrectomy. This patient had, in the last year, a diagnostic for prostatic adenocarcinoma and changes in dietary habits. We presented the clinical and neuropathological features of the Wernicke-Korsakoff syndrome. As well as some aspects in the treatment and prognosis.

Genetic counseling and cascade genetic testing in Lynch syndrome.

Science.gov (United States)

Hampel, Heather

2016-07-01

Lynch syndrome is the most common cause of inherited colorectal and endometrial cancers. Individuals with Lynch syndrome have a 10-80 % lifetime risk for colorectal cancer and a 15-60 % lifetime risk for endometrial cancer. Both cancers are preventable through chemoprevention, intensive cancer surveillance, and risk-reducing surgery options. Efforts to identify as many individuals with Lynch syndrome as possible will prevent cancers and save lives. This includes the traditional cancer genetic counseling model whereby individuals with and without cancer are evaluated for a possible Lynch syndrome diagnosis based on their personal and family history of colon polyps and cancers. It also includes universal tumor screening for Lynch syndrome whereby all individuals with colorectal or endometrial cancer are screened for tumor features of Lynch syndrome at the time of diagnosis. Those with tumors suspicious for Lynch syndrome are referred for cancer genetic counseling regardless of their family history of cancer. This two approaches must be maximized to attain high patient reach. Finally, and perhaps most importantly, cascade testing among the at-risk relatives of those diagnosed with Lynch syndrome is critically important to maximize the diagnosis of individuals with Lynch syndrome. In fact, the cost-effectiveness of universal tumor screening for Lynch syndrome relies entirely on counseling and testing as many at-risk individuals as possible since young unaffected individuals stand to benefit the most from an early diagnosis of Lynch syndrome. This approach must be optimized to achieve high family reach. It will take a concerted effort from patients, clinicians and public health officials to improve current approaches to the diagnosis of Lynch syndrome and the prevention and treatment of Lynch syndrome-associated cancer but these lessons can be applied to other conditions as the ultimate example of personalized medicine.

Screening for Lynch syndrome using risk assessment criteria in patients with ovarian cancer.

Science.gov (United States)

Takeda, Takashi; Tsuji, Kosuke; Banno, Kouji; Yanokura, Megumi; Kobayashi, Yusuke; Tominaga, Eiichiro; Aoki, Daisuke

2018-05-01

Lynch syndrome is a cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes. Lynch syndrome only causes about 0.4% of cases of ovarian cancer, which suggests that universal screening may not be cost-efficient. However, the frequency of Lynch syndrome in ovarian cancer is unclear in the Asian population. The goal of the study was to investigate a screening strategy using family history. The subjects were 129 patients with ovarian cancer. Clinical and family history were collected using a self-administered questionnaire, and Society of Gynecologic Oncology (SGO) criteria 2007 and PREMM₅ were used for risk assessment. Microsatellite instability, immunohistochemistry, and methylation of MMR genes were analyzed. Of the 129 cases, 25 (19.4%) met the SGO criteria, and 4 of these 25 had MSI-high and MMR deficiency. Two cases had loss of MSH2 and MSH6, indicating MSH2 mutation, and the other two had loss of MLH1 and PMS2, including one without MLH1 methylation indicating MLH1 mutation. These results show that screening using family history can detect Lynch syndrome in 12.0% (3/25) of ovarian cancer cases. The 3 cases were positive for PREMM₅, but negative for Amsterdam II criteria and revised Bethesda guidelines. Genetic testing in one case with MSH2 and MSH6 deficiency confirmed the diagnosis of Lynch syndrome with MSH2 mutation. This is the first study of screening for Lynch syndrome in ovarian cancer using clinical and family history in an Asian population. This approach may be effective for diagnosis in these patients. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Guillain-Barré syndrome- and Miller Fisher syndrome-associated Campylobacter jejuni lipopolysaccharides induce anti-GM1 and anti-GQ1b Antibodies in rabbits.

NARCIS (Netherlands)

M.A. de Klerk; H.P. Endtz (Hubert); B.C. Jacobs (Bart); J.D. Laman (Jon); F.G.A. van der Meché (Frans); P.A. van Doorn (Pieter); C.W. Ang (Wim)

2001-01-01

textabstractCampylobacter jejuni infections are thought to induce antiganglioside antibodies in patients with Guillain-Barre syndrome (GBS) and Miller Fisher syndrome (MFS) by molecular mimicry between C. jejuni lipopolysaccharides (LPS) and gangliosides. We used

Distinctive pattern of expression of spermatogenic molecular markers in testes of azoospermic men with non-mosaic Klinefelter syndrome.

Science.gov (United States)

Kleiman, Sandra E; Yogev, Leah; Lehavi, Ofer; Yavetz, Haim; Hauser, Ron

2016-06-01

Mature sperm cells can be found in testicular specimens extracted from azoospermic men with non-mosaic Klinefelter syndrome (KS). The present study evaluates the expression of various known molecular markers of spermatogenesis in a population of men with KS and assesses the ability of those markers to predict spermatogenesis. Two groups of men with non-obstructive azoospermia who underwent testicular sperm-retrieval procedures were included in the study: 31 had non-mosaic KS (KS group) and 91 had normal karyotype (NK group). Each group was subdivided into mixed atrophy (containing some mature sperm cells) or Sertoli cell only syndrome according to testicular histology and cytology observations. Semi-quantitative histological morphometric analysis (interstitial hyperplasia and hyalinization, tubules with cells and abnormal thickness of the basement membrane) and expression of spermatogenetic markers (DAZ, RBM, BOLL, and CDY1) were evaluated and compared among those subgroups. Clear differences in the histological morphometry and spermatogenetic marker expression were noted between the KS and NK groups. There was a significant difference in the expression of spermatogenetic markers between the subgroups of the NK group (as expected), while no difference could be discerned between the two subgroups in the KS group. We conclude that molecular spermatogenetic markers have a pattern of expression in men with KS that is distinctively different from that of men with NK, and that it precludes and limits their use for predicting spermatogenesis in the former. It is suggested that this difference might be due to the specific highly abnormal histological morphometric parameters in KS specimens.

Hermansky-Pudlak syndrome; a Case Report

Directory of Open Access Journals (Sweden)

Abbas Bagheri

2010-01-01

Full Text Available Purpose: To report a case of Hermansky-Pudlak syndrome. Case Report: A seven-year-old boy presented with marked generalized hypopigmentation, ocular exodeviation and nystagmus. He had history of easy bruising. Examination revealed green irides with marked transillumination, hypopigmented fundi and foveal hypoplasia. Further investigations disclosed platelet storage defect with adenosine diphosphate deficiency and abnormal aggregation compatible with Hermansky-Pudlak syndrome. The patient underwent strabismus surgery taking necessary precautions such as reserving platelet concentrates in case of a hemorrhagic event. Conclusion: Patients with albinism should be evaluated for Hermansky-Pudlak syndrome especially before surgery to prevent life-threatening complications.

Trigeminal Trophic Syndrome Associated With the Use of Synthetic Marijuana.

Science.gov (United States)

Khan, Fawad A; Manacheril, Rinu; Ulep, Robin; Martin, Julie E; Chimakurthy, Anil

2017-01-01

Trigeminal trophic syndrome (TTS) is an uncommon disorder of the trigeminal nerve tract and trigeminal brainstem nucleus. The syndrome is characterized by a triad of unilateral crescentic ulcers with anesthesia and paresthesias of the involved trigeminal dermatomes. A 24-year-old right-handed black female presented to our emergency department with a 4-week history of rapidly progressive painless desquamation/denudation of skin over her right face and scalp. Four weeks prior, she had been admitted to another institution for seizures and was diagnosed with seizures provoked by synthetic marijuana use. She was afebrile during her initial presentation at our institution. Dermatologic examination revealed denudation of the epidermis and partial dermis over the right frontal, parietal, and temporal scalp with associated alopecia. To our knowledge, the association of disorders of the trigeminal nerve pathway, including TTS, with the use of synthetic marijuana has not been previously reported. The long-term neurologic effects of synthetic marijuana are difficult to predict, and the pathologic underpinnings of TTS are largely unknown. Further studies dedicated to exploring the underlying molecular and cellular mechanisms may translate into effective therapies and approaches to halt and reverse the process and prevent tissue destruction and cosmetic disfigurement.

Clinical and Molecular Epidemiology of Staphylococcal Toxic Shock Syndrome in the United Kingdom

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Sharma, Hema; Smith, Debra; Turner, Claire E.; Game, Laurence; Pichon, Bruno; Hope, Russell; Hill, Robert; Kearns, Angela

2018-01-01

Staphylococcal toxic shock syndrome (TSS) was originally described in menstruating women and linked to TSS toxin 1 (TSST-1)–producing Staphylococcus aureus. Using UK national surveillance data, we ascertained clinical, molecular and superantigenic characteristics of TSS cases. Average annual TSS incidence was 0.07/100,000 population. Patients with nonmenstrual TSS were younger than those with menstrual TSS but had the same mortality rate. Children <16 years of age accounted for 39% of TSS cases, most caused by burns and skin and soft tissue infections. Nonmenstrual TSS is now more common than menstrual TSS in the UK, although both types are strongly associated with the tst+ clonal complex (CC) 30 methicillin-sensitive S. aureus lineage, which accounted for 49.4% of all TSS and produced more TSST-1 and superantigen bioactivity than did tst+ CC30 methicillin-resistant S. aureus strains. Better understanding of this MSSA lineage and infections in children could focus interventions to prevent TSS in the future. PMID:29350159

Rendu-Osler-Weber syndrome presenting with pulmonary arteriovenous fistula

International Nuclear Information System (INIS)

Halefoglu, A.M.

2005-01-01

A pulmonary arteriovenous fistula is an abnormal connection between pulmonary arteries and veins. Patients with Rendu-Osler-Weber syndrome may present with this vascular malformation, which is a typical finding of the disease. Approximately 5-15% of Rendu-Osler-Weber syndrome patients have pulmonary arteriovenous malformations (AVM) and there is usually a family history of AVM in these patients. The malformations are usually located in the lower lobes. In this paper, I describe a 49-year-old male patient with dyspnoea, cough, haemoptysis and epistaxis. Physical examination showed nasal telangiectasias, cyanosis of the lips and nails, and a systolic bruit over the left lung. Chest X-ray revealed a 5-cm mass in the left lower lobe and after magnetic resonance examination, together with 3-D magnetic resonance angiography, it was demonstrated to be a pulmonary arteriovenous fistula. The history of a niece with a similar history of suspected pulmonary arteriovenous fistula led me to consider the possibility of Rendu-Osler-Weber syndrome presenting with a pulmonary arteriovenous fistula. Copyright (2005) Blackwell Science Pty Ltd

Psychological factors in the irritable bowel syndrome.

Science.gov (United States)

Solmaz, M; Kavuk, I; Sayar, K

2003-12-09

The role of psychological factors in the irritable bowel syndrome (IBS) is a matter of debate. The prevalence of psychiatric disorders is high in IBS patients. Positive response to antidepressant therapy and presence of family history of depression in IBS patients have led speculations whether this syndrome might be regarded as an affective spectrum disorder. In this study we tried to examine the possible association of IBS with affective spectrum disorders. Forty IBS patients from gastroenterology outpatient clinics of a university hospital and state hospital, 32 controls with inflammatory bowel disease and 34 healthy hospital workers were included in the study. Psychiatric interviews were done using SCID-NP (Structured Clinical Interview for DSM-Non-patients) and psychological factors were assessed by the SCL-90-R (Symptom Checklist-90-Revised), the Beck Depression Inventory, the Beck Anxiety Scale and the Hamilton Rating Scale for Depression. Family histories were obtained by FH-RDC (Family History Research Diagnostic Criteria). All groups were matched for sociodemographic variables. The prevalence of psychiatric disorders and mood disorders was higher in the IBS group than the control groups. Also IBS group rated higher on anxiety and depression scales than the other groups, where the differences were statistically significant. Presence of positive family history for mood disorders was higher in the IBS group. These results support the hypothesis that IBS might be linked to affective spectrum disorder. Psychiatric assessment and therapy might be useful in the course of irritable bowel syndrome.

Genetic analysis of Tunisian families with Usher syndrome type 1: toward improving early molecular diagnosis.

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Ben-Rebeh, Imen; Grati, Mhamed; Bonnet, Crystel; Bouassida, Walid; Hadjamor, Imen; Ayadi, Hammadi; Ghorbel, Abdelmonem; Petit, Christine; Masmoudi, Saber

2016-01-01

Usher syndrome accounts for about 50% of all hereditary deaf-blindness cases. The most severe form of this syndrome, Usher syndrome type I (USH1), is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. Six USH1 genes have been identified, MYO7A, CDH23, PCDH15, USH1C, SANS, and CIB2, encoding myosin VIIA, cadherin-23, protocadherin-15, harmonin, scaffold protein containing ankyrin repeats and a sterile alpha motif (SAM) domain, and calcium- and integrin-binding member 2, respectively. In the present study, we recruited four Tunisian families with a diagnosis of USH1, together with healthy unrelated controls. Affected members underwent detailed audiologic and ocular examinations. We used the North African Deafness (NADf) chip to search for known North African mutations associated with USH. Then, we selected microsatellite markers covering USH1 known loci to genotype the DNA samples. Finally, we performed DNA sequencing of three known USH1 genes: MYO7A, PCDH15, and USH1C. Four biallelic mutations, all single base changes, were found in the MYO7A, USH1C, and PCDH15 genes. These mutations consist of a previously reported splicing defect c.470+1G>A in MYO7A, three novel variants, including two nonsense (p.Arg3X and p.Arg134X) in USH1C and PCDH15, respectively, and one frameshift (p.Lys615Asnfs*6) in MYO7A. We found a remarkable genetic heterogeneity in the studied families with USH1 with a variety of mutations, among which three were novel. These novel mutations will be included in the NADf mutation screening chip that will allow a higher diagnosis efficiency of this extremely genetically heterogeneous disease. Ultimately, efficient molecular diagnosis of USH in a patient's early childhood is of utmost importance, allowing better educational and therapeutic management.

p.Ser252Trp and p.Pro253Arg mutations in FGFR2 gene causing Apert syndrome: the first clinical and molecular report of Indonesian patients.

Science.gov (United States)

Mundhofir, Farmaditya E P; Sistermans, Erik A; Faradz, Sultana M H; Hamel, Ben C J

2013-03-01

Apert syndrome (AS) is a rare autosomal dominant disorder characterised by craniosynostosis and limb malformations, and is associated with congenital heart disease and other systemic malformations, including intellectual disability. We report two Indonesian patients with AS, in whom molecular analysis detected p.Ser252Trp (c.755C>G) and p.Pro253Arg (c.758C>G) mutations in the fibroblast growth factor receptor 2 (FGFR2) gene, respectively. Although the syndrome has been frequently described, this is the first clinical report of AS confirmed by molecular analysis in Indonesia. The difference in severity of clinical features in the two patients may be consistent with a genotype-phenotype correlation of the FGFR2mutation. The management of individuals with AS is best achieved within a multidisciplinary setting. However, in most developing countries, early intervention may be delayed due to late diagnosis, a lack of facilities and financial constraints. This report underpins the benefits of early diagnosis for AS management.

Molecular analysis of T-B-NK+ severe combined immunodeficiency and Omenn syndrome cases in Saudi Arabia

Directory of Open Access Journals (Sweden)

Al-Kayal Fadi

2009-11-01

Full Text Available Abstract Background Children with Severe Combined Immunodeficiency (SCID lack autologous T lymphocytes and present with multiple infections early in infancy. Omenn syndrome is characterized by the sole emergence of oligoclonal auto-reactive T lymphocytes, resulting in erythroderma and enteropathy. Omenn syndrome (OS shares the genetic aetiology of T-B-NK+ SCID, with mutations in RAG1, RAG2, or DCLRE1C. Methods Patients diagnosed with T-B-NK+ SCID or phenotypes suggestive of Omenn syndrome were investigated by molecular genetic studies using gene tightly linked microsatellite markers followed by direct sequencing of the coding regions and splice sites of the respective candidate genes. Results We report the molecular genetic basis of T-B-NK+ SCID in 22 patients and of OS in seven patients all of Arab descent from Saudi Arabia. Among the SCID patients, six (from four families displayed four homozygous missense mutations in RAG1 including V433M, R624H, R394W, and R559S. Another four patients (from three familes showed 3 novel homozygous RAG2 mutations including K127X, S18X, and Q4X; all of which predict unique premature truncations of RAG2 protein. Among Omenn patients, four (from two families have S401P and R396H mutations in RAG1, and a fifth patient has a novel I444M mutation in RAG2. Seven other patients (six SCID and one OS showed a gross deletion in exons 1-3 in DCLRE1C. Altogether, mutations in RAG1/2 and DCLRE1C account for around 50% and 25%, respectively, in our study cohort, a proportion much higher than in previous reported series. Seven (24% patients lack a known genetic aetiology, strongly suggesting that they carry mutations in novel genes associated with SCID and Omenn disorders that are yet to be discovered in the Saudi population. Conclusion Mutation-free patients who lack a known genetic aetiology are likely to carry mutations in the regulatory elements in the SCID-causing genes or in novel genes that are yet to be discovered

Increased risk of metabolic disorders in healthy young adults with family history of diabetes: from the Korea National Health and Nutrition Survey.

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Moon, Joon Ho; Roh, Eun; Oh, Tae Jung; Kim, Kyoung Min; Moon, Jae Hoon; Lim, Soo; Jang, Hak Chul; Choi, Sung Hee

2017-01-01

We assessed the impact of a family history of diabetes on type 2 diabetes, metabolic syndrome, and behavioral traits in young Korean adults. Subjects aged 25-44 years were included, and the presence of a family history of diabetes was obtained by a self-reported questionnaire (the Korea National Health and Nutrition Survey 2010). We compared the prevalence of type 2 diabetes and metabolic syndrome, and other metabolic parameters, including blood pressure and lipid profile. Of 2059 participants, those with a family history of diabetes involving first-degree relatives (n = 489, 23.7%) had a significantly higher prevalence of impaired fasting glucose (14.3 vs. 11.7%) and type 2 diabetes (6.7 vs. 1.8%), compared to those without a family history ( P  metabolic syndrome (21.3 vs. 12.1%, P  family history of diabetes. Among subjects exhibiting normal glucose tolerance (n = 1704), those with a family history of diabetes had higher fasting glucose (89.0 vs. 87.8 mg/dL, P  family history of diabetes. Young adults with a family history of diabetes had an increased risk of type 2 diabetes and metabolic syndrome, even though they currently exhibited a normal glycemic profile. Proactive lifestyle consultation is requested especially among healthy young population with a family history of diabetes.

Epidemiological predictors of metabolic syndrome in urban West Bengal, India.

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Chakraborty, Sasthi Narayan; Roy, Sunetra Kaviraj; Rahaman, Md Abdur

2015-01-01

Metabolic syndrome is one of the emerging health problems of the world. Its prevalence is high in urban areas. Though pathogenesis is complex, but the interaction of obesity, sedentary lifestyle, dietary, and genetic factors are known as contributing factors. Community-based studies were very few to find out the prevalence or predictors of the syndrome. To ascertain the prevalence and epidemiological predictors of metabolic syndrome. A total of 690 study subjects were chosen by 30 clusters random sampling method from 43 wards of Durgapur city. Data were analyzed in SPSS version 20 software and binary logistic regression was done to find out statistical significance of the predictors. Among 32.75% of the study population was diagnosed as metabolic syndrome according to National Cholesterol Education Program Adult Treatment Panel III definition with a modification for Asia Pacific cut-off of waist circumference. Odds were more among females (2.43), upper social class (14.89), sedentary lifestyle (17.00), and positive family history. The overall prevalence of metabolic syndrome was high in urban areas of Durgapur. Increased age, female gender, higher social status, sedentary lifestyle, positive family history, and higher education were the statistically significant predictors of metabolic syndrome.

Cyclic Vomiting Syndrome in Children

Directory of Open Access Journals (Sweden)

T.V. Sorokman

2016-08-01

Full Text Available Introduction. Cyclic vomiting syndrome (CVS — is a fairly common disease of unknown etiology that affects children of all age groups and sometimes adult population and refers to the functional disorders of the gastrointestinal tract. Objective: to evaluate the effectiveness of the usage of Rehydron Optim for oral rehydration therapy in children. Materials and methods. The treatment of 40 children aged 3 to 11 years with CVS (15 persons and primary acetonemic syndrome (25 persons in the period of acetonemic crisis, including 15 boys and 25 girls, was analyzed. All children were observed in the outpatient department of the Regional children’s hospital of Chernivtsi. Diagnosis was established based on anamnesis, clinical and laboratory data. Patients underwent required clinico-biological tests and instrumental examinations. The dynamics of the following syndromes was investigated: pain, vomiting, dehydration and intoxication. Rehydration therapy in all cases was oral with the usage of Rehydron Optim. Results of the study and their discussion. A cyclical vomiting was observed in children with primary acetonemic syndrome with satisfactory condition in attack-free period. Migraine-like headaches prevailed in 36 patients (80 %, and the age of these patients was older than 7 years. Same children had episodes of paroxysmal autonomic failure. Almost all surveyed children had in their family history the risk factors for CVS development. All children had positive dynamics of the main basic clinical manifestations on the background of oral rehydration therapy using Rehydron Optim. Within the 1st day of oral rehydration therapy with Rehydron Optim in children, we have noted a significant decrease in the incidence of lethargy, vomiting, spastic abdominal pain, smell of acetone in the exhaled air (p < 0.05. In children with the I degree of dehydration, clinical signs of dehydration were not seen before the treatment, and children with the II degree had an

Gilles de la Tourette's syndrome in a patient with 47(XXX) syndrome: a case report.

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Chiappedi, Matteo; de Vincenzi, Silvia; Dolci, Roberta; De Luca, Sara; Bejor, Maurizio

2011-11-05

To the best of our knowledge, this is the first report of a comorbidity between Gilles de la Tourette's syndrome and 47 (XXX) syndrome. The clinical picture of Gilles de la Tourette's Syndrome is well described, while 47 (XXX) syndrome is much more rare and has a broader spectrum of possible phenotypic presentations. An Italian Caucasian girl was referred at the age of 11 to our Rehabilitation Center for anxiety and learning difficulties. The girl had already been diagnosed as having 47(XXX) syndrome; she had some rather typical features of the chromosomal abnormality, but she also showed a high level of anxiety and the presence of motor and vocal tics. When an accurate history was taken, a diagnosis of Gilles de la Tourette's Syndrome emerged. The possible interaction between peculiar features of these two syndromes in terms of neuropsychological and affective functioning is both interesting for the specific case and to hypothesize models of rehabilitation for patients with one or both syndromes. Executive functions are specifically reduced in both syndromes, therefore it might be hard to discriminate the contribution of each one to the general impairment; the same applies to anxiety. Moreover, mental retardation (with a significantly lower verbal cognitive functioning) poses relevant problems when suggesting cognitive behavioral or psychoeducational rehabilitative approaches.

Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome Type III and Ehlers-Danlos syndrome hypermobility type): Clinical description and natural history.

Science.gov (United States)

Tinkle, Brad; Castori, Marco; Berglund, Britta; Cohen, Helen; Grahame, Rodney; Kazkaz, Hanadi; Levy, Howard

2017-03-01

The hypermobile type of Ehlers-Danlos syndrome (hEDS) is likely the most common hereditary disorder of connective tissue. It has been described largely in those with musculoskeletal complaints including joint hypermobility, joint subluxations/dislocations, as well as skin and soft tissue manifestations. Many patients report activity-related pain and some go on to have daily pain. Two undifferentiated syndromes have been used to describe these manifestations-joint hypermobility syndrome and hEDS. Both are clinical diagnoses in the absence of other causation. Current medical literature further complicates differentiation and describes multiple associated symptoms and disorders. The current EDS nosology combines these two entities into the hypermobile type of EDS. Herein, we review and summarize the literature as a better clinical description of this type of connective tissue disorder. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Proteomic profiles in hyperandrogenic syndromes.

Science.gov (United States)

Misiti, S; Stigliano, A; Borro, M; Gentile, G; Michienzi, S; Cerquetti, L; Bucci, B; Argese, N; Brunetti, E; Simmaco, M; Toscano, V

2010-03-01

Polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (CAH) represent the most common causes of hyperandrogenism. Although the etiopathogeneses of these syndromes are different, they share many clinical and biochemical signs, such as hirsutism, acne, and chronic anovulation. Experimental data have shown that peripheral T-lymphocytes function as molecular sensors, being able to record molecular signals either at staminal and mature cell levels, or hormones at systemic levels. Twenty PCOS women and 10 CAH with 21-hydroxylase deficiency, aged between 18-35 yr, were studied. T-cells purified from all patients and 20 healthy donors have been analyzed by 2-dimensional gel electrophoresis. Silver-stained proteomic map of each patient was compared with a control map obtained by pooling protein samples of the 20 healthy subjects. Spots of interest were identified by peptide mass fingerprint. Computer analysis evidenced several peptidic spots significantly modulated in all patients examined. Some proteins were modulated in both syndromes, others only in PCOS or in CAH. These proteins are involved in many physiological processes as the functional state of immune system, the regulation of the cytoskeleton structure, the oxidative stress, the coagulation process, and the insulin resistance. Identification of the physiological function of these proteins could help to understand ethiopathogenetic mechanisms of hyperandrogenic syndromes and its complications.

Noonan's and DiGeorge syndromes with monosomy 22q11.

OpenAIRE

Wilson, D I; Britton, S B; McKeown, C; Kelly, D; Cross, I E; Strobel, S; Scambler, P J

1993-01-01

A boy with the dysmorphic features of Noonan's syndrome and pulmonary valve stenosis who had evidence of hypoparathyroidism and abnormal T lymphocyte numbers in the neonatal period is reported. He had a normal karyotype but molecular analysis revealed a submicroscopic deletion within chromosome 22q11, the region deleted in DiGeorge syndrome. Thus this child has both Noonan's syndrome and DiGeorge syndrome; 22q11 is a candidate region for a gene defective in Noonan's syndrome.

History of preeclampsia is not associated with an increased risk of thyroid dysfunction

NARCIS (Netherlands)

Dekker, Ruth R.; Jochemsen, B.M.; van Pampus, M.G.; Santema, J.G.; Roozendaal, C.; Groen, H.; Links, T.P.; van Doormaal, J.J.

Objective. We evaluated the thyroid function in women with a history of preeclampsia and/or HELLP syndrome at least 2 years after delivery. Design. Observational retrospective study. Setting. University Medical Center Groningen, The Netherlands. Population. Women with a history of preeclampsia

Metabolic syndrome as a risk factor for neurological disorders.

Science.gov (United States)

Farooqui, Akhlaq A; Farooqui, Tahira; Panza, Francesco; Frisardi, Vincenza

2012-03-01

The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the hypothalamic 'bodyweight/appetite/satiety set point,' resulting in the initiation and development of metabolic syndrome. Metabolic syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer's disease. The molecular mechanism underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However, it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders such as stroke, Alzheimer's disease and depression. The purpose of this review is not only to describe the involvement of brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical changes in stroke, Alzheimer's disease and depression to a wider audience of neuroscientists with the hope that this discussion will initiate more studies on the relationship between metabolic syndrome and neurological disorders. © Springer Basel AG 2011

Elastins from patients with Williams-Beuren syndrome and healthy individuals differ on the molecular level

DEFF Research Database (Denmark)

Heinz, Andrea; Huertas, Angela C Mora; Schräder, Christoph U

2016-01-01

Williams-Beuren syndrome (WBS) is a congenital disorder, which involves the heterozygous deletion of the elastin gene and other genes on chromosome 7. Clinical symptoms that are associated with hemizygosity of the essential extracellular matrix protein elastin include premature aging of the skin...... and supravalvular aortic stenosis. However, only little is known about the molecular basis of structural abnormalities in the connective tissue of WBS patients. Therefore, for the first time this study aimed to systematically characterize and compare the structure and amount of elastin present in skin and aortic...... tissue from WBS patients and healthy individuals. Elastin fibers were isolated from tissue biopsies, and it was found that skin of WBS patients contains significantly less elastin compared to skin of healthy individuals. Scanning electron microscopy and mass spectrometric measurements combined...

Compartment syndrome in a labrador retriever

International Nuclear Information System (INIS)

Williams, J.; Bailey, M.Q.; Schertel, E.R.; Valentine, A.

1994-01-01

Compartment syndrome is an elevation of interstitial pressure in a closed osseofascial compartment that results in microvascular compromise. This report documents a clinical syndrome in the crus of a fourteen-month-old intact male Labrador Retriever which was consistent with trauma-induced compartment syndrome. A six month history of recurring trauma or complications resulted in the need for referral. Survey radiography and ultrasonography aided in the diagnosis, but the definitive answer was provided by femoral angiography. The patient was successfully treated and was discharged with normal limb function. One year later, there were no complications observed. Compartment syndrome is not uncommon in humans, and is routinely considered in certain blunt and most penetrating traumas. However, few reports of this complication in animals are found

Gorlin-Goltz syndrome.

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Şereflican, Betül; Tuman, Bengü; Şereflican, Murat; Halıcıoğlu, Sıddıka; Özyalvaçlı, Gülzade; Bayrak, Seval

2017-09-01

Gorlin-Goltz syndrome is a rare multisystemic disease inherited in an autosomal dominant pattern. It is characterized by numerous basal cell carcinoma of the skin, jaw cysts, and skeletal anomalies such as frontal bossing, vertebral anomalies, palmoplantar pits, and falx cerebri calcification. There is a tendency to tumors including medullablastoma, fibroma, rabdomyoma, leiomyosarcoma etc.. The diagnosis is based on major and minor clinical and radiologic criteria. Early diagnosis and treatment are of utmost importance in reducing the severity of long-term sequelae of this syndrome. In this article, we present a 15-year-old boy who was admitted to our clinic with brown-black papules and plaques on his scalp and was thought to have Gorlin-Goltz syndrome. He had a history of medulloblastoma that was treated with surgical resection followed by cranial radiotherapy and unilateral retinoblastoma. We present this case, because association of Gorlin-Goltz syndrome and retinoblastoma has not been described previously in the literature and we aimed to draw attention to radiation-induced basal cell carcinomas.

Catastrophic antiphospholipid Syndrome

International Nuclear Information System (INIS)

Medina Velasquez, Yimy; Felix Restrepo Suarez, Jose; Iglesias Gamarra, Antonio

2001-01-01

The antiphospholipid syndrome (APS) is characterized by venous, arterial thrombosis and miscarriages along with lupic anticoagulant and antibodies against anticardiolipin. The catastrophic antiphospholipid syndrome (CAPS) has been described since 1992 like a multiple organic dysfunction caused by multiple vascular thrombosis in three or more organs. The patients who suffer from this syndrome may have or not history of APS. There are two or three mechanisms that may cause the CAPS, alone or in combination: These are: 1. The multisystemic thrombotic disease with emphasis in microvasculature occlusion of the organs and occlusion of big arterial or veins 2. The disseminated intravascular coagulation (DIC) superimpose in 15% to 50% of the patients that, of course, conducted to an occlusive disease of arterioles, veins or capillaries. 3. A systemic inflammatory response syndrome (SIRS) induced by citoquines. In this review it is described clinical and laboratory features, pathogenesis and treatment of CAPS. For this purpose, it was searched for Medline from 1993 to 2000 and revised the most significant issues obtained by this medium

Clinical aspects of Usher syndrome and the USH2A gene in a cohort of 433 patients.

Science.gov (United States)

Blanco-Kelly, Fiona; Jaijo, Teresa; Aller, Elena; Avila-Fernandez, Almudena; López-Molina, María Isabel; Giménez, Ascensión; García-Sandoval, Blanca; Millán, José M; Ayuso, Carmen

2015-02-01

A new statistical approach is needed to describe the clinical differences between type I and type II Usher syndrome and between the 2 most frequent mutations in the USH2A gene. To describe the primary phenotypic characteristics and differences between type I and type II Usher syndrome and to establish a phenotype-genotype correlation for the 2 most frequent mutations in the USH2A gene. Cross-sectional study at a genetics department, in which clinical evaluations were performed for 433 patients (297 unrelated families) who were classified as having type I, II, III, atypical, or unclassified Usher syndrome according to their clinical history, pedigree data, results from ophthalmological studies, and audiological, neurophysiological, and vestibular test results. Molecular studies were performed for 304 patients (256 unrelated families). The Mann-Whitney U test or the χ2 test was used for calculating the differences between mean values for the analyzed parameters. Age at diagnosis; age at onset of night blindness, visual field loss, visual acuity loss, and cataracts; and severity and age at diagnosis of hearing loss. The comparison between patients with type I Usher syndrome and those with type II Usher syndrome revealed P Usher syndrome and between the 2 most frequent mutations in the USH2A gene. Detailed genotype-phenotype correlations, as presented in our study, allow for a better correlation of clinical signs with a known genotype and can improve the clinical management, genetic counseling, and risk assessment of patients with Usher syndrome because an estimated prognosis of their disease can be made.

Concepts, Diagnosis and the History of Medicine: Historicising Ian Hacking and Munchausen Syndrome.

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Millard, Chris

2017-08-01

Concepts used by historians are as historical as the diagnoses or categories that are studied. The example of Munchausen syndrome (deceptive presentation of illness in order to adopt the 'sick role') is used to explore this. Like most psychiatric diagnoses, Munchausen syndrome is not thought applicable across time by social historians of medicine. It is historically specific, drawing upon twentieth-century anthropology and sociology to explain motivation through desire for the 'sick role'. Ian Hacking's concepts of 'making up people' and 'looping effects' are regularly utilised outside of the context in which they are formed. However, this context is precisely the same anthropological and sociological insight used to explain Munchausen syndrome. It remains correct to resist the projection of Munchausen syndrome into the past. However, it seems inconsistent to use Hacking's concepts to describe identity formation before the twentieth century as they are given meaning by an identical context.

Outcome of genetic evaluation of patients with kidney cancer referred for suspected hereditary cancer syndromes.

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Stratton, Kelly L; Alanee, Shaheen; Glogowski, Emily A; Schrader, Kasmintan A; Rau-Murthy, Rohini; Klein, Robert; Russo, Paul; Coleman, Jonathan; Offit, Kenneth

2016-05-01

To analyze patients with kidney cancer referred for evaluation at a high-volume genetics service at a comprehensive cancer center and identify factors associated with positive tests for hereditary cancer syndromes. A retrospective review of patients referred to the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center was performed, and patients with a personal history of kidney cancer were identified. Patient and disease characteristics were reviewed. In all, 4 variables including age at diagnosis of kidney tumor, presence of syndromic manifestations, family history of kidney cancer, and number of primary malignancies were evaluated for association with positive test results in 2 groups: patients tested for renal cell carcinoma syndromes and Lynch syndrome. Guidance for genetic testing strategy in patients with kidney cancer is provided. Between 1999 and 2012, 120 patients with a history of kidney cancer were evaluated by the Clinical Genetics Service. The mean age at kidney cancer diagnosis was 52 years (interquartile range: 42-63), with 57% being women. A family history of kidney cancer was reported by 39 patients (33%). Time between diagnosis of first cancer and genetic consultation was 5 years in the remaining 23%. Overall, 95 patients were tested for genetic abnormalities with 27 (28%) testing positive. Testing for renal cell carcinoma (RCC)-related syndromes was performed on 43 patients, with 13 testing positive (30%). Lynch syndrome testing was positive in 9 patients (32%) after 28 were tested. In RCC-associated syndromes, young age of diagnosis was associated with positive test results. Conversely, syndromic manifestations and increasing number of primary malignancies were associated with positive Lynch testing. The discovery of inherited kidney cancer syndromes has provided a unique opportunity to identify patients at increased risk for cancer. Factors associated with positive genetic testing are unique to different syndromes. These data

Metabolic Syndrome and Breast Cancer Risk.

Science.gov (United States)

Wani, Burhan; Aziz, Shiekh Aejaz; Ganaie, Mohammad Ashraf; Mir, Mohammad Hussain

2017-01-01

The study was meant to estimate the prevalence of metabolic syndrome in patients with breast cancer and to establish its role as an independent risk factor on occurrence of breast cancer. Fifty women aged between 40 and 80 years with breast cancer and fifty controls of similar age were assessed for metabolic syndrome prevalence and breast cancer risk factors, including age at menarche, reproductive status, live births, breastfeeding, and family history of breast cancer, age at diagnosis of breast cancer, body mass index, and metabolic syndrome parameters. Metabolic syndrome prevalence was found in 40.0% of breast cancer patients, and 18.0% of those in control group ( P = 0.02). An independent and positive association was seen between metabolic syndrome and breast cancer risk (odds ratio = 3.037; 95% confidence interval 1.214-7.597). Metabolic syndrome is more prevalent in breast cancer patients and is an independent risk factor for breast cancer.

Mouse models of long QT syndrome

Science.gov (United States)

Salama, Guy; London, Barry

2007-01-01

Congenital long QT syndrome is a rare inherited condition characterized by prolongation of action potential duration (APD) in cardiac myocytes, prolongation of the QT interval on the surface electrocardiogram (ECG), and an increased risk of syncope and sudden death due to ventricular tachyarrhythmias. Mutations of cardiac ion channel genes that affect repolarization cause the majority of the congenital cases. Despite detailed characterizations of the mutated ion channels at the molecular level, a complete understanding of the mechanisms by which individual mutations may lead to arrhythmias and sudden death requires study of the intact heart and its modulation by the autonomic nervous system. Here, we will review studies of molecularly engineered mice with mutations in the genes (a) known to cause long QT syndrome in humans and (b) specific to cardiac repolarization in the mouse. Our goal is to provide the reader with a comprehensive overview of mouse models with long QT syndrome and to emphasize the advantages and limitations of these models. PMID:17038432

Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

Science.gov (United States)

Popov, Dmitri

Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

Benign joint hypermobility syndrome

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Iwona Słowińska

2014-11-01

Full Text Available Benign joint hypermobility syndrome (BJHS, commonly known as loose ligament syndrome, is a non-inflammatory rheumatic condition. It is characterised by a greater than normal range of motion of the joints of the limbs and spine. The prevalence of the syndrome in preschool-age children is estimated to be between 2% and 30%, depending on ethnic background (with higher prevalence in Asian and African populations, occurring most often in families with a history of the condition and more frequently in girls. This paper presents a case report of a 12-year-old girl. A broad differential diagnostic approach to recurrent joint inflammation with joint effusion and pain made it possible to establish a diagnosis of benign joint hypermobility syndrome. The child met the Brighton criteria; her Beighton score was 7 out of 9. Patient education aimed at eliminating abnormal joint movement and an appropriate rehabilitation programme play key roles in the treatment of BJHS.

Mutation of Mitochondrial DNA G13513A Presenting with Leigh Syndrome, Wolff-Parkinson-White Syndrome and Cardiomyopathy

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Shi-Bing Wang

2008-08-01

Full Text Available Mutation of mitochondrial DNA (mtDNA G13513A, encoding the ND5 subunit of respiratory chain complex I, can cause mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS and Leigh syndrome. Wolff-Parkinson-White (WPW syndrome and optic atrophy were reported in a high proportion of patients with this mutation. We report an 18-month-old girl, with an 11-month history of psychomotor regression who was diagnosed with WPW syndrome and hypertrophic cardiomyopathy, in association with Leigh syndrome. Supplementation with coenzyme Q10, thiamine and carnitine prevented further regression in gross motor function but the patient's heart function deteriorated and dilated cardiomyopathy developed 11 months later. She was found to have a mutation of mtDNA G13513A. We suggest that mtDNA G13513A mutation is an important factor in patients with Leigh syndrome associated with WPW syndrome and/or optic atrophy, and serial heart function monitoring by echocardiography is recommended in this group of patients.

Molecular Study of Three Lebanese and Syrian Patients with Waardenburg Syndrome and Report of Novel Mutations in the EDNRB and MITF Genes

Science.gov (United States)

Haddad, N.M.; Ente, D.; Chouery, E.; Jalkh, N.; Mehawej, C.; Khoueir, Z.; Pingault, V.; Mégarbané, A.

2011-01-01

Waardenburg syndrome (WS) is a genetic disorder characterized primarily by depigmentation of the skin and hair, heterochromia of the irides, sensorineural deafness, and sometimes by dystopia canthorum, and Hirschsprung disease. WS presents a large clinical and genetic heterogeneity. Four different types have been individualized and linked to 5 different genes. We report 2 cases of WS type II and 1 case of WS type IV from Lebanon and Syria. The genetic studies revealed 2 novel mutations in the MITF gene of the WS type II cases and 1 novel homozygous mutation in the EDNRB gene of the WS type IV case. This is the first molecular study of patients from the Arab world. Additional cases will enable a more detailed description of the clinical spectrum of Waardenburg syndrome in this region. PMID:21373256

Molecular Study of Three Lebanese and Syrian Patients with Waardenburg Syndrome and Report of Novel Mutations in the EDNRB and MITF Genes.

Science.gov (United States)

Haddad, N M; Ente, D; Chouery, E; Jalkh, N; Mehawej, C; Khoueir, Z; Pingault, V; Mégarbané, A

2011-01-01

Waardenburg syndrome (WS) is a genetic disorder characterized primarily by depigmentation of the skin and hair, heterochromia of the irides, sensorineural deafness, and sometimes by dystopia canthorum, and Hirschsprung disease. WS presents a large clinical and genetic heterogeneity. Four different types have been individualized and linked to 5 different genes. We report 2 cases of WS type II and 1 case of WS type IV from Lebanon and Syria. The genetic studies revealed 2 novel mutations in the MITF gene of the WS type II cases and 1 novel homozygous mutation in the EDNRB gene of the WS type IV case. This is the first molecular study of patients from the Arab world. Additional cases will enable a more detailed description of the clinical spectrum of Waardenburg syndrome in this region.

Symptoms Before Sudden Arrhythmic Death Syndrome

DEFF Research Database (Denmark)

Glinge, Charlotte; Jabbari, Reza; Risgaard, Bjarke

2015-01-01

INTRODUCTION: No studies in an unselected and nationwide setting have characterized the symptoms and medical history of patients with sudden arrhythmic death syndrome (SADS). The aim of this study was to identify and describe the symptoms and medical history of patients before the presentation......%), palpitations (n = 2, 1%), presyncope/syncope (n = 23, 17%), and aborted SCD (n = 2, 1%). In addition, seizures (n = 25, 18%) were prevalent. In 61 (45%) SADS cases, no previous medical history were recorded. CONCLUSION: In this unselected, nationwide study of 136 young SADS patients, 35% had experienced...

Mismatch repair genes in Lynch syndrome: a review

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Felipe Cavalcanti Carneiro da Silva

Full Text Available Lynch syndrome represents 1-7% of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2; mutL homolog 1 (MLH1; mutS homolog 6 (MSH6; postmeiotic segregation increased 2 (PMS2; and postmeiotic segregation increased 1 (PMS1. It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3, also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors, approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50% and MSH2 (40%, while others account for 10%. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.

[The syndrome of Cotard: an overview].

Science.gov (United States)

Van den Eynde, F; Debruyne, H; Portzky, M; De Saedeleer, S; Audenaert, K

2008-01-01

There is increasing controversy about whether psychiatric illnesses should be divided into categories. One of the reasons is that such a categorial system, by its very nature, cannot provide a detailed description of specific psychopathological symptoms. A patient with Cotard's syndrome, for instance, is characterised by a nihilistic delusion relating to his own body and the syndrome does not fit into any one category. We report on a case of Cotard's syndrome encountered at our clinic. To provide an overview of the characteristics of Cotard's syndrome, including its history, phenomenology, pathogenesis and treatment. A Medline search was conducted for the period 1980-2006 using the search term 'Cotard$'. This resulted in 68 publications, of which 18 were not used. Cross-references were used as well. Cotard's syndrome cannot be fitted unambiguously into any one category of the current classification system. Current evidence regarding Cotard's syndrome is based mainly on case studies and therefore no clarity can be obtained about the various aspects of the syndrome, such as prevalence, pathogenesis, treatment.

Noonan syndrome – a new survey

Science.gov (United States)

Tafazoli, Alireza; Eshraghi, Peyman; Koleti, Zahra Kamel

2016-01-01

Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate. Noonan syndrome shares clinical features with other rare conditions, including LEOPARD syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair, and Costello syndrome. Germline mutations in the RAS-MAPK (mitogen-activated protein kinase) signal transduction pathway are responsible for NS and other related disorders. Noonan syndrome diagnosis is primarily based on clinical features, but molecular testing should be performed to confirm it in patients. Due to the high number of genes associated with NS and other RASopathy disorders, next-generation sequencing is the best choice for diagnostic testing. Patients with NS also have higher risk for leukemia and specific solid tumors. Age-specific guidelines for the management of NS are available. PMID:28144274

Lynch Syndrome: An Updated Review

Directory of Open Access Journals (Sweden)

Rishabh Sehgal

2014-06-01

Full Text Available Lynch syndrome is one of the most common cancer susceptibility syndromes. Individuals with Lynch syndrome have a 50%–70% lifetime risk of colorectal cancer, 40%–60% risk of endometrial cancer, and increased risks of several other malignancies. It is caused by germline mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2. In a subset of patients, Lynch syndrome is caused by 3' end deletions of the EPCAM gene, which can lead to epigenetic silencing of the closely linked MSH2. Relying solely on age and family history based criteria inaccurately identifies eligibility for Lynch syndrome screening or testing in 25%–70% of cases. There has been a steady increase in Lynch syndrome tumor screening programs since 2000 and institutions are rapidly adopting a universal screening approach to identify the patients that would benefit from genetic counseling and germline testing. These include microsatellite instability testing and/or immunohistochemical testing to identify tumor mismatch repair deficiencies. However, universal screening is not standard across institutions. Furthermore, variation exists regarding the optimum method for tracking and disclosing results. In this review, we summarize traditional screening criteria for Lynch syndrome, and discuss universal screening methods. International guidelines are necessary to standardize Lynch syndrome high-risk clinics.

Comprehensive Molecular Screening in Chinese Usher Syndrome Patients.

Science.gov (United States)

Sun, Tengyang; Xu, Ke; Ren, Yanfan; Xie, Yue; Zhang, Xiaohui; Tian, Lu; Li, Yang

2018-03-01

Usher syndrome (USH) refers to a group of autosomal recessive disorders causing deafness and blindness. The objectives of this study were to determine the mutation spectrum in a cohort of Chinese patients with USH and to describe the clinical features of the patients with mutations. A total of 119 probands who were clinically diagnosed with USH were recruited for genetic analysis. All probands underwent ophthalmic examinations. A combination of molecular screening methods, including targeted next-generation sequencing, Sanger-DNA sequencing, and multiplex ligation probe amplification assay, was used to detect mutations. We found biallelic mutations in 92 probands (77.3%), monoallelic mutations in 5 patients (4.2%), and 1 hemizygous mutation in 1 patient (0.8%), resulting in an overall mutation detection rate of 78.2%. Overall, 132 distinct disease-causing mutations involving seven USH (ABHD12, CDH23, GPR98, MYO7A, PCDH15, USH1C, and USH2A) genes; 5 other retinal degeneration genes (CHM, CNGA1, EYS, PDE6B, and TULP1); and 1 nonsyndromic hearing loss gene (MYO15A) were identified, and 78 were novel. Mutations of MYOA7 were responsible for 60% of USH1 families, followed by PCDH15 (20%) and USH1C (10%). Mutations of USH2A accounted for 67.7% of USH2 families, and mutation c.8559-2A>G was the most frequent one, accounting for 19.1% of the identified USH2A alleles. Our results confirm that the mutation spectrum for each USH gene in Chinese patients differs from those of other populations. The formation of the mutation profile for the Chinese population will enable a precise genetic diagnosis for USH patients in the future.

Cardiovascular risk factors in Chinese women with a history of gestational diabetes mellitus.

Science.gov (United States)

Mai, Caiyuan; Hou, Minming; Chen, Rong; Duan, Dongmei; Xu, Huikun; Lin, Xiaohong; Wen, Jiying; Lv, Lijuan; Lei, Qiong; Niu, Jianmin

2015-01-01

Women with a history of gestational diabetes (GDM) are at increased risk of developing cardiovascular diseases compared with normal women. This study aimed to evaluate the cardiovascular risk factors in Chinese women with GDM. 453 women with GDM (cases) and 1,180 healthy women (controls) were included in this study. The post-partum examinations included 2 h 75 g oral glucose tolerance tests, lipid profiles, anthropometric measurements (blood pressure, height, weight) and documentation of medical history, diet, and lifestyle. Compared with controls, the risks of abnormal glucose metabolism, obesity, hypertension, metabolic syndrome in women with a history of GDM were 4.61, 1.30, 1.57 and 3.52, respectively. Fasting blood glucose, progestational body mass index (pBMI) and antenatal insulin resistance at antenatal visit were predictors for abnormal glucose metabolism. pBMI and antenatal diastolic blood pressure were predictors for hypertension. pBMI and weight gain during pregnancy were predictors for obesity/overweight. pBMI, antenatal systolic blood pressure and antenatal triglyceride were predictors for metabolic syndrome. Women with a history of GDM have increased rates of cardiovascular disease risk factors including abnormal glucose metabolism, obesity, hypertension, metabolic syndrome. pBMI is the common independent predictors of cardiometabolic disease in the post-partum.

Gender dysphoria in Asperger's syndrome: a caution.

Science.gov (United States)

Parkinson, John

2014-02-01

The incidence of Asperger's syndrome is reported as above average in young people presenting with gender dysphoria. Patients with Asperger's syndrome, however, are prone to obsessive preoccupations. This paper points out that the apparent dysphoria may in some cases prove to be a transient obsession. Cases from the author's clinical practice were reviewed. Two young men with histories suggesting Asperger's syndrome presented with strong convictions of gender dysphoria, asking for hormonal and surgical treatment. Treatment was withheld and after several years both came to repudiate their 'transgender phase'. Patients asking for sex reassignment should be assessed for indications of Asperger's syndrome. Irreversible treatments should be withheld until it is clear there is a genuine issue of transsexualism.

Overset Wolff-Parkinson-White-syndrom

DEFF Research Database (Denmark)

Nielsen, Trine Skov; Dalager, Søren; Larsen, Maiken Kudahl

2010-01-01

An autopsy in a 28-year-old man did not explain the cause of sudden unexpected death. However, a history of episodes with tachycardia and dizziness and a reassessed previous electrocardiogram exhibiting ventricular pre-excitation was consistent with Wolff-Parkinson-White (WPW) syndrome...

The alcohol withdrawal syndrome.

LENUS (Irish Health Repository)

McKeon, A

2008-08-01

The alcohol withdrawal syndrome (AWS) is a common management problem in hospital practice for neurologists, psychiatrists and general physicians alike. Although some patients have mild symptoms and may even be managed in the outpatient setting, others have more severe symptoms or a history of adverse outcomes that requires close inpatient supervision and benzodiazepine therapy. Many patients with AWS have multiple management issues (withdrawal symptoms, delirium tremens, the Wernicke-Korsakoff syndrome, seizures, depression, polysubstance abuse, electrolyte disturbances and liver disease), which requires a coordinated, multidisciplinary approach. Although AWS may be complex, careful evaluation and available treatments should ensure safe detoxification for most patients.

Spectrum of novel mutations found in Waardenburg syndrome types 1 and 2: implications for molecular genetic diagnostics.

Science.gov (United States)

Wildhardt, Gabriele; Zirn, Birgit; Graul-Neumann, Luitgard M; Wechtenbruch, Juliane; Suckfüll, Markus; Buske, Annegret; Bohring, Axel; Kubisch, Christian; Vogt, Stefanie; Strobl-Wildemann, Gertrud; Greally, Marie; Bartsch, Oliver; Steinberger, Daniela

2013-03-18

Till date, mutations in the genes PAX3 and MITF have been described in Waardenburg syndrome (WS), which is clinically characterised by congenital hearing loss and pigmentation anomalies. Our study intended to determine the frequency of mutations and deletions in these genes, to assess the clinical phenotype in detail and to identify rational priorities for molecular genetic diagnostics procedures. Prospective analysis. 19 Caucasian patients with typical features of WS underwent stepwise investigation of PAX3 and MITF. When point mutations and small insertions/deletions were excluded by direct sequencing, copy number analysis by multiplex ligation-dependent probe amplification was performed to detect larger deletions and duplications. Clinical data and photographs were collected to facilitate genotype-phenotype analyses. All analyses were performed in a large German laboratory specialised in genetic diagnostics. 15 novel and 4 previously published heterozygous mutations in PAX3 and MITF were identified. Of these, six were large deletions or duplications that were only detectable by copy number analysis. All patients with PAX3 mutations had typical phenotype of WS with dystopia canthorum (WS1), whereas patients with MITF gene mutations presented without dystopia canthorum (WS2). In addition, one patient with bilateral hearing loss and blue eyes with iris stroma dysplasia had a de novo missense mutation (p.Arg217Ile) in MITF. MITF 3-bp deletions at amino acid position 217 have previously been described in patients with Tietz syndrome (TS), a clinical entity with hearing loss and generalised hypopigmentation. On the basis of these findings, we conclude that sequencing and copy number analysis of both PAX3 and MITF have to be recommended in the routine molecular diagnostic setting for patients, WS1 and WS2. Furthermore, our genotype-phenotype analyses indicate that WS2 and TS correspond to a clinical spectrum that is influenced by MITF mutation type and position.

[The acute renal and cerebral toxicity of lithium: a cerebro-renal syndrome? A case report].

Science.gov (United States)

Prencipe, M; Cicchella, A; Del Giudice, A; Di Giorgio, A; Scarlatella, A; Vergura, M; Aucella, F

2013-01-01

This descriptive report describes the case of a 50 year-old woman with bipolar disorder, whose maintenance therapy comprised risperidone, sodium valproato and lithium carbonate without any past occurrence of toxicity. Her past medical history was significant for hypertension, cardiopathy and obesity. She presented with a 1-week history of fever, increasing confusion and slurred speech. At presentation, the patient was somnolent. Laboratory investigations revealed a serum creatinine of 3,6 mg/dl, BUN 45 mg/dl serum lithium 3,0 mEq/L with polyuria defined as more than 3 litres a day. EEG and ECG were abnormal. CT brain scanning and lumbar puncture were negative for brain haemorrage or infection. Lithium toxicity causes impairment of renal concentration and encephalopathy due to lithium recirculation, a mechanism responsible for the so-called cerebro-renal syndrome, where dialysis plays an important role in treatment.The patient was treated with continous veno-venous haemodiafiltration (CVVHDF) over 35 hours with gradual improvement of her general condition and efficacy of renal concentration. Our case highlights a few important points. Lithium nefrotoxicity and neurotoxicity can cause a cerebro-renal syndrome even when serum lithium levels are not particularly raised (2,5-3,5 mEq/L). Haemodialysis is the treatment of choice to reduce the molecular mechanisms of lithium-related changes in urinary concentration and reinstate dopaminergic activity in the brain.

[Cotard's syndrome: historical and conceptual aspects].

Science.gov (United States)

Luque Luque, R; Valls Blanco, J M

1994-01-01

The history of the concept of Cotard's syndrome is traced from its inception in 1880 to the present day. Nihilistic delusions were described by Cotard to refer to a special type of hypochondriacal delusion associated to melancholia. Although Cotard himself and other XIX and XX centuries' psychiatrists have considered it from different approaches a specific clinical entity, most of the authors estimate that nihilistic delusion is either a syndrome or a symptom which can appear in different psychiatric disorders.

[30-year-old Patient with suspected Marfan Syndrome and Progressive Gait disturbance].

Science.gov (United States)

Balke, Maryam; Lehmann, Helmar C; Fink, Gereon R; Wunderlich, Gilbert

2017-07-01

History  A 30-year-old man presented with a history of progressive muscle weakness, difficulty in concentrating, and a slender habitus since early childhood. Marfan syndrome was suspected since the age of 14. Examinations  13 years later he was examined by Marfan experts and by genetic testing and Marfan syndrome could not be confirmed. Further neurological examination revealed the suspected diagnosis of myotonic dystrophy type 1, which was confirmed by genetic testing. Treatment and course  Similar to Marfan syndrome, myotonic dystrophy is a multisystemic disorder with the risk of cardiac arrythmias. It is necessary to provide an interdisciplinary care by neurologists, internists, ophthalmologists, speech therapists, and physiotherapists. Conclusion  It is not enough to take the habitus as the principle sign to diagnose Marfan syndrome. Furthermore, it is essential to consider symptoms that are not typical for Marfan syndrome, such as cognitive deficiencies or progressive paresis. © Georg Thieme Verlag KG Stuttgart · New York.

Wolf-Hirschhorn syndrome (WHS): a history in pictures.

Science.gov (United States)

Battaglia, A; Carey, J C; Viskochil, D H; Cederholm, P; Opitz, J M

2000-01-01

The Wolf-Hirschhorn syndrome (WHS) is a well known chromosomal disorder, due to a deletion of distal chromosome 4p. The classical gestalt is striking and poses few diagnostic problems. However, due to the difficulty of detecting very small deletions by standard cytogenetics, diagnosis can be sometimes very difficult, particularly in older patients. In this paper we show the changes, occurring over time, in facial appearance of affected individuals, to improve insight into the evolution of the phenotype, and to increase its diagnostic potential.

An unusual presentation of Brown-Sequard syndrome.

Science.gov (United States)

Herr, R D; Barrett, J

1987-11-01

We report the case of a man with Brown-Sequard syndrome following a fall in which he sustained fractures of the thoracic and lumbosacral spine. Despite characteristic neurological findings, the diagnosis was delayed due to the absence of history of penetrating spinal trauma and incorrect attribution of unilateral-like weakness and numbness to lumbosacral trauma. A directed history and examination revealed that the patient was stabbed in the back with a penknife while leaving a bus and stepped down onto a paralyzed leg, which collapsed beneath him. The patient was given an antibiotic, underwent a negative peritoneal lavage, and had myelography and nerve conduction velocity confirmatory for Brown-Sequard syndrome. With rehabilitation he became ambulatory with a cane one month after the stabbing.

Facet joint syndrome

International Nuclear Information System (INIS)

Zigrai, M.; Zakovic, J.; Brezinova, M.; Pavlovicova, M.

2002-01-01

It is the purpose of the study to demonstrate the clinical relevance of degenerative changes in the facet joint of patients with low back pain irradiating to the lower extremities, and discuss some problems relating to diagnosis and different diagnosis. 119 patients presenting the listed bellow syndromes are covered by the study: scoliosis, polytopic pain vertebral syndrome, paresis and history of trauma. all patients undergo comprehensive neurological examination with special attention focused on the spine: CT and plain x-rays are taken of the lumbosacral segment to assess the condition of the facet joints. The neurological examination demonstrates in all cases pain syndrome in the lumbar spine referred to one or both lower extremities. In 56% it is a matter of persisting pain, and in 44% - recurrent. More than half of the patients complain of sacroiliac (SI) dislocation and palpatory pain. Unilateral or bilateral degenerative changes are documented by imaging studies in all patients, including: subchondral thickening, osteopathy narrowing the lateral or central part of the spinal canal with ensuing nerve root compression. The lumbosacral zygoapophyseal joints are source of pseudoradicular pain. A correlation between clinical picture and GT changes is noted in all patients with facet joint syndrome. CT is an indispensable method in diagnosing facet joint syndrome. (authors)

Nelson syndrome: definition and management.

Science.gov (United States)

Barber, T M; Adams, E; Wass, J A H

2014-01-01

Nelson syndrome is an important complication of treatment with total bilateral adrenalectomy (TBA) for patients with refractory Cushing's disease. Although early cases of Nelson syndrome often presented with the clinical features of large sellar masses, the modern face of Nelson syndrome has changed primarily due to earlier detection (with highly resolved magnetic resonance imaging (MRI) and sensitive ACTH assays) and greater awareness of the condition, resulting in reduced morbidity and mortality. Although lack of administration of neoadjuvant pituitary radiotherapy post-TBA surgery may predict future development of Nelson syndrome, other predictive factors remain controversial. Therefore, Nelson syndrome should be screened for closely and long-term in all patients with a history of Cushing's disease and TBA. The diagnosis of Nelson syndrome remains controversial, and the pathogenesis of this condition is incompletely understood. Current hypotheses include the "released negative feedback" mechansism (residual pituitary corticotropinoma cells are "released" from the negative feedback effects of cortisol following TBA), and the "aggressive corticotropinoma" mechanism (Nelson syndrome is most likely to develop in those patients with refractory treatments - including TBA - for an underlying aggressive corticotropinoma). Effective management of Nelson syndrome with pituitary surgery and radiotherapy is often a challenge. Other therapies (such as Gamma Knife surgery and temozolomide) play an important role and merit further research into their efficacy and placement in the management pathway of Nelson syndrome. © 2014 Elsevier B.V. All rights reserved.

Hereditary periodic fever syndromes

NARCIS (Netherlands)

McDermott, MF; Frenkel, J

Hereditary periodic fever syndromes are defined by recurrent attacks of generalised inflammation for which no infectious or auto-immune cause can be identified. For most of these disorders, the molecular basis has recently been elucidated. This has opened the prospect of novel therapeutic

[Prevalence of metabolic syndrome and associated factors in children and adolescents with obesity].

Science.gov (United States)

Romero-Velarde, Enrique; Aguirre-Salas, Liuba Marina; Álvarez-Román, Yussani Arelhi; Vásquez-Garibay, Edgar Manuel; Casillas-Toral, Erika; Fonseca-Reyes, Salvador

2016-01-01

The prevalence of overweight and obesity in children in Mexico are high, as well as the complications associated with their presence. The objective of this work was to estimate the prevalence of metabolic syndrome in obese children and adolescents attending a Hospital Clinic and identify the associated factors. Cross sectional design with 120 children and adolescents; of either sex, with exogenous obesity and BMI > 2.0 standard deviations. Personal and family history was collected, blood pressure was measured and determination of serum glucose, insulin, lipoprotein HDL cholesterol and triglycerides were performed. The presence of metabolic syndrome with the ATPIII, WHO and International Diabetes Federation criteria was identified. The association of metabolic syndrome with different variables was identified with chi square test and calculation of odds ratio. Mean age was 10.6 ± 2.7 years. The prevalence of metabolic syndrome was 37.5% to 54.5% depending on the criteria used. The presence of metabolic syndrome was associated with a history of large birth weight (OR= 2.21 [1.01-4.82]), and insulin resistance (OR= 6.53 [2.40-18.2]). The prevalence of metabolic syndrome is high in this group of children and adolescents with obesity. The history of large birth weight and the presence of insulin resistance should alert us to the presence of the disease.

Importance of updating family cancer history in childhood cancer survivors.

Science.gov (United States)

Russo, Selena; Warby, Meera; Tucker, Katherine M; Wakefield, Claire E; Cohn, Richard J

2017-10-01

Estimates of the number of childhood cancers with a genetic basis range from 5-8.5% found in germline samples to 29% based on clinical criteria. Family history-taking practice is a fundamental first step in detecting at risk individuals and families. This study focused on Li-Fraumeni Syndrome (LFS), a highly penetrant cancer syndrome. Reported family history in a cohort of 648 of cancer survivor cohort (CCS) was examined. Eligible CCS were: (i) aged up to 14 years at diagnosis; (ii) more than 5 years postdiagnosis; (iii) treated for a childhood cancer at the study hospitals in NSW, Australia; (iv) in remission for more than 3 years. CCS completed self-administered questionnaires. Medical records confirmed diagnosis and treatment-related information. Our findings reveal an increased cancer risk among sibling and relatives of CCS. 91% of siblings diagnosed with cancer were diagnosed under the age of 40 and about 30% diagnosed under the aged of 15 revealing a 5- (RR = 5.1; 95% CI, 3.3-7.9) and 44-fold (RR = 44.6; 95% CI, 18.4-108.3) increased risked of cancer compared with the Australian population, respectively. About 2% of CCS reported that they had been diagnosed with a genetic cancer syndrome. However, 11% of survivors described a family history pattern which met Chompret criteria for screening for TP53 mutations associated with LFS. Our data suggests that familial cancer predispositions may be initially overlooked. Aperiodic and accurate ascertainment of family cancer history of childhood cancer patients and survivors is therefore recommended.

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

African Journals Online (AJOL)

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 ...

Clinical and molecular phenotype of Aicardi-Goutieres syndrome

NARCIS (Netherlands)

Rice, Gillian; Patrick, Teresa; Parmar, Rekha; Taylor, Claire F.; Aeby, Alec; Aicardi, Jean; Artuch, Rafael; Montalto, Simon Attard; Bacino, Carlos A.; Barroso, Bruno; Baxter, Peter; Benko, Willam S.; Bergmann, Carsten; Bertini, Enrico; Biancheri, Roberta; Blair, Edward M.; Blau, Nenad; Bonthron, David T.; Briggs, Tracy; Brueton, Louise A.; Brunner, Han G.; Burke, Christopher J.; Carr, Ian M.; Carvalho, Daniel R.; Chandler, Kate E.; Christen, Hans-Jurgen; Corry, Peter C.; Cowan, Frances M.; Cox, Helen; D'Arrigo, Stefano; Dean, John; de Laet, Corinne; de Praeter, Claudine; Dery, Catherine; Ferrie, Colin D.; Flintoff, Kim; Frints, Suzanna G. M.; Garcia-Cazorla, Angels; Gener, Blanca; Goizet, Cyril; Goutieres, Francoise; Green, Andrew J.; Guet, Agnes; Hamel, Ben C. J.; Hayward, Bruce E.; Heiberg, Arvid; Hennekam, Raoul C.; Husson, Marie; Jackson, Andrew P.; Jayatunga, Rasieka; Jiang, Yong-Hui; Kant, Sarina G.; Kao, Amy; King, Mary D.; Kingston, Helen M.; Klepper, Joerg; van der Knaap, Marjo S.; Kornberg, Andrew J.; Kotzot, Dieter; Kratzer, Wilfried; Lacombe, Didier; Lagae, Lieven; Landrieu, Pierre Georges; Lanzi, Giovanni; Leitch, Andrea; Lim, Ming J.; Livingston, John H.; Lourenco, Charles M.; Lyall, E. G. Hermione; Lynch, Sally A.; Lyons, Michael J.; Marom, Daphna; McClure, John P.; McWilliam, Robert; Melancon, Serge B.; Mewasingh, Leena D.; Moutard, Marie-Laure; Nischal, Ken K.; Ostergaard, John R.; Prendiville, Julie; Rasmussen, Magnhild; Rogers, R. Curtis; Roland, Dominique; Rosser, Elisabeth M.; Rostasy, Kevin; Roubertie, Agathe; Sanchis, Amparo; Schiffmann, Raphael; Scholl-Burgi, Sabine; Seal, Sunita; Shalev, Stavit A.; Corcoles, C. Sierra; Sinha, Gyan P.; Soler, Doriette; Spiegel, Ronen; Stephenson, John B. P.; Tacke, Uta; Tan, Tiong Yang; Till, Marianne; Tolmie, John L.; Tomlin, Pam; Vagnarelli, Federica; Valente, Enza Maria; van Coster, Rudy N. A.; van der Aa, Nathalie; Vanderver, Adeline; Vles, Johannes S. H.; Voit, Thomas; Wassmer, Evangeline; Weschke, Bernhard; Whiteford, Margo L.; Willemsen, Michel A. A.; Zankl, Andreas; Zuberi, Sameer M.; Orcesi, Simona; Fazzi, Elisa; Lebon, Pierre; Crow, Yanick J.

2007-01-01

Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease

History of psychiatry and the psychiatric profession.

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Beer, Michael D

2009-11-01

The present article reviews the English language literature on the history of psychiatry published within the previous year. Research has been conducted in the history of clinical syndromes, famous people and psychiatrists, psychiatric institutions, treatments and legislations. The importance of the sociocultural contexts has been shown, particularly in research emanating from Europe and North America, which addresses late 18th to late 20th century issues. Much varied and important research on the history of psychiatry is being performed around the world. This scholarship provides insight into the cultural context and ways in which psychiatry was practised in the past and can help shed light on the way in which psychiatry is conducted today.

Co-occurring Down syndrome and SUCLA2-related mitochondrial depletion syndrome.

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Couser, Natario L; Marchuk, Daniel S; Smith, Laurie D; Arreola, Alexandra; Kaiser-Rogers, Kathleen A; Muenzer, Joseph; Pandya, Arti; Gucsavas-Calikoglu, Muge; Powell, Cynthia M

2017-10-01

Mitochondrial DNA depletion syndrome 5 (MIM 612073) is a rare autosomal recessive disorder caused by homozygous or compound heterozygous pathogenic variants in the beta subunit of the succinate-CoA ligase gene located within the 13q14 band. We describe two siblings of Hispanic descent with SUCLA2-related mitochondrial depletion syndrome (encephalomyopathic form with methylmalonic aciduria); the older sibling is additionally affected with trisomy 21. SUCLA2 sequencing identified homozygous p.Arg284Cys pathogenic variants in both patients. This mutation has previously been identified in four individuals of Italian and Caucasian descent. The older sibling with concomitant disease has a more severe phenotype than what is typically described in patients with either SUCLA2-related mitochondrial depletion syndrome or Down syndrome alone. The younger sibling, who has a normal female chromosome complement, is significantly less affected compared to her brother. While the clinical and molecular findings have been reported in about 50 patients affected with a deficiency of succinate-CoA ligase caused by pathogenic variants in SUCLA2, this report describes the first known individual affected with both a mitochondrial depletion syndrome and trisomy 21. © 2017 Wiley Periodicals, Inc.

Esthesioneuroblastoma in Maffucci's syndrome

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Kurian, Sobha; Crowell, Edward B. [West Virginia University, Section of Hematology/Oncology, Department of Medicine, Health Science Center, Morgantown (United States); Ertan, Esmer; Rassekh, Christopher [West Virginia University, Department of Otolaryngology, Morgantown (United States); Ducatman, Barbara [West Virginia University, Department of Pathology, Morgantown (United States)

2004-10-01

Maffucci's syndrome consists of multiple cutaneous hemangiomas, dyschondroplasia, and enchondromas with potential for malignant change. We report a case of a 33-year-old man with Maffucci's syndrome who presented with a several month history of nasal congestion, facial pain, and diminished vision in his left eye. Radiological studies showed a large soft tissue mass centered in the sinonasal area, extending bilaterally into maxillary sinuses and orbits with compression of left optic nerve. Biopsy of the mass showed esthesioneuroblastoma (olfactory neuroblastoma). Chemotherapy resulted in initial improvement, but the tumor recurred and did not respond to further treatment, resulting in his death. Sarcomatous tumors are reported in Maffucci's syndrome, but this is a rare case of a neuroendocrine tumor in a patient with Maffucci's syndrome. (orig.)

A case Report of Wolfram Syndrome

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Zahra Razavi

2007-01-01

Full Text Available Wolfram syndrome is the association of diabetes mellitus, optic atrophy, diabetes insipidus and sensorineural deafness and is sometimes called DIDMOAD (Diabetes Insipidus, Diabets Mellitus, Optic Atrophy, and Deafness. It is a rare autosomal recessive disease with prevalence of one per 770,000. Natural history of Wolfram syndrome suggests that most patients will eventually develop most complications of this progressive neurodegenerative disorder. Juvenile–onset diabetes mellitus and optic atrophy are the best available diagnostic criteria for Wolfram syndrome. In this report clinical features of a patient with DIDMOAD syndrome is presented. A 12 year old male presented with short standing diabetes mellitus and diabetes insipidus. Further investigations showed bilateral optic atrophy, mild hearing loss and short stature. His parents were relative and he is first case in his family.

Gilles de la Tourette's syndrome in a patient with 47(XXX syndrome: a case report

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Chiappedi Matteo

2011-11-01

Full Text Available Abstract Introduction To the best of our knowledge, this is the first report of a comorbidity between Gilles de la Tourette's syndrome and 47 (XXX syndrome. The clinical picture of Gilles de la Tourette's Syndrome is well described, while 47 (XXX syndrome is much more rare and has a broader spectrum of possible phenotypic presentations. Case presentation An Italian Caucasian girl was referred at the age of 11 to our Rehabilitation Center for anxiety and learning difficulties. The girl had already been diagnosed as having 47(XXX syndrome; she had some rather typical features of the chromosomal abnormality, but she also showed a high level of anxiety and the presence of motor and vocal tics. When an accurate history was taken, a diagnosis of Gilles de la Tourette's Syndrome emerged. Conclusions The possible interaction between peculiar features of these two syndromes in terms of neuropsychological and affective functioning is both interesting for the specific case and to hypothesize models of rehabilitation for patients with one or both syndromes. Executive functions are specifically reduced in both syndromes, therefore it might be hard to discriminate the contribution of each one to the general impairment; the same applies to anxiety. Moreover, mental retardation (with a significantly lower verbal cognitive functioning poses relevant problems when suggesting cognitive behavioral or psychoeducational rehabilitative approaches.

Familial co-segregation of Coffin-Lowry syndrome inherited from the mother and autosomal dominant Waardenburg type IV syndrome due to deletion of EDNRB inherited from the father.

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Loupe, Jacob; Sampath, Srirangan; Lacassie, Yves

2014-10-01

We report an African-American family that was identified after the proposita was referred for diagnostic evaluation at 4½ months with a history of Hirschsprung and dysmorphic features typical of Waardenburg syndrome (WS). Family evaluation revealed that the father had heterochromidia irides and hypertelorism supporting the clinical diagnosis of WS; however, examination of the mother revealed characteristic facial and digital features of Coffin-Lowry syndrome (CLS). Molecular testing of the mother identified a novel 2 bp deletion (c.865_866delCA) in codon 289 of RPS6KA3 leading to a frame-shift and premature termination of translation 5 codons downstream (NM_004586.2:p.Gln289ValfsX5). This deletion also was identified in the proposita and her three sisters with a clinical suspicion of CLS, all of whom as carriers for this X-linked disorder had very subtle manifestations. The molecular confirmation of WS type 4 (Shah-Waardenburg; WS4) was not as straightforward. To evaluate WS types 1-4, multiple sequential molecular tests were requested, including Sanger sequencing of all exons, and deletion/duplication analysis using MLPA for PAX3, MITF, SOX10, EDN3 and EDNRB. Although sequencing did not identify any disease causing variants, MLPA identified a heterozygous deletion of the entire EDNRB in the father. This deletion was also found in the proposita and the oldest child. Since the heterozygous deletion was the only change identified in EDNRB, this family represents one of the few cases of an autosomal dominant inheritance of WS4 involving the endothelin pathway. Altogether, clinical evaluation of the family revealed one child to be positive for WS4 and two positive for CLS, while two children were positive for both diseases simultaneously (including the proposita) while another pair test negative for either disease. This kinship is an example of the coincidence of two conditions co-segregating in one family, with variable phenotypes requiring molecular testing to

Pig models for the human heart failure syndrome

DEFF Research Database (Denmark)

Hunter, Ingrid; Terzic, Dijana; Zois, Nora Elisabeth

2014-01-01

Human heart failure remains a challenging illness despite advances in the diagnosis and treatment of heart failure patients. There is a need for further improvement of our understanding of the failing myocardium and its molecular deterioration. Porcine models provide an important research tool...... in this respect as molecular changes can be examined in detail, which is simply not feasible in human patients. However, the human heart failure syndrome is based on symptoms and signs, where pig models mostly mimic the myocardial damage, but without decisive data on clinical presentation and, therefore, a heart...... to elucidate the human heart failure syndrome....

[Psychiatric disturbances in five patients with MELAS syndrome].

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Magner, Martin; Honzik, Tomas; Tesarova, Marketa; Dvorakova, Veronika; Hansiková, Hana; Raboch, Jiři; Zeman, Jiři

2014-01-01

Mitochondrial disorders of energetic metabolism (MD) represent a heterogeneous group of diseases manifesting at any age with a broad spectrum of clinical symptoms, including psychiatric disorders. The aim of the study was to characterize psychiatric symptoms and diagnoses in five patients with MELAS syndrome between the ages of 17 and 53 years. Four of MELAS patients them harbored the prevalent mitochondrial DNA (mtDNA) mutation 3243A>G, and one patient had the mtDNA mutation 12706T>C. Three patients had positive family histories for MELAS syndrome. In one patient, depression was diagnosedas the first symptom ofMELAS syndrome. Depression also preceded a stroke-like episode in one patient. Four patients had disturbed cognitive functions, confusional states occurred in three patients. One patient manifested psychotic (schizophrenia-like) symptoms. Mitochondrial disorders deserve consideration as part of the differential diagnosis, especially, if there is suspected involvement of other organ groups or positive family history of MD.

Epidemiological predictors of metabolic syndrome in urban West Bengal, India

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Sasthi Narayan Chakraborty

2015-01-01

Full Text Available Introduction: Metabolic syndrome is one of the emerging health problems of the world. Its prevalence is high in urban areas. Though pathogenesis is complex, but the interaction of obesity, sedentary lifestyle, dietary, and genetic factors are known as contributing factors. Community-based studies were very few to find out the prevalence or predictors of the syndrome. Objectives: To ascertain the prevalence and epidemiological predictors of metabolic syndrome. Materials and Methods: A total of 690 study subjects were chosen by 30 clusters random sampling method from 43 wards of Durgapur city. Data were analyzed in SPSS version 20 software and binary logistic regression was done to find out statistical significance of the predictors. Results: Among 32.75% of the study population was diagnosed as metabolic syndrome according to National Cholesterol Education Program Adult Treatment Panel III definition with a modification for Asia Pacific cut-off of waist circumference. Odds were more among females (2.43, upper social class (14.89, sedentary lifestyle (17.00, and positive family history. Conclusion: The overall prevalence of metabolic syndrome was high in urban areas of Durgapur. Increased age, female gender, higher social status, sedentary lifestyle, positive family history, and higher education were the statistically significant predictors of metabolic syndrome.

[Pseudomeigs syndrome in a patient with Krukenberg's tumor].

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Bayod, M J Herráiz; Carlón, M Elorz; Idoate, M A

2007-01-01

We report the case of a fiftyone-year-old woman with a past medical history of Linfoma no Hodking and a gastric adenocarcinoma with signet ring cells. She came to our institution with a twenty month history of dysnea secondary to pleural effussion, bilateral lower extremity edema and probably had ascitis. On CT and US two bilateral pelvic masses were found and biopsied. The anatomopathological analysis showed bilateral ovarian implants from signet ring cell adenocarcinoma (Krukenberg tumor). This patient developed a PseudoMeigs syndrome consisting on malignant ovarian tumor asociated with ascitis and pleural effusion without malignant cells. Oncological patients who present with ascitis and benign pleural effusion, the diagnosis of PseudoMeigs syndrome should be considered.

Multilocus phylogeny reconstruction: new insights into the evolutionary history of the genus Petunia.

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Reck-Kortmann, Maikel; Silva-Arias, Gustavo Adolfo; Segatto, Ana Lúcia Anversa; Mäder, Geraldo; Bonatto, Sandro Luis; de Freitas, Loreta Brandão

2014-12-01

The phylogeny of Petunia species has been difficult to resolve, primarily due to the recent diversification of the genus. Several studies have included molecular data in phylogenetic reconstructions of this genus, but all of them have failed to include all taxa and/or analyzed few genetic markers. In the present study, we employed the most inclusive genetic and taxonomic datasets for the genus, aiming to reconstruct the evolutionary history of Petunia based on molecular phylogeny, biogeographic distribution, and character evolution. We included all 20 Petunia morphological species or subspecies in these analyses. Based on nine nuclear and five plastid DNA markers, our phylogenetic analysis reinforces the monophyly of the genus Petunia and supports the hypothesis that the basal divergence is more related to the differentiation of corolla tube length, whereas the geographic distribution of species is more related to divergences within these main clades. Ancestral area reconstructions suggest the Pampas region as the area of origin and earliest divergence in Petunia. The state reconstructions suggest that the ancestor of Petunia might have had a short corolla tube and a bee pollination floral syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

INHERITED PATHOLOGY OF β2-LAMININ (PIERSON SYNDROME: CLINICAL AND GENETIC ASPECTS

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M.Yu. Kagan

2010-01-01

Full Text Available For the last decade a great successes were attained in the study of molecular bases of glomerular diseases. It was certain that the most frequent reasons of congenital and infantile nephrotic syndrome are mutations in the genes of NPHS1, NPHS2, and WT1. Nevertheless, until now, a number of patients, having combination of early nephrotic syndrome with inherent pathology of other organs, which etiology remains un known. These cases continue to be intensively probed. One of the most important recent achievements in understanding of molecular mechanisms of early nephrotic syndrome is the discovery of mutations of gene of LAMB2, encoding β2 laminin, as the cause of Pearson syndrome (OMIM#609049. In this article the author presents the basic genetic and clinical descriptions of this recently identified pathology. Key words: Pearson syndrome, congenital nephrotic syndrome, β2 laminin, malformation of organ of vision. (Pediatric Pharmacology. – 2010; 7(3:114-117

Usher syndrome: molecular links of pathogenesis, proteins and pathways.

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Kremer, Hannie; van Wijk, Erwin; Märker, Tina; Wolfrum, Uwe; Roepman, Ronald

2006-10-15

Usher syndrome is the most common form of deaf-blindness. The syndrome is both clinically and genetically heterogeneous, and to date, eight causative genes have been identified. The proteins encoded by these genes are part of a dynamic protein complex that is present in hair cells of the inner ear and in photoreceptor cells of the retina. The localization of the Usher proteins and the phenotype in animal models indicate that the Usher protein complex is essential in the morphogenesis of the stereocilia bundle in hair cells and in the calycal processes of photoreceptor cells. In addition, the Usher proteins are important in the synaptic processes of both cell types. The association of other proteins with the complex indicates functional links to a number of basic cell-biological processes. Prominently present is the connection to the dynamics of the actin cytoskeleton, involved in cellular morphology, cell polarity and cell-cell interactions. The Usher protein complex can also be linked to the cadherins/catenins in the adherens junction-associated protein complexes, suggesting a role in cell polarity and tissue organization. A third link can be established to the integrin transmembrane signaling network. The Usher interactome, as outlined in this review, participates in pathways common in inner ear and retina that are disrupted in the Usher syndrome.

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis.

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Bonnet, Crystel; Grati, M'hamed; Marlin, Sandrine; Levilliers, Jacqueline; Hardelin, Jean-Pierre; Parodi, Marine; Niasme-Grare, Magali; Zelenika, Diana; Délépine, Marc; Feldmann, Delphine; Jonard, Laurence; El-Amraoui, Aziz; Weil, Dominique; Delobel, Bruno; Vincent, Christophe; Dollfus, Hélène; Eliot, Marie-Madeleine; David, Albert; Calais, Catherine; Vigneron, Jacqueline; Montaut-Verient, Bettina; Bonneau, Dominique; Dubin, Jacques; Thauvin, Christel; Duvillard, Alain; Francannet, Christine; Mom, Thierry; Lacombe, Didier; Duriez, Françoise; Drouin-Garraud, Valérie; Thuillier-Obstoy, Marie-Françoise; Sigaudy, Sabine; Frances, Anne-Marie; Collignon, Patrick; Challe, Georges; Couderc, Rémy; Lathrop, Mark; Sahel, José-Alain; Weissenbach, Jean; Petit, Christine; Denoyelle, Françoise

2011-05-11

Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool. We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3). Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel. Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis

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Lacombe Didier

2011-05-01

Full Text Available Abstract Background Usher syndrome (USH combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3. Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool. Methods We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3. Results Biallelic mutations were detected in 39 patients (72% and monoallelic mutations in an additional 10 patients (18.5%. In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%, and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48% were novel. Conclusions Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.

Relationships among personality traits, metabolic syndrome, and metabolic syndrome scores: The Kakegawa cohort study.

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Ohseto, Hisashi; Ishikuro, Mami; Kikuya, Masahiro; Obara, Taku; Igarashi, Yuko; Takahashi, Satomi; Kikuchi, Daisuke; Shigihara, Michiko; Yamanaka, Chizuru; Miyashita, Masako; Mizuno, Satoshi; Nagai, Masato; Matsubara, Hiroko; Sato, Yuki; Metoki, Hirohito; Tachibana, Hirofumi; Maeda-Yamamoto, Mari; Kuriyama, Shinichi

2018-04-01

Metabolic syndrome and the presence of metabolic syndrome components are risk factors for cardiovascular disease (CVD). However, the association between personality traits and metabolic syndrome remains controversial, and few studies have been conducted in East Asian populations. We measured personality traits using the Japanese version of the Eysenck Personality Questionnaire (Revised Short Form) and five metabolic syndrome components-elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose-in 1322 participants aged 51.1±12.7years old from Kakegawa city, Japan. Metabolic syndrome score (MS score) was defined as the number of metabolic syndrome components present, and metabolic syndrome as having the MS score of 3 or higher. We performed multiple logistic regression analyses to examine the relationship between personality traits and metabolic syndrome components and multiple regression analyses to examine the relationship between personality traits and MS scores adjusted for age, sex, education, income, smoking status, alcohol use, and family history of CVD and diabetes mellitus. We also examine the relationship between personality traits and metabolic syndrome presence by multiple logistic regression analyses. "Extraversion" scores were higher in those with metabolic syndrome components (elevated waist circumference: P=0.001; elevated triglycerides: P=0.01; elevated blood pressure: P=0.004; elevated fasting glucose: P=0.002). "Extraversion" was associated with the MS score (coefficient=0.12, P=0.0003). No personality trait was significantly associated with the presence of metabolic syndrome. Higher "extraversion" scores were related to higher MS scores, but no personality trait was significantly associated with the presence of metabolic syndrome. Copyright © 2018 Elsevier Inc. All rights reserved.

A rare type of Usher's syndrome.

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Antunica, Antonela Gverović; Kastelan, Snjezana; Bućan, Kajo; Ivanković, Mira; Radman, Maja; Karaman, Ksenija

2013-12-01

A case is presented of a very rare type of Usher's syndrome detected in a 30-year-old woman in her 28th week of pregnancy. She reported left eye visual impairment with a one-month history. She underwent standard ophthalmologic examination with additional procedures scheduled after childbirth, including fluorescein angiography, visual field (Goldman and Octopus) and electroretinography. Fundus examination revealed pallor of the optic disk, diffuse retinal blood vessel narrowing, no retinal pigmentation, left macular edema, vitreous liquefaction, and posterior vitreous detachment. Goldman perimetry showed narrowing of all isopters to 10 degrees, and Octopus perimetry showed peripheral decrease of retinal sensitivity. Electroretinography confirmed the diagnosis of retinitis pigmentosa sine pigmento. Upon collecting case history records, hearing disorders originating from childhood were discovered. To our knowledge, this type of retinitis in Usher's syndrome has been reported only once in the available literature.

[Differential diagnosis of polyarthritis pain syndrome of the locomotor apparatus].

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Menninger, H

1998-02-28

Widespread pain syndromes of the musculoskeletal system present to general practitioners, internists, neurologists and orthopedic surgeons every day. The syndromes may result both from organic diseases (inflammatory joint diseases, rheumatic manifestations of organ diseases) as well as dysfunctional syndromes, the latter including mainly biomechanically induced syndromes and fibromyalgia. The approach is predominantly clinically oriented and requires laboratory means or technical procedures only in a limited extend. The duration of history, the recognition of synovitis and of myofascial trigger points or of integumental tender points allow in most patients to achieve appropriate diagnostic criteria.

A Severe Case of Pigmentary Glaucoma in a Child With a Family History of Pigment Dispersion Syndrome.

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Aragno, Vittoria; Zeboulon, Pierre; Baudouin, Christophe; Labbé, Antoine

2016-08-01

To report a case of severe pigmentary glaucoma (PG) in a 13-year-old boy of a family affected by pigment dispersion syndrome (PDS). A 13-year-old child was referred to our hospital for severe bilateral glaucoma. A complete ophthalmologic evaluation including refraction, intraocular pressure, central corneal thickness, slit-lamp biomicroscopy, gonioscopy, fundus examination, and ultrasound biomicroscopy was performed. Family members were also examined and a family pedigree was obtained. Ophthalmologic examination revealed a severe bilateral PG with Krukenberg spindle and a widely open heavily pigmented iridocorneal angle. Ultrasound biomicroscopy showed a deep anterior chamber with pronounced iris concavity in both eyes. Within his family, his 15-year-old sister and 7-year-old brother were both affected by PDS diagnosed on gonioscopy findings. We report for the first time a severe case of pediatric PG with a family history of PDS. This case demonstrates that accurate screening is necessary in cases of familial PDS and PG, even in the pediatric population.

Molecular and cellular mechanisms of tight junction dysfunction in the irritable bowel syndrome.

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Cheng, Peng; Yao, Jianning; Wang, Chunfeng; Zhang, Lianfeng; Kong, Wuming

2015-09-01

The pathophysiological mechanisms of the irritable bowel syndrome (IBS), one of the most prevalent gastrointestinal disorders, are complex and have not been fully elucidated. The present study aimed to investigate the molecular and cellular mechanisms of tight junction (TJ) dysfunction in IBS. Intestinal tissues of IBS and non‑IBS patients were examined to observe cellular changes by cell chemical tracer electron microscopy and transmission electron microscopy, and intestinal claudin‑1 protein was detected by immunohistochemistry, western blot analysis and fluorescence quantitative polymerase chain reaction. Compared with the control group, TJ broadening and the tracer extravasation phenomenon were observed in the diarrhea‑predominant IBS group, and a greater number of neuroendocrine cells and mast cells filled with high‑density particles in the endocrine package pulp as well as a certain extent of vacuolization were present. The expression of claudin‑1 in diarrhea‑predominant IBS patients was decreased, while it was increased in constipation‑predominant IBS patients. In conclusion, the results of the present study indicated that changes in cellular structure and claudin‑1 levels were associated with Tjs in IBS.

Nelson syndrome: historical perspectives and current concepts.

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Hornyak, Mark; Weiss, Martin H; Nelson, Don H; Couldwell, William T

2007-01-01

The appearance of an adrenocorticotropic hormone (ACTH)-producing tumor after bilateral adrenalectomy for Cushing disease was first described by Nelson in 1958. The syndrome that now bears his name was characterized by hyperpigmentation, a sellar mass, and increased plasma ACTH levels. The treatment of Cushing disease has changed drastically since the 1950s, when the choice was adrenalectomy. Thus, the occurrence, diagnosis, and treatment of Nelson syndrome have changed as well. In the modern era of high-resolution neuroimaging, transsphenoidal microneurosurgery, and stereotactic radiosurgery, Nelson syndrome has become a rare entity. The authors describe the history of the diagnosis and treatment of Nelson syndrome. In light of the changes described, the authors believe this disease must be reevaluated in the contemporary era and a modern paradigm adopted.

Churg-Strauss syndrome and hemorragic vasculitis

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Rui Moreira Marques

2011-12-01

Full Text Available Churg-Strauss syndrome (CSS is a rare syndrome characterized by sinusitis, asthma and peripheral eosinophilia. This vasculitic syndrome affects medium and small-sized vessels, the lung being the most commonly affected organ, followed by the skin. The authors report a case of a 59-year-old male with a past history of asthma and allergic rhinitis. He presented necrohemorragic lesions in the distal phalanx of the 2nd, 3rd and 4th fingers of the lefthand and petechial lesions in the plant of both feet, accompanied by asthenia, anorexia and weight loss. The analytical study revealed leukocytosis with eosinophilia, elevated inflammatory parameters and p-ANCA positive antibodies. The diagnosis of CSS was established based on clinical and histopathological data. Cutaneous manifestations of hemorragic vasculitis are rare in CSS syndrome but can be the first manifestation of the disease. The recognition of this presentation is important for the early diagnosis and treatment of this syndrome.

Churg-Strauss syndrome and hemorrhagic vasculitis

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Marques, Rui Moreira; Cabral, Ana Rita; Monteiro, Antonio; Henriques, Pedro

2011-01-01

Churg-Strauss syndrome (CSS) is a rare syndrome characterized by sinusitis, asthma and peripheral eosinophilia. This vasculitic syndrome affects medium and small-sized vessels, the lung being the most commonly affected organ, followed by the skin. The authors report a case of a 59-year-old male with a past history of asthma and allergic rhinitis. He presented necrohemorragic lesions in the distal phalanx of the 2nd, 3rd and 4th fingers of the left-hand and petechial lesions in the plant of both feet, accompanied by asthenia, anorexia and weight loss. The analytical study revealed leukocytosis with eosinophilia, elevated inflammatory parameters and p-ANCA positive antibodies. The diagnosis of CSS was established based on clinical and histopathological data. Cutaneous manifestations of hemorragic vasculitis are rare in CSS syndrome but can be the first manifestation of the disease. The recognition of this presentation is important for the early diagnosis and treatment of this syndrome. PMID:25386301

Idiopathic Harlequin syndrome – case report

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Marcelina Grochowiec

2015-09-01

Full Text Available Introduction. Harlequin syndrome is a very rare neurological condition characterized by redness and excessive sweating of one half of the face in response to exercise and emotions. In most cases this disorder is not life-threatening. Objective. To present diagnostic difficulties of Harlequin syndrome in dermatological practice. Case report. We present a case of a 30-year-old man with redness and excessive sweating of the right half of the face as a result of exercise that was observed during the diagnosis of chronic urticaria at the Department of Dermatology. The patient was examined ophthalmologically and neurologically, had a CT scan of the head, and the Minor test performed. Idiopathic Harlequin syndrome was diagnosed based on case history and workup results. Conclusions . Harlequin syndrome occurs most often in the form of an idiopathic condition, but neurologic and ophthalmologic assessment should be performed since some diseases, such as brainstem infarction and schwannoma of the upper chest, may initially appear as Harlequin syndrome.

Linguistic history of posterior reversible encephalopathy syndrome: mirror of developing knowledge.

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Maizlin, Zeev V; Ghandehari, Hournaz; Maizels, Leonid; Shewchuk, Jason R; Kirby, John M; Vora, Parag; Clement, Jason J

2011-01-01

the term posterior reversible encephalopathy syndrome (PRES) was first proposed in 2000. Since then, the acronym PRES has become very popular in imaging and clinical literature as it is short, easy to say and remember, and neatly couples the frequent localization of neuroimaging findings along with the typical outcome of this syndrome. Another possible reason for the popularity of this acronym in clinical circles is the connotation of PRES with (elevated blood) PRESsure, as a majority of cases are believed to be associated with hypertension. However, problems exist with the interpretation and common understanding of PRES, questioning the appropriateness of "P" and "R" in the acronym. The linguistic issues related to the acronym of PRES are interesting. the aim of this work is to analyze the controversies related to the acronym of PRES. in 2006, modifying the meaning of the acronym was suggested, renaming it Potentially Reversible Encephalopathy Syndrome in order to adjust to the cases when posterior involvement is not prominent and emphasize that the reversibility is not spontaneous. This meant the creation of a backronym, where the new phrase is constructed by starting with an existing acronym. this new backronym indicates that the original acronym of PRES has become a misnomer.

Turner syndrome and meningioma: support for a possible increased risk of neoplasia in Turner syndrome.

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Pier, Danielle B; Nunes, Fabio P; Plotkin, Scott R; Stemmer-Rachamimov, Anat O; Kim, James C; Shih, Helen A; Brastianos, Priscilla; Lin, Angela E

2014-01-01

Neoplasia is uncommon in Turner syndrome, although there is some evidence that brain tumors are more common in Turner syndrome patients than in the general population. We describe a woman with Turner syndrome (45,X) with a meningioma, in whom a second neoplasia, basal cell carcinomas of the scalp and nose, developed five years later in the absence of therapeutic radiation. Together with 7 cases of Turner syndrome with meningioma from a population-based survey in the United Kingdom, and 3 other isolated cases in the literature, we review this small number of patients for evidence of risk factors related to Turner syndrome, such as associated structural anomalies or prior treatment. We performed histological and fluorescent in situ hybridization (FISH) of 22q (NF2 locus) analyses of the meningeal tumor to search for possible molecular determinants. We are not able to prove causation between these two entities, but suggest that neoplasia may be a rare associated medical problem in Turner syndrome. Additional case reports and extension of population-based studies are needed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Three Cases of Palatal Tics and Gilles De La Tourette Syndrome.

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Rizzo, Renata; Cath, Danielle; Pavone, Piero; Tijssen, Marina; Robertson, Mary M

2015-08-01

Five patients with palatal tics and Gilles de la Tourette syndrome have been previously reported. Little is known about the characteristics of palatal tics given that there are so few reports. On one hand, palatal tics may be rare. Alternatively, they may be less well recognized than repetitive eye blinking or sniffing, which are both obvious and, therefore, more often reported. We describe 3 patients with palatal tics and Gilles de la Tourette syndrome. We also review the 5 patients reported in the literature and explore whether there are characteristic features among this group of 8 cases. The 8 patients had the following features: (1) Personal history of other multiple motor/vocal tics, (2) the presence of typical Gilles de la Tourette syndrome comorbidities, (3) positive family history of tics and/or Gilles de la Tourette syndrome comorbidities, (4) the presence of audible "ear clicks," (5) younger age at onset (2 years). We suggest that palatal tics are underreported. © The Author(s) 2014.

[Adipocytokines and metabolic syndrome--molecular mechanism and clinical implication].

Science.gov (United States)

Matsuda, Morihiro; Shimomura, Iichiro

2004-06-01

Recent progress in adipocyte-biology shows that adipocytes are not merely fat-storing cells but that they secrete a variety of hormones, cytekines, growth factors and other bioactive substabces, conceptualized as adipocytokines. These include plasminogen activator inhibitor 1(PAI-1), tumor necrosis factor(TNF-alpha), leptin and adiponectin. Dysregulated productions of these adipocytekines participate in the pathogenesis of obesity-associated metabolic syndrome such as insulin resistance, type 2 diabetes, hyperlipidemia, and vascular diseases. Increased productions of PAI-1 and TNF-alpha from accumulated fat contribute to the formation of thrombosis and insulin resistance in obesity, respectively. Lack of leptin causes metabolic syndrome. Adiponectin exerts insulin-sensitizing and anti-atherogenic effects, hence decrease of plasma adiponectin is causative for insulin resistance and atherosclerosis in obesity.

Association of biomarkers with health-related quality of life and history of stressors in myalgic encephalomyelitis/chronic fatigue syndrome patients.

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Fenouillet, Emmanuel; Vigouroux, Aude; Steinberg, Jean Guillaume; Chagvardieff, Alexandre; Retornaz, Frédérique; Guieu, Regis; Jammes, Yves

2016-08-31

Myalgic encephalomyelitis chronic fatigue syndrome (ME/CFS) is a common debilitating disorder associated with an intense fatigue, a reduced physical activity, and an impaired quality of life. There are no established biological markerof the syndrome. The etiology is unknown and its pathogenesis appears to be multifactorial. Various stressors, including intense physical activity, severe infection, and emotional stress are reported in the medical history of ME/CFS patients which raises the question whether any physiological and biological abnormalities usually found in these patients could be indicative of the etiology and/or the quality-of-life impairment. Thirty-six patients and 11 age-matched healthy controls were recruited. The following variables that appear to address common symptoms of ME/CFS were studied here: (1) muscle fatigue during exercise has been investigated by monitoring the compound muscle action potential (M-wave); (2) the excessive oxidative stress response to exercise was measured via two plasma markers (thiobarbituric acid reactive substances: TBARS; reduced ascorbic-acid: RAA); (3) a potential inflammatory component was addressed via expression of CD26 on peripheral blood mononuclear cells; (4) quality-of-life impairment was assessed using the London Handicap Scale (LHS) and the Medical Outcome Study Short Form-36 (SF-36). The medical history of each patient, including the presence of stressors such as intense sports practice, severe acute infection and/or severe emotional stress was documented. We observed that: (1) there were striking differences between cases and controls with regard to three biological variables: post-exercise M-wave, TBARS variations and CD26-expression at rest; (2) each of these three variables correlated with the other two; (3) abnormalities in the biomarkers associated with health-related quality of life: the LHS score was negatively correlated with the exercise-induced TBARS increase and positively correlated with CD26

The Greig cephalopolysyndactyly syndrome

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Biesecker Leslie G

2008-04-01

Full Text Available Abstract The Greig cephalopolysyndactyly syndrome (GCPS is a pleiotropic, multiple congenital anomaly syndrome. It is rare, but precise estimates of incidence are difficult to determine, as ascertainment is erratic (estimated range 1–9/1,000,000. The primary findings include hypertelorism, macrocephaly with frontal bossing, and polysyndactyly. The polydactyly is most commonly preaxial of the feet and postaxial in the hands, with variable cutaneous syndactyly, but the limb findings vary significantly. Other low frequency findings include central nervous system (CNS anomalies, hernias, and cognitive impairment. GCPS is caused by loss of function mutations in the GLI3 transcription factor gene and is inherited in an autosomal dominant pattern. The disorder is allelic to the Pallister-Hall syndrome and one form of the acrocallosal syndrome. Clinical diagnosis is challenging because the findings of GCPS are relatively non-specific, and no specific and sensitive clinical have been delineated. For this reason, we have proposed a combined clinical-molecular definition for the syndrome. A presumptive diagnosis of GCPS can be made if the patient has the classic triad of preaxial polydactyly with cutaneous syndactyly of at least one limb, hypertelorism, and macrocephaly. Patients with a phenotype consistent with GCPS (but which may not manifest all three attributes listed above and a GLI3 mutation may be diagnosed definitively with GCPS. In addition, persons with a GCPS-consistent phenotype who are related to a definitively diagnosed family member in a pattern consistent with autosomal dominant inheritance may be diagnosed definitively as well. Antenatal molecular diagnosis is technically straightforward to perform. Differential diagnoses include preaxial polydactyly type 4, the GCPS contiguous gene syndrome, acrocallosal syndrome, Gorlin syndrome, Carpenter syndrome, and Teebi syndrome. Treatment of the disorder is symptomatic, with plastic or

Eagle's Syndrome

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Pinheiro, Thaís Gonçalves; Soares, Vítor Yamashiro Rocha; Ferreira, Denise Bastos Lage; Raymundo, Igor Teixeira; Nascimento, Luiz Augusto; Oliveira, Carlos Augusto Costa Pires de

2013-01-01

Summary Introduction: Eagle's syndrome is characterized by cervicopharyngeal signs and symptoms associated with elongation of the styloid apophysis. This elongation may occur through ossification of the stylohyoid ligament, or through growth of the apophysis due to osteogenesis triggered by a factor such as trauma. Elongation of the styloid apophysis may give rise to intense facial pain, headache, dysphagia, otalgia, buzzing sensations, and trismus. Precise diagnosis of the syndrome is difficult, and it is generally confounded by other manifestations of cervicopharyngeal pain. Objective: To describe a case of Eagle's syndrome. Case Report: A 53-year-old man reported lateral pain in his neck that had been present for 30 years. Computed tomography (CT) of the neck showed elongation and ossification of the styloid processes of the temporal bone, which was compatible with Eagle's syndrome. Surgery was performed for bilateral resection of the stylohyoid ligament by using a transoral and endoscopic access route. The patient continued to present pain laterally in the neck, predominantly on his left side. CT was performed again, which showed elongation of the styloid processes. The patient then underwent lateral cervicotomy with resection of the stylohyoid process, which partially resolved his painful condition. Final Comments: Patients with Eagle's syndrome generally have a history of chronic pain. Appropriate knowledge of this disease is necessary for adequate treatment to be provided. The importance of diagnosing this uncommon and often unsuspected disease should be emphasized, given that correct clinical-surgical treatment is frequently delayed. The diagnosis of Eagle's syndrome is clinical and radiographic, and the definitive treatment in cases of difficult-to-control pain is surgical. PMID:25992033

Eagle's Syndrome

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Pinheiro, Thaís Gonçalves

2014-01-01

Full Text Available Introduction: Eagle's syndrome is characterized by cervicopharyngeal signs and symptoms associated with elongation of the styloid apophysis. This elongation may occur through ossification of the stylohyoid ligament, or through growth of the apophysis due to osteogenesis triggered by a factor such as trauma. Elongation of the styloid apophysis may give rise to intense facial pain, headache, dysphagia, otalgia, buzzing sensations, and trismus. Precise diagnosis of the syndrome is difficult, and it is generally confounded by other manifestations of cervicopharyngeal pain. Objective: To describe a case of Eagle's syndrome. Case Report: A 53-year-old man reported lateral pain in his neck that had been present for 30 years. Computed tomography (CT of the neck showed elongation and ossification of the styloid processes of the temporal bone, which was compatible with Eagle's syndrome. Surgery was performed for bilateral resection of the stylohyoid ligament by using a transoral and endoscopic access route. The patient continued to present pain laterally in the neck, predominantly on his left side. CT was performed again, which showed elongation of the styloid processes. The patient then underwent lateral cervicotomy with resection of the stylohyoid process, which partially resolved his painful condition. Final Comments: Patients with Eagle's syndrome generally have a history of chronic pain. Appropriate knowledge of this disease is necessary for adequate treatment to be provided. The importance of diagnosing this uncommon and often unsuspected disease should be emphasized, given that correct clinical-surgical treatment is frequently delayed. The diagnosis of Eagle's syndrome is clinical and radiographic, and the definitive treatment in cases of difficult-to-control pain is surgical.

Cytogenetic and molecular characterization of 57 individuals with the Parder-Willi syndrome

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Butler, M.G.; Forrest, K.B.; Miller, L.K. [Vanderbilt Univ. School of Medicine, Nashville, TN (United States)

1994-09-01

Prader-Willi syndrome (PWS) is characterized by hypotonia, early childhood obesity, mental deficiency, hypogonadism and an interstitial deletion of 15q11q13 of paternal origin in 50-70% of patients. The remaining patients have either submicroscopic deletions, maternal disomy or other anomalies of chromosome 15. We have undertaken cytogenetic and molecular genetic studies of 57 individuals presenting with features consistent with PWS (28 males and 29 females; age range of 3 months to 38 years), 25 with recognizable 15q11q13 deletions (44%), 28 with normal appearing chromosomes (49%), and four patients with other chromosome 15 anomalies (7%). High resolution chromosome analysis and PCR amplification were performed utilizing 17 STRs from 15q11q13 region, quantitative Southern hybridization using seven 15q11q13 probes, and fluorescence in situ hybridization (FISH) using four 15q11q13 probes (4-3R, SNRPN, 3-21, and GABRB3). The cytogenetic deletion was paternal in all PWS families studied but the deletion varied in size in 10 patients. Parental DNA studies from 20 of 28 non-deletion patients showed maternal disomy in 7 patients and biparental inheritance in 13 non-deletion patients. In order to evaluate for submicroscopic deletions, PCR amplification with several loci in the area of the PWS minimal critical region, FISH using SNRPN and quantitative hybridization using a PCR product generated from primers of exons E and H of the SNRPN gene were undertaken on the non-deletion patients. Quantitative hybridization and FISH using SNRPN from 3 of 11 non-deletion patients (excluding maternal disomy cases) showed a submicroscopic deletion. One of these patients also showed a paternal deletion of D15S128 and MN1. We furthur support the use of both cytogenetic and molecular genetic methods for determining the genetic status of PWS patients.

Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes

NARCIS (Netherlands)

Zhou, X.; Hampel, H.; Thiele, H.; Gorlin, R. J.; Hennekam, R. C.; Parisi, M.; Winter, R. M.; Eng, C.

2001-01-01

The molecular aetiology of Proteus syndrome (PS) remains elusive. Germline mutations in PTEN cause Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, which are hereditary hamartoma syndromes. Some features-eg, macrocephaly, lipomatosis, and vascular malformations-can be seen in all three

Insulin Resistance, Metabolic Syndrome, and Polycystic Ovary Syndrome in Obese Youth.

Science.gov (United States)

Platt, Adrienne M

2015-07-01

School nurses are well aware of the childhood obesity epidemic in the United States, as one in three youth are overweight or obese. Co-morbidities found in overweight or obese adults were not commonly found in youth three decades ago but are now increasingly "normal" as the obesity epidemic continues to evolve. This article is the second of six related articles discussing the co-morbidities of childhood obesity and discusses the complex association between obesity and insulin resistance, metabolic syndrome, and polycystic ovary syndrome. Insulin resistance increases up to 50% during puberty, which may help to explain why youth are more likely to develop co-morbidities as teens. Treatment of these disorders is focused on changing lifestyle habits, as a child cannot change his or her pubertal progression, ethnicity, or family history. School nurses and other personnel can assist youth with insulin resistance, metabolic syndrome, and polycystic ovary syndrome by supporting their efforts to make changes, reinforcing that insulin resistance is not necessarily type 2 diabetes even if the child is taking medication, and intervening with negative peer pressure. © 2015 The Author(s).

Noonans syndrom kan diagnosticere sklinisk og molekylærgenetisk

DEFF Research Database (Denmark)

Krab Henningsen, Marie; Jelsig, Anne Marie; Andersen, Helle

2015-01-01

Noonan syndrome is part of the group of RASopathies caused by germ line mutations in genes involved in the RAS/MAPK pathway. There is substantial phenotypic overlap among the RASopathies. Diagnosis of Noonan syndrome is often based on clinical features including dysmorphic facial features, short...... stature and congenital heart disease. Rapid advances in sequencing technology have made molecular genetic analyses a helpful tool in diagnosing and distinguishing Noonan syndrome from other RASopathies....

Dyslipidaemia in nephrotic syndrome: mechanisms and treatment

Science.gov (United States)

Agrawal, Shipra; Zaritsky, Joshua J.; Fornoni, Alessia; Smoyer, William E.

2018-01-01

Nephrotic syndrome is a highly prevalent disease that is associated with high morbidity despite notable advances in its treatment. Many of the complications of nephrotic syndrome, including the increased risk of atherosclerosis and thromboembolism, can be linked to dysregulated lipid metabolism and dyslipidaemia. These abnormalities include elevated plasma levels of cholesterol, triglycerides and the apolipoprotein B containing lipoproteins VLDL and IDL; decreased lipoprotein lipase activity in the endothelium, muscle and adipose tissues; decreased hepatic lipase activity; and increased levels of the enzyme PCSK9. In addition, there is an increase in the plasma levels of immature HDL particles and reduced cholesterol efflux. Studies from the past few years have markedly improved our understanding of the molecular pathogenesis of nephrotic syndrome associated dyslipidaemia, and also heightened our awareness of the associated exacerbated risks of cardiovascular complications, progressive kidney disease and thromboembolism. Despite the absence of clear guidelines regarding treatment, various strategies are being increasingly utilized, including statins, bile acid sequestrants, fibrates, nicotinic acid and ezetimibe, as well as lipid apheresis, which seem to also induce partial or complete clinical remission of nephrotic syndrome in a substantial percentage of patients. Future potential treatments will likely also include inhibition of PCSK9 using recently developed anti PCSK9 monoclonal antibodies and small inhibitory RNAs, as well as targeting newly identified molecular regulators of lipid metabolism that are dysregulated in nephrotic syndrome. PMID:29176657

Gorlin-Goltz Syndrome: case report and review of literature

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Adrianne Rahde Bischoff

2014-10-01

Full Text Available Description of a case report of Gorlin-Goltz Syndrome diagnosed in a male newborn who presented increased head circumference and bifid ribs. Mother and grandmother presented typical physical findings of the syndrome, including palmar pits, odontogenic cysts, and history of multiple skin cancer resections. The diagnosis was based on clinical findings of three relatives. A literature review is also presented.

Uncovering a Role for SK2 in Angelman Syndrome

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Sofia B. Lizarraga

2015-07-01

Full Text Available Angelman syndrome is a severe neurodevelopmental disorder caused by mutations in UBE3A. Sun et al. (2015 report SK2 as a UBE3A substrate and provide insight into the molecular mechanisms that might underlie impaired neuronal function in individuals affected by Angelman syndrome.

High-risk Long QT Syndrome Mutations in the Kv7.1 (KCNQ1) Pore Disrupt the Molecular Basis for Rapid K+ Permeation

Science.gov (United States)

Burgess, Don E.; Bartos, Daniel C.; Reloj, Allison R.; Campbell, Kenneth S.; Johnson, Jonathan N.; Tester, David J.; Ackerman, Michael J.; Fressart, Véronique; Denjoy, Isabelle; Guicheney, Pascale; Moss, Arthur J.; Ohno, Seiko; Horie, Minoru; Delisle, Brian P.

2012-01-01

Type 1 long QT syndrome (LQT1) syndrome is caused by loss-of-function mutations in the KCNQ1, which encodes the K+ channel (Kv7.1) that underlies the slowly activating delayed rectifier K+ current in the heart. Intragenic risk stratification suggests LQT1 mutations that disrupt conserved amino acid residues in the pore are an independent risk factor for LQT1-related cardiac events. The purpose of this study is to determine possible molecular mechanisms that underlie the loss-of-function for these high-risk mutations. Extensive genotype-phenotype analyses of LQT1 patients showed that T322M-, T322A-, or G325R-Kv7.1 confer a high risk for LQT1-related cardiac events. Heterologous expression of these mutations with KCNE1 revealed they generated non-functional channels and caused dominant negative suppression of WT-Kv7.1 current. Molecular dynamic simulations (MDS) of analogous mutations in KcsA (T85M-, T85A-, and G88R-KcsA) demonstrated that they disrupted the symmetrical distribution of the carbonyl oxygen atoms in the selectivity filter, which upset the balance between the strong attractive and K+-K+ repulsive forces required for rapid K+ permeation. We conclude high-risk LQT1 mutations in the pore likely disrupt the architectural and physical properties of the K+ channel selectivity filter. PMID:23092362

Rhabdomyosarcoma in patients with constitutional mismatch-repair-deficiency syndrome.

Science.gov (United States)

Kratz, C P; Holter, S; Etzler, J; Lauten, M; Pollett, A; Niemeyer, C M; Gallinger, S; Wimmer, K

2009-06-01

Biallelic germline mutations in the mismatch repair genes MLH1, MSH2, MSH6 or PMS2 cause a recessive childhood cancer syndrome characterised by early-onset malignancies and signs reminiscent of neurofibromatosis type 1 (NF1). Alluding to the underlying genetic defect, we refer to this syndrome as constitutional mismatch repair-deficiency (CMMR-D) syndrome. The tumour spectrum of CMMR-D syndrome includes haematological neoplasias, brain tumours and Lynch syndrome-associated tumours. Other tumours, such as neuroblastoma, Wilm tumour, ovarian neuroectodermal tumour or infantile myofibromatosis, have so far been found only in individual cases. We analysed two consanguineous families that had members with suspected CMMR-D syndrome who developed rhabdomyosarcoma among other neoplasias. In the first family, we identified a pathogenic PMS2 mutation for which the affected patient was homozygous. In family 2, immunohistochemistry analysis showed isolated loss of PMS2 expression in all tumours in the affected patients, including rhabdomyosarcoma itself and the surrounding normal tissue. Together with the family history and microsatellite instability observed in one tumour this strongly suggests an underlying PMS2 alteration in family 2 also. Together, these two new cases show that rhabdomyosarcoma and possibly other embryonic tumours, such as neuroblastoma and Wilm tumour, belong to the tumour spectrum of CMMR-D syndrome. Given the clinical overlap of CMMR-D syndrome with NF1, we suggest careful examination of the family history in patients with embryonic tumours and signs of NF1 as well as analysis of the tumours for loss of one of the mismatch repair genes and microsatellite instability. Subsequent mutation analysis will lead to a definitive diagnosis of the underlying disorder.

Environmental Catastrophes in the Earth's History Due to Solar Systems Encounters with Giant Molecular Clouds

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Pavlov, Alexander A.

2011-01-01

In its motion through the Milky Way galaxy, the solar system encounters an average density (>=330 H atoms/cubic cm) giant molecular cloud (GMC) approximately every 108 years, a dense (approx 2 x 103 H atoms/cubic cm) GMC every approx 109 years and will inevitably encounter them in the future. However, there have been no studies linking such events with severe (snowball) glaciations in Earth history. Here we show that dramatic climate change can be caused by interstellar dust accumulating in Earth's atmosphere during the solar system's immersion into a dense (approx ,2 x 103 H atoms/cubic cm) GMC. The stratospheric dust layer from such interstellar particles could provide enough radiative forcing to trigger the runaway ice-albedo feedback that results in global snowball glaciations. We also demonstrate that more frequent collisions with less dense GMCs could cause moderate ice ages.

Research on culture-bound syndromes: new directions.

Science.gov (United States)

Guarnaccia, P J; Rogler, L H

1999-09-01

The unprecedented inclusion of culture-bound syndromes in DSM-IV provides the opportunity for highlighting the need to study such syndromes and the occasion for developing a research agenda to study them. The growing ethnic and cultural diversity of the U.S. population presents a challenge to the mental health field to develop truly cross-cultural approaches to mental health research and services. In this article, the authors provide a critique of previous analyses of the relationship between culture-bound syndromes and psychiatric diagnoses. They highlight the problems in previous classificatory exercises, which tend to focus on subsuming the culture-bound syndromes into psychiatric categories and fail to fully investigate these syndromes on their own terms. A detailed research program based on four key questions is presented both to understand culture-bound syndromes within their cultural context and to analyze the relationship between these syndromes and psychiatric disorders. Results of over a decade of research on ataques de nervios, a Latino-Caribbean cultural syndrome, are used to illustrate this research program. The four questions focus on the nature of the phenomenon, the social-cultural location of sufferers, the relationship of culture-bound syndromes to psychiatric disorders, and the social and psychiatric history of the syndrome in the life course of the sufferer.

Utility of the History and Physical Examination in the Detection of Acute Coronary Syndromes in Emergency Department Patients

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Zachary DW Dezman

2017-05-01

Full Text Available Chest pain accounts for approximately 6% of all emergency department (ED visits and is the most common reason for emergency hospital admission. One of the most serious diagnoses emergency physicians must consider is acute coronary syndrome (ACS. This is both common and serious, as ischemic heart disease remains the single biggest cause of death in the western world. The history and physical examination are cornerstones of our diagnostic approach in this patient group. Their importance is emphasized in guidelines, but there is little evidence to support their supposed association. The purpose of this article was to summarize the findings of recent investigations regarding the ability of various components of the history and physical examination to identify which patients presenting to the ED with chest pain require further investigation for possible ACS. Previous studies have consistently identified a number of factors that increase the probability of ACS. These include radiation of the pain, aggravation of the pain by exertion, vomiting, and diaphoresis. Traditional cardiac risk factors identified by the Framingham Heart Study are of limited diagnostic utility in the ED. Clinician gestalt has very low predictive ability, even in patients with a non-diagnostic electrocardiogram (ECG, and gestalt does not seem to be enhanced appreciably by clinical experience. The history and physical alone are unable to reduce a patient’s risk of ACS to a generally acceptable level (<1%. Ultimately, our review of the evidence clearly demonstrates that “atypical” symptoms cannot rule out ACS, while “typical” symptoms cannot rule it in. Therefore, if a patient has symptoms that are compatible with ACS and an alternative cause cannot be identified, clinicians must strongly consider the need for further investigation with ECG and troponin measurement.

Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer

Science.gov (United States)

Carethers, John M; Stoffel, Elena M

2015-01-01

Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management. PMID:26309352

Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer.

Science.gov (United States)

Carethers, John M; Stoffel, Elena M

2015-08-21

Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management.

Pediatric Toxic Shock Syndrome

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Jennifer Yee

2017-09-01

Full Text Available Audience: This scenario was developed to educate emergency medicine residents on the diagnosis and management of a pediatric patient with toxic shock syndrome. The case is also appropriate for teaching of medical students and advanced practice providers, as well as a review of the principles of crisis resource management, teamwork, and communication. Introduction: Toxic shock syndrome is a low-frequency, high-acuity scenario requiring timely identification and aggressive management. If patients suffering from this condition are managed incorrectly, they may progress into multi-organ dysfunction and potentially death. Toxic shock syndrome has been associated with Streptococcus and Staphylococcus aureus (Staph. Approximately half of Staph cases are associated with menstruation, which was first described in the 1970s-1980s and was associated with the use of absorbent tampons.1 Group A Streptococcus may cause complications such as necrotizing fasciitis and gangrenous myositis.2 Pediatric patients may present critically ill from toxic shock syndrome. Providers need to perform a thorough history and physical exam to discern the source of infection. Management requires aggressive care with antibiotics and IV fluids. Objectives: By the end of this simulation session, the learner will be able to: 1 Recognize toxic shock syndrome. 2 Review the importance of a thorough physical exam. 3 Discuss management of toxic shock syndrome, including supportive care and the difference in antibiotic choices for streptococcal and staphylococcal toxic shock syndrome. 4 Appropriately disposition a patient suffering from toxic shock syndrome. 5 Communicate effectively with team members and nursing staff during a resuscitation of a critically ill patient. Method: This session was conducted using high-fidelity simulation, followed by a debriefing session and lecture on toxic shock syndrome.

De Novo Truncating Mutations in AHDC1 in Individuals with Syndromic Expressive Language Delay, Hypotonia, and Sleep Apnea

Science.gov (United States)

Xia, Fan; Bainbridge, Matthew N.; Tan, Tiong Yang; Wangler, Michael F.; Scheuerle, Angela E.; Zackai, Elaine H.; Harr, Margaret H.; Sutton, V. Reid; Nalam, Roopa L.; Zhu, Wenmiao; Nash, Margot; Ryan, Monique M.; Yaplito-Lee, Joy; Hunter, Jill V.; Deardorff, Matthew A.; Penney, Samantha J.; Beaudet, Arthur L.; Plon, Sharon E.; Boerwinkle, Eric A.; Lupski, James R.; Eng, Christine M.; Muzny, Donna M.; Yang, Yaping; Gibbs, Richard A.

2014-01-01

Clinical whole-exome sequencing (WES) for identification of mutations leading to Mendelian disease has been offered to the medical community since 2011. Clinically undiagnosed neurological disorders are the most frequent basis for test referral, and currently, approximately 25% of such cases are diagnosed at the molecular level. To date, there are approximately 4,000 “known” disease-associated loci, and many are associated with striking dysmorphic features, making genotype-phenotype correlations relatively straightforward. A significant fraction of cases, however, lack characteristic dysmorphism or clinical pathognomonic traits and are dependent upon molecular tests for definitive diagnoses. Further, many molecular diagnoses are guided by recent gene-disease association discoveries. Hence, there is a critical interplay between clinical testing and research leading to gene-disease association discovery. Here, we describe four probands, all of whom presented with hypotonia, intellectual disability, global developmental delay, and mildly dysmorphic facial features. Three of the four also had sleep apnea. Each was a simplex case without a remarkable family history. Using WES, we identified AHDC1 de novo truncating mutations that most likely cause this genetic syndrome. PMID:24791903

Familly with two different cases of post- and pre-natal l1 syndrome: When hydrocephaly become “multidisciplinary headache”

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Bukvic Nenad

2016-01-01

Full Text Available In middle 90’s the scientific community classified as CRASH syndrome a clinical situation characterized by Corpus callosum hypoplasia, Retardation, Adducted thumbs, Spastic paraplegia, and Hydrocephalus. This pathology is also known as L1 syndrome and includes a spectrum of related neurological disorders with an X-linked recessive mode of inheritance associated to mutations in the human L1 Cell Adhesion Molecule gene (L1CAM;OMIM 308840. Here we report regarding a couple pass through our Genetic Counseling, during clinical diagnostic procedure in ~3 years old son, due to presence of multiple malformations such as hydrocephalus, agenesis of corpus callosum, tetraparesys, axial hypotony, cognitive and motor incompetency. The proband was the first male child of a healthy, non-consanguineous Italian couple with no family history of brain abnormalities, recurrent miscarriages, other birth defects and/or genetic illnesses. During Genetic Counseling, a diagnostic hypothesis of L1 syndrome was made, with in deep explanation of genetic testing possibilities. On the basis of our protocol, we fixed another appointment 2 weeks later, but unfortunately the family never showed up. Approximately one year later, the Department of Gynecology and Obstetrics requested Genetic Counseling for a 33 years old woman, secondigravida (22° gestation week, with abnormal ultrasound findings showing severe fetal ventriculomegaly. The family history was unremarkable with no consanguinity; she was one of two sisters and had a healthy brother. Surprisingly the woman was the mother of our proband. On the basis of a diagnostic hypothesis of L1 syndrome (includes a spectrum of related neurological disorders with an X-linked recessive mode of inheritance, we performed molecular analysis on the proband’s DNA, mother’s DNA and fetal DNA. The mutational screening revealed the presence of a non sense c.2701C>T (p.Arg901

Molecular characterization of Salmonella strains in individuals with acute diarrhea syndrome in the State of Sucre, Venezuela.

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Rodulfo, Hectorina; De Donato, Marcos; Luiggi, Jesús; Michelli, Elvia; Millán, Adriana; Michelli, Miriam

2012-06-01

In Venezuela, acute diarrheic syndrome (ADS) is a primary cause of morbi-mortality, often involving the Salmonella genus. Salmonella infections are associated with acute gastroenteritis, one of the most common alimentary intoxications, and caused by the consumption of contaminated water and food, especially meat. Conventional and molecular methods were used to detect Salmonella strains from 330 fecal samples from individuals of different ages and both sexes with ADS. Polymerase chain reaction (PCR) was used for the molecular characterization of Salmonella, using invA, sefA, and fliC genes for the identification of this genus and the serotypes Enteritidis and Typhimurium, respectively. The highest frequency of individuals with ADS was found in children 0-2 years old (39.4%), and the overall frequency of positive coprocultures was 76.9%. A total of 14 (4.2%) strains were biochemically and immunologically identified as Salmonella enterica subsp. enterica, of which 7 were classified as belonging to the Enteritidis serotype, 4 to the Typhimurium serotype, and 3 to other serotypes. The S. enterica strains were distributed more frequently in the age groups 3-4 and 9-10 years old. The molecular characterization method used proved to be highly specific for the typing of S. enterica strains using DNA extracted from both the isolated colonies and selective enrichment broths directly inoculated with fecal samples, thus representing a complementary tool for the detection and identification of ADS-causing bacteria.

The potential impact of family history of metabolic syndrome and risk of type 2 diabetes mellitus: In a highly endogamous population

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Abdulbari Bener

2014-01-01

Full Text Available Aim: This study aims to determine the potential impact of positive family history of Metabolic Syndrome (MetS among two generations, on developing Type 2 Diabetes Mellitus (T2DM and the potential relation of consanguineous marriage among patients with MetS to the risk of developing T2DM among a sample of Qataris. Design: A cross-sectional study. Setting: Primary healthcare (PHC centers. Materials and Methods: The survey and measurement were conducted from April 2011 to December 2012 among Qatari nationals above 20 years of age. Of the 2,182 subjects, who were approached to participate in the study, 1,552 (71% gave their consent. Face-to-face interviews were conducted using a structured questionnaire followed by anthropometric measurements and laboratory tests. Metabolic syndrome was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (ATP III as well as International Diabetes Federation (IDF. Results: Overall, the prevalence of MetS was 26.2% according to ATP III and 36.9% according to IDF (P < 0.0001. The mean age of MetS patients with T2DM was significantly higher than those without T2DM (Mean 48 ± 9.9 vs. 42.5 ± 9.2; P < 0.001. The proportion of females was higher among MetS patients with T2DM as compared to those without T2DM (61% vs. 51%; P = 0.053. In addition, there were significant differences between MetS patients with and without DM in terms of co-morbidities of hypertension, coronary heart disease, and high cholesterol. The proportion of MetS patients with positive family history for MetS was significantly higher in MetS patients with T2DM as compared to those without T2DM (46.7% vs. 33.8%; P = 0.009. The proportion of positive family history of MetS among fathers (35% vs. 21.9%; P = 0.005, mothers (30.5% vs. 18.8%; P = 0.008, maternal aunt (18.3% vs. 11.2%; P = 0.055, and maternal grand father (19.5% vs. 10%; P = 0.010 were significantly higher in MetS patients with T2DM as compared to the

Complex Regional Pain Syndrome and Treatment Approaches

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Neslihan Gokcen

2013-08-01

Full Text Available Complex Regional Pain Syndrome is a symptom complex including severe pain which is disproportioned by the initiating event. Formerly, it was known as reflex sympathetic dystropy, Sudeck’s atrophy and algoneurodystrophy. There are two types of complex regional pain syndrome (CPRS. CRPS type 1 (Reflex sympathetic dystropy occurs after a minor trauma of the extremities, CRPS type 2 (Causalgia occurs following peripheral nevre injury. Diagnosis is made according to the history, symptoms and physical findings of the patients. Patient education, physical therapy and medical treatment are the most common treatment approaches of complex regional pain syndrome. The aim of this review is to revise the treatment options ofcomplex regional pain syndrome, as well as to overview the new treatment approaches and options for the refractory complex regional pain syndrome cases. [Archives Medical Review Journal 2013; 22(4.000: 514-531

Antiphospholipid Antibody Syndrome Presenting with Hemichorea

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Yezenash Ayalew

2012-01-01

Full Text Available A 25-year-old Bangladeshi lady presented to neurology with a three-month history of involuntary movements of her right arm, associated with loss of power. There was progression to the right leg, and she subsequently developed episodes of slurred speech and blurred vision. At the time of presentation, she was 12 weeks pregnant and the symptoms were reported to have started at conception. Past medical history was unremarkable apart from one first trimester miscarriage and there was no significant family history suggestive of a hereditary neurological condition. MRI of the head revealed no abnormalities but serology showed positive antinuclear antibodies (ANAs at a titre of 1/400. Further investigations revealed strongly positive anticardiolipin antibodies (>120 and positive lupus anticoagulant antibodies. The patient had a second miscarriage at 19 weeks gestation strengthening the possibility that the chorea was related to antiphospholipid antibody syndrome and she was started on a reducing dose of Prednisolone 40 mg daily and aspirin 300 mg daily. Six months later, she had complete resolution of neurological symptoms. There are several reports of chorea as a feature of antiphospholipid syndrome, but no clear consensus on underlying pathophysiology.

Like Father, Like Daughter-inherited cutis aplasia occurring in a family with Marfan syndrome: a case report.

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Islam, Yasmin Florence Khodeja; Williams, Charles A; Schoch, Jennifer Jane; Andrews, Israel David

2017-01-01

We present the case of a newborn with co-occurrence of Marfan syndrome and aplasia cutis congenita (ACC) and a family history significant for Marfan syndrome and ACC in the father. This case details a previously unreported mutation in Marfan syndrome and describes a novel coinheritance of Marfan syndrome and ACC.

History of vaccination.

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Plotkin, Stanley

2014-08-26

Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

History of vaccination

OpenAIRE

Plotkin, Stanley

2014-01-01

Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

Femur Neck Fracture in a Young Marfan Syndrome Patient.

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Kwon, Yong-Uk; Kong, Gyu-Min; Park, Jun-Ho

2016-12-01

Marfan syndrome is an autosomal dominant and could decrease bone mineral density. So patients with Marfan syndrome could vulnerable to trauma in old ages. We present the first report, to the best of our knowledge, of a rare fracture of the femoral neck with a minor traumatic history in a juvenile Marfan syndrome patient whose physis is still open. Although the patient is young, her bone mineral density was low and the geometry of femur is changed like old ages. The femur neck fracture in children is very rare and only caused by high energy trauma, we concluded that the Marfan syndrome makes the bone weaker in young age and preventative medications to avoid fractures in younger Marfan syndrome patients are necessary in early ages.

Tardive or Atypical Tourette's Disorder in a Population with Down Syndrome?

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Myers, Beverly; Pueschel, Siegfried M.

1995-01-01

In a population of 425 individuals with Down's syndrome, 5 persons (1.2%) were identified as having Tourette's disorder. The lack of interrelationship between Down's syndrome and Tourette's disorder argues against an atypical Tourette's disorder. Diagnoses of tardive Tourette's disorder were based on absence of family history of Tourette's, late…

Infectious Causes of Right Middle Lobe Syndrome.

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Rashid, Aatif; Nanjappa, Sowmya; Greene, John N

2017-01-01

Right middle lobe (RML) syndrome is defined as recurrent or chronic obstruction or infection of the middle lobe of the right lung. Nonobstructive causes of middle lobe syndrome include inflammatory processes and defects in the bronchial anatomy and collateral ventilation. We report on 2 case patients with RML syndrome, one due to infection with Mycobacterium avium complex followed by M asiaticum infection and the other due to allergic bronchopulmonary aspergillosis. A history of atopy, asthma, or chronic obstructive pulmonary disease has been reported in up to one-half of those with RML. The diagnosis can be made by plain radiography, computed tomography, and bronchoscopy. Medical treatment consists of bronchodilators, mucolytics, and antimicrobials. Patients whose disease is unresponsive to treatment and those with obstructive RML syndrome can be offered surgical treatment.

Natural history of aortic root dilation through young adulthood in a hypermobile Ehlers-Danlos syndrome cohort.

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Ritter, Alyssa; Atzinger, Carrie; Hays, Brandon; James, Jeanne; Shikany, Amy; Neilson, Derek; Martin, Lisa; Weaver, Kathryn Nicole

2017-06-01

Hypermobile Ehlers-Danlos syndrome (hEDS) is a common inherited connective tissue disorder characterized by joint hypermobility. The natural history of aortic root dilation (AoD), a potential complication of EDS, has not been well characterized in this population. We describe the natural history of aortic root size in a large cohort of patients with hEDS. A cohort of 325 patients with HEDS was identified at Cincinnati Children's Hospital Medical Center (CCHMC), including 163 patients from a previous study. Medical records were reviewed and each participant's height, weight, and aortic dimensions from up to four echocardiograms were documented. Aortic root z-scores were calculated using two established formulas based on age (Boston or Devereux). Overall prevalence of AoD and prevalence by age were calculated and longitudinal regression was performed. The prevalence of AoD with a z-score ≥ 2.0 was 14.2% (46/325) and with a z-score of ≥3.0 was 5.5% (18/325). No significant increases in z-score were seen over time for patients with multiple echocardiograms. Participants under the age of 15 years had an average decline of 0.1 standard deviations (SDs)/year. No significant change was found after 15 of age. Between the ages of 15 and 21 years, Boston z-scores were 0.96 higher than Devereux z-scores. The nearly 1 z-score unit difference between formulas indicates caution prior to diagnosing AoD in patients with hEDS. In light of the low prevalence and lack of progression of AoD, routine echocardiograms may not be warranted for pediatric patients with hEDS. © 2017 Wiley Periodicals, Inc.

Molecular diagnosis of Prader-Willi syndrome: Parent-of-origin dependent methylation sites and non-isotopic detection of (CA){sub n} dinucleotide repeat polymorphisms

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Lerer, I.; Meiner, V.; Pashut-Lavon, I.; Abeliovich, D.

1994-08-01

We describe our experience in the molecular diagnosis of 22 patients suspected of Prader-Willi syndrome (PWS) using a DNA probe PW71 (D15S63) which detects a parent-of-origin specific methylated site in the PWS critical region. The cause of the syndrome was determined as deletion or uniparental disomy according to the segregation of (CA){sub n} dinucleotide repeat polymorphisms of the PWS/AS region and more distal markers of chromosome 15. In 10 patients the clinical diagnosis was confirmed by the segregation of (CA){sub n}, probably due to paternal microdeletion in the PWs critical region which did not include the loci D15S97, D15S113, GABRB3, and GABRA5. This case demonstrates the advantage of the DNA probe PW71 in the diagnosis of PWS. 31 refs., 2 figs., 3 tabs.

Universal Point of Care Testing for Lynch Syndrome in Patients with Upper Tract Urothelial Carcinoma.

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Metcalfe, Michael J; Petros, Firas G; Rao, Priya; Mork, Maureen E; Xiao, Lianchun; Broaddus, Russell R; Matin, Surena F

2018-01-01

Patients with Lynch syndrome are at risk for upper tract urothelial carcinoma. We sought to identify the incidence and most reliable means of point of care screening for Lynch syndrome in patients with upper tract urothelial carcinoma. A total of 115 consecutive patients with upper tract urothelial carcinoma without a history of Lynch syndrome were universally screened during followup from January 2013 through July 2016. We evaluated patient and family history using AMS (Amsterdam criteria) I and II, and tumor immunohistochemistry for mismatch repair proteins and microsatellite instability. Patients who were positive for AMS I/II, microsatellite instability or immunohistochemistry were classified as potentially having Lynch syndrome and referred for clinical genetic analysis and counseling. Patients with known Lynch syndrome served as positive controls. Of the 115 patients 16 (13.9%) screened positive for potential Lynch syndrome. Of these patients 7.0% met AMS II criteria, 11.3% had loss of at least 1 mismatch repair protein and 6.0% had high microsatellite instability. All 16 patients were referred for germline testing, 9 completed genetic analysis and counseling, and 6 were confirmed to have Lynch syndrome. All 7 patients with upper tract urothelial carcinoma who had a known history of Lynch syndrome were positive for AMS II criteria and at least a single mismatch repair protein loss while 5 of 6 had high microsatellite instability. We identified 13.9% of upper tract urothelial carcinoma cases as potential Lynch syndrome and 5.2% as confirmed Lynch syndrome at the point of care. These findings have important implications for universal screening of upper tract urothelial carcinoma, representing one of the highest rates of undiagnosed genetic disease in a urological cancer. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bilateral ovarian fibroma associated with Gorlin syndrome

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Shahnaz Aram

2009-02-01

Full Text Available

• Gorlin syndrome (GS, also known as nevoid basal cell carcinoma syndrome (NBCCS, is a rare inherited multisystem disorder. This paper presents a 22-years-old Iranian woman with this syndrome whose past history was multiple keratocysts of maxillary bone. She was referred to gynecology clinic with the chief complaint of irregular menses and vaginal spotting. On examination, frontal bossing and hypertelorism were detected. Physical examination of genitalia disclosed bilateral adnexal masses. Pelvic ultrasound showed two solid, echogenous and calcified masses measuring 100*50*10 & 60*50*45 mm in the left and right ovaries, respectively. The patient underwent right oophorectomy and ovarian mass resection with preservation of intact ovarian tissue on the left side. On frozen and permanent histological sections, bilateral and calcified ovarian fibromas were diagnosed. Surprisingly, during the last follow-up one year after the surgery, we found that our patient was expecting a baby. It can be concluded that in the presence of bilateral and calcified ovarian fibromas, the possibility of GS should be considered. Accurate diagnosis is only possible with close attention to the familial and past medical history and physical examination. In these patients, careful follow up for detecting malignancies and other complications is highly recommended.
• KEY WORDS: Gorlin syndrome, ovarian fibroma, multiple keratocysts.

A rare case of short stature: Say Meyer syndrome.

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Karthik, T S; Prasad, N Rajendra; Rani, P Radha; Maheshwari, Rushikesh; Reddy, P Amaresh; Chakradhar, B V S; Menon, Bindu

2013-10-01

Say Meyer syndrome is rare X linked condition characterized by developmental delay, short stature and metopic suture synostosis. We are reporting a case of Say Meyer syndrome presented to our hospital for short stature and developmental delay at age 3½ years. A 3½-year-old boy presented to our hospital for decreased growth velocity from the age of 1 year. History revealed the boy had a birth weight of 2.3 kg, had an episode of seizures in the neonatal period. He was born to non-consanguineous marriage. He had global developmental delay and there was a lack of bowel and bladder control. History did not reveal any hearing or visual impairment. No history of any chronic systemic illnesses. Magnetic resonance imaging (MRI) brain revealed mild diffuse frontotemporal atrophy with multiple irregular gliotic areas in bilateral frontal lobes. Diffuse white matter volume loss in bilateral cerebral hemispheres. Diffuse thinning of corpus callosum. Diffuse periventricular hyper intensity on T2W and fluid attenuated inversion recovery sequences. Say Meyer syndrome is rare X linked condition characterized by developmental delay, short stature and metopic suture synostosis. Characteristic MRI brain findings include diffuse frontotemporal atrophy with multiple gliotic areas in frontal lobes. Diffuse white matter volume loss in bilateral cerebral hemispheres.

Acute coronary syndrome associated with Churg-Strauss syndrome

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Annette Doris Wagner

2007-11-01

Full Text Available Annette Doris Wagner1, Gerd Peter Meyer2, Markus Rihl3, Anke Rathmann2, Ulrike Wittkop1, Henning Zeidler4, Hermann Haller1, Joachim Lotz51Department Internal Medicine, Division of Nephrology; 2Division of Cardiology; 3Division of Rheumatology; 4Rheumatologikum Hannover; 5Department of Diagnostic Radiology; Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, GermanyAbstract: A 41-year old female patient was admitted with acute onset of dyspnea and chest pain. Previous history revealed asthma, chronic sinusitis and eosinophilic proctitis. Electrocardiogram showed anterior ST-segment elevations and inferior ST-segment depression. Immediate heart catheterization revealed a distally occluded left anterior descending coronary artery, the occlusion being reversible after nitroglycerine. Cardiac magnetic resonance imaging was consistent with perimyocarditis. Hypereosinophilia and IgE elevation were present and Churg-strauss syndrome was diagnosed.Keywords: Churg-Strauss syndrome (CSS, carditis, cardiac MRI

Caroli's syndrom in ultrasound and CT

International Nuclear Information System (INIS)

Jend, H.H.; Heller, M.

1981-01-01

Until a few years ago diagnosis of congenital saccular intrahepatic dilatation of bile ducts (Caroli's syndrome) was established intraoperatively or postmortem only. Intravenous cholangiocholecystography and intraoperative cholangiography will often furnish insufficient information. Preoperative diagnosis has become possible for some time now via percutaneous transhepatic and endoscopic retrograde cholangiography. Basing on a case history it is shown that non-invasive diagnosis of Caroli's syndrome has now become possible without the risk of a possible life-threatening cholangitis relapse. This is the merit of new techniques such as sonography and computerized tomography. (orig.) [de

Clinical and molecular phenotype of Aicardi-Goutieres syndrome.

Science.gov (United States)

Rice, Gillian; Patrick, Teresa; Parmar, Rekha; Taylor, Claire F; Aeby, Alec; Aicardi, Jean; Artuch, Rafael; Montalto, Simon Attard; Bacino, Carlos A; Barroso, Bruno; Baxter, Peter; Benko, Willam S; Bergmann, Carsten; Bertini, Enrico; Biancheri, Roberta; Blair, Edward M; Blau, Nenad; Bonthron, David T; Briggs, Tracy; Brueton, Louise A; Brunner, Han G; Burke, Christopher J; Carr, Ian M; Carvalho, Daniel R; Chandler, Kate E; Christen, Hans-Jurgen; Corry, Peter C; Cowan, Frances M; Cox, Helen; D'Arrigo, Stefano; Dean, John; De Laet, Corinne; De Praeter, Claudine; Dery, Catherine; Ferrie, Colin D; Flintoff, Kim; Frints, Suzanna G M; Garcia-Cazorla, Angels; Gener, Blanca; Goizet, Cyril; Goutieres, Francoise; Green, Andrew J; Guet, Agnes; Hamel, Ben C J; Hayward, Bruce E; Heiberg, Arvid; Hennekam, Raoul C; Husson, Marie; Jackson, Andrew P; Jayatunga, Rasieka; Jiang, Yong-Hui; Kant, Sarina G; Kao, Amy; King, Mary D; Kingston, Helen M; Klepper, Joerg; van der Knaap, Marjo S; Kornberg, Andrew J; Kotzot, Dieter; Kratzer, Wilfried; Lacombe, Didier; Lagae, Lieven; Landrieu, Pierre Georges; Lanzi, Giovanni; Leitch, Andrea; Lim, Ming J; Livingston, John H; Lourenco, Charles M; Lyall, E G Hermione; Lynch, Sally A; Lyons, Michael J; Marom, Daphna; McClure, John P; McWilliam, Robert; Melancon, Serge B; Mewasingh, Leena D; Moutard, Marie-Laure; Nischal, Ken K; Ostergaard, John R; Prendiville, Julie; Rasmussen, Magnhild; Rogers, R Curtis; Roland, Dominique; Rosser, Elisabeth M; Rostasy, Kevin; Roubertie, Agathe; Sanchis, Amparo; Schiffmann, Raphael; Scholl-Burgi, Sabine; Seal, Sunita; Shalev, Stavit A; Corcoles, C Sierra; Sinha, Gyan P; Soler, Doriette; Spiegel, Ronen; Stephenson, John B P; Tacke, Uta; Tan, Tiong Yang; Till, Marianne; Tolmie, John L; Tomlin, Pam; Vagnarelli, Federica; Valente, Enza Maria; Van Coster, Rudy N A; Van der Aa, Nathalie; Vanderver, Adeline; Vles, Johannes S H; Voit, Thomas; Wassmer, Evangeline; Weschke, Bernhard; Whiteford, Margo L; Willemsen, Michel A A; Zankl, Andreas; Zuberi, Sameer M; Orcesi, Simona; Fazzi, Elisa; Lebon, Pierre; Crow, Yanick J

2007-10-01

Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P=.001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified.

Genetics Home Reference: Chediak-Higashi syndrome

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... 68(2):283-303. Review. Citation on PubMed Kaplan J, De Domenico I, Ward DM. Chediak-Higashi ... 22. Citation on PubMed Ward DM, Shiflett SL, Kaplan J. Chediak-Higashi syndrome: a clinical and molecular ...

Hennekam lymphangiectasia syndrome

OpenAIRE

Lakshminarayana, G.; Mathew, A.; Rajesh, R.; Kurien, G.; Unni, V. N.

2011-01-01

Hennekam lymphangiectasia syndrome is a rare disorder comprising of intestinal and renal lymphangiectasia, dysmorphic facial appearance and mental retardation. The facial features include hypertelorism with a wide, flat nasal bridge, epicanthic folds, small mouth and small ears. We describe a case of a multigravida with bad obstetric history and characteristic facial and dental anomalies and bilateral renal lymphangiectasia. To our knowledge this is the first case of Hennekam lymphangiectasia...

Gastrointestinal manifestation's history in the systemic lupus erythematosus

International Nuclear Information System (INIS)

Iglesias Gamarra, Antonio; Chalem, Philippe; Restrepo Suarez, Jose Felix

2000-01-01

In this paper we reviewed the history of the gastrointestinal manifestations in systemic lupus erythematosus since century XIX to our days, making a review of every organ and system involved, with special emphasis in gastropathy, enteritis, ileitis, malabsorption syndrome vasculitis bowel vasculopathy, mesenteric thrombosis, pancreatitis, ascites, peritonitis autoimmune hepatitis and more

Two Antarctic penguin genomes reveal insights into their evolutionary history and molecular changes related to the Antarctic environment.

Science.gov (United States)

Li, Cai; Zhang, Yong; Li, Jianwen; Kong, Lesheng; Hu, Haofu; Pan, Hailin; Xu, Luohao; Deng, Yuan; Li, Qiye; Jin, Lijun; Yu, Hao; Chen, Yan; Liu, Binghang; Yang, Linfeng; Liu, Shiping; Zhang, Yan; Lang, Yongshan; Xia, Jinquan; He, Weiming; Shi, Qiong; Subramanian, Sankar; Millar, Craig D; Meader, Stephen; Rands, Chris M; Fujita, Matthew K; Greenwold, Matthew J; Castoe, Todd A; Pollock, David D; Gu, Wanjun; Nam, Kiwoong; Ellegren, Hans; Ho, Simon Yw; Burt, David W; Ponting, Chris P; Jarvis, Erich D; Gilbert, M Thomas P; Yang, Huanming; Wang, Jian; Lambert, David M; Wang, Jun; Zhang, Guojie

2014-01-01

Penguins are flightless aquatic birds widely distributed in the Southern Hemisphere. The distinctive morphological and physiological features of penguins allow them to live an aquatic life, and some of them have successfully adapted to the hostile environments in Antarctica. To study the phylogenetic and population history of penguins and the molecular basis of their adaptations to Antarctica, we sequenced the genomes of the two Antarctic dwelling penguin species, the Adélie penguin [Pygoscelis adeliae] and emperor penguin [Aptenodytes forsteri]. Phylogenetic dating suggests that early penguins arose ~60 million years ago, coinciding with a period of global warming. Analysis of effective population sizes reveals that the two penguin species experienced population expansions from ~1 million years ago to ~100 thousand years ago, but responded differently to the climatic cooling of the last glacial period. Comparative genomic analyses with other available avian genomes identified molecular changes in genes related to epidermal structure, phototransduction, lipid metabolism, and forelimb morphology. Our sequencing and initial analyses of the first two penguin genomes provide insights into the timing of penguin origin, fluctuations in effective population sizes of the two penguin species over the past 10 million years, and the potential associations between these biological patterns and global climate change. The molecular changes compared with other avian genomes reflect both shared and diverse adaptations of the two penguin species to the Antarctic environment.

Invader population speeds up life history during colonization

OpenAIRE

Amundsen, Per-Arne; Salonen, Erno; Niva, Teuvo; Gjelland, Karl Øystein; Præbel, Kim; Sandlund, Odd Terje; Knudsen, Rune; Bøhn, Thomas

2012-01-01

We explore the long-term developments in population biology and life history during the invasion and establishment of the fish species vendace Coregonus albula in a subarctic watercourse by comparing life-history traits and molecular genetic estimates between the source and the colonist population. The two populations exhibited highly contrasting life-history strategies. Relative to the source population, the colonist population was characterized by slower somatic growth rates, earlier sexual...

Nevoid Basal Cell Carcinoma Syndrome: A Case Report

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Razavi

2016-09-01

Full Text Available Nevoid basal cell carcinoma syndrome (BCNS is an autosomal dominant inherited disorder. Multiple organ systems may be affected in this syndrome including abnormalities of the skin, skeletal system, genitourinary system and central nevus system. In this report, we present a case of Nevoid basal cell carcinoma syndrome in a 26-year-old male patient. The patient had multiple odontogenic keratocyst in the posterior of mandible, syndactyly in both hand and bifid rib. After enucleation and curettage, he was followed for two years. A number of both clinical and radiological criteria are used to diagnose this syndrome. Basal cell carcinoma syndrome is diagnosed with two major criteria or one major and two minor criteria. We must suspect this disorder in young patients with multiple odontogenic keratocyst and dental abnormalities whether related or not with other clinical manifestations or familial history.

Programmed Ventricular Stimulation for Risk Stratification in the Brugada Syndrome: A Pooled Analysis

NARCIS (Netherlands)

Sroubek, Jakub; Probst, Vincent; Mazzanti, Andrea; Delise, Pietro; Hevia, Jesus Castro; Ohkubo, Kimie; Zorzi, Alessandro; Champagne, Jean; Kostopoulou, Anna; Yin, Xiaoyan; Napolitano, Carlo; Milan, David J.; Wilde, Arthur; Sacher, Frederic; Borggrefe, Martin; Ellinor, Patrick T.; Theodorakis, George; Nault, Isabelle; Corrado, Domenico; Watanabe, Ichiro; Antzelevitch, Charles; Allocca, Giuseppe; Priori, Silvia G.; Lubitz, Steven A.

2016-01-01

The role of programmed ventricular stimulation in identifying patients with Brugada syndrome at the highest risk for sudden death is uncertain. We performed a systematic review and pooled analysis of prospective, observational studies of patients with Brugada syndrome without a history of sudden

Sexual orientation and medical history among Iranian people with Complete Androgen Insensitivity Syndrome and Congenital Adrenal Hyperplasia.

Science.gov (United States)

Khorashad, Behzad S; Roshan, Ghasem M; Reid, Alistair G; Aghili, Zahra; Hiradfar, Mehran; Afkhamizadeh, Mozhgan; Talaei, Ali; Aarabi, Azadeh; Ghaemi, Nosrat; Taghehchian, Negin; Saberi, Hedieh; Farahi, Nazanin; Abbaszadegan, Mohammad Reza

2017-01-01

To report sexual orientation, relationship status and medical history of Iranian people with Differences of Sex Development (DSD) who were raised female. Our participants consisted of nineteen 46,XY individuals with Complete Androgen Insensitivity Syndrome (CAIS) and eighteen 46,XX individuals with Congenital Adrenal Hyperplasia (CAH) who were raised as females and older than 13years. As well as their relationship status and detailed medical history, an expert psychiatrist assessed their sexual orientation by a semi-structured psychiatric interview with them and, where applicable, their parents. Five percent of CAH participants and 42% of CAIS participants were in a relationship, which was significantly different. All CAH individuals had been diagnosed at birth; 89% of CAIS had been diagnosed after puberty and due to primary amenorrhea and 11% were diagnosed in childhood due to inguinal hernia. Genital reconstructive surgery had been performed in 100% of CAH participants and 37% of CAIS. Regarding sexual contact experiences and sexual fantasies (androphilic, gynephilic or both), no significant differences were found. However, CAH females had significantly more gynephilic dreams (P=0.045). This study, notable as one of the rare from a non-western culture, described sexual, medical and socioeconomic status of 46,XX CAH and 46,XY CAIS individuals living in Iran. Although broadly in line with previous findings from Western cultures, Iranian CAH individuals had fewer romantic relationships, but in contrast to previous studies their sexual orientation was only different from CAIS in the contents of sexual dreams. Copyright © 2016 Elsevier Inc. All rights reserved.

Down syndrome: a risk factor for mycotic aneurysm?

LENUS (Irish Health Repository)

Naughton, Peter A

2011-03-29

Down syndrome, or trisomy 21, has a characteristic constellation of clinical findings, including various congenital heart defects. We report a case of an adult male with Down syndrome who presented with a 3-week history of lower limb pain and swelling, attributed to cellulitis. Clinical and angiographic evaluation identified a below-knee mycotic pseudoaneurysm secondary to infective endocarditis. Surgical aneurysmal repair and revascularization were performed. Various management options are outlined in this report.

Refeeding syndrome in a cat with hepatic lipidosis.

Science.gov (United States)

Brenner, Karen; KuKanich, Kate S; Smee, Nicole M

2011-08-01

Refeeding syndrome is characterized by severe hypophosphatemia occurring in patients given enteral or parenteral nutrition after severe weight loss. There are few veterinary reports that describe this syndrome but it is well documented in human medicine. This report describes a case of a domestic shorthair cat diagnosed with hepatic lipidosis following a 4-week history of decreased appetite and weight loss and in whom refeeding syndrome was documented after initiation of enteral nutrition. Clinical findings, blood work abnormalities and disease progression in this patient are described from the time of diagnosis through to recovery. A review of the current literature pertinent to this clinical syndrome is included. Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Impaired inhibition of prepotent motor actions in patients with Tourette syndrome.

Science.gov (United States)

Wylie, Scott A; Claassen, Daniel O; Kanoff, Kristen E; Ridderinkhof, K Richard; van den Wildenberg, Wery P M

2013-09-01

Evidence that tic behaviour in individuals with Tourette syndrome reflects difficulties inhibiting prepotent motor actions is mixed. Response conflict tasks produce sensitive measures of response interference from prepotent motor impulses and the proficiency of inhibiting these impulses as an act of cognitive control. We tested the hypothesis that individuals with Tourette syndrome show a deficit in inhibiting prepotent motor actions. Healthy controls and older adolescents/adults with persistent Tourette syndrome without a history of obsessive-compulsive disorder or attention-deficit/hyperactivity disorder and presenting with stable mood functioning (i.e., no history of well-treated anxiety or depression) participated in this study. They performed a Simon task that induced conflict between prepotent actions and goal-directed actions. A novel theoretical framework distinguished group differences in acting impulsively (i.e., fast motor errors) from the proficiency of inhibiting interference by prepotent actions (i.e., slope of interference reduction). We included 27 controls and 28 individuals with Tourette syndrome in our study. Both groups showed similar susceptibility to making fast, impulsive motor errors (Tourette syndrome 26% v. control 23%; p = 0.10). The slope (m) reduction of the interference effect was significantly less pronounced among participants with Tourette syndrome than controls (Tourette syndrome: m = -0.07 v. control: m = -0.23; p = 0.022), consistent with deficient inhibitory control over prepotent actions in Tourette syndrome. This study does not address directly the role of psychiatric comorbidities and medication effects on inhibitory control over impulsive actions in individuals with Tourette syndrome. The results offer empirical evidence for deficient inhibitory control over prepotent motor actions in individuals with persistent Tourette syndrome with minimal to absent psychiatric comorbidities. These findings also suggest that the frontal

Undifferentiated seronegative spondyloarthritis with inflammatory bowel disease and a family history of psoriasis. Sicca syndrome

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Norma Marigliano

2013-04-01

Full Text Available Background: Seronegative spondyloarthritis is characterized by the presence of subcutaneous nodules, asymmetrical peripheral arthritis, sacroileitis with or without spondylitis, and rheumatoid-factor negativity. Other common clinical manifestations include oral ulcers, conjunctivitis, and cutaneous lesions such as psoriasis. Familial aggregation has also been described. According to the 1986 classification, corresponding clinical entities include ankylosing spondylitis, psoriatic arthritis, Reiter’s syndrome, arthritis associated with inflammatory bowel disease (IBD, and undifferentiated spondyloarthritis. The disease is also frequently associated with the HLA B27 antigen. From the clinical point of view, there are often incomplete forms of spondyloarthritis, such as reactive arthritis triggered by asymptomatic infections, psoriatic arthritis without psoriasis itself, initial phases of specific forms of spondyloarthritis or the phase of ankylosing spondylitis characterized by sacroiliac lesions, and all forms that remain undifferentiated for long periods of time. Moreover, there are close relations between arthropathy and IBDs, such as Crohn’s disease, ulcerative colitis, and Whipple’s syndrome. Recently, microscopic inflammatory bowel lesions and psoriatic arthritis have been described. Case report: A 30-year-old man (HLA B27-negative who had been vaccinated against TBC and HBV presented with a 6-year history of recurrent episodes of predominantly left-sided sciatica. The pain was worse at night and during rest. He was suffering from bilateral sacroileitis without spondylitis. Three to five times a day, usually after eating, he passed watery feces containing mucous and small amounts of bright red blood. Colonoscopy revealed pancolitis with histological evidence of chronic inflammation interspersed with areas of acute inflammation, edema, hyperemia, and glandular distortion. One year later, the clinical manifestations and histological

Inherited Wolff–Parkinson–White Syndrome

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Yang Liu, MD, PhD

2016-02-01

Full Text Available Wolff–Parkinson–White (WPW syndrome is a congenital disorder of cardiac conduction system characterized by electrocardiographic preexcitation and episodes of paroxysmal supraventricular tachycardia. It is caused by a cardiac developmental defect in the electrical insulation between the atria and the ventricles due to the presence of an accessory pathway. WPW syndrome is a common cause of supraventricular tachycardia with benign prognosis. However, this clinical entity also predisposes patients to an increased risk of sudden cardiac death, especially in the setting of preexcited atrial fibrillation. WPW syndrome is usually sporadic and of unknown etiology in most cases. During the past 10 years, a significant heritable factor is increasingly recognized. Identification of the genetic basis among patients with WPW syndrome has important implications for understanding the molecular mechanism of ventricular preexcitation and the development of therapeutic strategies for risk stratification and management. The goal of this review is to examine the previous studies on hereditary variants, as well as to outline potential future avenues toward defining the heritability of WPW syndrome.

'Omics' Approaches to Understanding Interstitial Cystitis/Painful Bladder Syndrome/Bladder Pain Syndrome

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Sungyong You

2012-12-01

Full Text Available Recent efforts in the generation of large genomics, transcriptomics, proteomics, metabolomics and other types of 'omics' data sets have provided an unprecedentedly detailed view of certain diseases, however to date most of this literature has been focused on malignancy and other lethal pathological conditions. Very little intensive work on global profiles has been performed to understand the molecular mechanism of interstitial cystitis/painful bladder syndrome/bladder pain syndrome (IC/PBS/BPS, a chronic lower urinary tract disorder characterized by pelvic pain, urinary urgency and frequency, which can lead to long lasting adverse effects on quality of life. A lack of understanding of molecular mechanism has been a challenge and dilemma for diagnosis and treatment, and has also led to a delay in basic and translational research focused on biomarker and drug discovery, clinical therapy, and preventive strategies against IC/PBS/BPS. This review describes the current state of 'omics' studies and available data sets relevant to IC/PBS/BPS, and presents opportunities for new research directed at understanding the pathogenesis of this complex condition.

Adult respiratory distress syndrome

International Nuclear Information System (INIS)

Svendsen, J.; Jespersen, J.; Skjoedt, T.

1986-01-01

Our present-day knowledge concerning the clinico-chemical and radiological findings in adult respiratory distress syndrome are described. Three typical case histories have been selected to illustrate this condition; they were due to multiple trauma or sepsis. It is stressed that radiology is in a key position for making the diagnosis and for observing the course of the illness. (orig) [de

Cushing's syndrome complicated by multiple opportunistic infections

NARCIS (Netherlands)

Bakker, R. C.; Gallas, P. R.; Romijn, J. A.; Wiersinga, W. M.

1998-01-01

The case history of a 56-year-old man is described who suffered from severe adrenocorticotrophic hormone (ACTH)-dependent Cushing's syndrome. The clinical course was complicated by simultaneous infections with Pneumocystis carinii, Staphylococcus aureus, Candida albicans, Aspergillus fumigatus and

A rare case of choroid plexus carcinoma that led to the diagnosis of Lynch syndrome (hereditary nonpolyposis colorectal cancer).

Science.gov (United States)

Zhu, Viola W; Hinduja, Sanjay; Knezevich, Stevan R; Silveira, William R; DeLozier, Celia D

2017-07-01

Lynch syndrome (hereditary nonpolyposis colorectal cancer) is an autosomal dominant disorder characterized by a significant risk of colorectal and endometrial cancers. A variety of other epithelial cancers may be associated with this syndrome. Brian tumors are infrequent, but have been reported in series. Here, we report a case of a 34-year-old Caucasian woman with WHO grade III choroid plexus carcinoma (CPC). Comprehensive genomic profiling of the patient's resected brain tumor revealed mutations in six genes: PTEN, VHL, MSH6, NOTCH1, RB1, and TP53. Family history is significant for endometrial cancer in her mother and sister as well as colon cancer in her maternal grandfather suggestive of Lynch syndrome. Site-specific mutational analysis showed the MSH6 mutation (p.R482*) in peripheral lymphocytes. Subsequently we performed immunohistochemical staining of the tumor tissue which demonstrated widespread loss of MSH6 with intact MSH2, MLH1, and PMS2. The diagnosis of Lynch syndrome due to a mutation in MSH6 was therefore established. Our patient elected to have adjuvant radiation to the surgical bed only followed by prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy and is doing very well. To our knowledge, this is the first case report of CPC in an adult patient with a germline MSH6 mutation. We believe our data have provided molecular evidence to suggest that CPC could potentially be part of the Lynch syndrome spectrum. Published by Elsevier B.V.

Musculo-Skeletal Abnormalities in Patients with Marfan Syndrome

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Ali Al Kaissi

2013-01-01

Full Text Available Background A leptosomic body type is tall and thin with long hands. Marfanoid features may be familial in nature or pathological, as occurs in congenital contractual arachnodactyly (Beal's syndrome and Shprintzen-Goldberg syndrome mimicking some of the changes of Marfan syndrome, although not accompanied by luxation of lens and dissecting aneurysm of aorta. Methods In this article we collected eight patients who were consistent with the diagnosis of Marfan syndrome via phenotypic and genotypic characterization. Results Our patients manifested a constellation of variable presentations of musculo-skeletal abnormalities ranging from developmental dysplasia of the hip, protrusio acetabuli, leg length inequality, patellar instability, scoliosis, to early onset osteoarthritis. Each abnormality has been treated accordingly. Conclusion This is the first paper which includes the diagnosis and the management of the associated musculo-skeletal abnormalities in patients with Marfan syndrome, stressing that patients with Marfan syndrome are exhibiting great variability in the natural history and the severity of musculo-skeletal abnormalities.

Spectrum of novel mutations found in Waardenburg syndrome types 1 and 2: implications for molecular genetic diagnostics

Science.gov (United States)

Wildhardt, Gabriele; Zirn, Birgit; Graul-Neumann, Luitgard M; Wechtenbruch, Juliane; Suckfüll, Markus; Buske, Annegret; Bohring, Axel; Kubisch, Christian; Vogt, Stefanie; Strobl-Wildemann, Gertrud; Greally, Marie; Bartsch, Oliver; Steinberger, Daniela

2013-01-01

Objectives Till date, mutations in the genes PAX3 and MITF have been described in Waardenburg syndrome (WS), which is clinically characterised by congenital hearing loss and pigmentation anomalies. Our study intended to determine the frequency of mutations and deletions in these genes, to assess the clinical phenotype in detail and to identify rational priorities for molecular genetic diagnostics procedures. Design Prospective analysis. Patients 19 Caucasian patients with typical features of WS underwent stepwise investigation of PAX3 and MITF. When point mutations and small insertions/deletions were excluded by direct sequencing, copy number analysis by multiplex ligation-dependent probe amplification was performed to detect larger deletions and duplications. Clinical data and photographs were collected to facilitate genotype–phenotype analyses. Setting All analyses were performed in a large German laboratory specialised in genetic diagnostics. Results 15 novel and 4 previously published heterozygous mutations in PAX3 and MITF were identified. Of these, six were large deletions or duplications that were only detectable by copy number analysis. All patients with PAX3 mutations had typical phenotype of WS with dystopia canthorum (WS1), whereas patients with MITF gene mutations presented without dystopia canthorum (WS2). In addition, one patient with bilateral hearing loss and blue eyes with iris stroma dysplasia had a de novo missense mutation (p.Arg217Ile) in MITF. MITF 3-bp deletions at amino acid position 217 have previously been described in patients with Tietz syndrome (TS), a clinical entity with hearing loss and generalised hypopigmentation. Conclusions On the basis of these findings, we conclude that sequencing and copy number analysis of both PAX3 and MITF have to be recommended in the routine molecular diagnostic setting for patients, WS1 and WS2. Furthermore, our genotype–phenotype analyses indicate that WS2 and TS correspond to a clinical spectrum

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.

Genetics Home Reference: 5q31.3 microdeletion syndrome

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... up of a patient with 5q31.3 microdeletion syndrome and the smallest de novo 5q31.2q31.3 deletion involving PURA. Mol Cytogenet. 2015 Nov 14;8:89. doi: 10.1186/s13039-015-0193-9. eCollection 2015. ... 5q31.3 Microdeletion syndrome: clinical and molecular characterization of two further cases. ...

A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling.

Science.gov (United States)

Wieczorek, Dagmar; Bögershausen, Nina; Beleggia, Filippo; Steiner-Haldenstätt, Sabine; Pohl, Esther; Li, Yun; Milz, Esther; Martin, Marcel; Thiele, Holger; Altmüller, Janine; Alanay, Yasemin; Kayserili, Hülya; Klein-Hitpass, Ludger; Böhringer, Stefan; Wollstein, Andreas; Albrecht, Beate; Boduroglu, Koray; Caliebe, Almuth; Chrzanowska, Krystyna; Cogulu, Ozgur; Cristofoli, Francesca; Czeschik, Johanna Christina; Devriendt, Koenraad; Dotti, Maria Teresa; Elcioglu, Nursel; Gener, Blanca; Goecke, Timm O; Krajewska-Walasek, Malgorzata; Guillén-Navarro, Encarnación; Hayek, Joussef; Houge, Gunnar; Kilic, Esra; Simsek-Kiper, Pelin Özlem; López-González, Vanesa; Kuechler, Alma; Lyonnet, Stanislas; Mari, Francesca; Marozza, Annabella; Mathieu Dramard, Michèle; Mikat, Barbara; Morin, Gilles; Morice-Picard, Fanny; Ozkinay, Ferda; Rauch, Anita; Renieri, Alessandra; Tinschert, Sigrid; Utine, G Eda; Vilain, Catheline; Vivarelli, Rossella; Zweier, Christiane; Nürnberg, Peter; Rahmann, Sven; Vermeesch, Joris; Lüdecke, Hermann-Josef; Zeschnigk, Michael; Wollnik, Bernd

2013-12-20

Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. De novo dominant mutations in different members of the SWI/SNF chromatin remodeling complex have recently been described in individuals with Coffin-Siris (CSS) and Nicolaides-Baraitser (NCBRS) syndromes. Using a combination of whole-exome sequencing, NGS-based sequencing of 23 SWI/SNF complex genes, and molecular karyotyping in 46 previously undescribed individuals with CSS and NCBRS, we identified a de novo 1-bp deletion (c.677delG, p.Gly226Glufs*53) and a de novo missense mutation (c.914G>T, p.Cys305Phe) in PHF6 in two individuals diagnosed with CSS. PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex implicating dysfunction of a second chromatin remodeling complex in the pathogenesis of CSS-like phenotypes. Altogether, we identified mutations in 60% of the studied individuals (28/46), located in the genes ARID1A, ARID1B, SMARCB1, SMARCE1, SMARCA2, and PHF6. We show that mutations in ARID1B are the main cause of CSS, accounting for 76% of identified mutations. ARID1B and SMARCB1 mutations were also found in individuals with the initial diagnosis of NCBRS. These individuals apparently belong to a small subset who display an intermediate CSS/NCBRS phenotype. Our proposed genotype-phenotype correlations are important for molecular screening strategies.

Unique presentation of LHON/MELAS overlap syndrome caused by m.13046T>C in MTND5.

Science.gov (United States)

Kolarova, Hana; Liskova, Petra; Tesarova, Marketa; Kucerova Vidrova, Vendula; Forgac, Martin; Zamecnik, Josef; Hansikova, Hana; Honzik, Tomas

2016-12-01

Leber hereditary optic neuropathy (LHON) and mitochondrial encephalopathy, myopathy, lactic acidosis and stroke-like episodes (MELAS) syndromes are mitochondrially inherited disorders characterized by acute visual failure and variable multiorgan system presentation, respectively. A 12-year-old girl with otherwise unremarkable medical history presented with abrupt, painless loss of vision. Over the next few months, she developed moderate sensorineural hearing loss, vertigo, migraines, anhedonia and thyroiditis. Ocular examination confirmed bilateral optic nerve atrophy. Metabolic workup documented elevated cerebrospinal fluid lactate. Initial genetic analyses excluded the three most common LHON mutations. Subsequently, Sanger sequencing of the entire mitochondrial DNA (mtDNA) genome was performed. Whole mtDNA sequencing revealed a pathogenic heteroplasmic mutation m.13046T>C in MTND5 encoding the ND5 subunit of complex I. This particular variant has previously been described in a single case report of MELAS/Leigh syndrome (subacute necrotizing encephalopathy). Based on the constellation of clinical symptoms in our patient, we diagnose the condition as LHON/MELAS overlap syndrome. We describe a unique presentation of LHON/MELAS overlap syndrome resulting from a m.13046T>C mutation in a 12-year-old girl. In patients with sudden vision loss in which three of the most prevalent LHON mitochondrial mutations have been ruled out, molecular genetic examination should be extended to other mtDNA-encoded subunits of MTND5 complex I. Furthermore, atypical clinical presentations must be considered, even in well-described phenotypes.

Surveyor assay to diagnose persistent Müllerian duct syndrome in Miniature Schnauzers.

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Kim, Young June; Kwon, Hyuk Jin; Byun, Hyuk Soo; Yeom, Donguk; Choi, Jea-Hong; Kim, Joong-Hyun; Shim, Hosup

2017-12-31

Persistent Müllerian duct syndrome (PMDS) is a pseudohermaphroditism in males characterized by the presence of Müllerian duct derivatives. As PMDS dogs often lack clinical symptoms, a molecular diagnosis is essential to identify the syndrome in these animals. In this study, a new molecular method using DNA mismatch-specific Surveyor nuclease was developed. The Surveyor nuclease assay identified the AMHR2 mutation that produced PMDS in a Miniature Schnauzer as accurately as that obtained by using the conventional method based on restriction digestion. As an alternative to the current molecular diagnostic method, the new method may result in increased accuracy when detecting PMDS.

Dysmobility syndrome: current perspectives

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Hill KD

2017-01-01

Full Text Available Keith D Hill,1 Kaela Farrier,1 Melissa Russell,2 Elissa Burton1 1School of Physiotherapy and Exercise Science, Faculty of Health Sciences, Curtin University, Perth, WA, Australia; 2Department of Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia Background: A new term, dysmobility syndrome, has recently been described as a new approach to identify older people at risk of poor health outcomes. The aim was to undertake a systematic review of the existing research literature on dysmobility syndrome.Method: All articles reporting dysmobility syndrome were identified in a systematic review of Medline (Proquest, CINAHL, PubMed, PsycInfo, EMBASE, and Scopus databases. Key characteristics of identified studies were extracted and summarized.Results: The systematic review identified five papers (three cross-sectional, one case control, and one longitudinal study. No intervention studies were identified. Prevalence of dysmobility syndrome varied between studies (22%–34% in three of the studies. Dysmobility syndrome was shown to be associated with reduced function, increased falls and fractures, and a longitudinal study showed its significant association with mortality.Conclusion: Early research on dysmobility syndrome indicates that it may be a useful classification approach to identify older people at risk of adverse health outcomes and to target for early interventions. Future research needs to standardize the optimal mix of measures and cut points, and investigate whether balance performance may be a more useful factor than history of falls for dysmobility syndrome. Keywords: mobility, elderly, functional decline

Obstetric antiphospholipid syndrome.

Science.gov (United States)

Esteve-Valverde, E; Ferrer-Oliveras, R; Alijotas-Reig, J

2016-04-01

Obstetric antiphospholipid syndrome is an acquired autoimmune disorder that is associated with various obstetric complications and, in the absence of prior history of thrombosis, with the presence of antiphospholipid antibodies directed against other phospholipids, proteins called cofactors or PL-cofactor complexes. Although the obstetric complications have been related to the procoagulant properties of antiphospholipid antibodies, pathological studies of human placenta have shown the proinflammatory capacity of antiphospholipid antibodies via the complement system and proinflammatory cytokines. There is no general agreement on which antiphospholipid antibodies profile (laboratory) confers the greatest obstetric risk, but the best candidates are categories I and IIa. Combined treatment with low doses of aspirin and heparin achieves good obstetric and maternal outcomes. In this study, we also review the therapeutic possibilities in refractory cases, although the likelihood of progressing to other autoimmune diseases is low. We briefly comment on incomplete obstetric antiphospholipid syndrome, also known as antiphospholipid antibody-mediated pregnancy morbidity syndrome. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

[Cannabinoid hyperemesis syndrome].

Science.gov (United States)

Stuijvenberg, Marleen P; Ramaekers, Guy M G I; Bijpost, Yan

2011-01-01

A 22-year-old man was referred to our clinic with a 7-year history of episodes of severe vomiting interspersed with symptom-free periods. We saw another patient, a 22-year-old woman, after she had been admitted for the second time with dehydration and hypokalaemia following severe vomiting. We saw a third patient, a 25-year-old woman with a personality disorder and cannabis addiction, after she had gone to the casualty department following several days of persistent excessive vomiting. All three patients seemed to be suffering from cannabinoid hyperemesis syndrome. This is a rarely described syndrome, characterised by the triad of chronic cannabis abuse, unexplained cyclical excessive vomiting and compulsive taking of hot baths for symptom relief. A subgroup of chronic frequent cannabis users suffer from this syndrome, which can appear for the first time several years after initial cannabis use. The exact mechanism of origin is unknown, though various theories exist. In the case of unexplained chronic symptoms of nausea and vomiting our advice is always to question the patient about substance misuse, and showering and bathing habits.

Prune belly syndrome in an adult Nigerian: case report.

Science.gov (United States)

Salako, A A; Takure, A O; Olajide, A O; Aarowolo, O A; Egberongbe, A A

2009-12-01

Prune Belly Syndrome is a rare congenital anomaly characterized by deficient anterior abdominal wall musculature, bilateral cryptorchidism, bilateral megaureters and often unilateral or bilateral vesico-ureteric junction obstruction. The report of prune belly syndrome in the adult is scanty. We report a case of prune belly syndrome in a 24 year old Nigerian who presented with 3 year history of recurrent right loin pain. Examination showed wrinkled abdominal skin, bilateral undescended testes and an hypoplastic rectus abdominis, below the umbilicus. Further evaluation revealed enlarged bladder, bilateral megaureters and right intra-abdominal testis. A diagnosis of Prune Belly Syndrome was made. The challenges in the diagnosis and management of this rare condition are highlighted in this presentation.

The Natural History of Femoroacetabular Impingement

Directory of Open Access Journals (Sweden)

Benjamin D. Kuhns

2015-11-01

Full Text Available Femoroacetabular impingement (FAI is a clinical syndrome resulting from abnormal hip joint morphology and is a common cause of hip pain in young adults. FAI has been posited as a precursor to hip osteoarthritis, however, conflicting evidence exists and the true natural history of the disease is unclear. The purpose of this article is to review the current understanding of how FAI damages the hip joint by highlighting its pathomechanics and etiology. We then review the current evidence relating FAI to osteoarthritis. Lastly, we will discuss the potential of hip preservation surgery to alter the natural history of FAI, reduce the risk of developing osteoarthritis and the need for future arthroplasty.

Molecular genetics of preeclampsia and HELLP syndrome - A review

NARCIS (Netherlands)

Jebbink, Jiska; Wolters, Astrid; Fernando, Febilla; Afink, Gijs; van der Post, Joris; Ris-Stalpers, Carrie

2012-01-01

Preeclampsia is characterised by new onset hypertension and proteinuria and is a major obstetrical problem for both mother and foetus. Haemolysis elevated liver enzymes and low platelets (HELLP) syndrome is an obstetrical emergency and most cases occur in the presence of preeclampsia. Preeclampsia

Cannabinoid Hyperemesis Syndrome: A Paradoxical Cannabis Effect

Directory of Open Access Journals (Sweden)

Ivonne Marie Figueroa-Rivera

2015-01-01

Full Text Available Despite well-established antiemetic properties of marijuana, there has been increasing evidence of a paradoxical effect in the gastrointestinal tract and central nervous system, given rise to a new and underrecognized clinical entity called the Cannabinoid Hyperemesis Syndrome. Reported cases in the medical literature have established a series of patients exhibiting a classical triad of symptoms: cyclic vomiting, chronic marijuana use, and compulsive bathing. We present a case of a 29-year-old man whose clinical presentation strongly correlates with cannabinoid hyperemesis syndrome. Despite a diagnosis of exclusion, this syndrome should be considered plausible in the setting of a patient with recurrent intractable vomiting and a strong history of cannabis use as presented in this case.

Complete heart block in a patient with POEMS syndrome: A case report

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Farzaneh Ashrafi

2014-09-01

Full Text Available BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, monoclonal syndrome (POEMS is a rare paraneoplastic syndrome associated with plasma cell dyscrasia. CASE REPORT: A 48-year-old man presented with a 1-year history of paresthesia and progressive weakness of extremities. Diagnosis of POEMS syndrome was made for him on the basis of clinical presentation, additional physical findings, typical sclerotic bone lesion, and bone marrow findings. In last admission, he explained episodes of dyspnea and chest pain that associated with frequent premature ventricular contraction in his electrocardiograph. Patient heart monitoring showed some episodes of complete heart block. Infra-His atrioventricular block in electro-physiologic study was detected. He had no history of ischemic heart disease. His cardiopulmonary findings on examination were normal. All results of cardiac biomarkers and serum electrolytes and repeated echocardiography were within normal range. Cong red staining of rectal fat pad biopsy was negative. After pacemaker insertion radiation of sclerotic bone, lesion started for him, but radiotherapy was ineffective, and he expired with respiratory failure. Complete heart block in POEMS syndrome has not been reported previously, and it is the first POEMS case with complete heart block. CONCLUSION: Complete heart block is a cardiac manifestation of POEMS syndrome.   Keywords: Complete Heart Block, POEM Syndrome, Multiple Meloma 

Clinical aspects of the hand-arm vibration syndrome. A review.

Science.gov (United States)

Pyykkö, I

1986-10-01

At present it seems likely that the different components of the hand-arm vibration syndrome, eg, vibration-induced white finger (VWF), numbing of the hands and arms, muscular fatigue, and occasionally prevalent bone degeneration, may arise independently, and therefore they should be evaluated separately. Evidence of changes caused in the autonomic nervous functions of the body by local vibration is not conclusive. The vascular history should be confirmed objectively with a cold provocation test under laboratory conditions. In individual diagnostics it is useful to record (with modern plethysmographic techniques) the recovery of digital temperature, digital blood pressure, and flow after local cooling. Vibrotactile perception measurement seems to be suitable for group diagnosis. Much of the diagnostic weight for VWF can be obtained from accurate case histories, although, for early changes, the history may be atypical. The lack of simple objective tests for evaluating the hand-arm vibration syndrome makes it difficult to, eg, confirm the history of its different components objectively and estimate the extent of the disability it causes.

High-resolution molecular epidemiology and evolutionary history of HIV-1 subtypes in Albania.

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Marco Salemi

2008-01-01

Full Text Available HIV-1 epidemic in Western Europe is largely due to subtype B. Little is known about the HIV-1 in Eastern Europe, but a few studies have shown that non-B subtypes are quite common. In Albania, where a recent study estimated a ten-fold increase of AIDS incidence during the last six years, subtype A and B account for 90% of the know infections.We investigated the demographic history of HIV-1 subtype A and B in Albania by using a statistical framework based on coalescent theory and phylogeography. High-resolution phylogenetic and molecular clock analysis showed a limited introduction to the Balkan country of subtype A during the late 1980s followed by an epidemic outburst in the early 1990 s. In contrast, subtype B was apparently introduced multiple times between the mid-1970s and mid-1980s. Both subtypes are growing exponentially, although the HIV-1A epidemic displays a faster growth rate, and a significantly higher basic reproductive number R(0. HIV-1A gene flow occurs primarily from the capital Tirane, in the center of the country, to the periphery, while HIV-1B flow is characterized by a balanced exchange between center and periphery. Finally, we calculated that the actual number of infections in Albania is at least two orders of magnitude higher than previously thought.Our analysis demonstrates the power of recently developed computational tools to investigate molecular epidemiology of pathogens, and emphasize the complex factors involved in the establishment of HIV-1 epidemics. We suggest that a significant correlation exists between HIV-1 exponential spread and the socio-political changes occurred during the Balkan wars. The fast growth of a relatively new non-B epidemic in the Balkans may have significant consequences for the evolution of HIV-1 epidemiology in neighboring countries in Eastern and Western Europe.

Case report: waardenburg syndrome.

Science.gov (United States)

Dumayas, Grace Lea; Capó-Aponte, José E

2015-03-01

A case of Waardenburg syndrome type 1 is described and relevant literature is reviewed to raise awareness about this rare syndrome, including the classification of each subtype and the differentiating clinical manifestations. A 44-year-old African-American female presented for a routine evaluation with hearing loss, dystopia canthorum (W index = 2.74), and almost complete gray hair. In addition, she presented with heterochromia irides, different fundus pigmentation between eyes. The patient did not have any upper limbs defect, cranial skeletal abnormalities, or intestinal disorders. Facial abnormalities and a white forelock are prominent features difficult to overlook during a routine ophthalmological examination. A careful medical history in patients with suspected Waardenburg syndrome is important to accurately classify this rare condition and to identify potential systemic implications associated to each subtype. The associated systemic complications can be addressed and managed through referral to the appropriate subspecialties. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

The Molecular Era of Surfactant Biology

OpenAIRE

Whitsett, Jeffrey A.

2014-01-01

Advances in the physiology, biochemistry, molecular and cell biology of the pulmonary surfactant system transformed the clinical care and outcome of preterm infants with respiratory distress syndrome. The molecular era of surfactant biology provided genetic insights into the pathogenesis of pulmonary disorders, previously termed “idiopathic” that affect newborn infants, children and adults. Knowledge related to the structure and function of the surfactant proteins and their roles in alveolar ...

Molecular evolution and the natural history of select virus epidemics

DEFF Research Database (Denmark)

Bruhn, Christian Anders Wathne

Molecular evolution of pathogenic viruses with RNA based genomes is most often fast enough to leave an informative genomic sequence signal within a timeframe that is relevant for the study of both recent and on-­‐going epidemics (and epizootics). The true power of molecular evolutionary methodolo...

[Neonatal hyperbilirubinemia and molecular mechanisms of jaundice].

Science.gov (United States)

Jirsa, M; Sticová, E

2013-07-01

The introductory summarises the classical path of heme degradation and classification of jaundice. Subsequently, a description of neonatal types of jaundice is given, known as Crigler Najjar, Gilberts, DubinJohnson and Rotor syndromes, emphasising the explanation of the molecular mechanisms of these metabolic disorders. Special attention is given to a recently discovered molecular mechanism of the Rotor syndrome. The mechanism is based on the inability of the liver to retrospectively uptake the conjugated bilirubin fraction primarily excreted into the blood, not bile. A reduced ability of the liver to uptake the conjugated bilirubin contributes to the development of hyperbilirubinemia in common disorders of the liver and bile ducts and to the toxicity of xenobiotics and drugs using transport proteins for conjugated bilirubin.

TBX3 regulates splicing in vivo: a novel molecular mechanism for Ulnar-mammary syndrome.

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Pavan Kumar P

2014-03-01

Full Text Available TBX3 is a member of the T-box family of transcription factors with critical roles in development, oncogenesis, cell fate, and tissue homeostasis. TBX3 mutations in humans cause complex congenital malformations and Ulnar-mammary syndrome. Previous investigations into TBX3 function focused on its activity as a transcriptional repressor. We used an unbiased proteomic approach to identify TBX3 interacting proteins in vivo and discovered that TBX3 interacts with multiple mRNA splicing factors and RNA metabolic proteins. We discovered that TBX3 regulates alternative splicing in vivo and can promote or inhibit splicing depending on context and transcript. TBX3 associates with alternatively spliced mRNAs and binds RNA directly. TBX3 binds RNAs containing TBX binding motifs, and these motifs are required for regulation of splicing. Our study reveals that TBX3 mutations seen in humans with UMS disrupt its splicing regulatory function. The pleiotropic effects of TBX3 mutations in humans and mice likely result from disrupting at least two molecular functions of this protein: transcriptional regulation and pre-mRNA splicing.

TBX3 regulates splicing in vivo: a novel molecular mechanism for Ulnar-mammary syndrome.

Science.gov (United States)

Kumar P, Pavan; Franklin, Sarah; Emechebe, Uchenna; Hu, Hao; Moore, Barry; Lehman, Chris; Yandell, Mark; Moon, Anne M

2014-03-01

TBX3 is a member of the T-box family of transcription factors with critical roles in development, oncogenesis, cell fate, and tissue homeostasis. TBX3 mutations in humans cause complex congenital malformations and Ulnar-mammary syndrome. Previous investigations into TBX3 function focused on its activity as a transcriptional repressor. We used an unbiased proteomic approach to identify TBX3 interacting proteins in vivo and discovered that TBX3 interacts with multiple mRNA splicing factors and RNA metabolic proteins. We discovered that TBX3 regulates alternative splicing in vivo and can promote or inhibit splicing depending on context and transcript. TBX3 associates with alternatively spliced mRNAs and binds RNA directly. TBX3 binds RNAs containing TBX binding motifs, and these motifs are required for regulation of splicing. Our study reveals that TBX3 mutations seen in humans with UMS disrupt its splicing regulatory function. The pleiotropic effects of TBX3 mutations in humans and mice likely result from disrupting at least two molecular functions of this protein: transcriptional regulation and pre-mRNA splicing.

Trapped neutrophil syndrome in a Border Collie dog: clinical, clinico-pathologic, and molecular findings.

Science.gov (United States)

Mizukami, Keijiro; Shoubudani, Tomoaki; Nishimoto, Seira; Kawamura, Ryuta; Yabuki, Akira; Yamato, Osamu

2012-06-01

Trapped neutrophil syndrome (TNS) is an autosomal recessive inherited neutropenia known in Border Collies since the 1990's. Recently, the causative mutation has been identified in the canine VPS13B gene and a DNA-based diagnosis has now become available. The present paper describes clinical and clinico-pathologic findings in a Border Collie with TNS that was molecularly diagnosed for the first time in Japan. In a 10-week-old male Border Collie with microgenesis and symptoms related to recurrent infections, a hematological examination revealed severe leukopenia due to neutropenia, suggesting the dog to be affected by inherited neutropenic immunodeficiency. Direct DNA sequencing demonstrated that the dog was homozygous for the causative mutation of TNS and both its parents were heterozygous carriers. In addition, a simple and rapid polymerase chain reaction-based length polymorphism analysis coupled with microchip electrophoresis was developed for the genotyping of TNS. This assay could discriminate clearly all genotypes, suggesting that it was suitable for both individual diagnosis and large-scale surveys for prevention.

Caracterización clínica y molecular de individuos con el síndrome frágil X detectados por análisis inmunohistoquímico Clinical and molecular characterization of individuals with fragile X syndrome detected by immunohistochemical analysis

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Iván Hernández García

2004-09-01

Full Text Available Se realizó el estudio de 50 varones con retraso mental y/o autismo de etiología desconocida a fin de detectar individuos afectados con el síndrome frágil X a través del análisis inmunohistoquímico y caracterizarlos clínica y molecularmente. Entre los casos pesquisados se detectaron 3 individuos con baja expresión de la proteína relacionada con el síndrome, a quienes se les realizó la caracterización molecular. La correlación inmunohistoquímica y molecular en 2 de ellos fue positiva. La no correlación de un tercero sugiere que pudiera tratarse de una mutación puntual o una deleción del gen relacionado con la enfermedad. En otro paciente con el fenotipo neuropsicológico y físico característicos de la enfermedad se observó una expresión promedio normal baja, lo que motivó la indicación de la caracterización molecular, que resultó ser positiva. Se discuten los mecanismos genéticos y fisiopatológicos que pudieran explicar la presencia de la proteína en las células analizadas.50 males with mental retardation and/or autism of unknown etiology were studied aimed at detecting individuals affected with the Fragile X syndrome by the immunohistochemical analysis and at characterizing them from the clinical and molecular point of view. Among the screneed subjects, 3 individuals with low expression of the protein related to the syndrome were detected. Molecular characterization was performed in these cases. The immunohistochemical and molecular correlation was positive in 2 of them. The non correlation of the third suggests that it may be a punctual mutation or a deletion of the gene connected with the disease. In another patient with the neuropsychological and physical phenotype characteristic of the disease, it was observed an average normal low expression that led to the indication of the molecular characterization, which proved to be positive. The genetic and physiopathological mechanisms that could explain the presence of

Adult Reye-like syndrome associated with serologic evidence of acute parvovirus B19 infection

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Paulo Sérgio Gonçalves da Costa

Full Text Available Reye's syndrome is an infrequently diagnosed medical condition affecting mainly children. The etiology, epidemiology and natural history of Reye's syndrome have been cloudily written in footnotes of medical books and exotic papers since the initial description in early 1950s. We report here a case of adult Reye's syndrome associated with serologic evidence of parvovirus B19 infection.

Family History of Type 2 Diabetes is Associated with Metabolic Syndrome in Obese Female Subjects

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Ticiana Costa Rodrigues

2008-08-01

Full Text Available The aim of this study was to evaluate the association between the family history (FH of type 2 diabetes and metabolic syndrome (MetS in a group of non-diabetic obese female subjects. A cross-sectional study was conducted in 239 female patients with obesity, regularly attending the Internal Medicine Division’s outpatient clinic (Hospital de Clínicas de Porto Alegre, Brazil. The inclusion criteria were patients with body mass index ?30 kg/m2 and absence of type 2 diabetes. The FH was considered positive if a first degree relative had a diagnosis of diabetes. Seventy-four of 239 patients evaluated (30% had a positive FH for type 2 diabetes. Patients with positive FH had higher waist/hip ratio and MetS more often than patients with negative FH. FH of type 2 diabetes was associated with MetS in this sample of non-diabetic obese female patients. Waist/hip ratio and fasting plasma glucose, markers of insulin resistance, were also associated with FH of type 2 diabetes. The simple question: “Do you have a FH of type 2 diabetes?” may help to identify the obese patients that should be better evaluated and intensively treated with the objective of preventing type 2 diabetes.

Respiratory Failure due to Severe Obesity and Kyphoscoliosis in a 24-Year-Old Male with Molecularly Confirmed Prader-Willi Syndrome in Tertiary Hospital in Northern Tanzania

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Elichilia R. Shao

2017-01-01

Full Text Available Obesity, mild intellectual disability, hypotonia, poor sucking, cryptorchidism in males, hypogonadism, and kyphoscoliosis are common features of Prader-Willi syndrome (PWS. We report a case who had severe respiratory complications due to extreme obesity and kyphoscoliosis, which are important causes of morbidity and mortality, and discuss management. Furthermore, this is the first molecularly confirmed PWS case in Sub-Saharan Africa outside South Africa.

An Unusual Case of Posterior Reversible Encephalopathy Syndrome

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Robert P. Zemple

2017-07-01

Full Text Available A 21-year-old pregnant female with no significant past medical history presented with acute onset headache and nausea as well as tonic-clonic seizures, then rapidly decompensated into a coma with complete absence of brainstem reflexes. The patient was ultimately diagnosed with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome and subsequent posterior reversible encephalopathy syndrome (PRES with brainstem involvement. Emergent delivery and blood pressure control resulted in rapid and complete neurologic recovery.

[Retrospective analysis of risk factors in 900 patients with ischemic cerebral stroke of wind-phlegm collateral obstruction syndrome and qi deficiency blood stasis syndrome in Wuhan District].

Science.gov (United States)

Qiu, Xin; Wang, Kai-xin; Chen, Guo-hua

2011-11-01

To analyze the correlation between risk factors and ischemic cerebral stroke of wind-phlegm collateral obstruction syndrome and qi deficiency blood stasis syndrome. Totally 900 patients of the two syndrome types were recruited. Risk factors correlated to ischemic cerebral stroke such as gender, age, time of onset, site of infarction, tongue proper, tongue fur, pulse picture, hypertension, diabetes, past stroke history, hyperlipidemia, hematocrit, smoking, drinking, genetic factor, blood type, complications were analyzed using Chi-square test and non-conditional Logistic regression analysis. Statistical significance existed between the two syndrome types in age (X2 = 8.2392, P = 0.0413), hyperlipidemia (X2 = 4.8386, P = 0.0278), tongue proper (X2 = 7.9470, P = 0.0048), and tongue fur (X2 = 4.3298, P = 0.0375). Statistical significance existed between the two syndrome types in hyperlipidemia, tongue proper, and tongue fur, and their OR value was 0.699 (P = 0.0282), 0.332 (P =0.0071), and 0.667 (P = 0.0382) respectively. The OR value of the past stroke history was 3.226 (P = 0.0314), that of complications 0.203 (P = 0.0705), and that of anterior circulation infarction 0.214 (P = 0.0098). Among different ages groups, the constituent ratio of qi deficiency blood stasis syndrome was obviously higher than that of wind-phlegm collateral obstruction syndrome. Besides, patients of qi deficiency blood stasis syndrome were liable to suffer from hyperlipidemia, anterior circulation infarction, and complications. The age, blood lipid levels, site of infarction, complications are closely correlated with Chinese syndrome types of ischemic cerebral stroke, which can provide objective indices for typing ischemic cerebral stroke.

Diagnosis of 20 cases with chronic radiation syndrome

International Nuclear Information System (INIS)

Zhang, Hongshou; Shen, Zhezhong; Wen Zhigen; Xie, Xiaoping; Ni, Jinxian

1984-01-01

Twenty cases with chronic radiation syndrome were diagnosed in our department during 1957-1980. All except one were radiologists, and eight of them had worked in radiological departments for over 20 years. Owing to the use of out-dated x-ray machines as well as radium sources without adequate protection, all these cases were apparently overexposed to radiation. They presented following signs and symptoms of chronic radiation syndrome: excitability, palpitation, fatigue, general weakness, loss of weight, oversweating accompanied by tendency of lowered metabolism, peripheral blood cell changes, and chromosome aberrations. The diagnosis of this syndrome was based on definitive professional and over-exposure history, clinical picture and abnormal laboratory findings. (author)

Churg-Strauss syndrome: a case with unusual manifestations

International Nuclear Information System (INIS)

Restrepo, Mauricio; Gonzalez, Luis Alonso; Vasquez, Gloria

2008-01-01

Churg-Strauss syndrome, a necrotizing systemic vasculitis which involves the small and (more rarely) the medium-sized vessels, is a primary vasculitis strongly associated with anti neutrophil cytoplasm antibodies (ANCA). It is characterized by the presence of asthma, eosinophilia and extravascular eosinophilic granulomas. Herein, we report a 36-year-old woman with a history of late onset asthma and allergic rhinitis who developed central nervous system involvement, peripheral neuropathy, leucocytoclastic vasculitis and eosinophilia. Interestingly, unusual clinical manifestations of Churg-Strauss syndrome such as mesenteric micro aneurysms and jaw claudication were present in this particular patient. A brief review of the literature of Churg-Strauss syndrome is presented.

Dress Syndrome - A Case Report

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Kremić Zorana

2016-06-01

Full Text Available The drug reaction with eosinophilia and systemic symptoms (DRESS syndrome is an adverse drug-induced reaction that occurs most commonly after exposure to drugs, most frequently anticonvulsants, sulfa derivates, antidepressants, nonsteroidal anti-inflammatory drugs, and antimicrobials. We present a 61-year-old male, with a generalized maculopapular exanthema on the trunk, face, extremities, palms, soles, palate, and fever (38°C. His medical history was notable for generalized epilepsy, treated with carbamazepine during 1 month. The diagnosis of DRESS syndrome was confirmed by specific RegiSCAR criteria. In our case, skin eruptions were successfully treated with oral methylprednisolone, cephalexin, and topical corticosteroid ointment.

Cornelia de Lange Syndrome: Evolution of the Phenotype

Science.gov (United States)

Passarge, Eberhard; And Others

1971-01-01

The medical case history of a 2-year-old girl who developed, during the second year of life, the classical phenotype (typical appearance) indicative of the deLange syndrome, with both mental and physical impairment. (KW)

The molecular genetics of Usher syndrome.

Science.gov (United States)

Ahmed, Z M; Riazuddin, S; Riazuddin, S; Wilcox, E R

2003-06-01

Association of sensorineural deafness and progressive retinitis pigmentosa with and without a vestibular abnormality is the hallmark of Usher syndrome and involves at least 12 loci among three different clinical subtypes. Genes identified for the more commonly inherited loci are USH2A (encoding usherin), MYO7A (encoding myosin VIIa), CDH23 (encoding cadherin 23), PCDH15 (encoding protocadherin 15), USH1C (encoding harmonin), USH3A (encoding clarin 1), and USH1G (encoding SANS). Transcripts from all these genes are found in many tissues/cell types other than the inner ear and retina, but all are uniquely critical for retinal and cochlear cell function. Many of these protein products have been demonstrated to have direct interactions with each other and perform an essential role in stereocilia homeostasis.

Does the Risk of Metabolic Syndrome Increase in Thyroid Cancer Survivors?

Science.gov (United States)

Kim, Min-Hee; Huh, Jin-Young; Lim, Dong-Jun; Kang, Moo-Il

2017-07-01

The steep rise in thyroid cancer observed in recent decades has caused an increase in the population of long-term thyroid cancer survivors. Other than recurrences of cancer, the long-term health consequences of surviving thyroid cancer, particularly metabolic syndrome, have not yet been determined. The aim of this study was to estimate the risk of metabolic syndrome in thyroid cancer survivors. Population-based data from the Korean National Health and Nutrition Examination Survey (KNHANES) were used for the analysis. The data of KNHANES IV-VI from 2007-2014 were obtained. After excluding subjects who were under 19 years old, whose fasting interval was less than 8 hours, and whose data for predefined variables including metabolic syndrome components were incomplete, 34,347 subjects were analyzed. The incidence of metabolic syndrome and its components were evaluated in three groups: subjects with no history of thyroid cancer, subjects diagnosed with thyroid cancer within 3 years of the survey date, and subjects diagnosed more than 3 years before the survey date. Thyroid cancer diagnoses were made within 3 years of the survey date for 95 subjects (group 1, short-term survivors) and more than 3 years earlier than the survey date for 60 subjects (group 2, long-term survivors). Metabolic syndrome was frequently observed with clinical significance (odds ratio [OR] 1.986 [95% confidence interval [CI] 1.0-3.70], p = 0.030) in short-term survivors compared with subjects with no thyroid cancer history. Risks for having high blood pressure and high fasting glucose were estimated to be higher in the short-term survivor group (OR 2.115 [CI 1.23-3.64], p = 0.006 and OR 1.792 [CI 1.03-3.11], p = 0.038, respectively). No significant associations were noticed in the long-term survivor group when compared with the group with no thyroid cancer history. Risks for metabolic syndrome, especially high blood pressure and high fasting glucose, were increased in short

Editorial: X-chromosome-linked Kallmann's syndrome: Pathology at the molecular level

Energy Technology Data Exchange (ETDEWEB)

Prager, D.; Braunstein, G.D. (Cedars-Sinai Medical Center, Los Angeles, CA (United States))

1993-04-01

Kallmann's syndrome or olfactogenital dysplasia refers to a disorder characterized by hypogonadotropic hypogonadism and anosmia or hyposmia which can occur sporadically or in a familial setting. Originally described in 1856, the first familial cases were reported by Kallmann et al., in 1944. Based on segregation analysis of multiple families, three modes of transmission have been documented: X-linked, autosomal dominant with variable penetrance, and autosomal recessive. Kallmann's syndrome occurs in less than 1 in 10,000 male births, with a 5-fold excess of affected males to females, suggesting that the X-linked form is the most frequent. By genetic linkage analysis the X-linked form of Kallmann's syndrome was localized to Xp22.3. This was confirmed by the description of patients with contiguous gene syndromes due to deletions of various portions of the distal short arm of the X-chromosome. Such patients present with complex phenotypes characterized by a combination of Kallmann's syndrome with X-linked icthyosis due to steroid sulfatase deficiency, chondrodysplasia punctata, short stature, and mental retardation. DNA analysis has identified and mapped the genes responsible for these disorders. 10 refs., 1 fig., 1 tab.

Genome Size, Molecular Phylogeny, and Evolutionary History of the Tribe Aquilarieae (Thymelaeaceae, the Natural Source of Agarwood

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Azman H. Farah

2018-05-01

Full Text Available The tribe Aquilarieae of the family Thymelaeaceae consists of two genera, Aquilaria and Gyrinops, with a total of 30 species, distributed from northeast India, through southeast Asia and the south of China, to Papua New Guinea. They are an important botanical resource for fragrant agarwood, a prized product derived from injured or infected stems of these species. The aim of this study was to estimate the genome size of selected Aquilaria species and comprehend the evolutionary history of Aquilarieae speciation through molecular phylogeny. Five non-coding chloroplast DNA regions and a nuclear region were sequenced from 12 Aquilaria and three Gyrinops species. Phylogenetic trees constructed using combined chloroplast DNA sequences revealed relationships of the studied 15 members in Aquilarieae, while nuclear ribosomal DNA internal transcribed spacer (ITS sequences showed a paraphyletic relationship between Aquilaria species from Indochina and Malesian. We exposed, for the first time, the estimated divergence time for Aquilarieae speciation, which was speculated to happen during the Miocene Epoch. The ancestral split and biogeographic pattern of studied species were discussed. Results showed no large variation in the 2C-values for the five Aquilaria species (1.35–2.23 pg. Further investigation into the genome size may provide additional information regarding ancestral traits and its evolution history.

Erasmus syndrome in a marble worker

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S. Bello

2016-02-01

Full Text Available Erasmus syndrome is defined as the association of silica exposure and subsequent development of systemic sclerosis. The limited number of cases reported in the literature mainly involves miners and only sporadically other professionals. We describe a case of Erasmus syndrome in a marble worker. A 68 year old man came to our observation complaining pelvic and scapular girdle pain, evening fever, intense weakness and emaciation for about 1 month. He also reported to have had Raynaud’s phenomenon in his hands for the last 13 years. Also, his occupational history revealed a chronic exposure to silica dust. The patient presented pain in his shoulders and hips, moderate skin thickening and sclerosis in his hands and fingers extending proximally to his wrists. The diagnosis of systemic sclerosis was determined according to his clinical and medical history, the positivity of anti-Scl 70 antibodies, the nailfold capillaroscopy suggestive of an active scleroderma pattern and the detection of a mild restrictive pulmonary syndrome. The evaluation of the organbased complications excluded a gastroenterological and cardiovascular involvement, while the chest computed tomography (CT detected multiple small nodules with a mantle distribution and enlarged lymph nodes with no signs of interstitial lung disease and fibrosis. Additional tests (positron emission tomography-CT, flexible bronchoscopy and broncho-alveolar lavage excluded infectious diseases and cancer. However, given the pulmonary involvement, we performed a histological examination of the parenchyma and lymph nodes, which revealed a picture of pneumoconiosis. In the end, the occupational history and the findings from the diagnostic procedures led to the diagnosis of pulmonary silicosis. The precise definition of the pulmonary involvement was essential to the therapeutic approach to this patient.

Erasmus syndrome in a marble worker.

Science.gov (United States)

Bello, S; Rinaldi, A; Trabucco, S; Serafino, L; Bonali, C; Lapadula, G

2015-12-30

Erasmus syndrome is defined as the association of silica exposure and subsequent development of systemic sclerosis. The limited number of cases reported in the literature mainly involves miners and only sporadically other professionals. We describe a case of Erasmus syndrome in a marble worker. A 68 year old man came to our observation complaining pelvic and scapular girdle pain, evening fever, intense weakness and emaciation for about 1 month. He also reported to have had Raynaud's phenomenon in his hands for the last 13 years. Also, his occupational history revealed a chronic exposure to silica dust. The patient presented pain in his shoulders and hips, moderate skin thickening and sclerosis in his hands and fingers extending proximally to his wrists. The diagnosis of systemic sclerosis was determined according to his clinical and medical history, the positivity of anti-Scl 70 antibodies, the nailfold capillaroscopy suggestive of an active scleroderma pattern and the detection of a mild restrictive pulmonary syndrome. The evaluation of the organbased complications excluded a gastroenterological and cardiovascular involvement, while the chest computed tomography (CT) detected multiple small nodules with a mantle distribution and enlarged lymph nodes with no signs of interstitial lung disease and fibrosis. Additional tests (positron emission tomography-CT, flexible bronchoscopy and broncho-alveolar lavage) excluded infectious diseases and cancer. However, given the pulmonary involvement, we performed a histological examination of the parenchyma and lymph nodes, which revealed a picture of pneumoconiosis. In the end, the occupational history and the findings from the diagnostic procedures led to the diagnosis of pulmonary silicosis. The precise definition of the pulmonary involvement was essential to the therapeutic approach to this patient.

Clinical, Endocrine, and Molecular Genetic Analysis of a Large Cohort of Saudi Arabian Patients with Laron Syndrome.

Science.gov (United States)

Al-Ashwal, Abdullah A; Al-Sagheir, Afaf; Ramzan, Khushnooda; Al-Owain, Mohammed; Allam, Rabab; Qari, Alya; Al-Numair, Nouf S; Imtiaz, Faiqa

2017-01-01

Laron syndrome (LS) is an autosomal recessive disease characterized by marked short stature and very low serum IGF-1 and IGFBP-3 levels. This study assessed the clinical and endocrine features alongside determining the growth hormone receptor gene (GHR) mutation in Saudi Arabian patients with LS in order to establish whether or not a genotype/phenotype correlation is evident in this large cohort. A total of 40 Saudi Arabian patients with a suspected diagnosis of LS were recruited and subjected to a full clinical and endocrine investigation together with direct sequencing of the coding regions of the GHR gene. GHR mutations were identified in 34 patients from 22 separate nuclear families. All 34 molecularly confirmed patients had the typical clinical and endocrinological manifestations of LS. Eleven different mutations (9 previously unreported) were detected in this cohort of patients, all inherited in an autosomal recessive homozygous form. No genotype/phenotype correlation was apparent. The identification of pathogenic mutations causing LS will be of tremendous use for the molecular diagnosis of patients in Saudi Arabia and the region in general, with respect to prevention of this disease in the forms of future carrier testing, prenatal testing, premarital screening and preimplantation genetic diagnosis. © 2017 S. Karger AG, Basel.

Prenatal diagnosis of Carpenter syndrome: looking beyond craniosynostosis and polysyndactyly.

Science.gov (United States)

Victorine, Anna S; Weida, Jennifer; Hines, Karrie A; Robinson, Barrett; Torres-Martinez, Wilfredo; Weaver, David D

2014-03-01

Carpenter syndrome is an autosomal recessive disorder comprising craniosynostosis, polysyndactyly, and brachydactyly. It occurs in approximately 1 birth per million. We present a patient with Carpenter syndrome (confirmed by molecular diagnosis) who has several unique and previously unreported manifestations including a large ovarian cyst and heterotaxy with malrotation of stomach, intestine, and liver. These findings were first noted by prenatal ultrasound and may assist in prenatally diagnosing additional cases of Carpenter syndrome. © 2014 Wiley Periodicals, Inc.

Pericentrin expression in Down's syndrome.

Science.gov (United States)

Salemi, Michele; Barone, Concetta; Romano, Carmelo; Salluzzo, Roberto; Caraci, Filippo; Cantarella, Rita Anna; Salluzzo, Maria Grazia; Drago, Filippo; Romano, Corrado; Bosco, Paolo

2013-11-01

Down's syndrome (DS) is the most frequent genetic cause of intellectual disability and is a chromosomal abnormality of chromosome 21 trisomy. The pericentrin gene (PCNT) has sequenced in 21q22.3 inside of the minimal critical region for Down's syndrome. Alterations of PCNT gene are associated with dwarfism, cardiomyopathy and other pathologies. In this study, we have evaluated the possible differential expression of PCNT mRNA, by qRT-PCR, in peripheral blood leukocytes of DS subjects compared with the normal population. In the present case-control study, PCNT gene expression was increased by 72.72% in 16 out 22 DS samples compared with normal subjects. Our data suggest that changes in the expression levels of PCNT in DS subjects may be involved into the molecular mechanism of Down's syndrome.

Improving patient outcomes in fibrous dysplasia/McCune-Albright syndrome: an international multidisciplinary workshop to inform an international partnership.

Science.gov (United States)

Boyce, A M; Turner, A; Watts, L; Forestier-Zhang, L; Underhill, A; Pinedo-Villanueva, R; Monsell, F; Tessaris, D; Burren, C; Masi, L; Hamdy, N; Brandi, M L; Chapurlat, R; Collins, M T; Javaid, Muhammad Kassim

2017-12-01

To develop consensus on improving the management of patients, we convened an international workshop involving patients, clinicians, and researchers. Key findings included the diagnostic delay and variability in subsequent management with agreement to develop an international natural history study. We now invite other stakeholders to join the partnership. The aim of this study was develop a consensus on how to improve the management of patients with fibrous dysplasia and prioritize areas for research METHODS: An international workshop was held over 3 days involving patients, clinicians, and researchers. Each day had a combination of formal presentations and facilitated discussions that focused on clinical pathways and research. The patient workshop day highlighted the variability of patients' experience in getting a diagnosis, the knowledge of general clinical staff, and understanding long-term outcomes. The research workshop prioritized collaborations that improved understanding of the contemporary natural history of fibrous dysplasia/McCune-Albright syndrome (FD/MAS). The clinical workshop outlined the key issues around diagnostics, assessment of severity, treatment and monitoring of patients. In spite of advances in understanding the genetic and molecular underpinnings of fibrous dysplasia/McCune-Albright syndrome, clinical management remains a challenge. From the workshop, a consensus was reached to create an international, multi-stakeholder partnership to advance research and clinical care in FD/MAS. We invite other stakeholders to join the partnership.

A unique association of Noonan syndrome and 47,XYY syndrome in a male presenting with failure to thrive.

Science.gov (United States)

Bellfield, Edward J; Shad, Zohra

2017-09-01

We describe a 24-month-old male patient who presented to our Genetics-Endocrinology Clinic with a history of failure to thrive, short stature and cryptorchidism. Soon after birth he was diagnosed with 47,XYY syndrome, but due unusual facial features had further diagnostic workup which revealed Noonan syndrome (NS) as well. This report illustrates significant phenotypic-cytogenetic variability within the clinical presentation of NS and 47,XYY syndrome, as well as the need to investigate patients for other genetic defects when phenotype does not correlate with genotype. Furthermore, in this case, the cellular pathways attenuating growth via PTPN11 mutation appear to supersede the SHOX overdosage-an observation that can lead to further research in genetic mechanisms of growth physiology.

Goldenhar syndrome and medulloblastoma: a coincidental association? The first case report.

Science.gov (United States)

Aizenbud, Dror; Shoham, Natasha V; Constantini, Shlomi; Nevo, Neta; Ben Arush, Myriam; Raz, Michal; Rachmiel, Adi; Goldsher, Dorit

2014-07-01

Features of Goldenhar syndrome include several craniofacial anomalies of structures derived from the first and second pharyngeal arches, as well as vertebral, cardiac and renal systems abnormalities. In addition, Goldenhar patients were reported to manifest a variety of central nervous system anomalies and several types of neoplasias. The first case of medulloblastoma in a patient with Goldenhar syndrome is presented here. There is no clear association between these two pathologies. We speculate that aberrant events during the migration of neural crest cells in early stages of development could be the basis of an association between medulloblastoma and Goldenhar syndrome. The case history suggests other possible etiological contributing factors to the development of medulloblastoma, such as patient's history of trauma and/or early childhood exposure to ionizing radiation. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Teaching Molecular Biology with Microcomputers.

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Reiss, Rebecca; Jameson, David

1984-01-01

Describes a series of computer programs that use simulation and gaming techniques to present the basic principles of the central dogma of molecular genetics, mutation, and the genetic code. A history of discoveries in molecular biology is presented and the evolution of these computer assisted instructional programs is described. (MBR)

Lynch Syndrome: Female Genital Tract Cancer Diagnosis and Screening.

Science.gov (United States)

Mills, Anne M; Longacre, Teri A

2016-06-01

Lynch syndrome is responsible for approximately 5% of endometrial cancers and 1% of ovarian cancers. The molecular basis for Lynch syndrome is a heritable functional deficiency in the DNA mismatch repair system, typically due to a germline mutation. This review discusses the rationales and relative merits of current Lynch syndrome screening tests for endometrial and ovarian cancers and provides pathologists with an informed algorithmic approach to Lynch syndrome testing in gynecologic cancers. Pitfalls in test interpretation and strategies to resolve discordant test results are presented. The potential role for next-generation sequencing panels in future screening efforts is discussed. Copyright © 2016 Elsevier Inc. All rights reserved.