WorldWideScience

Sample records for causing griscelli syndrome

  1. Griscelli syndrome

    Directory of Open Access Journals (Sweden)

    Kumar T

    2006-01-01

    Full Text Available Partial albinism with immunodeficiency is a rare and fatal immunologic disorder characterized by pigmentary dilution and variable cellular immunodeficiency. It was initially described in 1978. Primary abnormalities included silvery grayish sheen to the hair, large pigment agglomerations in hair shafts and an abundance of mature melanosomes in melanocytes, with reduced pigmentation of adjacent keratinocytes. We describe a child with Griscelli syndrome who presented with hepatitis, pancytopenia and silvery hair. The diagnosis was confirmed by microscopic skin and hair examination.

  2. Griscelli syndrome type-3

    Directory of Open Access Journals (Sweden)

    Bela J Shah

    2016-01-01

    Full Text Available Griscelli syndrome (GS is a rare autosomal recessive multisystem disorder of pigmentary dilution of skin, silver gray hair, variable immunodeficiency, neurological impairment, and abnormal accumulation of melanosomes in melanocytes. GS type 3 is characterized by hypomelanosis with no immunological and neurological manifestation. Prognosis is very good in type 3 GS and usually require no active intervention, as opposed to type 1 and 2 where early diagnosis and treatment plays a crucial role in patient's survival. The characteristic phenotypic appearance, especially the pigment dilution of the patient's hair, is emphasized here.

  3. Griscelli Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    Seyed Ebrahim MANSOURI NEJAD

    2014-12-01

    Full Text Available How to Cite This Article: Mansouri Nejad SE, Yazdan panah MJ, Tayyebi Meibodi N, Ashrafzadeh F, Akhondian J, BeiraghiToosi M, Eslamieh H. Griscelli Syndrome: A Case Report. Iran J Child Neurol. 2014 Autumn;8(4: 72-75.ObjectiveGriscelli syndrome (GS is a rare autosomal recessive immune deficiency disorder that presents with pigmentary dilution of the skin and hair, recurrent skin and pulmonary infections, neurologic problems, hypogammaglobulinemia, and variable cellular immunodeficiency. Three mutations have been described in different phenotypes of the disease. In most of cases, GS leads to death in the first decade of life. In this article, we report a one-year-old child with type 2 GS who suffers from pigmentation disorder and hypogammaglobulinemia.ReferencesKharkar V, Pande S, Mahajan S, Dwiwedi R, Khopkar U. Griscelli syndrome: a new phenotype with circumscribed pigment loss? Dermatol Online J 2007 1;13(2:17.Sheela SR, Latha M, Susy JI. Griscelli syndrome: Rab 27a mutation. Indian Pediatrics 2004; 41:944-947.González Carretero P, Noguera Julian A, Ricart Campos S, Fortuny Guasch C, Martorell Sampol L. Griscelli-Prunieras syndrome: report of two cases. An Pediatr (Barc 2009 ; 70(2:164-7.Szczawinska-Poplonyk A, Kycler Z, Breborowicz A, Klaudel-Dreszler M, Pac M, Zegadlo-Mylik M, et al. Pulmonary lymphomatoid granulomatosis in Griscelli syndrome type 2. Viral Immunol 2011 Dec;24(6:471-3.Durmaz A, Ozkinay F, Onay H, Tombuloglu M, Atay A, Gursel O, et al. Molecular analysis and clinical findings of Griscelli syndrome patients. J Pediatr Hematol Oncol 2012 Oct;34(7:541-4.Reddy RR, Babu BM, Venkateshwaramma B, Hymavathi Ch. Silvery hair syndrome in two cousins: Chediak-Higashi syndrome vs Griscelli syndrome, with rare associations. Int J Trichology 2011; 3(2:107-11.Sahana M, Sacchidanand S, Hiremagalore R, Asha G. Silvery grey hair: clue to diagnose immunodeficiency. Int J Trichology 2012;4(2:83-5.Mahalingashetti PB, Krishnappa MH, Kalyan PS

  4. GRISCELLI SYNDROME; A CASE REPORT AND REVIEW OF THE LITERATURE

    Directory of Open Access Journals (Sweden)

    B.Sh. Shamsian MD

    2009-01-01

    Full Text Available Abstract:Griscelli syndrome (GS is a rare disease first described in 1978. It is inherited in autosomal recessive pattern. This disease is characterized by partial albinism, pigmentation dilution, cellular immunodeficiency, neurological involvement & uncontrolled phases of macrophage & lymphocyte activation.We report a 5 months Old Iranian girl presenting with silver-gray hair,eyelashes and eyebrows, hepatosplenomegaly, pancytopenia, hemophagocytosis and progressive neurologic deterioration. Griscelli syndrome can be suggested according to her symptoms. The chemotherapy was not effective for her and she died due to multi organ failure.Key words:Griscelli syndrome, Hemophagocytosis, Albinism.

  5. Oral and dental findings of griscelli syndrome type 3

    Directory of Open Access Journals (Sweden)

    Ozlem Marti Akgun

    2015-09-01

    Full Text Available Griscelli syndrome (GS is a rare autosomal recessive genetic disorder characterized by variable immunodeficiency, partial albinism, abnormal accumulation of melanosomes in melanocytes, pigmentary dilution of the skin, and shiny silver-gray hair. GS has three types, with the first and second types caused by mutations in two genes being located at band 15q21: RAB27A and MYO5A. The expression of the third form of GS is restricted to the characteristic hypopigmentation of GS, and results from mutation in the gene that encodes melanophilin MLPH. It has also been shown that an identical phenotype can result from the deletion of the MYO5A F-exon. The aim of this case report is the presentation of oral and dental features and SEM images of the hair of a 12-year-old girl with GS type 3. [Arch Clin Exp Surg 2015; 4(3.000: 164-167

  6. Griscelli syndrome type 2: A rare and fatal syndrome in a South Indian boy

    Directory of Open Access Journals (Sweden)

    R Rajyalakshmi

    2016-01-01

    Full Text Available Griscelli syndrome (GS is a rare autosomal recessive disorder caused by mutation in the MYO5A (GS1, RAB27A (GS2, and MLPH (GS3 genes, characterized by a common feature, partial albinism. The common variant of three, GS type 2, in addition, shows primary immunodeficiency which leads to recurrent infections and hemophagocytic lymphohistiocytosis. We, herewith, describe a case of GS type 2, in a 4-year-old male child who presented with chronic and recurrent fever, lymphadenopathy, hepatosplenomegaly, and secondary neurological deterioration; highlighting the cytological and histopathological features of lymph nodes. Hair shaft examination of the child confirmed the diagnosis.

  7. Griscelli Syndrome Type 2; A Pediatric Case with Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Parviz Tabatabaie

    2007-09-01

    Full Text Available A 3.5 month-old girl was admitted with silvery gray hair, light  colored skin, recurrent diarrhea, chest infections, hepatosplenomegaly, episodes of pancytopenia, and hemophagocytosis in the bone marrow. Light microscopy of hair showed characteristic large and irregular clumps of melanin in the middle of hair shaft. Peripheral blood smear examination did not show giant granules in granulocytes. On the basis of these clinical and laboratory findings, Griscelli syndrome was diagnosed. The child succumbed to infection during an accelerated phase of the disease.

  8. GRISCELLI SYNDROME; A CASE REPORT AND REVIEW OF THE LITERATURE

    Directory of Open Access Journals (Sweden)

    B.Sh. Shamsian

    2007-02-01

    Full Text Available Griscelli syndrome (GS is a rare disease first described in 1978. It isinherited in autosomal recessive pattern. This disease is characterizedby partial albinism, pigmentation dilution, cellular immunodeficiency,neurological involvement & uncontrolled phases of macrophage &lymphocyte activation.We report a 5 months Old Iranian girl presenting with silver-gray hair,eyelashes and eyebrows, hepatosplenomegaly, pancytopenia,hemophagocytosis and progressive neurologic deterioration. Griscellisyndrome can be suggested according to her symptoms. Thechemotherapy was not effective for her and she died due to multiorgan failure.

  9. Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Born, Alfred Peter; Müller, Klaus; Marquart, Hanne Vibeke;

    2010-01-01

    Griscelli syndrome is an autosomal recessive disorder characterized by pigmentary dilution and is occasionally associated with a hemophagocytic syndrome (type 2). We present a 13-year-old girl with Griscelli syndrome type 2, who developed a hemophagocytic syndrome along with marked muscle weakness...... and elevated plasma creatine kinase. Muscle biopsy showed massive inflammatory changes in some fascicles, while other fascicles were relatively spared. Clinical symptoms and biopsy changes resolved after immunosuppression and allogeneic hematopoietic cell transplantation. Our results suggest that muscle...

  10. Griscelli syndrome: A case report of Reye′s syndrome and atopic dermatitis history

    Directory of Open Access Journals (Sweden)

    Kirzioglu Z

    2008-12-01

    Full Text Available Griscelli syndrome (GS is a rare autosomal recessive disorder that results in pigmentary dilution of the skin and the hair (silver hair, with the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes. Sixty cases of GS have been reported in the literature, but we could find no description of its oro-dental symptoms. Reye′s syndrome (RS is characterized by acute noninflammatory encephalopathy and renal and hepatic failure, while atopic dermatitis (AD is a skin disorder with an immunologic basis. The aim of this paper is to describe the oro-dental and physical findings in a girl who had been diagnosed with GS at 3.5 years of age; she also had AD as well as a history of RS at infancy. We discuss the possible relationship between the three syndromes.

  11. Treatment of the X-linked lymphoproliferative, Griscelli and Chédiak-Higashi syndromes by HLH directed therapy

    DEFF Research Database (Denmark)

    Trottestam, Helena; Beutel, Karin; Meeths, Marie;

    2009-01-01

    be used for these syndromes. PROCEDURE: In the HLH-94/HLH-2004 treatment study registries, we evaluated all patients with GS2 (n = 5), XLP (n = 2) or CHS (n = 2) treated between 1994 and 2004. RESULTS: All patients responded to the therapy, and all are alive but one (suffering from CHS), with a mean...... follow-up of 5.6 years. All GS2, one XLP and one CHS patient underwent hematopoietic stem cell transplant. Mean follow-up post transplant was 6.0 years. Six of the seven transplanted children achieved non-active disease status at the time for SCT. Neurological sequelae were reported in all, except...

  12. Polarized light microscopy of hair shafts aids in the differential diagnosis of Chédiak-Higashi and Griscelli-Prunieras syndromes Contribuição do estudo dos cabelos com microscopia de luz polarizada ao diagnóstico diferencial das síndromes de Chédiak-Higashi and Grisceli-Prunieras

    Directory of Open Access Journals (Sweden)

    Neusa Y.S. Valente

    2006-08-01

    Full Text Available PURPOSE: To study and compare the appearance of hairs from patients with Chédiak-Higashi and Griscelli-Prunieras syndromes under light and polarized light microscopy. METHOD: Hairs from 2 Chédiak-Higashi and 2 Griscelli-Prunieras patients were obtained and examined under normal and polarized light microscopy. RESULTS: Under light microscopy, hairs from Chédiak-Higashi patients presented evenly distributed, regular melanin granules, larger than those seen in normal hairs. Under polarized light microscopy, shafts exhibited a bright and polychromatic refringence appearance. In contrast, hair from Griscelli-Prunieras patients, under light microscopy, exhibited bigger and irregular melanin granules, distributed mainly near the medulla. Under polarized light microscopy, shafts appeared monotonously white. CONCLUSION: Light microscopic examination of hair shafts of patients with Chédiak-Higashi or Griscelli-Prunieras syndrome reveals subtle differences that are useful in identifying both disorders, but not in distinguishing between them. We provide evidence that polarized light microscopy of hair shafts, an approach that has not been previously described, aids in differentiating between these syndromes. We propose hair study by polarized light microscopy as a helpful complementary diagnostic method for differential diagnosis between CHS and GPS, especially when the more sophisticated molecular studies are not available.OBJETIVO: Estudar e comparar o aspecto dos cabelos de portadores das síndromes de Chédiak-Higashi e Griscelli-Prunieras, tanto na microscopia óptica convencional quanto com luz polarizada. MÉTODO: Cabelos de dois doentes portadores da síndrome de Chédiak-Higashi e de dois portadores da síndrome de Griscelli-Prunieras foram obtidos e estudados tanto à microscopia convencional quanto com luz polarizada. RESULTADOS: Na microscopia óptica convencional, os cabelos dos doentes portadores da síndrome de Chédiak-Higashi mostraram

  13. What Causes Down Syndrome?

    Science.gov (United States)

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

  14. Genetics Home Reference: Griscelli syndrome

    Science.gov (United States)

    ... genes are found in pigment-producing cells called melanocytes . Within these cells, the proteins work together to ... pigmentation). Melanosomes are formed near the center of melanocytes, but they must be transported to the outer ...

  15. A novel missense mutation (G43S) in the switch I region of Rab27A causing Griscelli syndrome

    DEFF Research Database (Denmark)

    Westbroek, W.; Tuchman, M.; Tinloy, B.

    2008-01-01

    steps within cells. In melanocytes, the GTP-bound form of Rab27A associates with the membranes of mature fully-pigmented melanosomes through its geranylgeranyl group. Once attached, Rab27A recruits the downstream effector Melanophilin (Mlph) and the actin-dependent motor protein Myosin Va (Myo...... GSII patient. Laser scanning confocal microscopy showed that the G43S mutation, which is located in the highly conserved switch I region of Rab27A, induces perinuclear localization of melanosomes in normal melanocytes, and fails to restore melanosomes to the actin-rich periphery in GSII melanocytes. Co...

  16. Radiation nephritis causing nephrotic syndrome

    Energy Technology Data Exchange (ETDEWEB)

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

    1983-12-01

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

  17. Mutations in ANTXR1 Cause GAPO Syndrome

    NARCIS (Netherlands)

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

    2013-01-01

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

  18. Chronic Fatigue Syndrome (CFS): Causes

    Science.gov (United States)

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

  19. A rare cause of Cushing's syndrome

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2010-12-01

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

  1. Superior mesenteric artery syndrome causing growth retardation

    Directory of Open Access Journals (Sweden)

    Halil İbrahim Taşcı

    2013-03-01

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

  2. A Solitary Plasmocytoma Case Causing Horner Syndrome

    Directory of Open Access Journals (Sweden)

    Mustafa Vayvada

    2014-08-01

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

  3. Piriformis syndrome: a cause of nondiscogenic sciatica.

    Science.gov (United States)

    Cass, Shane P

    2015-01-01

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

  4. Ischemic syndromes causing dizziness and vertigo.

    Science.gov (United States)

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

    2016-01-01

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

  5. Mutations in ZBTB20 cause Primrose syndrome.

    Science.gov (United States)

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

    2014-08-01

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

  6. Goldenhar syndrome: a cause of secondary immunodeficiency?

    Directory of Open Access Journals (Sweden)

    De Golovine Serge

    2012-07-01

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

  7. Biliary stone causing afferent loop syndrome and pancreatitis

    Institute of Scientific and Technical Information of China (English)

    André Roncon Dias; Roberto Iglesias Lopes

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mustafa Volkan Demir

    2015-01-01

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

  9. Contact urticaria syndrome caused by haptens

    OpenAIRE

    Gomułka, Krzysztof; Panaszek, Bernard

    2014-01-01

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

  10. 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.

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

    OpenAIRE

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

    2015-01-01

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

  12. Infectious causes of sudden infant death syndrome.

    Science.gov (United States)

    Alfelali, Mohammad; Khandaker, Gulam

    2014-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-12-01

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

  14. Tourette Syndrome (TS): Risk Factors and Causes

    Science.gov (United States)

    ... having TS. The causes of TS and other tic disorders are not well understood. Although the risk ... whether certain children are more likely to develop tics following a group A ß-hemolytic streptococcal (“strep”) ...

  15. A nonsense mutation in FMR1 causing fragile X syndrome

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mariana Heid Rocha Hemerly

    2014-06-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2013-04-04

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

  19. A Rare Cause of Macroscobic Hematuria: Nutcracker Syndrome

    Directory of Open Access Journals (Sweden)

    Nilgün Selçuk Duru

    2015-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Adam W Amundson

    2013-01-01

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

  1. Methylene Blue Causing Serotonin Syndrome Following Cystocele Repair.

    Science.gov (United States)

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

    2016-11-01

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

  2. Methylene Blue Causing Serotonin Syndrome Following Cystocele Repair

    Directory of Open Access Journals (Sweden)

    Kailash Kapadia

    2016-11-01

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

  3. Infraclavicular subpectoral lipoma causing thoracic outlet syndrome

    Directory of Open Access Journals (Sweden)

    Stefano Elia

    2015-01-01

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

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

    Science.gov (United States)

    Imai, Shinji; Kodama, Narihito; Matsusue, Yoshitaka

    2008-01-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

  6. A Rare Cause of Secondary Hypertension: Conn Syndrom

    Directory of Open Access Journals (Sweden)

    Samet Sayilan

    2016-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  8. Unilateral facial paralysis caused by Ramsay Hunt syndrome.

    Science.gov (United States)

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

    2011-09-01

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

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

    Science.gov (United States)

    Kauh, Courtney Y; Bursztyn, Lulu L C D

    2015-09-01

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

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

    Science.gov (United States)

    Lewis, D A; Settas, L

    1983-08-01

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

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

    OpenAIRE

    Lewis, D A; Settas, L

    1983-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jaykar R. Panchmatia

    2012-01-01

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

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

    LENUS (Irish Health Repository)

    Hannon, M J

    2010-06-01

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

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

    Science.gov (United States)

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

    2006-04-28

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

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

    Directory of Open Access Journals (Sweden)

    Alparslan Bayram Carli

    2015-08-01

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

  16. Prevalence and causes of back pain syndromes in children

    Directory of Open Access Journals (Sweden)

    A.A. Smirnova

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Narayanathu Chellappantilla Sreekumar

    2014-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Emanuele Cigna

    2010-01-01

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

  19. Intronic splicing mutations in PTCH1 cause Gorlin syndrome.

    Science.gov (United States)

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

    2014-09-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Fukuoka, Toshiki; Tsurumi, Yuko; Tsurumi, Arihito

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Toshiki Fukuoka

    2017-01-01

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

  3. Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Born, Alfred Peter; Müller, Klaus; Marquart, Hanne Vibeke;

    2010-01-01

    and elevated plasma creatine kinase. Muscle biopsy showed massive inflammatory changes in some fascicles, while other fascicles were relatively spared. Clinical symptoms and biopsy changes resolved after immunosuppression and allogeneic hematopoietic cell transplantation. Our results suggest that muscle...

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

    Science.gov (United States)

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

    2008-10-01

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

  5. Proteus syndrome: A rare cause of gigantic limb

    Directory of Open Access Journals (Sweden)

    Nandini Chakrabarti

    2014-01-01

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

  6. Unusual cause of childhood anemia: Imerslund grasbeck syndrome

    Directory of Open Access Journals (Sweden)

    Kishan Prasad Hosapatna Laxminarayana

    2011-01-01

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

  7. Subacromial Impingement Syndrome Caused by a Voluminous Subdeltoid Lipoma

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Murray

    2014-01-01

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

  8. CtIP Mutations Cause Seckel and Jawad Syndromes.

    Directory of Open Access Journals (Sweden)

    Per Qvist

    2011-10-01

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

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

    Science.gov (United States)

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

    2015-07-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Abhijit Swami

    2011-01-01

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

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

    Science.gov (United States)

    Swami, Abhijit; Kar, Giridhari

    2011-01-01

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

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

    Science.gov (United States)

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

    2005-11-01

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

  14. Disruption of PTPRO Causes Childhood-Onset Nephrotic Syndrome

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2010-12-01

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

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

    OpenAIRE

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

    2016-01-01

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

  17. Homozygous Nonsense Mutations in TWIST2 Cause Setleis Syndrome

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    1982-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Erdal Bodakçi

    2015-06-01

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

  1. A rare cause of tall stature: Sotos syndrome

    Directory of Open Access Journals (Sweden)

    Nagehan Aslan

    2014-12-01

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

  2. An Aggressive Sphenoid Wing Meningioma Causing Foster Kennedy Syndrome

    Directory of Open Access Journals (Sweden)

    Harpreet S. Walia

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Finsterer J

    2014-01-01

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

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

    Science.gov (United States)

    GIGANTE, ANTONIO; BOTTEGONI, CARLO; BARBADORO, PAMELA

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Sahu

    2015-01-01

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

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

    Science.gov (United States)

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

    2002-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Dr. Vipul D Yagnik

    2010-07-01

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

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

    Science.gov (United States)

    Shankland, Wesley E

    2010-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2013-05-14

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

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

    Science.gov (United States)

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

    2014-02-24

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

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

    Directory of Open Access Journals (Sweden)

    Dörr Harald

    2011-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Mazhar Müslüm Tuna

    2014-09-01

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

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

    Science.gov (United States)

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

    1997-11-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Musso CG

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Massimo Politi

    2009-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2013-02-01

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

  1. Prevalence and causes of back pain syndromes in children

    OpenAIRE

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  3. KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  5. Staphylococcal Toxic Shock Syndrome Caused by Tampon Use

    Directory of Open Access Journals (Sweden)

    Cian McDermott

    2015-01-01

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2008-02-01

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

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

    Science.gov (United States)

    Ganesh, R; Janakiraman, L; Sathiyasekaran, M

    2008-06-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2012-04-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tarush Rustagi

    2011-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2002-05-01

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

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

    OpenAIRE

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-03-15

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

  17. Piriformis syndrome surgery causing severe sciatic nerve injury.

    Science.gov (United States)

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

    2012-09-01

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

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

    OpenAIRE

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-12-15

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

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

    Directory of Open Access Journals (Sweden)

    Seyitali Gumustas

    2014-04-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mishra Biswaranjan

    2007-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Ahmed Imran Siddiqi

    2011-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Biswadev Basu

    2013-11-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2004-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nonneman Dan J

    2012-06-01

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

  10. Syndromic albinism: a review of genetics and phenotypes.

    Science.gov (United States)

    Scheinfeld, Noah S

    2003-12-01

    There are several syndromes of albinism associated with systemic pathology. These include Chediak-Higashi Syndrome (CHS), Hermansky-Pudlack Syndrome (HPS), Griscelli Syndrome (GS), Elejalde Syndrome (ES) and Cross-McKusick-Breen Syndrome (CMBS). In the last several years the genetic defects underlying some of these syndromes have been described. HPS is related to 7 genes in humans. GS is related to 3 genes: MYOVA, Rab-27A, and melanophilin (Mlph). CHS is related to one gene: LYST. The genetic defects in ES and CMBS are yet to be defined. Syndromic forms of albinism are associated with defects in the packaging of melanin and other cellular proteins. As such they are distinct from oculocutaneous albinism, which is associated with defects in the production of melanin (e.g., TRP1, P gene, and tyrosinase).

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

    Directory of Open Access Journals (Sweden)

    Rooplekha

    2014-10-01

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

  12. Fetal alcohol syndromecauses, diagnostic criteria and prevalence

    Directory of Open Access Journals (Sweden)

    Agata Horecka-Lewitowicz

    2014-04-01

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

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

    Science.gov (United States)

    Arooj, Shumaila; Azeemuddin, Muhammad

    2014-08-01

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

  14. Lynch Syndrome Caused by Germline PMS2 Mutations

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Gonca Meriç

    2011-11-01

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

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

    Science.gov (United States)

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

    2011-09-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jay Ching Chieh Wang, MD

    2014-06-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Lucio Montebugnoli

    2010-01-01

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

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

    OpenAIRE

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

    2006-01-01

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

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

    OpenAIRE

    2013-01-01

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

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

    Science.gov (United States)

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

    2010-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Sukanta

    2014-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-01-15

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

  8. Empty Follicle Syndrome: The Possible Cause of Occurrence

    Directory of Open Access Journals (Sweden)

    Tahereh Madani

    2015-11-01

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

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

    NARCIS (Netherlands)

    Vrieze, A; Postma, DS; Kerstjens, HAM

    2003-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nadeem Ul Nazeer Kawoosa

    2011-01-01

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

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

    Science.gov (United States)

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

    2003-02-01

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

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

    Science.gov (United States)

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

    2013-04-01

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

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

    Institute of Scientific and Technical Information of China (English)

    潘远根

    2016-01-01

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

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

    Science.gov (United States)

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

    1999-01-01

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

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

    Science.gov (United States)

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

    1987-12-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2011-05-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2011-08-01

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    R. de la Fuente Cañibano

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

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

    NARCIS (Netherlands)

    Jaarsma, AS; Muis, N; DeGraaf, SSN

    1996-01-01

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

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

    OpenAIRE

    R. de la Fuente Cañibano; A. Muñoz Herrera

    2010-01-01

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

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-08-15

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

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

    Directory of Open Access Journals (Sweden)

    Valentín Roales-Gómez

    2014-08-01

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

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

    Science.gov (United States)

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

    1999-02-01

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

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

    Science.gov (United States)

    Sachdeva, Silonie; Sachdeva, Shabina; Kapoor, Pranav

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Silonie Sachdeva

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    A. Bruce Janati

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-01-15

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Sveinsson, Olafur; Kostulas, Nikolaos; Herrman, Lars

    2013-06-11

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

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

    Science.gov (United States)

    Singla, Manish; Perry, Alexandra; Lavery, Eric

    2012-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Yongxing Zhou

    2015-01-01

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

  20. Dumping Syndrome

    Science.gov (United States)

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

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

    Science.gov (United States)

    Heneghan, M A; Pavlov, H

    1984-01-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

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

    Science.gov (United States)

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

    2013-06-01

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

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

    Science.gov (United States)

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

    2014-10-01

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

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

    OpenAIRE

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

    1998-01-01

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

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

    Science.gov (United States)

    Wu, Carolyn M Yu; Noska, Amanda

    2016-03-10

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

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

    LENUS (Irish Health Repository)

    O'Connell, David

    2012-04-01

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

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

    Science.gov (United States)

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

    2012-06-01

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

  9. PIK3R1 Mutations Cause Syndromic Insulin Resistance with Lipoatrophy

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Jayesh Modi

    2015-01-01

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

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

    Science.gov (United States)

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

    2009-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Jovanović Svetlana

    2013-01-01

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

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

    Science.gov (United States)

    Brosnahan, Amanda J; Schlievert, Patrick M

    2011-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Takashi Yuri

    2014-05-01

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

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

    Science.gov (United States)

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

    2015-03-05

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

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

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

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Parag Chevli

    2014-09-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Science.gov (United States)

    Khalifa, M M; Struthers, J L

    2002-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-05-01

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

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

    Science.gov (United States)

    Sheth, Khushboo; Snyder, Aaron; Wu, Ulysses; Lahiri, Bimalin; Grover, Prashant

    2016-01-01

    We present the case ofa26-year-old female who presented to the hospital with pneumococcal meningitis. A review of her records showed atrophic spleen, and a hypercoagulable workup was positive for Systemic Lupus Erythematous (SLE)/Antiphospholipid Antibody Syndrome (APS). An autosplenectomy from thrombotic occlusion of the splenic artery made her susceptible to pneumococcal meningitis. Autoimmune conditions, particularly SLE and APS, are important causes of hypercoagulable states in a young population, and earlier detection of these conditions and appropriate treatment helps to decrease morbidity and mortality among these patients.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

  8. GBA2 Mutations Cause a Marinesco-Sjögren-Like Syndrome: Genetic and Biochemical Studies

    Science.gov (United States)

    Haugarvoll, Kristoffer; Johansson, Stefan; Rodriguez, Carlos E.; Boman, Helge; Haukanes, Bjørn Ivar; Bruland, Ove; Roque, Francisco; Jonassen, Inge; Blomqvist, Maria; Telstad, Wenche; Månsson, Jan-Eric

    2017-01-01

    Background With the advent new sequencing technologies, we now have the tools to understand the phenotypic diversity and the common occurrence of phenocopies. We used these techniques to investigate two Norwegian families with an autosomal recessive cerebellar ataxia with cataracts and mental retardation. Methods and Results Single nucleotide polymorphism (SNP) chip analysis followed by Exome sequencing identified a 2 bp homozygous deletion in GBA2 in both families, c.1528_1529del [p.Met510Valfs*17]. Furthermore, we report the biochemical characterization of GBA2 in these patients. Our studies show that a reduced activity of GBA2 is sufficient to elevate the levels of glucosylceramide to similar levels as seen in Gaucher disease. Furthermore, leucocytes seem to be the proper enzyme source for in vitro analysis of GBA2 activity. Conclusions We report GBA2 mutations causing a Marinesco-Sjögren-like syndrome in two Norwegian families. One of the families was originally diagnosed with Marinesco-Sjögren syndrome based on an autosomal recessive cerebellar ataxia with cataracts and mental retardation. Our findings highlight the phenotypic variability associated with GBA2 mutations, and suggest that patients with Marinesco-Sjögren-like syndromes should be tested for mutations in this gene. PMID:28052128

  9. Poland's syndrome and head-and-neck tumour: an unusual association causing a reconstruction dilemma.

    Science.gov (United States)

    Gerlinger, Imre; Járai, Tamás; Lujber, László; Pytel, József

    2007-05-01

    Poland's syndrome is a rare congenital anomaly characterized by unilateral chest wall hypoplasia and ipsilateral hand abnormalities. The literature data suggest its sporadic nature. The prevailing theory concerning its cause is hypoplasia of the subclavian artery or its branches, which may lead to a range of developmental changes. Relationships have been demonstrated between tumours and Poland's syndrome and also between tumours and other developmental defects. The explanation may lie in abnormal homeobox and tumour suppressor genes. This paper presents the first literature report of a malignant tonsillo-lingual tumour with metastatic neck involvement in a patient with partial Poland's sequence. In consequence of the aplasia of the pectoralis major muscle, an alternative (a free radical forearm flap) to the routine head-and-neck reconstruction (pedicled pectoralis major flap) was necessitated following tumour excision and radical neck dissection. This case report surveys the diagnostic and therapeutic considerations when previously unnoticed Poland's syndrome is diagnosed in a patient with head-and-neck cancer. One year following major head-and-neck surgery, our patient is tumour-free.

  10. Rules for distinguishing toxicants that cause type I and type II narcosis syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Veith, G.D.; Broderius, S.J. (Environmental Protection Agency, Environmental Research Laboratory-Duluth, MN (USA))

    1990-07-01

    Narcosis is a nonspecific reversible state of arrested activity of protoplasmic structures caused by a wide variety of organic chemicals. The vast majority of industrial organic chemicals can be characterized by a baseline structure-toxicity relationship as developed for diverse aquatic organisms, using only the n-octanol/water partition coefficient as a descriptor. There are, however, many apparent narcotic chemicals that are more toxic than baseline narcosis predicts. Some of these chemicals have been distinguished as polar narcotics. Joint toxic theory and isobole diagrams were used to show that chemicals strictly additive with phenol were generally more toxic than predicted by narcosis I models and characterized by a different mode of action called narcosis II syndrome. This type of toxicity is exemplified by certain amides, amines, phenols, and nitrogen heterocycles. Evidence is provided that suggests that narcosis II syndrome may result from the presence of a strong hydrogen bonding group on the molecule, and narcosis I syndrome results from hydrophobic bonding of the chemical to enzymes and/or membranes. This shift in toxic action is apparently indistinguishable for narcotic chemicals with log P greater than about 2.7. General rules for selecting the appropriate models are proposed.

  11. [Stevens-Johnson syndrome plus intrahepatic cholestasis caused by clindamycin or chlorpheniramine].

    Science.gov (United States)

    Sahagún Flores, J E; Soto Ortiz, J A; Tovar Méndez, C E; Cárdenas Ochoa, E C; Hernández Flores, G

    2009-05-15

    A 48-year-old woman was hospitalized with the diagnosis of hepatitis. She presented with symptoms of jaundice, headache, elevated bilirubin, and elevated hepatic enzymes. She related a recent episode of a bronchial infection that was treated during the previous eight days with paracetamol (500mg, 2 doses only), chlorpheniramine, betamethasone and clindamycin. After an initial clinical and laboratorial improvement, she began to complain of pruritus of the palms and soles. Thereafter, vesicles evolving to blisters developed and a deterioration of her general health ensued. Serologies for hepatitis A, B, and C viruses were negative. Intrahepatic cholestasis and Stevens Johnson Syndrome (SJS) were the final diagnosis. The association of the Stevens Johnson Syndrome and intrahepatic cholestasis simultaneously, related to adverse drug reactions, is very rare. The drugs reportedly involved are mainly antibiotics, such as ampicillin, vancomycin, amoxicillin/clavulinic acid and erythromycin. Other drugs involved are non-steroidal anti-inflamatory drugs, such as mefenamic acid, ibuprofen, and sulindac. The reactions can be minor or severe and can even cause death, an outcome that has been reported in patients of all races and ethnic groups, but appears to be more rare in patients of Latin origin. We present a discussion of this case and review the main characteristics of the Stevens Johnson Syndrome.

  12. Clinical study of lateral patellofemoral crush syndrome caused by military training

    Directory of Open Access Journals (Sweden)

    De-hui ZHANG

    2012-05-01

    Full Text Available Objective  To explore diagnostic method and surgical outcome of lateral patellofemoral crush syndrome caused by military training. Methods  Fifteen patients with lateral patellofemoral crush syndrome caused by military training from May 2006 to May 2008 were enrolled in this study, including 12 men (14 knees and 3 women (3 knees, aged from 22 to 43 years old with an average of 27.3 years. Randomly selected 18 healthy volunteers with similar age and gender but no knee pain symptom were selected to serve as a control group. Anteroposterior and lateral X-ray photographs of knee joint and axial photographs of the patella were taken in both groups for observing the bone architecture of the knee joint and measuring the femoral trochlear angle, patellofemoral congruence angle and patellofemoral index, and the data were compared. The 17 knee joints in patient group were treated with lateral patellar retinaculum release. Then the preoperative and postoperative pain severity was evaluated with visual analogue scale (VAS. Results  Patellofemoral congruence angle was 7.67°± 5.81° and patellofemoral index was 2.49±1.40 in patient group, while they were -2.2°±-2.71° and 1.25±0.15 in control group. The difference between two groups showed statistical significance (P < 0.05. The change in bone architecture was obvious in patient group. The preoperative pain score was 7.06±0.85, and postoperative pain score was 3.87±0.24 after 6 months and 3.01+0.17 after 1 year in patient group. The difference between preoperative pain score and postoperative pain score showed statistical significance (P < 0.05. Conclusions  Diagnosis of patellofemoral crush syndrome caused by military training requires a combination of case history, typical symptoms, objective sign and X-ray examination. Among these, X-ray examination is the fundamental auxiliary diagnostic tool for lateral patellofemoral crush syndrome, and the patellofemoral index is convenient for

  13. Progress of integrative Chinese and Western medicine in treating polycystic ovarian syndrome caused infertility.

    Science.gov (United States)

    Song, Juan-juan; Yan, Miao-e; Wu, Xiao-ke; Hou, Li-hui

    2006-12-01

    Polycystic ovarian syndrome (PCOS) is one of the most popular diseases that cause menstrual dysfunction and infertility in women. The present paper is a brief retrospection on the progress in treatment of PCOS caused infertility with integrative Chinese and Western medicine (ICWM). It can be seen from these materials that using traditional Chinese medicine (TCM) recipes formulated by Shen-replenishing herbs or acupuncture to reinforce Gan-Shen, regulate Chong-Ren Channels in treating PCOS, stable clinical efficacy could be obtained, with less adverse reaction, though the effect initiated somewhat late. Whereas, when Shen-replenishing recipe and acupuncture are combined with hormone or ovulation promoting drugs of Western medicine, the above-mentioned shortcomings would be overcome. So, this combined therapy is frequently used in clinical practice.

  14. Histidine decarboxylase deficiency causes Tourette syndrome: parallel findings in humans and mice

    Science.gov (United States)

    Baldan, Lissandra Castellan; Rapanelli, Maximiliano; Crowley, Michael; Anderson, George M.; Loring, Erin; Gorczyca, Roxanne; Billingslea, Eileen; Wasylink, Suzanne; Panza, Kaitlyn E.; Ercan-Sencicek, A. Gulhan; Krusong, Kuakarun; Leventhal, Bennett L.; Ohtsu, Hiroshi; Bloch, Michael H.; Hughes, Zoë A.; Krystal, John H.; Mayes, Linda; de Araujo, Ivan; Ding, Yu-Shin; State, Matthew W.; Pittenger, Christopher

    2013-01-01

    Tourette syndrome (TS) is characterized by tics, sensorimotor gating deficiencies, and abnormalities of cortico-basal ganglia circuits. A mutation in histidine decarboxylase (Hdc), the key enzyme for the biosynthesis of histamine (HA), has been implicated as a rare genetic cause. Hdc knockout mice exhibited potentiated tic-like stereotypies, recapitulating core phenomenology of TS; these were mitigated by the dopamine D2 antagonist haloperidol, a proven pharmacotherapy, and by HA infusion into the brain. Prepulse inhibition was impaired in both mice and humans carrying Hdc mutations. HA infusion reduced striatal dopamine (DA) levels; in Hdc knockout mice, striatal DA was increased and the DA-regulated immediate early gene Fos was upregulated. Dopamine D2/D3 receptor binding was altered both in mice and in humans carrying the Hdc mutation. These data confirm HDC deficiency as a rare cause of TS and identify histamine-dopamine interactions in the basal ganglia as an important locus of pathology. PMID:24411733

  15. A New Potential Cause in the Development of Toxic Anterior Segment Syndrome: Fibrin Glue

    Directory of Open Access Journals (Sweden)

    Selçuk Sızmaz

    2014-08-01

    Full Text Available Objectives: To present a potential cause for toxic anterior segment syndrome (TASS. Materials and Methods: We report 4 cases of TASS that occurred following uneventful phacoemulsification and intraocular lens implantation. Results: The 4 cases were the first consecutive 2 cases of 2 different surgery days, 5 months apart. The most prominent sign of TASS was limbus-to-limbus corneal edema. Pain and/or intraocular pressure rise were also common. All surgical and presurgical procedures were checked after the first outbreak, whereas the second outbreak required further investigation. Fibrin glue remnants from preceding pterygium surgery with conjunctival autografting were found to be the potential cause. Despite intensive corticosteroid therapy, corneal edema did not resolve in 2 patients who underwent keratoplasty. Conclusion: TASS is a sight-threatening condition which requires thorough investigation for prevention of new cases. All steps must be carefully revised. (Turk J Ophthalmol 2014; 44: 280-3

  16. Progress of Integrative Chinese and Western Medicine in Treating Polycystic Ovarian Syndrome Caused Infertility

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Polycystic ovarian syndrome (PCOS) is one of the most popular diseases that cause menstrual dysfunction and infertility in women. The present paper is a brief retrospection on the progress in treatment of PCOS caused infertility with integrative Chinese and Western medicine (ICWM). It can be seen from these materials that using traditional Chinese medicine (TCM) recipes formulated by Sheh-replenishing herbs or acupuncture to reinforce Gan-Shen, regulate Chong-Ren Channels in treating PCOS, stable clinical efficacy could be obtained, with less adverse reaction, though the effect initiated somewhat late. Whereas, when Shen-replenishing recipe and acupuncture are combined with hormone or ovulation promoting drugs of Western medicine, the above-mentioned shortcomings would be overcome. So, this combined therapy is frequently used in clinical practice.

  17. A Case of Idiopathic Hypereosinophilic Syndrome Causing Mitral Valve Papillary Muscle Rupture

    Directory of Open Access Journals (Sweden)

    Tiffany Tamse

    2015-01-01

    Full Text Available Idiopathic Hypereosinophilic Syndrome (IHES is a rare disease that can be difficult to diagnose as the differential is broad. This disease can cause significant morbidity and mortality if left untreated. Our patient is a 17-year-old adolescent female who presented with nonspecific symptoms of abdominal pain and malaise. She was incidentally found to have hypereosinophilia of 16,000 on complete blood count and nonspecific colitis and pulmonary edema on computed tomography. She went into cardiogenic shock due to papillary rupture of her mitral valve requiring extreme life support measures including intubation and extracorporal membrane oxygenation (ECMO as well as mitral valve replacement. Pathology of the valve showed eosinophilic infiltration as the underlying etiology. The patient was diagnosed with IHES after the exclusion of infectious, rheumatologic, and oncologic causes. She was treated with steroids with improvement of her symptoms and scheduled for close follow-up. In general patients with IHES that have cardiac involvement have poorer prognoses.

  18. Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro-costo-mandibular syndrome.

    Science.gov (United States)

    Lynch, Danielle C; Revil, Timothée; Schwartzentruber, Jeremy; Bhoj, Elizabeth J; Innes, A Micheil; Lamont, Ryan E; Lemire, Edmond G; Chodirker, Bernard N; Taylor, Juliet P; Zackai, Elaine H; McLeod, D Ross; Kirk, Edwin P; Hoover-Fong, Julie; Fleming, Leah; Savarirayan, Ravi; Majewski, Jacek; Jerome-Majewska, Loydie A; Parboosingh, Jillian S; Bernier, Francois P

    2014-07-22

    Elucidating the function of highly conserved regulatory sequences is a significant challenge in genomics today. Certain intragenic highly conserved elements have been associated with regulating levels of core components of the spliceosome and alternative splicing of downstream genes. Here we identify mutations in one such element, a regulatory alternative exon of SNRPB as the cause of cerebro-costo-mandibular syndrome. This exon contains a premature termination codon that triggers nonsense-mediated mRNA decay when included in the transcript. These mutations cause increased inclusion of the alternative exon and decreased overall expression of SNRPB. We provide evidence for the functional importance of this conserved intragenic element in the regulation of alternative splicing and development, and suggest that the evolution of such a regulatory mechanism has contributed to the complexity of mammalian development.

  19. Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes.

    Science.gov (United States)

    Moulson, Casey L; Fong, Loren G; Gardner, Jennifer M; Farber, Emily A; Go, Gloriosa; Passariello, Annalisa; Grange, Dorothy K; Young, Stephen G; Miner, Jeffrey H

    2007-09-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare precocious aging syndrome caused by mutations in LMNA that lead to synthesis of a mutant form of prelamin A, generally called progerin, that cannot be processed to mature lamin A. Most HGPS patients have a recurrent heterozygous de novo mutation in exon 11 of LMNA, c.1824C>T/p.G608G; this synonymous mutation activates a nearby cryptic splice donor site, resulting in synthesis of the mutant prelamin A, progerin, which lacks 50 amino acids within the carboxyl-terminal domain. Abnormal splicing is incomplete, so the mutant allele produces some normally-spliced transcripts. Nevertheless, the synthesis of progerin is sufficient to cause misshapen nuclei in cultured cells and severe disease phenotypes in affected patients. Here we present two patients with extraordinarily severe forms of progeria caused by unusual mutations in LMNA. One had a splice site mutation (c.1968+1G>A; or IVS11+1G>A), and the other had a novel synonymous coding region mutation (c.1821G>A/p.V607V). Both mutations caused very frequent use of the same exon 11 splice donor site that is activated in typical HGPS patients. As a consequence, the ratios of progerin mRNA and protein to wild-type were higher than in typical HGPS patients. Fibroblasts from both patients exhibited nuclear shape abnormalities typical of HGPS, and cells treated with a protein farnesyltransferase inhibitor exhibited fewer misshapen nuclei. Thus, farnesyltransferase inhibitors may prove to be useful even when progerin expression levels are higher than those in typical HGPS patients.

  20. Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system

    Directory of Open Access Journals (Sweden)

    Han Ruolan

    2008-04-01

    Full Text Available Abstract Background Cancer treatment with a variety of chemotherapeutic agents often is associated with delayed adverse neurological consequences. Despite their clinical importance, almost nothing is known about the basis for such effects. It is not even known whether the occurrence of delayed adverse effects requires exposure to multiple chemotherapeutic agents, the presence of both chemotherapeutic agents and the body's own response to cancer, prolonged damage to the blood-brain barrier, inflammation or other such changes. Nor are there any animal models that could enable the study of this important problem. Results We found that clinically relevant concentrations of 5-fluorouracil (5-FU; a widely used chemotherapeutic agent were toxic for both central nervous system (CNS progenitor cells and non-dividing oligodendrocytes in vitro and in vivo. Short-term systemic administration of 5-FU caused both acute CNS damage and a syndrome of progressively worsening delayed damage to myelinated tracts of the CNS associated with altered transcriptional regulation in oligodendrocytes and extensive myelin pathology. Functional analysis also provided the first demonstration of delayed effects of chemotherapy on the latency of impulse conduction in the auditory system, offering the possibility of non-invasive analysis of myelin damage associated with cancer treatment. Conclusions Our studies demonstrate that systemic treatment with a single chemotherapeutic agent, 5-FU, is sufficient to cause a syndrome of delayed CNS damage and provide the first animal model of delayed damage to white-matter tracts of individuals treated with systemic chemotherapy. Unlike that caused by local irradiation, the degeneration caused by 5-FU treatment did not correlate with either chronic inflammation or extensive vascular damage and appears to represent a new class of delayed degenerative damage in the CNS.

  1. Blue toe syndrome treated with sympathectomy in a patient with acute renal failure caused by cholesterol embolization

    Directory of Open Access Journals (Sweden)

    Min-Gang Kim

    2013-12-01

    Full Text Available Blue toe syndrome is the most frequent manifestation of tissue ischemia caused by cholesterol embolization (CE, which can lead to amputation of affected lower extremities, if severe. However, any effective treatment is lacking. We experienced a case of spontaneously presenting blue toe syndrome and concomitant acute renal failure in a patient with multiple atherosclerotic risk factors. CE was confirmed by renal biopsy. Despite medical treatment including prostaglandin therapy and narcotics, the toe lesion progressed to gangrene with worsening ischemic pain. Therefore, we performed lumbar sympathectomy, which provided dramatic pain relief as well as an adequate blood flow to the ischemic lower extremities, resulting in healing of the gangrenous lesion and avoiding toe amputation. This is the first reported case of a patient with intractable ischemic toe syndrome caused by CE that was treated successfully by sympathectomy. Our observations suggest that sympathectomy may be beneficial in some patients with CE-associated blue toe syndrome.

  2. Elizabeth Warrington Prize Lecture. Seeing why they cannot see: understanding the syndrome and causes of posterior cortical atrophy.

    Science.gov (United States)

    Crutch, Sebastian J

    2014-09-01

    Posterior cortical atrophy (PCA) is a syndrome defined by focal neurodegeneration of the parietal, occipital, and occipito-temporal cortices and associated with progressive dysfunction of visual processing, praxis, numeracy and reading. The condition is most commonly caused by (and viewed as an atypical presentation of) Alzheimer's disease, although can also be caused by other degenerative diseases. The current paper examines the relationship of PCA to other degenerative syndromes, and considers what comparisons of these syndromes and disease phenotypes can tell us about underlying disease mechanisms. The focus then turns to neuropsychological investigations of the cognitive basis of symptoms which, although unusual in the broader context of a dementia clinic, are particularly characteristic of the PCA syndrome, before exploring implications for clinical management and patient and carer support.

  3. Observational cohort study of ventricular arrhythmia in adults with Marfan syndrome caused by FBN1 mutations.

    Directory of Open Access Journals (Sweden)

    Ali Aydin

    Full Text Available BACKGROUND: Marfan syndrome is associated with ventricular arrhythmia but risk factors including FBN1 mutation characteristics require elucidation. METHODS AND RESULTS: We performed an observational cohort study of 80 consecutive adults (30 men, 50 women aged 42±15 years with Marfan syndrome caused by FBN1 mutations. We assessed ventricular arrhythmia on baseline ambulatory electrocardiography as >10 premature ventricular complexes per hour (>10 PVC/h, as ventricular couplets (Couplet, or as non-sustained ventricular tachycardia (nsVT, and during 31±18 months of follow-up as ventricular tachycardia (VT events (VTE such as sudden cardiac death (SCD, and sustained ventricular tachycardia (sVT. We identified >10 PVC/h in 28 (35%, Couplet/nsVT in 32 (40%, and VTE in 6 patients (8%, including 3 with SCD (4%. PVC>10/h, Couplet/nsVT, and VTE exhibited increased N-terminal pro-brain natriuretic peptide serum levels(P10/h and Couplet/nsVT also related to increased indexed end-systolic LV diameters (P = .024 and P = .020, to moderate mitral valve regurgitation (P = .018 and P = .003, and to prolonged QTc intervals (P = .001 and P = .006, respectively. Moreover, VTE related to mutations in exons 24-32 (P = .021. Kaplan-Meier analysis corroborated an association of VTE with increased NT-proBNP (P<.001 and with mutations in exons 24-32 (P<.001. CONCLUSIONS: Marfan syndrome with causative FBN1 mutations is associated with an increased risk for arrhythmia, and affected persons may require life-long monitoring. Ventricular arrhythmia on electrocardiography, signs of myocardial dysfunction and mutations in exons 24-32 may be risk factors of VTE.

  4. A Rare Cause of Bacteremia in a Pediatric Patient with Down Syndrome: Sphingomonas Paucimobilis

    Directory of Open Access Journals (Sweden)

    Mehmet Özdemir, Sevgi Pekcan, Mehmet Emin Demircili, Fatma Esenkaya Taşbent, Bahadır Feyzioğlu, Şerife Pirinç, Mahmut Baykan

    2011-01-01

    Full Text Available Sphingomonas paucimobilis, is a yellow-pigmented, aerobic, non fermentative, gram negative motile bacillus. S. paucimobilis which is widely found in nature and hospital environments rarely cause serious or life threatening infections. In this report, a case of hospital acquired bloodstream infection due to S. paucimobilis in a patient with Down syndrome who was on treatment for presumed pneumonia is presented.A one year-old child patient who was a known case of Down syndrome and had previously experienced cardiac surgery was hospitalized and treated for pneumonia. On the 12th day of hospitalization, blood cultures were taken because of a high body temperature. One of the blood cultures was positive for gram-negative rods. After 48 hour of incubation, the sub-cultures on blood agar medium yielded pure growth of a yellow, non-fermentative, gram-negative, rod-shaped bacterium. The microorganism was positive for oxidase, and esculin hydrolysis, while negative for urea and nitrate reduction, citrate utilisation and motility. The isolate had been identified as S. paucimobilis by using Vitek 2 system. The antibiotic susceptibility test was also performed with the same system and the strain was found to be susceptible to piperacillin-tazobactam and other antibiotics. Treatment with intravenous piperacilin-tazobactam (150 mg/kg/day was initiated. He responded well to the treatment and was discharged after 10 days. This case is reported to emphasize that S. paucimobilis should be kept in mind as a nosocomial infectious agent in patients with Down syndrome and immunosuppressive patients and the infections should be treated according to the sensitivity test results.

  5. Identification of novel mutation in cathepsin C gene causing Papillon-Lefèvre Syndrome in Mexican patients

    OpenAIRE

    2013-01-01

    Abstract Background Papillon-Lefèvre Syndrome (PLS) is a type IV genodermatosis caused by mutations in cathepsin C (CTSC), with a worldwide prevalence of 1–4 cases per million in the general population. In México, the prevalence of this syndrome is unknown, and there are few case reports. The diagnosis of twenty patients in the state of Sinaloa highlights the need to characterize this syndrome in Mexicans. Methods To understand the basis of PLS in Mexicans, the gene expression, enzymatic acti...

  6. Identification of novel mutation in cathepsin C gene causing Papillon-Lefèvre Syndrome in Mexican patients

    OpenAIRE

    2013-01-01

    Background Papillon-Lefèvre Syndrome (PLS) is a type IV genodermatosis caused by mutations in cathepsin C (CTSC), with a worldwide prevalence of 1–4 cases per million in the general population. In México, the prevalence of this syndrome is unknown, and there are few case reports. The diagnosis of twenty patients in the state of Sinaloa highlights the need to characterize this syndrome in Mexicans. Methods To understand the basis of PLS in Mexicans, the gene expression, enzymatic activity and ...

  7. Epidemiology of childhood Guillain-Barré syndrome as a cause of acute flaccid paralysis in Honduras: 1989-1999.

    Science.gov (United States)

    Molinero, Marco R; Varon, Daniel; Holden, Kenton R; Sladky, John T; Molina, Ida B; Cleaves, Francisco

    2003-11-01

    The objective of this study was to investigate the incidence of acute flaccid paralysis in the pediatric population of Honduras over an 11-year period, determine what percentage of acute flaccid paralysis was Guillain-Barré syndrome, and identify the epidemiologic features of Guillain-Barré syndrome. There were 546 childhood cases of acute flaccid paralysis seen between January 1989 and December 1999 at the Hospital Escuela Materno-Infantil in Tegucigalpa, Honduras. Of these cases with acute flaccid paralysis, 394 (72.2%) were diagnosed with Guillain-Barré syndrome. Our incidence of Guillain-Barré syndrome in the Honduran pediatric population (1.37/100,000 per year) is higher than that shown in other studies. There was a significantly higher incidence of Guillain-Barré syndrome in younger children (ages 1-4 years), a significant preponderance of cases from rural areas, and a mild predominance in boys but a typical clinical presentation. The Honduran pediatric Guillain-Barré syndrome population had an increased mortality rate. Guillain-Barré syndrome has become the leading cause of childhood paralysis in Honduras. A better understanding of the population at highest risk and opportunities for earlier intervention with more effective therapeutic modalities may permit reducing the mortality among Honduran children who develop Guillain-Barré syndrome.

  8. Obstructive sleep apnoea in Treacher Collins syndrome: prevalence, severity and cause.

    Science.gov (United States)

    Plomp, R G; Bredero-Boelhouwer, H H; Joosten, K F M; Wolvius, E B; Hoeve, H L J; Poublon, R M L; Mathijssen, I M J

    2012-06-01

    This cohort study in 35 patients (13 children) evaluates the prevalence, severity and anatomical cause of obstructive sleep apnoea syndrome (OSAS) in patients with Treacher Collins syndrome. Ambulatory polysomnography was performed cross-sectionally to determine OSAS prevalence and severity. All upper airway related surgical interventions were evaluated retrospectively. In 11 patients, sleep endoscopy, and flexible and rigid endoscopy were applied to determine the level of anatomical obstruction of the upper airway. The overall prevalence of OSAS in Treacher Collins patients was 46% (54% in children; 41% in adults). Thirty-eight upper airway related surgical interventions were performed in 17 patients. Examination of the upper airway revealed various anatomical levels of obstruction, from the nasal septum to the trachea. Most significant obstruction was found at the level of the oro/hypopharynx. OSAS in Treacher Collins patients is an important problem so all patients should be screened for OSAS by polysomnography. Endoscopy of the upper airways was helpful in determining the level of obstruction. Surgical treatment at one level will not resolve OSAS in most patients because OSAS in Treacher Collins has a multilevel origin. Non-invasive ventilation (continuous positive airway pressure or bilevel positive airway pressure) or tracheotomy should be considered as a treatment modality.

  9. Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome

    Science.gov (United States)

    Prasad, Rathi; Hadjidemetriou, Irene; Meimaridou, Eirini; Buonocore, Federica; Saleem, Moin; Hurcombe, Jenny; Bierzynska, Agnieszka; Barbagelata, Eliana; Bergadá, Ignacio; Cassinelli, Hamilton; Das, Urmi; Krone, Ruth; Hacihamdioglu, Bulent; Sari, Erkan; Yesilkaya, Ediz; Storr, Helen L.; Clemente, Maria; Fernandez-Cancio, Monica; Camats, Nuria; Ram, Nanik; Achermann, John C.; Van Veldhoven, Paul P.; Guasti, Leonardo; Braslavsky, Debora; Guran, Tulay; Metherell, Louise A.

    2017-01-01

    Primary adrenal insufficiency is life threatening and can present alone or in combination with other comorbidities. Here, we have described a primary adrenal insufficiency syndrome and steroid-resistant nephrotic syndrome caused by loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1). SGPL1 executes the final decisive step of the sphingolipid breakdown pathway, mediating the irreversible cleavage of the lipid-signaling molecule sphingosine-1-phosphate (S1P). Mutations in other upstream components of the pathway lead to harmful accumulation of lysosomal sphingolipid species, which are associated with a series of conditions known as the sphingolipidoses. In this work, we have identified 4 different homozygous mutations, c.665G>A (p.R222Q), c.1633_1635delTTC (p.F545del), c.261+1G>A (p.S65Rfs*6), and c.7dupA (p.S3Kfs*11), in 5 families with the condition. In total, 8 patients were investigated, some of whom also manifested other features, including ichthyosis, primary hypothyroidism, neurological symptoms, and cryptorchidism. Sgpl1–/– mice recapitulated the main characteristics of the human disease with abnormal adrenal and renal morphology. Sgpl1–/– mice displayed disrupted adrenocortical zonation and defective expression of steroidogenic enzymes as well as renal histology in keeping with a glomerular phenotype. In summary, we have identified SGPL1 mutations in humans that perhaps represent a distinct multisystemic disorder of sphingolipid metabolism. PMID:28165343

  10. Rubinstein-Taybi syndrome caused by submicroscopic deletions within 16p13. 3

    Energy Technology Data Exchange (ETDEWEB)

    Breuning, M.H.; Dauwerse, H.G.; Fugazza, G.; Saris, J.J.; Spruit, L.; Winjnen, H.; Beverstock, G.C.; Ommen, G.J.B. van (Leiden Univ. (Netherlands)); Tommerup, N. (John F. Kennedy Inst., Glostrup (Denmark) Avd. for Medisinsk Genetikk, Oslo (Norway)); Hagen, C.B. van der (John F. Kennedy Inst., Glostrup (Denmark)); Imaizumi, Kiyoshi; Kuroki, Yoshikazu (Kanagawa Children' s Medical Center, Yokohama (Japan)); Boogaard, M.J. van den; Pater, J.M. de; Hennekam, R.C.M. (Clinical Genetics Center, Utrecht (Netherlands)); Mariman, E.C.M.; Hamel, B.C.J. (University Hospital, Nijmegen (Netherlands)); Himmelbauer, H.; Frischauf, A.M. (Imperial Cancer Research Fund Laboratories, London (United Kingdom)); Stallings, R.L. (Los Alamos National Lab., NM (United States))

    1993-02-01

    The Rubinstein-Taybi syndrome (RTS) is a well-defined complex of congenital malformations characterized by facial abnormalities, broad thumbs and big toes, and mental retardation. The breakpoint of two distinct reciprocal translocations occurring in patients with a clinical diagnosis of RTS was located to the same interval on chromosome 16, between the cosmids N2 and RT1, in band 16p13.3. By using two-color fluorescence in situ hybridization, the signal from RT1 was found to be missing from one chromosome 16 in 6 of 24 patients with RTS. The parents of five of these patients did not show a deletion of RT1, indicating a de novo rearrangement. RTS is caused by submicroscopic interstitial deletions within 16p13.3 in approximately 25% of the patients. The detection of microdeletions will allow the objective confirmation of the clinical diagnosis in new patients and provides an excellent tool for the isolation of the gene causally related to the syndrome. 32 refs., 2 figs.

  11. [Brain abscess caused by Haemophilus influenzae type E in a pediatric patient suffering from Apert syndrome].

    Science.gov (United States)

    Isasmendi, Adela M; Pinheiro, José L; Escudé, Natalia García; Efrón, Adriana M; Moscoloni, María A; Hernández, Claudia M

    2014-01-01

    We report a case of a brain abscess caused by Haemophilus influenzae type e in a 12 year-old patient suffering from Apert syndrome. Apert syndrome is characterized by the premature closure of cranial sutures. In 2010 the patient suffered head trauma in the frontal area with cranial fracture and a cerebrospinal fluid fistula. In February 2013 he was admitted to hospital with fever, vomiting and generalized tonic-clonic seizure with deteriorating mental status/progressive sensory impairment. The computerized axial tomographic scan showed a right frontal lesion, perilesional edema, mild ventricular dilatation and pansinusitis. A brain abscess was diagnosed and drained. The clinical sample was then cultured. A gram negative coccobacillus was isolated and identified as Haemophilus influenzae serotype e. Empirical treatment was started with meropenem (120 mg/kg/day) and vancomycin (60 mg/kg/day), which was later switched to ceftriaxone (100 mg/kg/day) and metronidazole (500 mg/8 h) after culture results arrived. The patient was discharged in good clinical condition.

  12. Ectopic adrenocorticotropic hormone syndrome caused by neuroendocrine carcinoma of the colon.

    Science.gov (United States)

    Fujimoto, Kazuyo; Nakashima, Takatoshi; Sasaki, Kazunari; Hayashi, Kenichi; Hanafusa, Masao; Yoshida, Shiei; Myojo, Satoshi; Yoshida, Shun-Ichi; Sawai, Shigeaki; Sano, Nobuya

    A 48-year-old woman with a history of autoimmune hemolytic anemia and taking long-term corticosteroid therapy presented with a 3-month history of general fatigue, abdominal distension, and pigmentation. A computed tomography scan of the abdomen showed a tumor in the sigmoid colon and multiple metastatic nodules in the liver. A colonoscopy revealed an obstructing mass with the presence of an irregular ulcer in the sigmoid colon. Following biopsy and histopathological analysis, the patient was diagnosed with neuroendocrine carcinoma (NEC) of the colon. She received her first cycle of chemotherapy, with carboplatin and etoposide. During hospitalization, her pigmentation and hypertension worsened and hypokalemia was observed, all of which suggsted Cushing's syndrome. Her plasma adrenocorticotropic hormone (ACTH) and cortisol levels were high, and an ectopic ACTH-producing tumor was suspected. After a second chemotherapy cycle, she developed neutropenic fever and subsequently died. At autopsy, two histological types were found in the tumor: small cell carcinoma and large cell NEC. Immunohistochemical analysis revealed ACTH in the large cell NEC. This is the first reported case of an ectopic ACTH syndrome caused by NEC of the colon.

  13. Bannayan-Riley-Ruvalcaba syndrome: a cause of extreme macrocephaly and neurodevelopmental delay.

    LENUS (Irish Health Repository)

    Lynch, N E

    2012-02-01

    BACKGROUND: Bannayan-Riley-Ruvalcaba syndrome (BRRS) is an autosomal dominant condition characterised by macrocephaly, developmental delay and subtle cutaneous features. BRRS results from mutations in the PTEN gene. In adults, PTEN mutations cause Cowden syndrome where, in addition to the macrocephaly, there is a higher risk of tumour development. Diagnosis of BRRS is often delayed as presentation can be variable, even within families. AIMS: To identify characteristics of this condition which might facilitate early diagnosis. Prompt diagnosis not only avoids unnecessary investigations in the child but potentially identifies heterozygote parents who are at risk of tumour development. METHODS AND RESULTS: Six children with a PTEN mutation were identified. All had extreme macrocephaly. Four parents and a male sibling were found to have a PTEN mutation on subsequent testing. Affected parents had extreme macrocephaly and a history of thyroid adenoma, or breast or skin lesions. All six children had presented to medical attention before the age of 2.5 years (3\\/6 were investigated as neonates), but the median age at diagnosis was 5 years. Four of the children had multiple investigations prior to identification of a PTEN mutation. CONCLUSION: BRRS should be considered in children with extreme macrocephaly as it is the most consistent clinical feature seen, particularly where there is a family history of macrocephaly.

  14. Stent Implantation for Superior Vena Cava Syndrome of Malignant Cause.

    Science.gov (United States)

    Büstgens, Felix A; Loose, Reinhard; Ficker, Joachim H; Wucherer, Michael; Uder, Michael; Adamus, Ralf

    2017-02-02

    Purpose The purpose of this paper is the retrospective analysis of endovascular therapy for the treatment of superior vena cava syndrome (SVCS) of malignant cause. This study focuses on the effectiveness of the therapy regarding the duration of remission, symptom control and practicability. Materials and Methods From January 2003 to November 2012, therapeutic implantation of one or more stents was performed in 141 patients suffering from SVCS. The medical history was retrospectively researched using digitalized patient files. If those were incomplete, secondary research was conducted using the cancer registry of the General Hospital Nuremberg, the cancer registry of the tumor center at Friedrich-Alexander-University Erlangen-Nuremberg (FAU) or information given by physicians in private practice. This data was collected using Microsoft Office Excel(®) and statistically analyzed using IBM SPSS Statistics 22(®). Results 168 stents were implanted in 141 patients (median age: 64.6 years; range: 36 - 84), 86 being male and 55 being female. In 121 patients, SVCS was caused by lung cancer (85.8 %), in 9 patients by mediastinal metastasis of an extrathoracic carcinoma (6.4 %), in 3 patients by mesothelioma of the pleura (2.1 %) and in 1 patient by Hodgkin's disease (0.7 %). There was no histological diagnosis in 7 cases (4.9 %). The primary intervention was successful in 138 patients (97.9 %). Immediate thrombosis in the stent occurred in the remaining 3 cases. Recurrence of SVCS was observed in 22 patients (15.6 %), including 5 early and 17 late occlusions. Stent dislocation or breakage was not observed. As expected, the survival after implantation was poor. The median survival was 101 days, and the median occlusion-free survival was 80 days. Conclusion The symptomatic therapy of SVCS with endovascular stents is effective and safe. Despite effective symptom control and a low rate of recurrence, the patients' prognosis is poor. Key Points

  15. Drug-Induced Hypersensitivity Syndrome Caused by Carbamazepine Used for the Treatment of Trigeminal Neuralgia

    Directory of Open Access Journals (Sweden)

    Yuko Ono

    2016-01-01

    Full Text Available An 88-year-old man was diagnosed with trigeminal neuralgia, and treatment of carbamazepine 200 mg/day was initiated. About 6 weeks later, the patient developed a skin rash accompanied by fever. He was admitted to hospital and diagnosed with drug-induced hypersensitivity syndrome (DIHS caused by carbamazepine. Oral carbamazepine treatment was stopped, but blood tests showed acute liver and acute renal failure. Drug-induced lymphocyte stimulation test (DLST for carbamazepine, human herpes virus-6 (HHV-6 IgG, and CMV-HRP were negative. Oral prednisolone therapy was begun 18 days later. The titer of HHV-6 IgG antibodies was then detected (640 times. Following treatment, liver and renal function improved and the erythema disappeared.

  16. Nephrocalcinosis (Enamel Renal Syndrome) Caused by Autosomal Recessive FAM20A Mutations

    Science.gov (United States)

    Jaureguiberry, Graciana; De la Dure-Molla, Muriel; Parry, David; Quentric, Mickael; Himmerkus, Nina; Koike, Toshiyasu; Poulter, James; Klootwijk, Enriko; Robinette, Steven L.; Howie, Alexander J.; Patel, Vaksha; Figueres, Marie-Lucile; Stanescu, Horia C.; Issler, Naomi; Nicholson, Jeremy K.; Bockenhauer, Detlef; Laing, Christopher; Walsh, Stephen B.; McCredie, David A.; Povey, Sue; Asselin, Audrey; Picard, Arnaud; Coulomb, Aurore; Medlar, Alan J.; Bailleul-Forestier, Isabelle; Verloes, Alain; Le Caignec, Cedric; Roussey, Gwenaelle; Guiol, Julien; Isidor, Bertrand; Logan, Clare; Shore, Roger; Johnson, Colin; Inglehearn, Christopher; Al-Bahlani, Suhaila; Schmittbuhl, Matthieu; Clauss, François; Huckert, Mathilde; Laugel, Virginie; Ginglinger, Emmanuelle; Pajarola, Sandra; Spartà, Giuseppina; Bartholdi, Deborah; Rauch, Anita; Addor, Marie-Claude; Yamaguti, Paulo M.; Safatle, Heloisa P.; Acevedo, Ana Carolina; Martelli-Júnior, Hercílio; dos Santos Netos, Pedro E.; Coletta, Ricardo D.; Gruessel, Sandra; Sandmann, Carolin; Ruehmann, Denise; Langman, Craig B.; Scheinman, Steven J.; Ozdemir-Ozenen, Didem; Hart, Thomas C.; Hart, P. Suzanne; Neugebauer, Ute; Schlatter, Eberhard; Houillier, Pascal; Gahl, William A.; Vikkula, Miikka; Bloch-Zupan, Agnès; Bleich, Markus; Kitagawa, Hiroshi; Unwin, Robert J.; Mighell, Alan; Berdal, Ariane; Kleta, Robert

    2013-01-01

    Background/Aims Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood. Methods We investigated 25 patients from 16 families with unexplained nephrocalcinosis and characteristic dental defects (amelogenesis imperfecta, gingival hyperplasia, impaired tooth eruption). To identify the causative gene, we performed genome-wide linkage analysis, exome capture, next-generation sequencing, and Sanger sequencing. Results All patients had bi-allelic FAM20A mutations segregating with the disease; 20 different mutations were identified. Conclusions This au-tosomal recessive disorder, also known as enamel renal syndrome, of FAM20A causes nephrocalcinosis and amelogenesis imperfecta. We speculate that all individuals with biallelic FAM20A mutations will eventually show nephrocalcinosis. PMID:23434854

  17. Initially unrecognised lunate dislocation as a cause of carpal tunnel syndrome

    Science.gov (United States)

    Ott, Florian; Mattiassich, Georg; Kaulfersch, Christian; Ortmaier, Reinhold

    2013-01-01

    A patient was admitted reporting tingling pain and numbness in the right hand. Neurological examination—including nerve conduction studies—diagnosed carpal tunnel syndrome. Operative carpal tunnel release was performed without complications. Four months postoperatively the otherwise healthy patient presented again due to persistent complaints, although preoperative symptoms had improved. On this occasion, the patient reported loss of strength accompanied by rigidity in the wrist. Clinical examination showed some swelling adjacent to the operation wound. A postoperative ganglion cyst was suspected and a conservative treatment option—splinting the wrist—was chosen. Four weeks later the patient presented again with further swelling and increasing rigidity of the wrist. Surgical intervention was planned. Preoperative plain radiographs of the wrist revealed chronic palmar dislocation of the lunate to be the cause of the symptoms in our patient. Radiological signs of scapholunate advanced collapse arthritis (SLAC wrist) were also observed. PMID:23513027

  18. Endomyocardial fibrosis as a cause of Budd-Chiari syndrome and fatal pulmonary embolism.

    Science.gov (United States)

    Bestetti, Reinaldo B; Silva, Carolina M P D C; Ardito, Sabrina Q; Theodoropoulos, Tatiana A D; Cury, Patrícia M; Corbucci, Hélio A R

    2010-01-01

    A 24-year-old-man had right-sided heart failure of 3 months' duration. A Doppler echocardiogram revealed atrium and right ventricular enlargement, obliteration of the right ventricular apex, and a mass with an echolucent center measuring 20x21 mm in the right ventricular outlet. He died of pulmonary embolism. At autopsy, a huge organized thrombus obliterating the right ventricular apex passing through the tricuspid valve to the right atrium and then extending to the inferior vena cava up to the suprahepatic veins was seen. Histologically, an intense fibrotic thickening of the endomyocardium extending into the myocardium was observed. Cardiac thrombosis associated with endomyocardial fibrosis should be added to the list of causes of Budd-Chiari syndrome.

  19. Bite-related and septic syndromes caused by cats and dogs.

    Science.gov (United States)

    Oehler, Richard L; Velez, Ana P; Mizrachi, Michelle; Lamarche, Jorge; Gompf, Sandra

    2009-07-01

    Bite infections can contain a mix of anaerobes and aerobes from the patient's skin and the animal's oral cavity, including species of Pasteurella, Streptococcus, Fusobacterium, and Capnocytophaga. Domestic cat and dog bite wounds can produce substantial morbidity and often require specialised care techniques and specific antibiotic therapy. Bite wounds can be complicated by sepsis. Disseminated infections, particularly those caused by Capnocytophaga canimorsus and Pasteurella multocida, can lead to septic shock, meningitis, endocarditis, and other severe sequelae. An emerging syndrome in veterinary and human medicine is meticillin-resistant Staphylococcus aureus (MRSA) infections shared between pets and human handlers, particularly community-acquired MRSA disease involving the USA300 clone. Skin, soft-tissue, and surgical infections are the most common. MRSA-associated infections in pets are typically acquired from their owners and can potentially cycle between pets and their human acquaintances.

  20. Autosomal-Dominant Multiple Pterygium Syndrome Is Caused by Mutations in MYH3.

    Science.gov (United States)

    Chong, Jessica X; Burrage, Lindsay C; Beck, Anita E; Marvin, Colby T; McMillin, Margaret J; Shively, Kathryn M; Harrell, Tanya M; Buckingham, Kati J; Bacino, Carlos A; Jain, Mahim; Alanay, Yasemin; Berry, Susan A; Carey, John C; Gibbs, Richard A; Lee, Brendan H; Krakow, Deborah; Shendure, Jay; Nickerson, Deborah A; Bamshad, Michael J

    2015-05-01

    Multiple pterygium syndrome (MPS) is a phenotypically and genetically heterogeneous group of rare Mendelian conditions characterized by multiple pterygia, scoliosis, and congenital contractures of the limbs. MPS typically segregates as an autosomal-recessive disorder, but rare instances of autosomal-dominant transmission have been reported. Whereas several mutations causing recessive MPS have been identified, the genetic basis of dominant MPS remains unknown. We identified four families affected by dominantly transmitted MPS characterized by pterygia, camptodactyly of the hands, vertebral fusions, and scoliosis. Exome sequencing identified predicted protein-altering mutations in embryonic myosin heavy chain (MYH3) in three families. MYH3 mutations underlie distal arthrogryposis types 1, 2A, and 2B, but all mutations reported to date occur in the head and neck domains. In contrast, two of the mutations found to cause MPS in this study occurred in the tail domain. The phenotypic overlap among persons with MPS, coupled with physical findings distinct from other conditions caused by mutations in MYH3, suggests that the developmental mechanism underlying MPS differs from that of other conditions and/or that certain functions of embryonic myosin might be perturbed by disruption of specific residues and/or domains. Moreover, the vertebral fusions in persons with MPS, coupled with evidence of MYH3 expression in bone, suggest that embryonic myosin plays a role in skeletal development.

  1. Infectious Mimicry Complicates Diagnosis in Hemophagocytic Syndrome Caused by Anaplastic Large-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Michael J. Peluso

    2012-01-01

    Full Text Available Hemophagocytic syndrome (HPS arises secondary to genetic, rheumatologic, neoplastic, and infectious causes. We discuss a patient whose presentation was consistent with systemic infection but was discovered to have HPS of unknown etiology. The presenting symptoms, as well as unremarkable malignancy and rheumatologic workups, led to the pursuit of an infectious cause, but the patient was ultimately discovered to have an occult anaplastic large-cell lymphoma (ALCL. This case demonstrates the diagnostic challenges that result from infectious mimicry in the context of HPS—first, in distinguishing noninfectious HPS from the systemic inflammation that can result from a widespread infectious process, second, in the identification of the precipitating cause of HPS. While evidence of these challenges has been suggested by the limited literature on HPS and ALCL, our case illustrates the diagnostic dilemma that arises when tissue biopsy does not quickly reveal an etiology. It is important that all physicians be aware that HPS can mimic infection and be prepared to redirect the workup when an infectious etiology for HPS cannot be identified.

  2. Sudden infant death syndrome caused by cardiac arrhythmias: only a matter of genes encoding ion channels?

    Science.gov (United States)

    Sarquella-Brugada, Georgia; Campuzano, Oscar; Cesar, Sergi; Iglesias, Anna; Fernandez, Anna; Brugada, Josep; Brugada, Ramon

    2016-03-01

    Sudden infant death syndrome is the unexpected demise of a child younger than 1 year of age which remains unexplained after a complete autopsy investigation. Usually, it occurs during sleep, in males, and during the first 12 weeks of life. The pathophysiological mechanism underlying the death is unknown, and the lethal episode is considered multifactorial. However, in cases without a conclusive post-mortem diagnosis, suspicious of cardiac arrhythmias may also be considered as a cause of death, especially in families suffering from any cardiac disease associated with sudden cardiac death. Here, we review current understanding of sudden infant death, focusing on genetic causes leading to lethal cardiac arrhythmias, considering both genes encoding ion channels as well as structural proteins due to recent association of channelopathies and desmosomal genes. We support a comprehensive analysis of all genes associated with sudden cardiac death in families suffering of infant death. It allows the identification of the most plausible cause of death but also of family members at risk, providing cardiologists with essential data to adopt therapeutic preventive measures in families affected with this lethal entity.

  3. Structural and functional analyses of disease-causing missense mutations in Bloom syndrome protein.

    Science.gov (United States)

    Guo, Rong-Bing; Rigolet, Pascal; Ren, Hua; Zhang, Bo; Zhang, Xing-Dong; Dou, Shuo-Xing; Wang, Peng-Ye; Amor-Gueret, Mounira; Xi, Xu Guang

    2007-01-01

    Bloom syndrome (BS) is an autosomal recessive disorder characterized by genomic instability and the early development of many types of cancer. Missense mutations have been identified in the BLM gene (encoding a RecQ helicase) in affected individuals, but the molecular mechanism and the structural basis of the effects of these mutations remain to be elucidated. We analysed five disease-causing missense mutations that are localized in the BLM helicase core region: Q672R, I841T, C878R, G891E and C901Y. The disease-causing mutants had low ATPase and helicase activities but their ATP binding abilities were normal, except for Q672, whose ATP binding activity was lower than that of the intact BLM helicase. Mutants C878R, mapping near motif IV, and G891E and C901Y, mapping in motif IV, displayed severe DNA-binding defects. We used molecular modelling to analyse these mutations. Our work provides insights into the molecular basis of BLM pathology, and reveals structural elements implicated in coupling DNA binding to ATP hydrolysis and DNA unwinding. Our findings will help to explain the mechanism underlying BLM catalysis and interpreting new BLM causing mutations identified in the future.

  4. The molecular basis of variable phenotypic severity among common missense mutations causing Rett syndrome.

    Science.gov (United States)

    Brown, Kyla; Selfridge, Jim; Lagger, Sabine; Connelly, John; De Sousa, Dina; Kerr, Alastair; Webb, Shaun; Guy, Jacky; Merusi, Cara; Koerner, Martha V; Bird, Adrian

    2016-02-01

    Rett syndrome is caused by mutations in the X-linked MECP2 gene, which encodes a chromosomal protein that binds to methylated DNA. Mouse models mirror the human disorder and therefore allow investigation of phenotypes at a molecular level. We describe an Mecp2 allelic series representing the three most common missense Rett syndrome (RTT) mutations, including first reports of Mecp2[R133C] and Mecp2[T158M] knock-in mice, in addition to Mecp2[R306C] mutant mice. Together these three alleles comprise ∼25% of all RTT mutations in humans, but they vary significantly in average severity. This spectrum is mimicked in the mouse models; R133C being least severe, T158M most severe and R306C of intermediate severity. Both R133C and T158M mutations cause compound phenotypes at the molecular level, combining compromised DNA binding with reduced stability, the destabilizing effect of T158M being more severe. Our findings contradict the hypothesis that the R133C mutation exclusively abolishes binding to hydroxymethylated DNA, as interactions with DNA containing methyl-CG, methyl-CA and hydroxymethyl-CA are all reduced in vivo. We find that MeCP2[T158M] is significantly less stable than MeCP2[R133C], which may account for the divergent clinical impact of the mutations. Overall, this allelic series recapitulates human RTT severity, reveals compound molecular aetiologies and provides a valuable resource in the search for personalized therapeutic interventions.

  5. Pyridoxine for prevention of hand-foot syndrome caused by chemotherapy: a systematic review.

    Directory of Open Access Journals (Sweden)

    Min Chen

    Full Text Available BACKGROUND: Hand-foot syndrome (HFS is a relatively frequent dermatologic toxic reaction to certain anti-cancer chemotherapies. The syndrome can evolve into a distressing condition that limits function and affects quality of life. Pyridoxine (vitamin B6 has been used empirically for the prevention of HFS caused by anti-cancer therapy. However, evidence of its efficacy remains controversial. METHODOLOGY//PRINCIPAL FINDINGS: Systematic literature searches were conducted on the Cochrane Library, PUBMED, EMBASE, LILACS, CBM, CNKI, VIP, WANFANG and the U.S. ClinicalTrials.gov website. We included all related randomized controlled trials (RCTs irrespective of language. Reviewers from different professions independently assessed all potential studies and extracted data. Subgroup analysis was planned according to dose of pyridoxine. 5 RCTs involving 607 patients were contributed to the meta-analysis. No significant differences were found between patients receiving pyridoxine and placebo for prevention of incidence of HFS and grade 2 or worse HFS (relative risk (RR 0.96, 95%confidence interval (CI 0.86-1.06; RR0.95, 95%CI 0.73-1.24, respectively. Similarly, no significant improvement in quality of life was detected among patients. However, significant difference was found for prevention of grade 2 or worse HFS with pyridoxine 400 mg daily compared to 200 mg (RR0.55, 95%CI 0.33-0.92. CONCLUSIONS/SIGNIFICANCE: There is inadequate evidence to make any recommendation about using pyridoxine for prevention of HFS caused by chemotherapy. However, pyridoxine 400 mg may have some efficacy. Further studies of large sample sizes are needed to evaluate the efficacy and safety of pyridoxine, especially at high dose, in comparison with placebo.

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

    Science.gov (United States)

    Burrage, Lindsay C; Charng, Wu-Lin; Eldomery, Mohammad K; Willer, Jason R; Davis, Erica E; Lugtenberg, Dorien; Zhu, Wenmiao; Leduc, Magalie S; Akdemir, Zeynep C; Azamian, Mahshid; Zapata, Gladys; Hernandez, Patricia P; Schoots, Jeroen; de Munnik, Sonja A; Roepman, Ronald; Pearring, Jillian N; Jhangiani, Shalini; Katsanis, Nicholas; Vissers, Lisenka E L M; Brunner, Han G; Beaudet, Arthur L; Rosenfeld, Jill A; Muzny, Donna M; Gibbs, Richard A; Eng, Christine M; Xia, Fan; Lalani, Seema R; Lupski, James R; Bongers, Ernie M H F; Yang, Yaping

    2015-12-03

    Meier-Gorlin syndrome (MGS) is a genetically heterogeneous primordial dwarfism syndrome known to be caused by biallelic loss-of-function mutations in one of five genes encoding pre-replication complex proteins: ORC1, ORC4, ORC6, CDT1, and CDC6. Mutations in these genes cause disruption of the origin of DNA replication initiation. To date, only an autosomal-recessive inheritance pattern has been described in individuals with this disorder, with a molecular etiology established in about three-fourths of cases. Here, we report three subjects with MGS and de novo heterozygous mutations in the 5' end of GMNN, encoding the DNA replication inhibitor geminin. We identified two truncating mutations in exon 2 (the 1(st) coding exon), c.16A>T (p.Lys6(∗)) and c.35_38delTCAA (p.Ile12Lysfs(∗)4), and one missense mutation, c.50A>G (p.Lys17Arg), affecting the second-to-last nucleotide of exon 2 and possibly RNA splicing. Geminin is present during the S, G2, and M phases of the cell cycle and is degraded during the metaphase-anaphase transition by the anaphase-promoting complex (APC), which recognizes the destruction box sequence near the 5' end of the geminin protein. All three GMNN mutations identified alter sites 5' to residue Met28 of the protein, which is located within the destruction box. We present data supporting a gain-of-function mechanism, in which the GMNN mutations result in proteins lacking the destruction box and hence increased protein stability and prolonged inhibition of replication leading to autosomal-dominant MGS.

  7. FAM20A mutations can cause enamel-renal syndrome (ERS.

    Directory of Open Access Journals (Sweden)

    Shih-Kai Wang

    Full Text Available Enamel-renal syndrome (ERS is an autosomal recessive disorder characterized by severe enamel hypoplasia, failed tooth eruption, intrapulpal calcifications, enlarged gingiva, and nephrocalcinosis. Recently, mutations in FAM20A were reported to cause amelogenesis imperfecta and gingival fibromatosis syndrome (AIGFS, which closely resembles ERS except for the renal calcifications. We characterized three families with AIGFS and identified, in each case, recessive FAM20A mutations: family 1 (c.992G>A; g.63853G>A; p.Gly331Asp, family 2 (c.720-2A>G; g.62232A>G; p.Gln241_Arg271del, and family 3 (c.406C>T; g.50213C>T; p.Arg136* and c.1432C>T; g.68284C>T; p.Arg478*. Significantly, a kidney ultrasound of the family 2 proband revealed nephrocalcinosis, revising the diagnosis from AIGFS to ERS. By characterizing teeth extracted from the family 3 proband, we demonstrated that FAM20A(-/- molars lacked true enamel, showed extensive crown and root resorption, hypercementosis, and partial replacement of resorbed mineral with bone or coalesced mineral spheres. Supported by the observation of severe ectopic calcifications in the kidneys of Fam20a null mice, we conclude that FAM20A, which has a kinase homology domain and localizes to the Golgi, is a putative Golgi kinase that plays a significant role in the regulation of biomineralization processes, and that mutations in FAM20A cause both AIGFS and ERS.

  8. Cervical neuro-muscular syndrome: discovery of a new disease group caused by abnormalities in the cervical muscles.

    Science.gov (United States)

    Matsui, Takayoshi; Ii, Kunio; Hojo, Shuntaro; Sano, Keiji

    2012-01-01

    Our previous study of whiplash injury found that abnormalities in the cervical muscles cause autonomic dystonia. Further research has found that abnormalities in the cervical muscles cause headache, chronic fatigue syndrome, vertigo, and dizziness. We named this group of diseases cervical neuro-muscular syndrome. Patients treated within a 2-year period from April 1, 2002 to March 31, 2004 reported good outcomes in 83.8% for headache, 88.4% for vertigo and dizziness, 84.5% for chronic fatigue syndrome, 88.0% for autonomic dystonia, and 83.7% for whiplash-associated disorder. A large number of outpatients present with general malaise, including many general physical complaints without identifiable cause. We propose that treatment of the cervical muscle is effective for general malaise.

  9. Pilot Study: Colostomy and Urine Collection Protocol for Investigating Potential Inciting Causes of Hen Diuresis Syndrome.

    Science.gov (United States)

    Jones, Kelli; Turner, Bradley; Brandão, João; Hubbard, Sue Ann; Magee, Danny; Baughman, Brittany; Wills, Robert; Tully, Thomas

    2015-06-01

    Hen diuresis syndrome has emerged over the past 5 yr as a significant cause of mortality in the U.S. broiler breeder industry. The condition affects hens in production and is characterized by transient muscle weakness in the vent region, transient diuresis, and often urate deposits on the skin below the vent. Affected hens are often seen straining to lay an egg, which suggests oviduct contraction is also impaired. Related hen mortality, often reaching 1% or more a week, is believed to be primarily the result of male aggression of the vent region (Turner et al., "Investigating Causes of Excessive Urate Production in Broiler Breeder Hens Associated with Peritonitis and Cannibalism Mortality," Oral Presentation at The American Association of Avian Pathologists Annual Meeting, p. 139, 2010). The exact association between the cause of mortality and this syndrome is unknown, but it may be the consequence of transient partial to full oviduct prolapse, which predisposes or stimulates cannibalism and aggression. Based on unpublished work done prior to this study (Turner et al., ibid.), the evidence suggests the underlying problem is metabolic. We feel that urine collection and analysis is an essential component to understanding this condition. This study serves as a pilot study for future investigations that attempt to identify the nature and cause of the metabolic disturbance through paired urine and serum collection and analysis. For the purpose of this study, a small sample of 10 affected and 10 unaffected birds was used for sample collection. In order to collect pure urine, the birds were surgically colostomized. Colostomy did prove to be a useful means of collecting urine free of feces, and for the purposes of our study it yielded adequate urine samples for analysis. There were statistically relevant urine values observed. Affected birds had a higher presence of blood in the urine, a lower uric acid excretion rate (mg/hr), higher concentration (mEq/L) of urine Na+, and

  10. Mutations in the pre-replication complex cause Meier-Gorlin syndrome

    NARCIS (Netherlands)

    Bicknell, L.S.; Bongers, M.H.F.; Leitch, A.; Brown, S.; Schoots, J.; Harley, M.E.; Aftimos, S.; Al-Aama, J.Y.; Bober, M.; Brown, P.A.; Bokhoven, J.H.L.M. van; Dean, J.; Edrees, A.Y.; Feingold, M.; Fryer, A.; Hoefsloot, L.H.; Kau, N.; Knoers, N.V.A.M.; Mackenzie, J.; Opitz, J.M.; Sarda, P.; Ross, A.; Temple, I.K.; Toutain, A.; Wise, C.A.; Wright, M.; Jackson, A.P.

    2011-01-01

    Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears(1)(3). Both pre- and post-natal growth are impaired in this disorder, and although microcephaly is often evid

  11. Mutations in the TGF-beta repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm

    NARCIS (Netherlands)

    Doyle, A.J.; Doyle, J.J.; Bessling, S.L.; Maragh, S.; Lindsay, M.E.; Schepers, D.; Gillis, E.; Mortier, G.; Homfray, T.; Sauls, K.; Norris, R.A.; Huso, N.D.; Leahy, D.; Mohr, D.W.; Caulfield, M.J.; Scott, A.F.; Destree, A.; Hennekam, R.C.; Arn, P.H.; Curry, C.J.; Laer, L. van; McCallion, A.S.; Loeys, B.L.; Dietz, H.C.

    2012-01-01

    Elevated transforming growth factor (TGF)-beta signaling has been implicated in the pathogenesis of syndromic presentations of aortic aneurysm, including Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). However, the location and character of many of the causal mutations in LDS intuitively imply

  12. Catatonia in Down syndrome; a treatable cause of regression

    Directory of Open Access Journals (Sweden)

    Ghaziuddin N

    2015-04-01

    Full Text Available Neera Ghaziuddin,1 Armin Nassiri,2 Judith H Miles3 1Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, 2Community Psychiatry, San Jose, California, 3Thompson Center for Autism and Neurodevelopmental Disorders and Department of Child Health, University of Missouri, Columbia, Missouri, USA Objective: The main aim of this case series report is to alert physicians to the occurrence of catatonia in Down syndrome (DS. A second aim is to stimulate the study of regression in DS and of catatonia. A subset of individuals with DS is noted to experience unexplained regression in behavior, mood, activities of daily living, motor activities, and intellectual functioning during adolescence or young adulthood. Depression, early onset Alzheimer’s, or just “the Down syndrome” are often blamed after general medical causes have been ruled out. Clinicians are generally unaware that catatonia, which can cause these symptoms, may occur in DS.Study design: Four DS adolescents who experienced regression are reported. Laboratory tests intended to rule out causes of motor and cognitive regression were within normal limits. Based on the presence of multiple motor disturbances (slowing and/or increased motor activity, grimacing, posturing, the individuals were diagnosed with unspecified catatonia and treated with anti-catatonic treatments (benzodiazepines and electroconvulsive therapy [ECT].Results: All four cases were treated with a benzodiazepine combined with ECT and recovered their baseline functioning.Conclusion: We suspect catatonia is a common cause of unexplained deterioration in adolescents and young adults with DS. Moreover, pediatricians and others who care for individuals with DS are generally unfamiliar with the catatonia diagnosis outside schizophrenia, resulting in misdiagnosis and years of morbidity. Alerting physicians to catatonia in DS is essential to prompt diagnosis, appropriate treatment, and identification of the frequency

  13. Experimental infection of bats with Geomyces destructans causes white-nose syndrome

    Science.gov (United States)

    Lorch, J.M.; Meteyer, C.U.; Behr, M.J.; Boyles, J.G.; Cryan, P.M.; Hicks, A.C.; Ballmann, A.E.; Coleman, J.T.H.; Redell, D.N.; Reeder, D.M.; Blehert, D.S.

    2011-01-01

    White-nose syndrome (WNS) has caused recent catastrophic declines among multiple species of bats in eastern North America. The disease's name derives from a visually apparent white growth of the newly discovered fungus Geomyces destructans on the skin (including the muzzle) of hibernating bats. Colonization of skin by this fungus is associated with characteristic cutaneous lesions that are the only consistent pathological finding related to WNS. However, the role of G. destructans in WNS remains controversial because evidence to implicate the fungus as the primary cause of this disease is lacking. The debate is fuelled, in part, by the assumption that fungal infections in mammals are most commonly associated with immune system dysfunction. Additionally, the recent discovery that G. destructans commonly colonizes the skin of bats of Europe, where no unusual bat mortality events have been reported, has generated further speculation that the fungus is an opportunistic pathogen and that other unidentified factors are the primary cause of WNS. Here we demonstrate that exposure of healthy little brown bats (Myotis lucifugus) to pure cultures of G. destructans causes WNS. Live G. destructans was subsequently cultured from diseased bats, successfully fulfilling established criteria for the determination of G. destructans as a primary pathogen. We also confirmed that WNS can be transmitted from infected bats to healthy bats through direct contact. Our results provide the first direct evidence that G. destructans is the causal agent of WNS and that the recent emergence of WNS in North America may represent translocation of the fungus to a region with a naive population of animals. Demonstration of causality is an instrumental step in elucidating the pathogenesis and epidemiology of WNS and in guiding management actions to preserve bat populations against the novel threat posed by this devastating infectious disease. ?? 2011 Macmillan Publishers Limited. All rights reserved.

  14. Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy

    DEFF Research Database (Denmark)

    Arndt, Anne-Karin; Schafer, Sebastian; Drenckhahn, Jorg-Detlef

    2013-01-01

    Deletion 1p36 syndrome is recognized as the most common terminal deletion syndrome. Here, we describe the loss of a gene within the deletion that is responsible for the cardiomyopathy associated with monosomy 1p36, and we confirm its role in nonsyndromic left ventricular noncompaction...... cardiomyopathy (LVNC) and dilated cardiomyopathy (DCM). With our own data and publically available data from array comparative genomic hybridization (aCGH), we identified a minimal deletion for the cardiomyopathy associated with 1p36del syndrome that included only the terminal 14 exons of the transcription...... of cardiomyocytes and also revealed evidence of impaired cardiomyocyte proliferative capacity. In conclusion, mutation of PRDM16 causes the cardiomyopathy in 1p36 deletion syndrome as well as a proportion of nonsyndromic LVNC and DCM....

  15. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes.

    Science.gov (United States)

    Schubert, Julian; Siekierska, Aleksandra; Langlois, Mélanie; May, Patrick; Huneau, Clément; Becker, Felicitas; Muhle, Hiltrud; Suls, Arvid; Lemke, Johannes R; de Kovel, Carolien G F; Thiele, Holger; Konrad, Kathryn; Kawalia, Amit; Toliat, Mohammad R; Sander, Thomas; Rüschendorf, Franz; Caliebe, Almuth; Nagel, Inga; Kohl, Bernard; Kecskés, Angela; Jacmin, Maxime; Hardies, Katia; Weckhuysen, Sarah; Riesch, Erik; Dorn, Thomas; Brilstra, Eva H; Baulac, Stephanie; Møller, Rikke S; Hjalgrim, Helle; Koeleman, Bobby P C; Jurkat-Rott, Karin; Lehman-Horn, Frank; Roach, Jared C; Glusman, Gustavo; Hood, Leroy; Galas, David J; Martin, Benoit; de Witte, Peter A M; Biskup, Saskia; De Jonghe, Peter; Helbig, Ingo; Balling, Rudi; Nürnberg, Peter; Crawford, Alexander D; Esguerra, Camila V; Weber, Yvonne G; Lerche, Holger

    2014-12-01

    Febrile seizures affect 2-4% of all children and have a strong genetic component. Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B, that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature. Wild-type human syntaxin-1B but not a mutated protein rescued the effects of stx1b knockdown in zebrafish. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes.

  16. First Report of a Single Exon Deletion in TCOF1 Causing Treacher Collins Syndrome.

    Science.gov (United States)

    Beygo, J; Buiting, K; Seland, S; Lüdecke, H-J; Hehr, U; Lich, C; Prager, B; Lohmann, D R; Wieczorek, D

    2012-01-01

    Treacher Collins syndrome (TCS) is a rare craniofacial disorder characterized by facial anomalies and ear defects. TCS is caused by mutations in the TCOF1 gene and follows autosomal dominant inheritance. Recently, mutations in the POLR1D and POLR1C genes have also been identified to cause TCS. However, in a subset of patients no causative mutation could be found yet. Inter- and intrafamilial phenotypic variability is high as is the variety of mainly family-specific mutations identified throughout TCOF1. No obvious correlation between pheno- and genotype could be observed. The majority of described point mutations, small insertions and deletions comprising only a few nucleotides within TCOF1 lead to a premature termination codon. We investigated a cohort of 112 patients with a tentative clinical diagnosis of TCS by multiplex ligation-dependent probe amplification (MLPA) to search for larger deletions not detectable with other methods used. All patients were selected after negative screening for mutations in TCOF1, POLR1D and POLR1C. In 1 patient with an unequivocal clinical diagnosis of TCS, we identified a 3.367 kb deletion. This deletion abolishes exon 3 and is the first described single exon deletion within TCOF1. On RNA level we observed loss of this exon which supposedly leads to haploinsufficiency of TREACLE, the nucleolar phosphoprotein encoded by TCOF1.

  17. Duck egg-drop syndrome caused by BYD virus, a new Tembusu-related flavivirus.

    Directory of Open Access Journals (Sweden)

    Jingliang Su

    Full Text Available Since April 2010, a severe outbreak of duck viral infection, with egg drop, feed uptake decline and ovary-oviduct disease, has spread around the major duck-producing regions in China. A new virus, named BYD virus, was isolated in different areas, and a similar disease was reproduced in healthy egg-producing ducks, infecting with the isolated virus. The virus was re-isolated from the affected ducks and replicated well in primary duck embryo fibroblasts and Vero cells, causing the cytopathic effect. The virus was identified as an enveloped positive-stranded RNA virus with a size of approximately 55 nm in diameter. Genomic sequencing of the isolated virus revealed that it is closely related to Tembusu virus (a mosquito-borne Ntaya group flavivirus, with 87-91% nucleotide identity of the partial E (envelope proteins to that of Tembusu virus and 72% of the entire genome coding sequence with Bagaza virus, the most closely related flavivirus with an entirely sequenced genome. Collectively our systematic studies fulfill Koch's postulates, and therefore, the causative agent of the duck egg drop syndrome occurring in China is a new flavivirus. Flavivirus is an emerging and re-emerging zoonotic pathogen and BYD virus that causes severe egg-drop, could be disastrous for the duck industry. More importantly its public health concerns should also be evaluated, and its epidemiology should be closely watched due to the zoonotic nature of flaviviruses.

  18. Glutamatergic transmission aberration: a major cause of behavioral deficits in a murine model of Down's syndrome.

    Science.gov (United States)

    Kaur, Gurjinder; Sharma, Ajay; Xu, Wenjin; Gerum, Scott; Alldred, Melissa J; Subbanna, Shivakumar; Basavarajappa, Balapal S; Pawlik, Monika; Ohno, Masuo; Ginsberg, Stephen D; Wilson, Donald A; Guilfoyle, David N; Levy, Efrat

    2014-04-09

    Trisomy 21, or Down's syndrome (DS), is the most common genetic cause of intellectual disability. Altered neurotransmission in the brains of DS patients leads to hippocampus-dependent learning and memory deficiency. Although genetic mouse models have provided important insights into the genes and mechanisms responsible for DS-specific changes, the molecular mechanisms leading to memory deficits are not clear. We investigated whether the segmental trisomy model of DS, Ts[Rb(12.1716)]2Cje (Ts2), exhibits hippocampal glutamatergic transmission abnormalities and whether these alterations cause behavioral deficits. Behavioral assays demonstrated that Ts2 mice display a deficit in nest building behavior, a measure of hippocampus-dependent nonlearned behavior, as well as dysfunctional hippocampus-dependent spatial memory tested in the object-placement and the Y-maze spontaneous alternation tasks. Magnetic resonance spectra measured in the hippocampi revealed a significantly lower glutamate concentration in Ts2 as compared with normal disomic (2N) littermates. The glutamate deficit accompanied hippocampal NMDA receptor1 (NMDA-R1) mRNA and protein expression level downregulation in Ts2 compared with 2N mice. In concert with these alterations, paired-pulse analyses suggested enhanced synaptic inhibition and/or lack of facilitation in the dentate gyrus of Ts2 compared with 2N mice. Ts2 mice also exhibited disrupted synaptic plasticity in slice recordings of the hippocampal CA1 region. Collectively, these findings imply that deficits in glutamate and NMDA-R1 may be responsible for impairments in synaptic plasticity in the hippocampus associated with behavioral dysfunctions in Ts2 mice. Thus, these findings suggest that glutamatergic deficits have a significant role in causing intellectual disabilities in DS.

  19. A frameshift mutation in the melanophilin gene causes the dilute coat colour in rabbit (Oryctolagus cuniculus) breeds.

    Science.gov (United States)

    Fontanesi, L; Scotti, E; Allain, D; Dall'olio, S

    2014-04-01

    In rabbit, the dilute locus is determined by a recessive mutated allele (d) that causes the dilution of both eumelanic and pheomelanic pigmentations. In mice, similar phenotypes are determined by mutations in the myosin VA, Rab27a and melanophilin (MLPH) genes. In this study, we investigated the rabbit MLPH gene and showed that a mutation in this gene appears responsible for the dilute coat colour in this species. Checkered Giant F1 families segregating for black and grey (diluted or blue) coat colour were first genotyped for a complex indel in intron 1 of the MLPH gene that was completely associated with the coat colour phenotype (θ = 0.00; LOD = 4.82). Then, we sequenced 6357 bp of the MLPH gene in 18 rabbits of different coat colours, including blue animals. A total of 165 polymorphisms were identified: 137 were in non-coding regions and 28 were in coding exons. One of them was a frameshift deletion in exon 5. Genotyping the half-sib families confirmed the complete cosegregation of this mutation with the blue coat colour. The mutation was analysed in 198 rabbits of 23 breeds. All Blue Vienna and all other blue/grey/ash rabbits in other breeds (Californian, Castor Rex, Checkered Giant, English Spot, Fairy Marburg and Fairy Pearly) were homozygous for this deletion. The identification of MLPH as the responsible gene for the dilute locus in rabbit provides a natural animal model for human Griscelli syndrome type 3 and a new mutant to study the role of this gene on pigmentation.

  20. Novel TK2 mutations as a cause of delayed muscle maturation in mtDNA depletion syndrome.

    Science.gov (United States)

    Termglinchan, Thanes; Hisamatsu, Seito; Ohmori, Junko; Suzumura, Hiroshi; Sumitomo, Noriko; Imataka, George; Arisaka, Osamu; Murakami, Nobuyuki; Minami, Narihiro; Akihiko, Ishiyama; Sasaki, Masayuki; Goto, Yuichi; Noguchi, Satoru; Nonaka, Ikuya; Mitsuhashi, Satomi; Nishino, Ichizo

    2016-10-01

    Recessive mutations in TK2 cause a severe mitochondrial DNA depletion syndrome (MDS),(1) characterized by severe myopathy from early infancy. Recent reports have suggested a wider clinical spectrum including encephalomyopathic form.(1,2) We report a patient with infantile-onset fatal encephalomyopathy presenting with extreme muscle fiber immaturity.

  1. Clinical features and molecular genetic analysis of a boy with Prader-Willi syndrome caused by an imprinting defect

    DEFF Research Database (Denmark)

    Schulze, A; Hansen, Claus; Baekgaard, P;

    1997-01-01

    Prader-Willi syndrome (PWS) is a neuroendocrine disorder caused by a non-functioning paternally derived gene(s) within the chromosome region 15q11-q13. Most cases result from microscopically visible deletions of paternal origin, or maternal uniparental disomy of chromosome 15. In both instances...

  2. Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syndrome.

    NARCIS (Netherlands)

    Ruiz-Perez, V.L.; Tompson, S.W.; Blair, H.J.; Espinoza-Valdez, C.; Lapunzina, P.; Silva, E.O.; Hamel, B.C.J.; Gibbs, J.L.; Young, I.D.; Wright, M.J.; Goodship, J.A.

    2003-01-01

    Ellis-van Creveld syndrome (EvC) is an autosomal recessive skeletal dysplasia. Elsewhere, we described mutations in EVC in patients with this condition (Ruiz-Perez et al. 2000). We now report that mutations in EVC2 also cause EvC. These two genes lie in a head-to-head configuration that is conserved

  3. Protein causes hyperinsulinemia: a Chinese patient with hyperinsulinism/hyperammonaemia syndrome due to a glutamate dehydrogenase gene mutation

    Institute of Scientific and Technical Information of China (English)

    CHEN Shi; XIAO Xin-hua; DIAO Cheng-ming; TONG An-li; WANG Ou; QIU Zheng-qing; YU Kang; WANG Tong

    2010-01-01

    @@ Glucose is derived from three sources: intestinal absorption, glycogenolysis, and gluconeogenesis. Hypoglycemia in child is often attributed to depletion of glycogen stores. However, recently, congenital hyperinsulinism becomes an important cause of hypoglycaemia in early infancy. Mutations in the genes encoding SUR1 and KIR6.2 are the most frequent genetic causes of hyperinsulinism followed by mutations in the glutamate dehydrogenase (GDH) gene which encodes hyperinsulinism/hyperammonaemia (HI/HA) syndrome.

  4. Saethre-Chotzen syndrome : cranofacial anomalies caused by genetic changes in the TWIST gene

    OpenAIRE

    2004-01-01

    textabstractIn this thesis, one of the most frequently occurring and most variable craniosynostosis syndromes was investigated; Saethre-Chotzen syndrome. Craniosynostosis is the premature obliteration of cranial sutures in the developing embryo. It can also occur in the first few months of life. Saethre-Chotzen syndrome is, besides craniosynostosis, characterized by specific facial and limb abnormalities, of which the most frequently reported are ptosis, prominent crus helicis, cutaneous synd...

  5. Kabuki syndrome as a cause of non-immune fetal hydrops/ascites.

    Science.gov (United States)

    Long, Ashleigh; Sinkovskaya, Elena S; Edmondson, Andrew C; Zackai, Elaine; Schrier Vergano, Samantha A

    2016-12-01

    Kabuki syndrome (MIM 147920) is a well-described, multiple congenital anomaly syndrome characterized by growth and developmental delay, cardiac, renal, and vertebral anomalies, as well as persistent fetal finger pads and distinct facial features. Facies are characterized by long palpebral fissures with eversion of lateral third of the lower eyelid, resembling the "Kabuki make-up" theatre genre after which the syndrome is named. Kabuki syndrome is estimated to affect 1/32,000 births, with 55-80% of patients showing nonsense or frameshift mutations in the KMT2D (MLL2) gene, which encodes a histone transferase located on chromosome 12q. Additionally, owing to the heterogeneous nature of Kabuki syndrome, a smaller number of diagnosed patients have been identified with mutations or deletions in KDM6A (a component of the same transcriptional complex as KMT2D) with no mutations in KMT2D, or as those diagnosed with Kabuki syndrome and without alterations in either KMT2D or KDM6A. Diagnosis of the syndrome in newborns and infants is difficult, as the facial features are not as evident as in toddler- or childhood. There are no known "tell-tale" signs of Kabuki syndrome prenatally, and there are no reports of common, specific findings in fetuses that might suggest the diagnosis. We present here two infants who presented with prenatal hydrops/ascites, who were subsequently diagnosed with Kabuki syndrome. Although relatively non-specific, we suggest that Kabuki syndrome be added to the list of genetic syndromes that are suspected in cases of prenatal hydrops, review the molecular etiology of Kabuki syndrome, and broaden the phenotype of this well-described disorder. © 2016 Wiley Periodicals, Inc.

  6. De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

    DEFF Research Database (Denmark)

    Hoischen, Alexander; van Bon, Bregje W M; Rodríguez-Santiago, Benjamín;

    2011-01-01

    Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which...... is required for maintenance of both activation and silencing of Hox genes. In total, 7 out of 13 subjects with a Bohring-Opitz phenotype had de novo ASXL1 mutations, suggesting that the syndrome is genetically heterogeneous....

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

    OpenAIRE

    Shastri, Vivek M.; Schmidt, Kristina H.

    2015-01-01

    Abstract Background Bloom syndrome is an autosomal recessive disorder characterized by extraordinary cancer incidence early in life and an average life expectancy of ~27 years. Premature stop codons in BLM , which encodes a DNA helicase that functions in DNA double‐strand‐break repair, make up the vast majority of Bloom syndrome mutations, with only 13 single amino acid changes identified in the syndrome. Sequencing projects have identified nearly one hundred single nucleotide variants in BLM...

  8. Pearson's syndrome: a rare cause of non-immune hydrops fetalis

    Institute of Scientific and Technical Information of China (English)

    李澤荷; 林青雲; 李志偉; 鄺毅山; 司徒紹昌

    2003-01-01

    @@ Pearson's syndrome, or Pearson's marrow-pancreas syndrome, was first described in 1979 in four unrelated children.1 It is characterized by refractory sideroblastic anaemia with vacuolization of marrow progenitor cells, and exocrine pancreatic dysfunction. Its progressive nature, multisystem involvement and metabolic disturbances led to the subsequent identification of a unique mitochondrial DNA deletion in most affected patients.2 Despite the relentless clinical course, the majority of the patients with Pearson ' s syndrome present insidiously. Life-threatening presentation at birth is extremely rare. We report a case of Pearson ' s syndrome presenting with severe hydrops fetalis.

  9. [Proteus syndrome: Case report of bladder vascular malformation causing massive hematuria].

    Science.gov (United States)

    Abbo, O; Bouali, O; Galinier, P; Moscovici, J

    2012-02-01

    Proteus syndrome is a rare, sporadic disorder consisting of disproportionate overgrowth of multiple tissues, vascular malformations, and connective tissue or epidermal nevi. Due to mosaic pattern of distribution, the phenotypes are variable and diverse. Vascular malformations are part of the major criteria used to define and diagnose this syndrome. It can involve the gastrointestinal tract, spleen, or the urinary tract but bladder malformations are rare. We report here a case of bladder vascular malformation in a 12-year-old boy known to have Proteus syndrome and review the literature on bladder malformations or tumors in this syndrome.

  10. NEK1 mutations cause short-rib polydactyly syndrome type majewski.

    Science.gov (United States)

    Thiel, Christian; Kessler, Kristin; Giessl, Andreas; Dimmler, Arno; Shalev, Stavit A; von der Haar, Sigrun; Zenker, Martin; Zahnleiter, Diana; Stöss, Hartmut; Beinder, Ernst; Abou Jamra, Rami; Ekici, Arif B; Schröder-Kress, Nadja; Aigner, Thomas; Kirchner, Thomas; Reis, André; Brandstätter, Johann H; Rauch, Anita

    2011-01-01

    Defects of ciliogenesis have been implicated in a wide range of human phenotypes and play a crucial role in signal transduction and cell-cycle coordination. We used homozygosity mapping in two families with autosomal-recessive short-rib polydactyly syndrome Majewski type to identify mutations in NEK1 as an underlying cause of this lethal osteochondrodysplasia. NEK1 encodes a serine/threonine kinase with proposed function in DNA double-strand repair, neuronal development, and coordination of cell-cycle-associated ciliogenesis. We found that absence of functional full-length NEK1 severely reduces cilia number and alters ciliar morphology in vivo. We further substantiate a proposed digenic diallelic inheritance of ciliopathies by the identification of heterozygous mutations in NEK1 and DYNC2H1 in an additional family. Notably, these findings not only increase the broad spectrum of ciliar disorders, but suggest a correlation between the degree of defective microtubule or centriole elongation and organization and the severity of the resulting phenotype.

  11. Excessive heart rate response to orthostatic stress in postural tachycardia syndrome is not caused by anxiety.

    Science.gov (United States)

    Masuki, Shizue; Eisenach, John H; Johnson, Christopher P; Dietz, Niki M; Benrud-Larson, Lisa M; Schrage, William G; Curry, Timothy B; Sandroni, Paola; Low, Phillip A; Joyner, Michael J

    2007-03-01

    Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) without hypotension during orthostasis. The relationship between the tachycardia and anxiety is uncertain. Therefore, we tested whether the HR response to orthostatic stress in POTS is primarily related to psychological factors. POTS patients (n = 14) and healthy controls (n = 10) underwent graded venous pooling with lower body negative pressure (LBNP) to -40 mmHg while wearing deflated antishock trousers. "Sham" venous pooling was performed by 1) trouser inflation to 5 mmHg during LBNP and 2) vacuum pump activation without LBNP. HR responses to mental stress were also measured in both groups, and a questionnaire was used to measure psychological parameters. During LBNP, HR in POTS patients increased 39 +/- 5 beats/min vs. 19 +/- 3 beats/min in control subjects at -40 mmHg (P inflation markedly blunted the HR responses in the patients (9 +/- 2 beats/min) and controls (2 +/- 1 beats/min), and there was no HR increase during vacuum application without LBNP in either group. HR responses during mental stress were not different in the patients and controls (18 +/- 2 vs. 19 +/- 1 beats/min; P > 0.6). Anxiety, somatic vigilance, and catastrophic cognitions were significantly higher in the patients (P 0.1). These results suggest that the HR response to orthostatic stress in POTS patients is not caused by anxiety but that it is a physiological response that maintains arterial pressure during venous pooling.

  12. Narcissistic vulnerability is a common cause for depression in patients with Gilles de la Tourette syndrome.

    Science.gov (United States)

    Trillini, Morounke O; Müller-Vahl, Kirsten R

    2015-12-15

    The aim of this study was to assess for the first time different dimensions of narcissistic self-regulation in a large cohort of adult patients with Gilles de la Tourette syndrome (GTS) (n=50). From preliminary studies it is suggested that narcissistic personality trait and disorder, respectively, are relatively uncommon and occur in only 6-10% of GTS patients. In this study we used the Narcissism Inventory (NI), a 163-items questionnaire that measures four different dimensions of narcissism. The main result was that the prevalence of narcissism strongly depends on the subtype of narcissism: while the vulnerable narcissism ("threatened self" and "hypochondriac self") was common, the "classic narcissistic self" (grandiose narcissism) was rare. From our data an association between comorbid depression and increased values of the "threatened self" and comorbid OCD with increased values of the "hypochondriac self" is suggested. Narcissism correlated positively with the personality domain neuroticism and had a significantly negative impact on patients' quality of life. Therefore it can be speculated that vulnerable narcissism is - among several others - one cause for depression in patients with GTS. These findings may open new psychotherapeutic perspectives in the treatment of depression in patients with GTS.

  13. Temperature-dependent growth of Geomyces destructans, the fungus that causes bat white-nose syndrome

    Science.gov (United States)

    Verant, Michelle L.; Boyles, Justin G.; Waldrep, William; Wibbelt, Gudrun; Blehert, David S.

    2012-01-01

    White-nose syndrome (WNS) is an emergent disease estimated to have killed over five million North American bats. Caused by the psychrophilic fungus Geomyces destructans, WNS specifically affects bats during hibernation. We describe temperature-dependent growth performance and morphology for six independent isolates of G. destructans from North America and Europe. Thermal performance curves for all isolates displayed an intermediate peak with rapid decline in performance above the peak. Optimal temperatures for growth were between 12.5 and 15.8°C, and the upper critical temperature for growth was between 19.0 and 19.8°C. Growth rates varied across isolates, irrespective of geographic origin, and above 12°C all isolates displayed atypical morphology that may have implications for proliferation of the fungus. This study demonstrates that small variations in temperature, consistent with those inherent of bat hibernacula, affect growth performance and physiology of G. destructans, which may influence temperature-dependent progression and severity of WNS in wild bats.

  14. Identification and expression analysis of a novel intragenic EFNB1 mutation causing craniofrontonasal syndrome

    Directory of Open Access Journals (Sweden)

    Oscar F. Chacon-Camacho

    2014-12-01

    Full Text Available Craniofrontonasal syndrome (CFNS is an X-linked disorder caused by mutations in the EFNB1 gene and characterized by distinctive craniofacial and digital malformations. In contrast with most X-linked traits, female patients with CFNS display a more severe phenotype than males. In this report, the clinical, molecular and RNA expression analyses of a female subject with CFNS are described. A novel c.445_449delGAGGG deletion in exon 3 of EFNB1 was demonstrated in this patient. To assess the effect of this novel mutation at the transcript level, the expression of EFNB1 mRNA was studied by quantitative RT-PCR. To our knowledge, this is the first time that an EFNB1 transcript carrying a truncating mutation in exon 3 is demonstrated to undergo degradation by nonsense-mediated mRNA decay. Our results expand the mutational spectrum of CFNS and add to the functional consequences of truncating EFNB1 mutations.

  15. Hepatic sinusoidal obstruction syndrome caused by herbal medicine: CT and MRI features

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Hua; Lou, Hai Yan [Dept. of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China); Wang, Yi Xiang J. [Dept. of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China); Xu, Xiao Jun; Zhang, Min Ming [Dept. of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China)

    2014-04-15

    To describe the CT and MRI features of hepatic sinusoidal obstruction syndrome (HSOS) caused by herbal medicine Gynura segetum. The CT and MRI features of 16 consecutive Gynura segetum induced HSOS cases (12 men, 4 women) were analyzed. Eight patients had CT; three patients had MRI, and the remaining five patients had both CT and MRI examinations. Based on their clinical presentations and outcomes, the patients were classified into three categories: mild, moderate, and severe. The severity of the disease was also evaluated radiologically based on the abnormal hepatic patchy enhancement in post-contrast CT or MRI images. Ascites, patchy liver enhancement, and main right hepatic vein narrowing or occlusion were present in all 16 cases. Hepatomegaly and gallbladder wall thickening were present in 14 cases (87.5%, 14/16). Periportal high intensity on T2-weighted images was present in 6 cases (75%, 6/8). Normal liver parenchymal enhancement surrounding the main hepatic vein forming a clover-like sign was observed in 4 cases (25%, 4/16). The extent of patchy liver enhancement was statistically associated with clinical severity classification (kappa = 0.565). Ascites, patchy liver enhancement, and the main hepatic veins narrowing were the most frequent signs of herbal medicine induced HSOS. The grade of abnormal patchy liver enhancement was associated with the clinical severity.

  16. A CHRNE frameshift mutation causes congenital myasthenic syndrome in young Jack Russell Terriers.

    Science.gov (United States)

    Rinz, Caitlin J; Lennon, Vanda A; James, Fiona; Thoreson, James B; Tsai, Kate L; Starr-Moss, Alison N; Humphries, H Dale; Guo, Ling T; Palmer, Anthony C; Clark, Leigh Anne; Shelton, G Diane

    2015-12-01

    Congenital myasthenic syndromes (CMSs) are a group of rare genetic disorders of the neuromuscular junction resulting in structural or functional causes of fatigable weakness that usually begins early in life. Mutations in pre-synaptic, synaptic and post-synaptic proteins have been demonstrated in human cases, with more than half involving aberrations in nicotinic acetylcholine receptor (AChR) subunits. CMS was first recognized in dogs in 1974 as an autosomal recessive trait in Jack Russell Terriers (JRTs). A deficiency of junctional AChRs was demonstrated. Here we characterize a CMS in 2 contemporary cases of JRT littermates with classic clinical and electromyographic findings, and immunochemical confirmation of an approximately 90% reduction in AChR protein content. Loci encoding the 5 AChR subunits were evaluated using microsatellite markers, and CHRNB1 and CHRNE were identified as candidate genes. Sequences of the splice sites and exons of both genes revealed a single base insertion in exon 7 of CHRNE that predicts a frameshift mutation and a premature stop codon. We further demonstrated this pathogenic mutation in CHRNE in archival tissues from unrelated JRTs studied 34 years ago.

  17. Computer vision syndrome: a review of ocular causes and potential treatments.

    Science.gov (United States)

    Rosenfield, Mark

    2011-09-01

    Computer vision syndrome (CVS) is the combination of eye and vision problems associated with the use of computers. In modern western society the use of computers for both vocational and avocational activities is almost universal. However, CVS may have a significant impact not only on visual comfort but also occupational productivity since between 64% and 90% of computer users experience visual symptoms which may include eyestrain, headaches, ocular discomfort, dry eye, diplopia and blurred vision either at near or when looking into the distance after prolonged computer use. This paper reviews the principal ocular causes for this condition, namely oculomotor anomalies and dry eye. Accommodation and vergence responses to electronic screens appear to be similar to those found when viewing printed materials, whereas the prevalence of dry eye symptoms is greater during computer operation. The latter is probably due to a decrease in blink rate and blink amplitude, as well as increased corneal exposure resulting from the monitor frequently being positioned in primary gaze. However, the efficacy of proposed treatments to reduce symptoms of CVS is unproven. A better understanding of the physiology underlying CVS is critical to allow more accurate diagnosis and treatment. This will enable practitioners to optimize visual comfort and efficiency during computer operation.

  18. Dumping syndrome: an unusual cause of severe hyperinsulinemic hypoglycemia in neurologically impaired children with gastrostomy.

    Science.gov (United States)

    Bizzarri, C; Cervoni, M; Crea, F; Cutrera, R; Schiavino, A; Schiaffini, R; Cappa, M

    2011-02-01

    This paper describes severe hyperinsulinemic hypoglycemia during bolus enteral feeding in two neurologically impaired children. Both children were affected by dysphagia with swallowing difficulties; caloric intake was inadequate. For these reasons, percutaneous endoscopic gastrostomy had been positioned during the first months of life. In one patient due to persisting vomiting, after a few months, a gastrojejunal tube (PEG-J) was inserted. Hypoglycemia was revealed by routine blood tests, without evidence of specific symptoms. Continuous subcutaneous glucose monitoring showed wide glucose excursions, ranging from hypoglycemia to hyperglycemia. Extremely high levels of insulin were detected at the time of hypoglycemia. A diagnosis of dumping syndrome (DS) was suspected in both children. In the child with PEG, the tip of the gastrostomy catheter was found to be lying in the bulbus duodeni. Once this had been pulled back, hypoglycemic episodes disappeared. The child with PEG-J needed continuous enteral feeding to reach a normal glucose balance. DS is a relatively common complication in children with gastrostomy, but extremely irregular glucose levels, ranging from hypoglycemia to hyperglycemia, and increased insulin secretion had not been previously demonstrated. The incidence of DS is probably underestimated in children receiving enteral feeding for neurological impairment. In these patients intensive monitoring of blood glucose levels should be performed to calibrate meals. Repeated underestimated hypoglycemic episodes could worsen neurological damage and cause a deterioration in clinical conditions.

  19. Acute liver failure caused by drug-induced hypersensitivity syndrome associated with hyperferritinemia

    Institute of Scientific and Technical Information of China (English)

    Masayuki Miyazaki; Masatake Tanaka; Akihiro Ueda; Tsuyoshi Yoshimoto; Masaki Kato; Makoto Nakamuta; Kazuhiro Kotoh; Ryoichi Takayanagi

    2011-01-01

    Drug-induced hypersensitivity syndrome (DIHS) is a se-vere reaction usually characterized by fever, rash, and multiorgan failure, occurring 2-6 wk after drug introduction.It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release. A 54-year-old woman was diagnosed with rheumatic arthritis and initiated salazosulfapyridine by mouth. About 10 d later, she had a high fever, skin rash and liver dysfunction. She was admitted to hospital and diagnosed with a drug eruption. She was treated with oral prednisolone 30 mg/d; however, she developed high fever again and her blood tests showed acute liver failure and cytopenia associated with hyperferritinemia. She was diagnosed with acute liver failure and hemophagocytosis caused by DIHS. She was transferred to the Department of Medicine and Bioregulatory Science, Kyushu University, where she was treated with arterial steroid injection therapy. Following this treatment, her liver function improved and serum ferritin immediately decreased. We hypothesized that an immune-mediated reaction in DIHS may have generated over-activation of macrophages and T-lymphocytes, followed by a cytokine storm that affected various organs. The measurement of serum ferritin might be a useful marker of the severity of DIHS.

  20. Severe hyponatremia caused by nab-paclitaxel-induced syndrome of inappropriate antidiuretic hormone secretion

    Science.gov (United States)

    Neuzillet, Cindy; Babai, Samy; Kempf, Emmanuelle; Pujol, Géraldine; Rousseau, Benoît; Le-Louët, Hervé; Christophe Tournigand

    2016-01-01

    Abstract Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing. Most patients have advanced disease at diagnosis and therapeutic options in this setting are limited. Gemcitabine plus nab-paclitaxel regimen was demonstrated to increase survival compared with gemcitabine monotherapy and is therefore indicated as first-line therapy in patients with metastatic PDAC and performance status Eastern Cooperative Oncology Group (ECOG) 0-2. The safety profile of gemcitabine and nab-paclitaxel combination includes neutropenia, fatigue, and neuropathy as most common adverse events of grade 3 or higher. No case of severe hyponatremia associated with the use of nab-paclitaxel for the treatment of PDAC has been reported to date. We report the case of a 72-year-old Caucasian man with a metastatic PDAC treated with gemcitabine and nab-paclitaxel regimen, who presented with a severe hyponatremia (grade 4) caused by a documented syndrome of inappropriate antidiuretic hormone secretion (SIADH). This SIADH was attributed to nab-paclitaxel after a rigorous imputability analysis, including a rechallenge procedure with dose reduction. After dose and schedule adjustment, nab-paclitaxel was pursued without recurrence of severe hyponatremia and with maintained efficacy. Hyponatremia is a rare but potentially severe complication of nab-paclitaxel therapy that medical oncologists and gastroenterologists should be aware of. Nab-paclitaxel-induced hyponatremia is manageable upon dose and schedule adaptation, and should not contraindicate careful nab-paclitaxel reintroduction. This is of particular interest for a disease in which the therapeutic options are limited. PMID:27368013

  1. Stevens–Johnson syndrome/toxic epidermal necrolysis caused by cefadroxil in a cat

    Directory of Open Access Journals (Sweden)

    Roberta Sartori

    2016-06-01

    Full Text Available Case summary A 5-year-old, spayed female, indoor-only domestic shorthair cat was referred with an acute history of multifocal cutaneous and mucocutaneous erosive-ulcerative lesions and skin detachment. The lesions occurred on the seventh day of therapy with cefadroxil. Erosive-ulcerative and occasionally crusted lesions were apparent on the medial and lateral canthus of both eyes, ventral neck, abdomen, perivulvar region, periungual skin and medial aspect of the front and hindlimbs. Diffuse and severe exfoliation was present on the dorsum and tail base and in both external ear canals. The cat was also dehydrated, tachycardic and febrile. Histopathological examination revealed extensive epidermal ulceration, interface dermatitis with vacuolar degeneration, apoptosis at multiple epidermal levels and basal, suprabasal and spinous dermoepidermal detachment. The histopathological diagnosis was consistent with Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN. The recently reported Algorithm of Drug Causality in Epidermal Necrolysis (ALDEN, currently used in human medicine, was applied and a score of +6 was calculated; this supported the view that SJS/TEN in this cat was very likely to be associated with cefadroxil administration. Relevance and novel information This clinical communication reports cefadroxil as a very probable cause of SJS/TEN in a cat; the ALDEN was applied in this case and supported diagnosis.

  2. MASA syndrome is caused by mutations in the neural cell adhesion gene, L1CAM

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, C.E.; Wang, Y.; Schroer, R.J.; Stevenson, R.E. [Greenwood Genetic Center, SC (United States)

    1994-09-01

    The MASA syndrome is a recessive X-linked disorder characterized by Mental retardation, Adducted thumbs, Shuffling gait and Aphasia. Recently we found that MASA in one family was likely caused by a point mutation in exon 6 of the L1CAM gene. This gene has also been shown to be involved in X-linked hydrocephalus (HSAS). We have screened 60 patients with either sporadic HSAS or MASA as well as two additional families with MASA. For the screening, we initially utilized 3 cDNA probes for the L1CAM gene. In one of the MASA families, K8310, two affected males were found to have an altered BglII band. The band was present in their carrier mother but not in their normal brothers. This band was detected by the entire cDNA probe as well as the cDNA probe for 3{prime} end of the gene. Analysis of the L1CAM sequence indicated the altered BglII site is distal to the exon 28 but proximal to the punative poly A signal site. It is hypothesized that this point mutation alters the stability of the L1CAM mRNA. This is being tested using cell lines established from the two affected males.

  3. Mutations in SNRPB, encoding components of the core splicing machinery, cause cerebro-costo-mandibular syndrome.

    Science.gov (United States)

    Bacrot, Séverine; Doyard, Mathilde; Huber, Céline; Alibeu, Olivier; Feldhahn, Niklas; Lehalle, Daphné; Lacombe, Didier; Marlin, Sandrine; Nitschke, Patrick; Petit, Florence; Vazquez, Marie-Paule; Munnich, Arnold; Cormier-Daire, Valérie

    2015-02-01

    Cerebro-costo-mandibular syndrome (CCMS) is a developmental disorder characterized by the association of Pierre Robin sequence and posterior rib defects. Exome sequencing and Sanger sequencing in five unrelated CCMS patients revealed five heterozygous variants in the small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) gene. This gene includes three transcripts, namely transcripts 1 and 2, encoding components of the core spliceosomal machinery (SmB' and SmB) and transcript 3 undergoing nonsense-mediated mRNA decay. All variants were located in the premature termination codon (PTC)-introducing alternative exon of transcript 3. Quantitative RT-PCR analysis revealed a significant increase in transcript 3 levels in leukocytes of CCMS individuals compared to controls. We conclude that CCMS is due to heterozygous mutations in SNRPB, enhancing inclusion of a SNRPB PTC-introducing alternative exon, and show that this developmental disease is caused by defects in the splicing machinery. Our finding confirms the report of SNRPB mutations in CCMS patients by Lynch et al. (2014) and further extends the clinical and molecular observations.

  4. A functional alternative splicing mutation in AIRE gene causes autoimmune polyendocrine syndrome type 1.

    Directory of Open Access Journals (Sweden)

    Junyu Zhang

    Full Text Available Autoimmune polyendocrine syndrome type 1 (APS-1 is a rare autosomal recessive disease defined by the presence of two of the three conditions: mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease. Loss-of-function mutations of the autoimmune regulator (AIRE gene have been linked to APS-1. Here we report mutational analysis and functional characterization of an AIRE mutation in a consanguineous Chinese family with APS-1. All exons of the AIRE gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. We identified a homozygous missense AIRE mutation c.463G>A (p.Gly155Ser in two siblings with different clinical features of APS-1. In silico splice-site prediction and minigene analysis were carried out to study the potential pathological consequence. Minigene splicing analysis and subsequent cDNA sequencing revealed that the AIRE mutation potentially compromised the recognition of the splice donor of intron 3, causing alternative pre-mRNA splicing by intron 3 retention. Furthermore, the aberrant AIRE transcript was identified in a heterozygous carrier of the c.463G>A mutation. The aberrant intron 3-retaining transcript generated a truncated protein (p.G155fsX203 containing the first 154 AIRE amino acids and followed by 48 aberrant amino acids. Therefore, our study represents the first functional characterization of the alternatively spliced AIRE mutation that may explain the pathogenetic role in APS-1.

  5. Dysfunction of intraflagellar transport-A causes hyperphagia-induced obesity and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Damon T. Jacobs

    2016-07-01

    Full Text Available Primary cilia extend from the plasma membrane of most vertebrate cells and mediate signaling pathways. Ciliary dysfunction underlies ciliopathies, which are genetic syndromes that manifest multiple clinical features, including renal cystic disease and obesity. THM1 (also termed TTC21B or IFT139 encodes a component of the intraflagellar transport-A complex and mutations in THM1 have been identified in 5% of individuals with ciliopathies. Consistent with this, deletion of murine Thm1 during late embryonic development results in cystic kidney disease. Here, we report that deletion of murine Thm1 during adulthood results in obesity, diabetes, hypertension and fatty liver disease, with gender differences in susceptibility to weight gain and metabolic dysfunction. Pair-feeding of Thm1 conditional knock-out mice relative to control littermates prevented the obesity and related disorders, indicating that hyperphagia caused the obese phenotype. Thm1 ablation resulted in increased localization of adenylyl cyclase III in primary cilia that were shortened, with bulbous distal tips on neurons of the hypothalamic arcuate nucleus, an integrative center for signals that regulate feeding and activity. In pre-obese Thm1 conditional knock-out mice, expression of anorexogenic pro-opiomelanocortin (Pomc was decreased by 50% in the arcuate nucleus, which likely caused the hyperphagia. Fasting of Thm1 conditional knock-out mice did not alter Pomc nor orexogenic agouti-related neuropeptide (Agrp expression, suggesting impaired sensing of changes in peripheral signals. Together, these data indicate that the Thm1-mutant ciliary defect diminishes sensitivity to feeding signals, which alters appetite regulation and leads to hyperphagia, obesity and metabolic disease.

  6. Dysfunction of intraflagellar transport-A causes hyperphagia-induced obesity and metabolic syndrome.

    Science.gov (United States)

    Jacobs, Damon T; Silva, Luciane M; Allard, Bailey A; Schonfeld, Michael P; Chatterjee, Anindita; Talbott, George C; Beier, David R; Tran, Pamela V

    2016-07-01

    Primary cilia extend from the plasma membrane of most vertebrate cells and mediate signaling pathways. Ciliary dysfunction underlies ciliopathies, which are genetic syndromes that manifest multiple clinical features, including renal cystic disease and obesity. THM1 (also termed TTC21B or IFT139) encodes a component of the intraflagellar transport-A complex and mutations in THM1 have been identified in 5% of individuals with ciliopathies. Consistent with this, deletion of murine Thm1 during late embryonic development results in cystic kidney disease. Here, we report that deletion of murine Thm1 during adulthood results in obesity, diabetes, hypertension and fatty liver disease, with gender differences in susceptibility to weight gain and metabolic dysfunction. Pair-feeding of Thm1 conditional knock-out mice relative to control littermates prevented the obesity and related disorders, indicating that hyperphagia caused the obese phenotype. Thm1 ablation resulted in increased localization of adenylyl cyclase III in primary cilia that were shortened, with bulbous distal tips on neurons of the hypothalamic arcuate nucleus, an integrative center for signals that regulate feeding and activity. In pre-obese Thm1 conditional knock-out mice, expression of anorexogenic pro-opiomelanocortin (Pomc) was decreased by 50% in the arcuate nucleus, which likely caused the hyperphagia. Fasting of Thm1 conditional knock-out mice did not alter Pomc nor orexogenic agouti-related neuropeptide (Agrp) expression, suggesting impaired sensing of changes in peripheral signals. Together, these data indicate that the Thm1-mutant ciliary defect diminishes sensitivity to feeding signals, which alters appetite regulation and leads to hyperphagia, obesity and metabolic disease.

  7. A Turkish family with Sjögren-Larsson syndrome caused by a novel ALDH3A2 mutation

    Directory of Open Access Journals (Sweden)

    Faruk Incecik

    2013-01-01

    Full Text Available Sjögren-Larsson syndrome (SLS is an inherited neurocutaneous disorder caused by mutations in the aldehyde dehydrogenase family 3 member A2 (ALDH3A2 gene that encodes fatty aldehyde dehydrogenase. Affected patients display ichthyosis, mental retardation, and spastic diplegia. More than 70 mutations in ALDH3A2 have been discovered in SLS patients. We diagnosed two brothers age of 12 and 20 years with characteristic features of this rare syndrome. Magnetic resonance imaging showed demyelinating disease in both of them. We described a novel homozygous, c. 835 T > A (p.Y279N mutation in exon 6 in two patients.

  8. Concurrent nephrotic syndrome and acute renal failure caused by chronic lymphocytic leukemia (CLL): a case report and literature review.

    Science.gov (United States)

    Dou, Xianrui; Hu, Haitang; Ju, Yongle; Liu, Yongdong; Kang, Kaifu; Zhou, Shufeng; Chen, Wenfang

    2011-10-13

    Kidney injury associated with lymphocytic leukemia (CLL) is typically caused by direct tumor infiltration which occasionally results in acute renal failure. Glomerular involvement presenting as proteinuria or even nephrotic syndrome is exceptionally rare. Here we report a case of 54-year-old male CLL patient with nephrotic syndrome and renal failure. The lymph node biopsy confirmed that the patients had CLL with remarkable immunoglobulin light chain amyloid deposition. The renal biopsy demonstrated the concurrence of AL amyloidosis and neoplastic infiltration. Combined treatment of fludarabine, cyclophosphamide and rituximab resulted in remission of CLL, as well as the renal disfunction and nephrotic syndrome, without recurrence during a 12-month follow-up. To our knowledge, this is the first case of CLL patient showing the nephrotic syndrome and acute renal failure caused by AL amyloidosis and neoplastic infiltration. Though AL amyloidosis caused by plasma cell dyscrasia usually responses poorly to chemotherapy, this patient exhibited a satisfactory clinical outcome due to successful inhibition of the production of amylodogenic light chains by combined chemotherapy.

  9. Bovine Neonatal Pancytopenia: is this alloimmune syndrome caused by vaccine-induced alloreactive antibodies?

    Science.gov (United States)

    Bastian, Max; Holsteg, Mark; Hanke-Robinson, Heidrun; Duchow, Karin; Cussler, Klaus

    2011-07-18

    Bovine Neonatal Pancytopenia (BNP) is a new emerging disease observed since 2007 in Germany and neighbouring countries. The syndrome affects newborn calves and is characterized by pancytopenia, severe bleeding and high lethality. So far, a causative role of infectious or toxic agents has been ruled out. Instead, the syndrome is induced after ingestion of colostrum, the first milk that supplies the calf with maternal antibodies. In analogy to similar diseases in humans it has therefore been postulated that BNP is caused by alloreactive, maternal antibodies. There is a striking association between BNP and a previous vaccination of the respective dams with a particular vaccine against Bovine Virus Diarrhoea (BVD). This association has led to a suspension of the marketing authorisation for the vaccine, by the European Commission. The current study investigates the role of this vaccine in the pathogenesis of BNP. By flow cytometry we were able to demonstrate that sera of BNP dams (dams that gave birth to a BNP calf) harbour alloreactive antibodies binding to surface antigens on bovine leukocytes. A significantly weaker alloreactivity was observed with sera of non-BNP dams that have been vaccinated with the same vaccine but delivered healthy calves. No binding was seen with non-BVD-vaccinated control cows and animals that were vaccinated with other inactivated BVD vaccines so far not associated with BNP. The binding is functionally relevant, because opsonization of bovine leukocytes with alloantibodies led to an elevated cytophagocytosis by bovine macrophages. To test whether the vaccine induces alloreactive antibodies two strategies were employed: Guinea pigs were vaccinated with a panel of commercially available BVD-vaccines. Only the incriminated vaccine induced antibodies binding surface antigens on bovine leukocytes. Additionally, two calves were repeatedly vaccinated with the suspected vaccine and the development of alloreactivity was monitored. In dependence of

  10. A new mutation causing autosomal dominant periodic fever syndrome in a Danish family

    DEFF Research Database (Denmark)

    Weyhreter, Heike; Schwartz, Marianne; Kristensen, Tim D;

    2003-01-01

    We describe four members in a family of 8 individuals over 3 generations with the autosomal dominant inherited periodic fever syndrome tumor necrosis factor receptor-associated periodic syndrome (TRAPS). The patients had recurrent episodes of fever, abdominal pain, arthritis, and rash. We examine...

  11. Saethre-Chotzen syndrome : cranofacial anomalies caused by genetic changes in the TWIST gene

    NARCIS (Netherlands)

    I.M. de Heer (Marieke)

    2004-01-01

    textabstractIn this thesis, one of the most frequently occurring and most variable craniosynostosis syndromes was investigated; Saethre-Chotzen syndrome. Craniosynostosis is the premature obliteration of cranial sutures in the developing embryo. It can also occur in the first few months of life. Sae

  12. De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

    DEFF Research Database (Denmark)

    Hoischen, Alexander; van Bon, Bregje W M; Rodríguez-Santiago, Benjamín;

    2011-01-01

    Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which...

  13. Partial duplications of the ATRX gene cause the ATR-X syndrome.

    Science.gov (United States)

    Thienpont, Bernard; de Ravel, Thomy; Van Esch, Hilde; Van Schoubroeck, Dominique; Moerman, Philippe; Vermeesch, Joris Robert; Fryns, Jean-Pierre; Froyen, Guy; Lacoste, Caroline; Badens, Catherine; Devriendt, Koen

    2007-10-01

    ATR-X syndrome is a rare syndromic X-linked mental retardation disorder. We report that some of the patients suspected of ATR-X carry large intragenic duplications in the ATRX gene, leading to an absence of ATRX mRNA and of the protein. These findings underscore the need for including quantitative analyses to mutation analysis of the ATRX gene.

  14. A Novel MAPT Mutation Causing Corticobasal Syndrome Led by Progressive Apraxia of Speech.

    Science.gov (United States)

    Marshall, Charles R; Guerreiro, Rita; Thust, Steffi; Fletcher, Phillip; Rohrer, Jonathan D; Fox, Nick C

    2015-01-01

    The authors describe a case of corticobasal syndrome led by progressive apraxia of speech, associated with a novel mutation in exon 10 of the MAPT gene. Genetic bases for progressive apraxia of speech and corticobasal syndrome are only rarely described, and have not been described in conjunction.

  15. Moyamoya disease associated with asymptomatic mosaic Turner syndrome: a rare cause of hemorrhagic stroke.

    Science.gov (United States)

    Manjila, Sunil; Miller, Benjamin R; Rao-Frisch, Anitha; Otvos, Balint; Mitchell, Anna; Bambakidis, Nicholas C; De Georgia, Michael A

    2014-01-01

    Moyamoya disease is a rare cerebrovascular anomaly involving the intracranial carotid arteries that can present clinically with either ischemic or hemorrhagic disease. Moyamoya syndrome, indistinguishable from moyamoya disease at presentation, is associated with multiple clinical conditions including neurofibromatosis type 1, autoimmune disease, prior radiation therapy, Down syndrome, and Turner syndrome. We present the first reported case of an adult patient with previously unrecognized mosaic Turner syndrome with acute subarachnoid and intracerebral hemorrhage as the initial manifestation of moyamoya syndrome. A 52-year-old woman was admitted with a subarachnoid hemorrhage with associated flame-shaped intracerebral hemorrhage in the left frontal lobe. Physical examination revealed short stature, pectus excavatum, small fingers, micrognathia, and mild facial dysmorphism. Cerebral angiography showed features consistent with bilateral moyamoya disease, aberrant intrathoracic vessels, and an unruptured 4-mm right superior hypophyseal aneurysm. Genetic analysis confirmed a diagnosis of mosaic Turner syndrome. Our case report is the first documented presentation of adult moyamoya syndrome with subarachnoid and intracerebral hemorrhage as the initial presentation of mosaic Turner syndrome. It illustrates the utility of genetic evaluation in patients with cerebrovascular disease and dysmorphism.

  16. A new mutation causing autosomal dominant periodic fever syndrome in a Danish family

    DEFF Research Database (Denmark)

    Weyhreter, Heike; Schwartz, Marianne; Kristensen, Tim D

    2003-01-01

    We describe four members in a family of 8 individuals over 3 generations with the autosomal dominant inherited periodic fever syndrome tumor necrosis factor receptor-associated periodic syndrome (TRAPS). The patients had recurrent episodes of fever, abdominal pain, arthritis, and rash. We examined...

  17. Compound heterozygosity for mutations in LMNA causes a progeria syndrome without prelamin A accumulation.

    NARCIS (Netherlands)

    Verstraeten, V.L.; Broers, J.L.; Steensel, M.A.M. van; Zinn-Justin, S.; Ramaekers, F.C.S.; Steijlen, P.M.; Kamps, M.; Kuijpers, H.J.; Merckx, D.; Smeets, H.J.M.; Hennekam, R.C.M.; Marcelis, C.L.M.; Wijngaard, A. van de

    2006-01-01

    LMNA-associated progeroid syndromes have been reported with both recessive and dominant inheritance. We report a 2-year-old boy with an apparently typical Hutchinson-Gilford progeria syndrome (HGPS) due to compound heterozygous missense mutations (p.T528M and p.M540T) in LMNA. Both mutations affect

  18. Antiphospholipid Syndrome with Antiβ2glicoprotein-1 Antibodies as the Cause of Recurrent Tibial Vein Thrombosis in SAPHO syndrome.

    Science.gov (United States)

    Przepiera-Będzak, Hanna; Brzosko, Marek

    2016-12-01

    thrombosis in this syndrome, but the patient with multiple venous thrombosis presented in his case report was negative for aCL antibodies; however, he was not tested for anti-β2G-1 antibodies. There was a paper demonstrating increased level of aCL antibodies in 5 of 12 patients with SAPHO syndrome (11). In our observations of 17 patients with SAPHO syndrome, only 1 had increased level of aCL antibodies without symptoms of thrombosis (12). That patient was negative for aCL antibodies, aPT antibodies, aPS antibodies, and antiphosphatidylserine antibodies, but she was positive twice for anti-β2G-1 antibodies. The presence of anti-β2G-1antibodies may be caused by an infectious agent, but in our case bacteria culture of the discharge from pustules was negative. One year after the first episode of deep vein thrombosis, our patient met the criteria of antiphospholipid syndrome. We conclude that antiphospholipid syndrome, especially the presence of anti-β2G-1 antibodies, could be the cause of increased risk of vein thrombosis in SAPHO syndrome.

  19. Partial Oculocutaneous Albinism: Two Siblings with Features of both Hermansky Pudlak and Waardenburg's Syndrome.

    Science.gov (United States)

    Ishaq, Mazhar; Niazi, Muhammad Khizar; Khan, Muhammad Saim; Nadeem, Yasser

    2015-04-01

    Albinism is an inherited abnormality of melanin synthesis with incidence of one per 20,000 births. Its clinical manifestations are related to the reduction or absence of pigmentation in the visual system and/or the skin and teguments. The clinical spectrum of Oculocutaneous Albinism (OCA) has four types ranging from OCA 1 - 4, of which OCA 1, A-1 is the most severe form. Partial cutaneous albinism which is a subtype of OCA is associated with systemic immunodeficiency disorders like Chediak Higashi (CHS), Griscelli (GS) and Hermansky-Pudlak (HPS) syndromes. A7 years boy was labeled initially as a case of Hermansky Pudlak syndrome at the age of 01 year. He as well as his 4 years old younger brother when examined in detail along with audiological investigations were diagnosed as a rare presentation of both Hermansky Pudlak and Waardenburg's syndrome.

  20. Down Syndrome: Eye Problems

    Science.gov (United States)

    ... En Español Read in Chinese What causes Down syndrome? Down syndrome is caused by a duplication of all ... in persons with Down syndrome. How common is Down syndrome? The frequency of Down syndrome is approximately 1 ...

  1. NAA10 mutation causing a novel intellectual disability syndrome with Long QT due to N-terminal acetyltransferase impairment

    Science.gov (United States)

    Casey, Jillian P.; Støve, Svein I.; McGorrian, Catherine; Galvin, Joseph; Blenski, Marina; Dunne, Aimee; Ennis, Sean; Brett, Francesca; King, Mary D.; Arnesen, Thomas; Lynch, Sally Ann

    2015-01-01

    We report two brothers from a non-consanguineous Irish family presenting with a novel syndrome characterised by intellectual disability, facial dysmorphism, scoliosis and long QT. Their mother has a milder phenotype including long QT. X-linked inheritance was suspected. Whole exome sequencing identified a novel missense variant (c.128 A > C; p.Tyr43Ser) in NAA10 (X chromosome) as the cause of the family’s disorder. Sanger sequencing confirmed that the mutation arose de novo in the carrier mother. NAA10 encodes the catalytic subunit of the major human N-terminal acetylation complex NatA. In vitro assays for the p.Tyr43Ser mutant enzyme showed a significant decrease in catalytic activity and reduced stability compared to wild-type Naa10 protein. NAA10 has previously been associated with Ogden syndrome, Lenz microphthalmia syndrome and non-syndromic developmental delay. Our findings expand the clinical spectrum of NAA10 and suggest that the proposed correlation between mutant Naa10 enzyme activity and phenotype severity is more complex than anticipated; the p.Tyr43Ser mutant enzyme has less catalytic activity than the p.Ser37Pro mutant associated with lethal Ogden syndrome but results in a milder phenotype. Importantly, we highlight the need for cardiac assessment in males and females with NAA10 variants as both patients and carriers can have long QT. PMID:26522270

  2. Differentiating cause-of-death terminology for deaths coded as sudden infant death syndrome, accidental suffocation, and unknown cause: an investigation using US death certificates, 2003-2004.

    Science.gov (United States)

    Kim, Shin Y; Shapiro-Mendoza, Carrie K; Chu, Susan Y; Camperlengo, Lena T; Anderson, Robert N

    2012-03-01

    We compared written text on infant death certificates for deaths coded as sudden infant death syndrome (R95), unknown cause (R99), and accidental suffocation (W75). Using US mortality files supplemented with the death certifiers' written text for all infant deaths with International Classification of Diseases (ICD)-10 assigned codes R95, R99, and W75, we formed cause-of-death subcategories from common themes identified from the written text. Among all infant deaths in 2003-2004, the underlying cause of death was listed as R99 for 2128 deaths, R95 for 4408 deaths, and W75 for 931 deaths. Among the postneonatal deaths, the differences in subcategories varied between assigned ICD-10 codes: for R99-coded deaths, 45.8% were categorized as "Unknown" and 48.6% as "Pending"; for R95-coded deaths, 67.7% were categorized as "sudden infant death syndrome (SIDS)"; and for W75-coded deaths, 76.4% were categorized as "Suffocation." Examination of the written text on the death certificates demonstrates variability in the assigned ICD-10 codes which could have an important effect on the estimates of SIDS cases in the United States.

  3. A Novel Homozygous Mutation in FOXC1 Causes Axenfeld Rieger Syndrome with Congenital Glaucoma.

    Directory of Open Access Journals (Sweden)

    Shazia Micheal

    Full Text Available Anterior segment dysgenesis (ASD disorders are a group of clinically and genetically heterogeneous phenotypes in which frequently cornea, iris, and lens are affected. This study aimed to identify novel mutations in PAX6, PITX2 and FOXC1 in families with anterior segment dysgenesis disorders.We studied 14 Pakistani and one Mexican family with Axenfeld Rieger syndrome (ARS; n = 10 or aniridia (n = 5. All affected and unaffected family members underwent full ophthalmologic and general examinations. Total genomic DNA was isolated from peripheral blood. PCR and Sanger sequencing were performed for the exons and intron-exon boundaries of the FOXC1, PAX6, and PITX2 genes.Mutations were identified in five of the 15 probands; four variants were novel and one variant was described previously. A novel de novo variant (c.225C>A; p.Tyr75* was identified in the PAX6 gene in two unrelated probands with aniridia. In addition, a known variant (c.649C>T; p.Arg217* in PAX6 segregated in a family with aniridia. In the FOXC1 gene, a novel heterozygous variant (c.454T>C; p.Trp152Arg segregated with the disease in a Mexican family with ARS. A novel homozygous variant (c.92_100del; p.Ala31_Ala33del in the FOXC1 gene segregated in a Pakistani family with ARS and congenital glaucoma.Our study expands the mutation spectrum of the PAX6 and FOXC1 genes in individuals with anterior segment dysgenesis disorders. In addition, our study suggests that FOXC1 mutations, besides typical autosomal dominant ARS, can also cause ARS with congenital glaucoma through an autosomal recessive inheritance pattern. Our results thus expand the disease spectrum of FOXC1, and may lead to a better understanding of the role of FOXC1 in development.

  4. Quantitative and sensitive detection of GNAS mutations causing mccune-albright syndrome with next generation sequencing.

    Science.gov (United States)

    Narumi, Satoshi; Matsuo, Kumihiro; Ishii, Tomohiro; Tanahashi, Yusuke; Hasegawa, Tomonobu

    2013-01-01

    Somatic activating GNAS mutations cause McCune-Albright syndrome (MAS). Owing to low mutation abundance, mutant-specific enrichment procedures, such as the peptide nucleic acid (PNA) method, are required to detect mutations in peripheral blood. Next generation sequencing (NGS) can analyze millions of PCR amplicons independently, thus it is expected to detect low-abundance GNAS mutations quantitatively. In the present study, we aimed to develop an NGS-based method to detect low-abundance somatic GNAS mutations. PCR amplicons encompassing exons 8 and 9 of GNAS, in which most activating mutations occur, were sequenced on the MiSeq instrument. As expected, our NGS-based method could sequence the GNAS locus with very high read depth (approximately 100,000) and low error rate. A serial dilution study with use of cloned mutant and wildtype DNA samples showed a linear correlation between dilution and measured mutation abundance, indicating the reliability of quantification of the mutation. Using the serially diluted samples, the detection limits of three mutation detection methods (the PNA method, NGS, and combinatory use of PNA and NGS [PNA-NGS]) were determined. The lowest detectable mutation abundance was 1% for the PNA method, 0.03% for NGS and 0.01% for PNA-NGS. Finally, we analyzed 16 MAS patient-derived leukocytic DNA samples with the three methods, and compared the mutation detection rate of them. Mutation detection rate of the PNA method, NGS and PNA-NGS in 16 patient-derived peripheral blood samples were 56%, 63% and 75%, respectively. In conclusion, NGS can detect somatic activating GNAS mutations quantitatively and sensitively from peripheral blood samples. At present, the PNA-NGS method is likely the most sensitive method to detect low-abundance GNAS mutation.

  5. Quantitative and sensitive detection of GNAS mutations causing mccune-albright syndrome with next generation sequencing.

    Directory of Open Access Journals (Sweden)

    Satoshi Narumi

    Full Text Available Somatic activating GNAS mutations cause McCune-Albright syndrome (MAS. Owing to low mutation abundance, mutant-specific enrichment procedures, such as the peptide nucleic acid (PNA method, are required to detect mutations in peripheral blood. Next generation sequencing (NGS can analyze millions of PCR amplicons independently, thus it is expected to detect low-abundance GNAS mutations quantitatively. In the present study, we aimed to develop an NGS-based method to detect low-abundance somatic GNAS mutations. PCR amplicons encompassing exons 8 and 9 of GNAS, in which most activating mutations occur, were sequenced on the MiSeq instrument. As expected, our NGS-based method could sequence the GNAS locus with very high read depth (approximately 100,000 and low error rate. A serial dilution study with use of cloned mutant and wildtype DNA samples showed a linear correlation between dilution and measured mutation abundance, indicating the reliability of quantification of the mutation. Using the serially diluted samples, the detection limits of three mutation detection methods (the PNA method, NGS, and combinatory use of PNA and NGS [PNA-NGS] were determined. The lowest detectable mutation abundance was 1% for the PNA method, 0.03% for NGS and 0.01% for PNA-NGS. Finally, we analyzed 16 MAS patient-derived leukocytic DNA samples with the three methods, and compared the mutation detection rate of them. Mutation detection rate of the PNA method, NGS and PNA-NGS in 16 patient-derived peripheral blood samples were 56%, 63% and 75%, respectively. In conclusion, NGS can detect somatic activating GNAS mutations quantitatively and sensitively from peripheral blood samples. At present, the PNA-NGS method is likely the most sensitive method to detect low-abundance GNAS mutation.

  6. A comprehensive review on experimental and clinical findings in intermediate syndrome caused by organophosphate poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Abdollahi, Mohammad, E-mail: mohammad.abdollahi@utoronto.ca; Karami-Mohajeri, Somayyeh

    2012-02-01

    Acute organophosphate (OP) intoxication is important because of its high morbidity and mortality and occurrence of muscular paralysis associated by inhibition of acetylcholinesterase (AChE) activity at the neuromuscular junction. Cholinergic crisis, intermediate syndrome (IMS), and OP-induced delayed neuropathy (OPIDN) are the evidences that can be observed in OP intoxication. The main cause of morbidity due to OP poisoning is IMS that occurs 24–96 h after poisoning. Mechanisms underlying the IMS are not fully known. Although the electrophysiological aspects of delayed neuropathy are best characterized, the IMS remain very little studied. The aim of this study was to revisit current knowledge related to OP and the IMS. For this purpose, a systematic review without date limitation was performed. A total of 599 relevant articles were found and reviewed. Data were categorized according to experimental and clinical studies. Occurrences of persistent AChE inhibition, electromyography changes, muscle cell injury, and oxidative stress are the most important pieces of evidence for involvement of IMS in OP toxicity. Delayed AChE inhibition, muscle necrosis, down regulation or desensitization of postsynaptic ACh receptors, failure of postsynaptic ACh release, and oxidative stress-related myopathy are involved in IMS. Toxicokinetic factors, such as a high lipid-solubility, duration of AChE inhibition and metabolite excretion, evolution of alterations on repetitive nerve stimulation (RNS), type and frequency of muscle lesions can estimate the probability of the IMS. Plasma AChE of less than 200 units is a predictor and the 30 Hz RNS decremental response could be a useful marker for the IMS.

  7. Takotsubo Syndrome as a Cause of False Acute Abdomen in the Early Postoperative Period After Bariatric Surgery-a Report of Two Cases.

    Science.gov (United States)

    Viegas, Fabio; Viegas, Carla; França, Enio; Kleuser, Klaus; de Barros, Fernando

    2016-10-01

    Takotsubo syndrome, also known as broken-heart syndrome, stress-induced cardiomyopathy or transient apical ballooning syndrome, is a transient disorder characterized by segmental left ventricular failure in the absence of obstructive coronary artery disease. Most cases of Takotsubo syndrome are caused by acute stress that leads to a sudden, temporary weakening of the cardiac musculature. This stress triggers a rise in circulating catecholamine levels that results in acute ventricular dysfunction. In this report, we describe two cases of Takotsubo syndrome in the early postoperative period after bariatric surgery.

  8. Cerebral salt wasting syndrome in brain injury patients: a potential cause of hyponatremia.

    Science.gov (United States)

    Zafonte, R D; Mann, N R

    1997-05-01

    Hyponatremia is a common neuromedical problem seen in survivors of central nervous system injury. The etiology of this hyponatremia is often diagnosed as syndrome of inappropriate diuretic hormone (SIADH). Fluid restriction is usually the first line of treatment. However, this can exacerbate vasospasm and produce resultant ischemia. Cerebral salt wasting is a syndrome of renal sodium loss that may occur commonly after central nervous system injury, yet remains unrecognized. Treatment of cerebral salt wasting consists of hydration and salt replacement. This article uses a case report to discuss the importance of recognition of this syndrome, and treatment concerns are reviewed.

  9. Carpal tunnel syndrome caused by a giant cell tumour of the flexor tendon sheath.

    Science.gov (United States)

    Meek, Marcel F; Sheikh, Zahid A; Quinton, David N

    2014-02-01

    A 76-year-old woman developed right carpal tunnel syndrome after being conservatively treated for tenosynovitis of the flexor tendons with associated mild carpal tunnel syndrome. A magnetic resonance imaging scan showed a tumour in the carpal tunnel. Re-exploration showed that the median nerve was being compressed by a giant cell tumour of the flexor tendon sheaths. Appropriate imaging is advised in patients with additional findings (such as swelling) or in patients with secondary carpal tunnel syndrome and incomplete response to conservative treatment, to exclude a space-occupying lesion.

  10. Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy

    Science.gov (United States)

    Cullup, Thomas; Kho, Ay L.; Dionisi-Vici, Carlo; Brandmeier, Birgit; Smith, Frances; Urry, Zoe; Simpson, Michael A.; Yau, Shu; Bertini, Enrico; McClelland, Verity; Al-Owain, Mohammed; Koelker, Stefan; Koerner, Christian; Hoffmann, Georg F.; Wijburg, Frits A.; Hoedt, Amber E. ten; Rogers, Curtis; Manchester, David; Miyata, Rie; Hayashi, Masaharu; Said, Elizabeth; Soler, Doriette; Kroisel, Peter M.; Windpassinger, Christian; Filloux, Francis M.; Al-Kaabi, Salwa; Hertecant, Jozef; Del Campo, Miguel; Buk, Stefan; Bodi, Istvan; Goebel, Hans-Hilmar; Sewry, Caroline A.; Abbs, Stephen; Mohammed, Shehla; Josifova, Dragana; Gautel, Mathias; Jungbluth, Heinz

    2012-01-01

    Vici syndrome is a recessively inherited multisystem disorder characterized by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and hypopigmentation. To investigate the molecular basis of Vici syndrome, we carried out exome and Sanger sequence analysis in a cohort of 18 patients. We identified recessive mutations in EPG5 (previously KIAA1632), indicating a causative role in Vici syndrome. EPG5 is the human homologue of the metazoan-specific autophagy gene epg-5, encoding a key autophagy regulator (ectopic P-granules autophagy protein 5) implicated in the formation of autolysosomes. Further studies demonstrated a severe block of autophagosomal clearance in muscle and fibroblasts from EPG5 mutant patients, resulting in autophagic cargo accumulation in autophagosomes. These findings indicate Vici syndrome as a paradigm of a human multisystem disorder associated with defective autophagy, and suggest a fundamental role of the autophagy pathway in the anatomical and functional formation of organs such as the brain, the heart and the immune system. PMID:23222957

  11. Acute calcifying tendonitis--an unusual cause of carpal tunnel syndrome.

    Science.gov (United States)

    Din, R; Giannikas, K; El-Hadidi, M

    2001-03-01

    We report a rare case of acute calcifying tendinitis resulting in acute carpal tunnel syndrome. Acute medical staff should be aware of this condition and the importance of early referral to avoid long term median nerve neuropathy.

  12. POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker-Warburg syndrome

    NARCIS (Netherlands)

    van Reeuwijk, J; Janssen, M; van den Elzen, C; de Bernabe, DBV; Sabatelli, P; Merlini, L; Boon, M; Scheffer, H; Brockington, M; Muntoni, F; Huynen, MA; Verrips, A; Walsh, CA; Barth, PG; Brunner, HG; van Bokhoven, H

    2005-01-01

    Background: Walker-Warburg syndrome (WWS) is an autosomal recessive condition characterised by congenital muscular dystrophy, structural brain defects, and eye malformations. Typical brain abnormalities are hydrocephalus, lissencephaly, agenesis of the corpus callosum, fusion of the hemispheres, cer

  13. POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker-Warburg syndrome.

    NARCIS (Netherlands)

    Reeuwijk, J. van; Janssen, M.; Elzen, C. van der; Beltran Valero de Bernabe, D.; Sabatelli, P.; Merlini, L.; Boon, M.; Scheffer, H.; Brockington, M.; Muntoni, F.; Huynen, M.A.; Verrips, A.; Walsh, C.A.; Barth, P.G.; Brunner, H.G.; Bokhoven, J.H.L.M. van

    2005-01-01

    BACKGROUND: Walker-Warburg syndrome (WWS) is an autosomal recessive condition characterised by congenital muscular dystrophy, structural brain defects, and eye malformations. Typical brain abnormalities are hydrocephalus, lissencephaly, agenesis of the corpus callosum, fusion of the hemispheres, cer

  14. Feasibility of radiation dose range capable to cause subacute course of radiation syndrome

    Directory of Open Access Journals (Sweden)

    Krasnyuk V.I.

    2013-12-01

    Full Text Available There had been analysed cases of radiation syndrome which clinical picture takes an intermediate place between the acute radiation syndrome (ARS and the chronic radiation syndrome (CRS, and differs from them because of a subacute. This variant of disease can develop as a result of the fractioned or prolonged radiation lasting from several days to several weeks. Development of primary reaction took place only in the extremely hard cases which ends with an early fatality. After the general radiation the marrow failure was characterized by directly expressed formation and restoration period, specific features of which were defined by the radiation duration, a total dose and dose derivative. The most typical outcomes of a subacute radiation syndrome are death from infectious complications in the period of an eruptive phase or leukosis development in the remote period.

  15. Unilateral adrenalectomy can be an alternative therapy for infantile onset Cushing' s syndrome caused by ACTH-independent macronodular adrenal hyperplasia with McCune-Albright syndrome.

    Science.gov (United States)

    Hamajima, Takashi; Maruwaka, Kaori; Homma, Keiko; Matsuo, Kumihiro; Fujieda, Kenji; Hasegawa, Tomonobu

    2010-01-01

    We report herein the case of a 1-year-old boy with McCune-Albright syndrome (MAS) who presented with infantile-onset Cushing' s syndrome caused by ACTH independent macronodular adrenal hyperplasia (AIMAH). Abdominal CT, MRI, and adrenal scintigraphy with (131)I-adosterol identified bilateral adrenal involvement with the left adrenal gland being larger and functionally more active. Unilateral adrenalectomy of the left gland was performed and ameliorated many clinical symptoms, such as Cushingoid appearance and height restriction, and it also normalized many endocrinological data, such as diurnal rhythms of ACTH and cortisol, ACTH and cortisol responses to CRH, and urinary 24 hr free cortisol. Glucocorticoid was replaced for the first 1 year and 6 months after the operation. One adrenal crisis episode occurred at 3 weeks after the operation, but none have occurred since. These results suggest that unilateral adrenalectomy of the larger gland can be an alternative therapy for infantile onset Cushing' s syndrome caused by AIMAH with MAS, when asymmetric involvement is evident and the smaller gland is not markedly enlarged.

  16. Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome.

    Science.gov (United States)

    Sousa, Sérgio B; Jenkins, Dagan; Chanudet, Estelle; Tasseva, Guergana; Ishida, Miho; Anderson, Glenn; Docker, James; Ryten, Mina; Sa, Joaquim; Saraiva, Jorge M; Barnicoat, Angela; Scott, Richard; Calder, Alistair; Wattanasirichaigoon, Duangrurdee; Chrzanowska, Krystyna; Simandlová, Martina; Van Maldergem, Lionel; Stanier, Philip; Beales, Philip L; Vance, Jean E; Moore, Gudrun E

    2014-01-01

    Lenz-Majewski syndrome (LMS) is a syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. By using whole-exome sequencing and selecting variants consistent with the predicted dominant de novo etiology of LMS, we identified causative heterozygous missense mutations in PTDSS1, which encodes phosphatidylserine synthase 1 (PSS1). PSS1 is one of two enzymes involved in the production of phosphatidylserine. Phosphatidylserine synthesis was increased in intact fibroblasts from affected individuals, and end-product inhibition of PSS1 by phosphatidylserine was markedly reduced. Therefore, these mutations cause a gain-of-function effect associated with regulatory dysfunction of PSS1. We have identified LMS as the first human disease, to our knowledge, caused by disrupted phosphatidylserine metabolism. Our results point to an unexplored link between phosphatidylserine synthesis and bone metabolism.

  17. A common cause of irritable bowel syndrome and diverticulitis: chronic distal colon distention from sedentary behavior and excessive dietary fiber.

    Science.gov (United States)

    Robbins, Steven E

    2013-07-01

    A multidisciplinary analysis restricted to validated reports was applied to the cause and management of irritable bowel syndrome and diverticular formation and subsequent diverticulitis. There is evidence that they are linked - both caused by attenuation of gravitational aid to distal intestinal motility, resulting in damaging chronic intestinal distention. Both irritable bowel syndrome and diverticular formation and subsequent diverticulitis have worsened in recent years owing to excessive dietary fiber intake. Potential solutions include augmenting weight-bearing time, moderating dietary fiber consumption, stimulating distal colon evacuation through chemical means and developing pharmaceuticals to block the reflexive distal colon distention associated with fiber consumption. Amplified intestinal distention commenced when all classes of Renaissance Europeans became the first group in human history to wear shoes, which led to a sedentary lifestyle that moderates gravitational aid to colon motility and evacuation.

  18. [Kimura's disease: an unrecognized cause of adult-onset nephrotic syndrome with minimal change disease].

    Science.gov (United States)

    Shehwaro, N; Langlois, A-L; Gueutin, V; Debchi, L; Charlotte, F; Rouvier, P; Rottembourg, J; Izzedine, H

    2014-02-01

    Kimura's disease (KD) is an angiolymphoid proliferative disorder of soft tissue with eosinophilia, with a predilection for head and neck regions in young Oriental men. Kidney disease is thought to be rare in KD. About a case of adult-onset nephrotic syndrome with minimal change disease, we comment Kimura's disease and its associated kidney damage. Kimura disease should be suspected and included in the diagnosis of adult-onset nephrotic syndrome with minimal change disease.

  19. Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Buchanan DD

    2014-10-01

    Full Text Available Daniel D Buchanan,1,2 Christophe Rosty,1,3,4 Mark Clendenning,1 Amanda B Spurdle,5 Aung Ko Win2 1Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia; 2Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia; 3Envoi Specialist Pathologists, Herston, QLD, Australia; 4School of Medicine, University of Queensland, Herston, QLD, Australia; 5Molecular Cancer Epidemiology Laboratory, Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Herston, QLD, AustraliaAbstract: Carriers of a germline mutation in one of the DNA mismatch repair (MMR genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome. MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the

  20. Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study

    OpenAIRE

    Sun, Bing; He, Hangyong; Wang, Zheng; Qu, Jiuxin; Li, Xuyan; Chengjun BAN; Wan, Jun; Cao, Bin; Tong, Zhaohui; Wang, Chen

    2014-01-01

    Introduction Since 2008, severe cases of emerging human adenovirus type 55 (HAdV-55) in immunocompetent adults have been reported sporadically in China. The clinical features and outcomes of the most critically ill patients with severe acute respiratory distress syndrome (ARDS) caused by HAdV-55 requiring invasive mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation (ECMO) are lacking. Methods We conducted a prospective, single-center observational study of pneumonia with A...

  1. An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs

    OpenAIRE

    Fyfe, John C.; Hemker, Shelby L.; Venta, Patrick J.; Fitzgerald, Caitlin A.; Outerbridge, Catherine A.; Myers, Sherry L.; Giger, Urs

    2013-01-01

    Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9 M...

  2. Novel group A rotavirus G8 P[1] as primary cause of an ovine diarrheic syndrome outbreak in weaned lambs

    OpenAIRE

    Galindo-Cardiel, I.; Fernández-Jiménez, M.; Luján, L.; Buesa, J.; Espada, J.; Fantova, E.; Blanco, J; Segalés, J.; Badiola, J. J.

    2011-01-01

    Abstract Rotavirus is a worldwide major cause of diarrhea outbreaks in neonatal ruminants. An outbreak of ovine diarrheic syndrome (ODS) in 50-75 days-old lambs (weaned lambs) is described. Fecal immunochromatography and intestinal immunohistochemistry for rotavirus group A were performed. In addition, semi-nested multiplex RT-PCR for G and P rotavirus genotyping in combination with sequencing were performed, to support the diagnosis and identify the viral strain. A novel ovine rot...

  3. Heterozygous Pathogenic Variant in DACT1 Causes an Autosomal-Dominant Syndrome with Features Overlapping Townes–Brocks Syndrome

    Science.gov (United States)

    Webb, Bryn D.; Metikala, Sanjeeva; Wheeler, Patricia G.; Sherpa, Mingma D.; Houten, Sander M.; Horb, Marko E.; Schadt, Eric E.

    2017-01-01

    A heterozygous nonsense variant was identified in dapper, antagonist of beta-catenin, 1 (DACT1) via whole-exome sequencing in family members with imperforate anus, structural renal abnormalities, genitourinary anomalies, and/or ear anomalies. The DACT1 c.1256G>A;p.Trp419* variant segregated appropriately in the family consistent with an autosomal dominant mode of inheritance. DACT1 is a member of the Wnt-signaling pathway, and mice homozygous for null alleles display multiple congenital anomalies including absent anus with blind-ending colon and genitourinary malformations. To investigate the DACT1 c.1256G>A variant, HEK293 cells were transfected with mutant DACT1 cDNA plasmid, and immunoblotting revealed stability of the DACT1 p.Trp419* protein. Overexpression of DACT1 c.1256G>A mRNA in Xenopus embryos revealed a specific gastrointestinal phenotype of enlargement of the proctodeum. Together, these findings suggest that the DACT1 c.1256G>A nonsense variant is causative of a specific genetic syndrome with features overlapping Townes–Brocks syndrome. PMID:28054444

  4. Posterior Nutcracker Syndrome with Left Renal Vein Duplication: A Rare Cause of Haematuria in a 12-Year-Old Boy

    Directory of Open Access Journals (Sweden)

    J. Preza Fernandes

    2012-01-01

    Full Text Available The nutcracker syndrome (NCS is a rare cause of haematuria. It embraces an extended nonpathognomonic spectrum of symptoms that imply a difficult diagnosis. Ultimately it may be associated with substantial morbidity and even life-threatening events. We report a rare cause if a 12-year-old boy who presented with a history of frequent intermittent episodes of painless constant haematuria. The cystoscopy showed a bloody urine ejaculate from the left ureter meatus. The Doppler ultrasonography showed turbulent pattern of venous blood flow of the posterior renal vein branch behind the aorta. The abdominopelvic computer tomography (apCT revealed left renal vein (LRV duplication with a dilated retroaortic branch, entrapped between the aorta and the vertebral column, promoting the renal nutcracker syndrome. The patient was initially hospitalized and managed with oral iron supplements and continuous saline bladder irrigation, not requiring additional treatment. The child is currently asymptomatic, with haemoglobin value returning to normal and therefore proposed to conservative management with close followup. The authors present a case report of episodic haematuria caused by a rare entity—posterior nutcracker syndrome with renal vein duplication.

  5. PROTOCOL FOR THE EVALUATION AND FUNCTIONAL RE-EDUCATION OF THE LUMBARSACRAL PAIN SYNDROME WITH A MUSCULAR-LIGAMENT CAUSE

    Directory of Open Access Journals (Sweden)

    Călina Mirela-Lucia

    2009-03-01

    Full Text Available The current paper aims to evaluate the lumbar-sacral algo-functional syndromes with a muscular-ligament cause and to establish a staged program for its functional recovery which would also prevent reoccurrences and/ or complications, these being relatively frequent and with important functional implications [1]. These ailments,specific to patients who are at an active age have a particular social impact, important morbidity and can be easily mistaken for more serious lumbar-sacral ailments, thus leading to disproportionately serious, but inefficient for thereal cause, treatments [4].The study was made over a period of 6 months, on 18 patients with lumbar-sacral syndrome with a muscularligament cause, diagnosed as a result of clinical and paraclinic evaluation, an alternative etiology of the syndrome being excluded. The patients were integrated into a functional re-education programme which included drug therapy (anti-inflammatory +/- relaxant medication, physically-kinetically supported (thermal-kinetic-massage therapy, staged into 2 weeks, one and 3-6 months intervals, respectively. The results obtained emphasise the improvement in the clinical parameters form one stage to the other, in the third stage of the programme reaching asemi-complete (over 90% recovery of the affected areas, compared to the initial stages.

  6. Endothelial neuropilin disruption in mice causes DiGeorge syndrome-like malformations via mechanisms distinct to those caused by loss of Tbx1.

    Directory of Open Access Journals (Sweden)

    Jingjing Zhou

    Full Text Available The spectrum of human congenital malformations known as DiGeorge syndrome (DGS is replicated in mice by mutation of Tbx1. Vegfa has been proposed as a modifier of DGS, based in part on the occurrence of comparable phenotypes in Tbx1 and Vegfa mutant mice. Many additional genes have been shown to cause DGS-like phenotypes in mice when mutated; these generally intersect in some manner with Tbx1, and therefore impact the same developmental processes in which Tbx1 itself is involved. In this study, using Tie2Cre, we show that endothelial-specific mutation of the gene encoding the VEGFA coreceptor neuropilin-1 (Nrp1 also replicates the most prominent terminal phenotypes that typify DGS. However, the developmental etiologies of these defects are fundamentally different from those caused by absence of TBX1. In Tie2Cre/Nrp1 mutants, initial pharyngeal organization is normal but subsequent pharyngeal organ growth is impaired, second heart field differentiation is normal but cardiac outflow tract cushion organization is distorted, neural crest cell migration is normal, and palatal mesenchyme proliferation is impaired with no change in apoptosis. Our results demonstrate that impairment of VEGF-dependent endothelial pathways leads to a spectrum of DiGeorge syndrome-type malformations, through processes that are distinguishable from those controlled by Tbx1.

  7. Mutations in a TGF-β Ligand, TGFB3, Cause Syndromic Aortic Aneurysms and Dissections

    Science.gov (United States)

    Bertoli-Avella, Aida M.; Gillis, Elisabeth; Morisaki, Hiroko; Verhagen, Judith M.A.; de Graaf, Bianca M.; van de Beek, Gerarda; Gallo, Elena; Kruithof, Boudewijn P.T.; Venselaar, Hanka; Myers, Loretha A.; Laga, Steven; Doyle, Alexander J.; Oswald, Gretchen; van Cappellen, Gert W.A.; Yamanaka, Itaru; van der Helm, Robert M.; Beverloo, Berna; de Klein, Annelies; Pardo, Luba; Lammens, Martin; Evers, Christina; Devriendt, Koenraad; Dumoulein, Michiel; Timmermans, Janneke; Bruggenwirth, Hennie T.; Verheijen, Frans; Rodrigus, Inez; Baynam, Gareth; Kempers, Marlies; Saenen, Johan; Van Craenenbroeck, Emeline M.; Minatoya, Kenji; Matsukawa, Ritsu; Tsukube, Takuro; Kubo, Noriaki; Hofstra, Robert; Goumans, Marie Jose; Bekkers, Jos A.; Roos-Hesselink, Jolien W.; van de Laar, Ingrid M.B.H.; Dietz, Harry C.; Van Laer, Lut; Morisaki, Takayuki; Wessels, Marja W.; Loeys, Bart L.

    2015-01-01

    Background Aneurysms affecting the aorta are a common condition associated with high mortality as a result of aortic dissection or rupture. Investigations of the pathogenic mechanisms involved in syndromic types of thoracic aortic aneurysms, such as Marfan and Loeys-Dietz syndromes, have revealed an important contribution of disturbed transforming growth factor (TGF)-β signaling. Objectives This study sought to discover a novel gene causing syndromic aortic aneurysms in order to unravel the underlying pathogenesis. Methods We combined genome-wide linkage analysis, exome sequencing, and candidate gene Sanger sequencing in a total of 470 index cases with thoracic aortic aneurysms. Extensive cardiological examination, including physical examination, electrocardiography, and transthoracic echocardiography was performed. In adults, imaging of the entire aorta using computed tomography or magnetic resonance imaging was done. Results Here, we report on 43 patients from 11 families with syndromic presentations of aortic aneurysms caused by TGFB3 mutations. We demonstrate that TGFB3 mutations are associated with significant cardiovascular involvement, including thoracic/abdominal aortic aneurysm and dissection, and mitral valve disease. Other systemic features overlap clinically with Loeys-Dietz, Shprintzen-Goldberg, and Marfan syndromes, including cleft palate, bifid uvula, skeletal overgrowth, cervical spine instability and clubfoot deformity. In line with previous observations in aortic wall tissues of patients with mutations in effectors of TGF-β signaling (TGFBR1/2, SMAD3, and TGFB2), we confirm a paradoxical up-regulation of both canonical and noncanonical TGF-β signaling in association with up-regulation of the expression of TGF-β ligands. Conclusions Our findings emphasize the broad clinical variability associated with TGFB3 mutations and highlight the importance of early recognition of the disease because of high cardiovascular risk. PMID:25835445

  8. Mutations in CHD7 in patients with CHARGE syndrome cause T-B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome.

    NARCIS (Netherlands)

    Gennery, A.R.; Slatter, M.A.; Rice, J.; Hoefsloot, L.H.; Barge, D.; McLean-Tooke, A.; Montgomery, T.; Goodship, J.A.; Burt, A.D.; Flood, T.J.; Abinun, M.; Cant, A.J.; Johnson, D.

    2008-01-01

    More than 11 genetic causes of severe combined immunodeficiency (SCID) have been identified, affecting development and/or function of T lymphocytes, and sometimes B lymphocytes and natural killer (NK) cells. Deletion of 22q11.2 is associated with immunodeficiency, although less than 1% of cases are

  9. CHARGE syndrome as unusual cause of hypogonadism: endocrine and molecular evaluation.

    Science.gov (United States)

    Foppiani, Luca; Maffè, A; Forzano, F

    2010-10-01

    Coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies (CHARGE) syndrome is a genetic syndrome in which hypogonadism is a frequent feature. A causative mutation within the chromodomain helicase DNA-binding protein-7 gene, which plays an important role in the embryonic development, is present in 2/3 of affected patients. We describe the clinical, hormonal and molecular characteristics of a young man from Ecuador who was diagnosed as having CHARGE syndrome at an adult age. The patient showed several phenotypic features of the syndrome, associated with a prepubertal state and cryptorchidism; hypogonadotrophic hypogonadism with undetectable testosterone levels not responsive to hCG testing and severe osteoporosis were ascertained. Molecular evaluation of the CHD7 gene showed the novel frameshift truncating heterozygous mutation p.Tyr1046Glyfs*23 in exon 12. Magnetic resonance imaging revealed mild hypoplasia of the pituitary gland and hypoplasia of the posterior cranial fossa. Parenteral testosterone therapy led to sexual development over time and, in combination with diphophonate therapy and calcium-vitamin D supplementation, significantly improved bone mineralisation. Early proper hormonal treatment of hypogonadism in patients with complex genetic syndromes is important to achieve normal sexual maturation, improve quality of life and avoid significant comorbidities, such as osteoporosis.

  10. Hip abductor weakness is not the cause for iliotibial band syndrome.

    Science.gov (United States)

    Grau, S; Krauss, I; Maiwald, C; Best, R; Horstmann, T

    2008-07-01

    Muscular deficits in the hip abductors are presumed to be a major factor in the development of Iliotibial Band Syndrome in runners. No definite relationship between muscular weakness of the hip abductors and the development of Iliotibial Band Syndrome or different ratios between hip adduction to abduction have been reported so far. Isokinetic measurements were taken from 10 healthy runners and 10 runners with Iliotibial Band Syndrome. Primary outcome variables were concentric, eccentric, and isometric peak torque of the hip abductors and adductors at 30 degrees/s, and a concentric endurance quotient at the same angle velocity. Differences in muscle strength of the hip abductors between healthy (CO) and injured runners (ITBS) were not statistically significant in any of the muscle functions tested. Both groups showed the same strength differences between hip adduction and abduction, and increased strength in hip adduction. Weakness of hip abductors does not seem to play a role in the etiology of Iliotibial Band Syndrome in runners, since dynamic and static strength measurements did not differ between groups, and differences between hip abduction and adduction were the same. Strengthening of hip abductors seems to have little effect on the prevention of Iliotibial Band Syndrome in runners.

  11. Mutations in the TGF-β repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm.

    Science.gov (United States)

    Doyle, Alexander J; Doyle, Jefferson J; Bessling, Seneca L; Maragh, Samantha; Lindsay, Mark E; Schepers, Dorien; Gillis, Elisabeth; Mortier, Geert; Homfray, Tessa; Sauls, Kimberly; Norris, Russell A; Huso, Nicholas D; Leahy, Dan; Mohr, David W; Caulfield, Mark J; Scott, Alan F; Destrée, Anne; Hennekam, Raoul C; Arn, Pamela H; Curry, Cynthia J; Van Laer, Lut; McCallion, Andrew S; Loeys, Bart L; Dietz, Harry C

    2012-11-01

    Elevated transforming growth factor (TGF)-β signaling has been implicated in the pathogenesis of syndromic presentations of aortic aneurysm, including Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). However, the location and character of many of the causal mutations in LDS intuitively imply diminished TGF-β signaling. Taken together, these data have engendered controversy regarding the specific role of TGF-β in disease pathogenesis. Shprintzen-Goldberg syndrome (SGS) has considerable phenotypic overlap with MFS and LDS, including aortic aneurysm. We identified causative variation in ten individuals with SGS in the proto-oncogene SKI, a known repressor of TGF-β activity. Cultured dermal fibroblasts from affected individuals showed enhanced activation of TGF-β signaling cascades and higher expression of TGF-β-responsive genes relative to control cells. Morpholino-induced silencing of SKI paralogs in zebrafish recapitulated abnormalities seen in humans with SGS. These data support the conclusions that increased TGF-β signaling is the mechanism underlying SGS and that high signaling contributes to multiple syndromic presentations of aortic aneurysm.

  12. Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.

    Directory of Open Access Journals (Sweden)

    Dennis Lal

    Full Text Available The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic.We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients.We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%. Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1 are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test, previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.

  13. Loss-of-function mutations in PTPN11 cause metachondromatosis, but not Ollier disease or Maffucci syndrome.

    Science.gov (United States)

    Bowen, Margot E; Boyden, Eric D; Holm, Ingrid A; Campos-Xavier, Belinda; Bonafé, Luisa; Superti-Furga, Andrea; Ikegawa, Shiro; Cormier-Daire, Valerie; Bovée, Judith V; Pansuriya, Twinkal C; de Sousa, Sérgio B; Savarirayan, Ravi; Andreucci, Elena; Vikkula, Miikka; Garavelli, Livia; Pottinger, Caroline; Ogino, Toshihiko; Sakai, Akinori; Regazzoni, Bianca M; Wuyts, Wim; Sangiorgi, Luca; Pedrini, Elena; Zhu, Mei; Kozakewich, Harry P; Kasser, James R; Seidman, Jon G; Kurek, Kyle C; Warman, Matthew L

    2011-04-01

    Metachondromatosis (MC) is a rare, autosomal dominant, incompletely penetrant combined exostosis and enchondromatosis tumor syndrome. MC is clinically distinct from other multiple exostosis or multiple enchondromatosis syndromes and is unlinked to EXT1 and EXT2, the genes responsible for autosomal dominant multiple osteochondromas (MO). To identify a gene for MC, we performed linkage analysis with high-density SNP arrays in a single family, used a targeted array to capture exons and promoter sequences from the linked interval in 16 participants from 11 MC families, and sequenced the captured DNA using high-throughput parallel sequencing technologies. DNA capture and parallel sequencing identified heterozygous putative loss-of-function mutations in PTPN11 in 4 of the 11 families. Sanger sequence analysis of PTPN11 coding regions in a total of 17 MC families identified mutations in 10 of them (5 frameshift, 2 nonsense, and 3 splice-site mutations). Copy number analysis of sequencing reads from a second targeted capture that included the entire PTPN11 gene identified an additional family with a 15 kb deletion spanning exon 7 of PTPN11. Microdissected MC lesions from two patients with PTPN11 mutations demonstrated loss-of-heterozygosity for the wild-type allele. We next sequenced PTPN11 in DNA samples from 54 patients with the multiple enchondromatosis disorders Ollier disease or Maffucci syndrome, but found no coding sequence PTPN11 mutations. We conclude that heterozygous loss-of-function mutations in PTPN11 are a frequent cause of MC, that lesions in patients with MC appear to arise following a "second hit," that MC may be locus heterogeneous since 1 familial and 5 sporadically occurring cases lacked obvious disease-causing PTPN11 mutations, and that PTPN11 mutations are not a common cause of Ollier disease or Maffucci syndrome.

  14. Loss-of-function mutations in PTPN11 cause metachondromatosis, but not Ollier disease or Maffucci syndrome.

    Directory of Open Access Journals (Sweden)

    Margot E Bowen

    2011-04-01

    Full Text Available Metachondromatosis (MC is a rare, autosomal dominant, incompletely penetrant combined exostosis and enchondromatosis tumor syndrome. MC is clinically distinct from other multiple exostosis or multiple enchondromatosis syndromes and is unlinked to EXT1 and EXT2, the genes responsible for autosomal dominant multiple osteochondromas (MO. To identify a gene for MC, we performed linkage analysis with high-density SNP arrays in a single family, used a targeted array to capture exons and promoter sequences from the linked interval in 16 participants from 11 MC families, and sequenced the captured DNA using high-throughput parallel sequencing technologies. DNA capture and parallel sequencing identified heterozygous putative loss-of-function mutations in PTPN11 in 4 of the 11 families. Sanger sequence analysis of PTPN11 coding regions in a total of 17 MC families identified mutations in 10 of them (5 frameshift, 2 nonsense, and 3 splice-site mutations. Copy number analysis of sequencing reads from a second targeted capture that included the entire PTPN11 gene identified an additional family with a 15 kb deletion spanning exon 7 of PTPN11. Microdissected MC lesions from two patients with PTPN11 mutations demonstrated loss-of-heterozygosity for the wild-type allele. We next sequenced PTPN11 in DNA samples from 54 patients with the multiple enchondromatosis disorders Ollier disease or Maffucci syndrome, but found no coding sequence PTPN11 mutations. We conclude that heterozygous loss-of-function mutations in PTPN11 are a frequent cause of MC, that lesions in patients with MC appear to arise following a "second hit," that MC may be locus heterogeneous since 1 familial and 5 sporadically occurring cases lacked obvious disease-causing PTPN11 mutations, and that PTPN11 mutations are not a common cause of Ollier disease or Maffucci syndrome.

  15. Mapping and exome sequencing identifies a mutation in the IARS gene as the cause of hereditary perinatal weak calf syndrome.

    Directory of Open Access Journals (Sweden)

    Takashi Hirano

    Full Text Available We identified an IARS (isoleucyl-tRNA synthetase c.235G>C (p.Val79Leu substitution as the causative mutation for neonatal weakness with intrauterine growth retardation (perinatal weak calf syndrome. In Japanese Black cattle, the syndrome was frequently found in calves sired by Bull A. Hence, we employed homozygosity mapping and linkage analysis. In order to identify the perinatal weak calf syndrome locus in a 4.04-Mb region of BTA 8, we analysed a paternal half-sibling family with a BovineSNP50 BeadChip and microsatellites. In this critical region, we performed exome sequencing to identify a causative mutation. Three variants were detected as possible candidates for causative mutations that were predicted to disrupt the protein function, including a G>C (p.Val79Leu mutation in IARS c.235. The IARS c.235G>C mutation was not a homozygous risk allele in the 36 healthy offspring of Bull A. Moreover, the IARS Val79 residue and its flanking regions were evolutionarily and highly conserved. The IARS mutant (Leu79 had decreased aminoacylation activity. Additionally, the homozygous mutation was not found in any of 1526 healthy cattle. Therefore, we concluded that the IARS c.235G>C mutation was the cause of hereditary perinatal weak calf syndrome.

  16. Staphylococcal scalded skin syndrome in a premature newborn caused by methicillin-resistant Staphylococcus aureus: case report

    Directory of Open Access Journals (Sweden)

    Andreas Hörner

    Full Text Available CONTEXT: Staphylococcal scalded skin syndrome is an exfoliative skin disease. Reports of this syndrome in newborns caused by methicillin-resistant Staphylococcus aureus are rare but, when present, rapid diagnosis and treatment is required in order to decrease morbidity and mortality. CASE REPORT: A premature newly born girl weighing 1,520 g, born with a gestational age of 29 weeks and 4 days, developed staphylococcal scalded skin syndrome on the fifth day of life. Cultures on blood samples collected on the first and fourth days were negative, but Pseudomonas aeruginosa and Enterococcus sp. (vancomycin-sensitive developed in blood cultures performed on the day of death (seventh day, and Pseudomonas aeruginosa and Serratia marcescens were identified in cultures on nasopharyngeal, buttock and abdominal secretions. In addition to these two Gram-negative bacilli, methicillin-resistant Staphylococcus aureus was isolated in a culture on the umbilical stump (seventh day. The diagnosis of staphylococcal scalded skin syndrome was based on clinical criteria.

  17. Multiple nevoid basal cell carcinoma syndrome associated with congenital orbital teratoma, caused by a PTCH1 frameshift mutation.

    Science.gov (United States)

    Rodrigues, A L; Carvalho, A; Cabral, R; Carneiro, V; Gilardi, P; Duarte, C P; Puente-Prieto, J; Santos, P; Mota-Vieira, L

    2014-07-25

    Gorlin-Goltz syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), is a rare autosomal dominant disorder caused by mutations in the PTCH1 gene and shows a high level of penetrance and variable expressivity. The syndrome is characterized by developmental abnormalities or neoplasms and is diagnosed with 2 major criteria, or with 1 major and 2 minor criteria. Here, we report a new clinical manifestation associated with this syndrome in a boy affected by NBCCS who had congenital orbital teratoma at birth. Later, at the age of 15 years, he presented with 4 major and 4 minor criteria of NBCCS, including multiple basal cell carcinoma and 2 odontogenic keratocysts of the jaw, both confirmed by histology, more than 5 palmar pits, calcification of the cerebral falx, extensive meningeal calcifications, macrocephaly, hypertelorism, frontal bosses, and kyphoscoliosis. PTCH1 mutation analysis revealed the heterozygous germline mutation c.290dupA. This mutation generated a frameshift within exon 2 and an early premature stop codon (p.Asn97LysfsX43), predicting a truncated protein with complete loss of function. Identification of this mutation is useful for genetic counseling. Although the clinical symptoms are well-known, our case contributes to the understanding of phenotypic variability in NBCCS, highlighting that PTCH1 mutations cannot be used for predicting disease burden and reinforces the need of a multidisciplinary team in the diagnosis, treatment, and follow-up of NBCCS patients.

  18. A thymic neuroendocrine tumour in a young female: a rare cause of relapsing and remitting Cushing’s syndrome

    Directory of Open Access Journals (Sweden)

    M J Trott

    2016-05-01

    Full Text Available We present a case of a young female patient with a rare cause of relapsing and remitting Cushing’s syndrome due to ectopic ACTH secretion from a thymic neuroendocrine tumour. A 34-year-old female presented with a constellation of symptoms of Cushing’s syndrome, including facial swelling, muscle weakness and cognitive impairment. We use the terms ‘relapsing and remitting’ in this case report, given the unpredictable time course of symptoms, which led to a delay of 2 years before the correct diagnosis of hypercortisolaemia. Diagnostic workup confirmed ectopic ACTH secretion, and a thymic mass was seen on mediastinal imaging. The patient subsequently underwent thymectomy with complete resolution of her symptoms. Several case series have documented the association of Cushing’s syndrome with thymic neuroendocrine tumours (NETs, although to our knowledge there are a few published cases of patients with relapsing and remitting symptoms. This case is also notable for the absence of features of the MEN-1 syndrome, along with the female gender of our patient and her history of non-smoking.

  19. An unusual cause of recurrent spontaneous pneumothorax: the Mounier-Kuhn syndrome.

    Science.gov (United States)

    Unlu, Elif Nisa; Annakkaya, Ali Nihat; Balbay, Ege Gulec; Aydın, Leyla Yilmaz; Safcı, Sinem; Boran, Mertay; Guclu, Derya

    2016-01-01

    We present a case of 63-year-old man who was referred to the emergency department with a right-sided pneumothorax. He had a history of spontaneous pneumothorax for 2 times. The chest computed tomographic scan showed tracheobronchomegaly with an increase in the diameter of the trachea and right and left main bronchus. Fiberoptic bronchoscopy revealed enlarged trachea and both main bronchus with diverticulas. These findings are consistent with a diagnosis of Mounier-Kuhn syndrome. Mounier-Kuhn syndrome is a rare clinical and radiologic condition. It is characterized by a tracheal and bronchial dilation. Diagnosis is made by computed tomography and bronchoscopy. Mounier-Kuhn syndrome should be kept in mind in the differential diagnosis of recurrent spontaneous pneumothorax.

  20. A genetic and molecular update on adrenocortical causes of Cushing syndrome.

    Science.gov (United States)

    Lodish, Maya; Stratakis, Constantine A

    2016-05-01

    Primary adrenal Cushing syndrome is the result of cortisol hypersecretion mainly by adenomas and, rarely, by bilateral micronodular or macronodular adrenocortical hyperplasia. cAMP-dependent protein kinase A (PKA) signalling is the major activator of cortisol secretion in the adrenal cortex. Many adenomas and hyperplasias associated with primary hypercortisolism carry somatic or germline mutations in genes that encode constituents of the cAMP-PKA pathway. In this Review, we discuss Cushing syndrome and its linkage to dysregulated cAMP-PKA signalling, with a focus on genetic findings in the past few years. In addition, we discuss the presence of germline inactivating mutations in ARMC5 in patients with primary bilateral macronodular adrenocortical hyperplasia. This finding has implications for genetic counselling of affected patients; hitherto, most patients with this form of adrenal hyperplasia and Cushing syndrome were thought to have a sporadic and not a familial disorder.

  1. Catheter-directed Thrombolysis in Acute Superior Vena Cava Syndrome Caused by Central Venous Catheters.

    Science.gov (United States)

    Cui, Jie; Kawai, Tasuo; Irani, Zubin

    2015-01-01

    Indwelling central venous catheters have been reported to increase the risk of superior venous cava (SVC) syndrome. This case report describes the development of acute SVC syndrome in a 28-year-old woman with end-stage renal disease implanted with a left-side hemodialysis reliable outflow graft and a right-side double lumen hemodialysis catheter via internal jugular veins. Her symptoms were not alleviated after catheter removal and systemic anticoagulation therapy. She was eventually treated with catheter-directed thrombolysis and a predischarge computer tomographic venogram on postthrombolytic procedure day 7 showed patent central veins and patient remained asymptomatic. This case demonstrates that catheter-directed thrombolysis can be safely employed to treat refractory catheter-induced acute SVC syndrome in end-stage renal disease patients.

  2. Pallister-Killian Syndrome (PKS) as a Cause of Mental Retardation.

    Science.gov (United States)

    Shamdeen, A; Meyer, S; Gottschling, S; Oehl-Jaschkowitz, B; Gortner, L; Shamdeen, M G

    2009-01-01

    Pallister-Killian syndrome (PKS; OMIM: # 601803) is a rare sporadic syndrome of multiple congenital anomalies attributable to the presence of a de novo mosaic supernumerary isochromosome 12p [i(12p)]. The syndrome presents with a recognizable pattern of findings including: pigmentary skin changes, characteristic facial features (sparse anterior scalp hair, flattened midface, macrostomia, and coarsening of the facial features), and developmental delay. The developmental phenotype of PKS is quite variable, but most are considered to fall into the profound range of developmental retardation. We report on two individuals with classical features of PKS. Notably, in one child the neuropsychological development was significantly more favourable than commonly reported in the literature. This illustrates the loose correlation between geno- and phenotype in PKS.

  3. An unusual cause of spontaneous pneumothorax: the Mounier-Kuhn syndrome.

    LENUS (Irish Health Repository)

    Kent, B D

    2011-05-01

    We present the case of a 54-year old woman referred to our service with an unusual presentation of an under-diagnosed condition. A life-long non-smoker, she was referred to respiratory services by our emergency department with a left sided pneumothorax, progressive dyspnoea on exertion, and recurrent chest infections. Subsequent investigation yielded findings consistent with Mounier-Kuhn syndrome (Tracheobronchomegaly), a condition characterised by marked dilatation of the proximal airways, recurrent chest infection, and consequent emphysema and bronchiectasis. Although rarely diagnosed, some degree of Mounier-Kuhn syndrome may occur in up to 1 in 500 adults.

  4. Hemarthrosis due to a rare cause of hemorrhagic diathesis: Ehlers-Danlos syndrome.

    Science.gov (United States)

    Giordano, Paola; Del Vecchio, Giovanni Carlo; Scaraggi, Rosanna; Cardinale, Fabio; Moretti, Biagio; Lassandro, Giuseppe; De Mattia, Domenico

    2008-01-01

    The authors report a case of hemarthrosis complicated by severe anemia related to a congenital connective tissue disease: Ehlers-Danlos syndrome. A boy fell down and suffered tumefaction of both knees with bilateral rupture of the rotula tendon. He underwent surgical reinsertion of each tendon on the rotula. He later showed an unexpected ongoing hematic effusion, with severe anemia. He was screened for coagulation disorders with no results. On taking a more detailed history and investigating the patient's phenotypical features, the authors diagnosed Ehlers-Danlos syndrome, hypermobile variant. The hemarthrosis and anemia were thus concluded to be consequences of excessive tissue fragility due to a congenital connective tissue disease.

  5. An unusual cause of spontaneous pneumothorax: the Mounier-Kuhn syndrome.

    LENUS (Irish Health Repository)

    Kent, B D

    2012-02-01

    We present the case of a 54-year old woman referred to our service with an unusual presentation of an under-diagnosed condition. A life-long non-smoker, she was referred to respiratory services by our emergency department with a left sided pneumothorax, progressive dyspnoea on exertion, and recurrent chest infections. Subsequent investigation yielded findings consistent with Mounier-Kuhn syndrome (Tracheobronchomegaly), a condition characterised by marked dilatation of the proximal airways, recurrent chest infection, and consequent emphysema and bronchiectasis. Although rarely diagnosed, some degree of Mounier-Kuhn syndrome may occur in up to 1 in 500 adults.

  6. Mosaicism for c.431_454dup in ARX causes a mild Partington syndrome phenotype

    DEFF Research Database (Denmark)

    Grønskov, Karen; Diness, Birgitte; Stahlhut, Michelle;

    2014-01-01

    to expand. Detection of the duplication by DNA sequencing was difficult due to preferential sequencing of the normal allele, demonstrating the superiority of fragment length analysis in mosaic cases. The clinical symptoms were mild to moderate developmental delay with only the hand dystonia to suggest...... Partington syndrome. This patient is the first male reported to be mosaic for the duplication, and his clinical features are subtle. This study shows that in males with a phenotype of mild Partington syndrome and in heterozygous females fragment length analysis should be preferred over DNA sequencing....

  7. Edward’s syndrome: A rare cause of difficult intubation-utility of left molar approach

    Directory of Open Access Journals (Sweden)

    Teena Bansal

    2016-04-01

    Full Text Available Edward’s syndrome (trisomy 18 is an autosomal abnormality with dysmorphic face, visceral deformities and delayed mental and motor development including congenital heart disease. Challenges may arise during mask ventilation, laryngoscopy and/or intubation of the trachea due to dysmorphic face. Difficult airway cart should be kept ready. Left molar approach using a standard Macintosh blade improves the laryngoscopic view in patients with difficult midline laryngoscopy. We hereby present a case report of a 2 year old male child with Edward’s syndrome posted for evacuation and drainage of brain abscess, intubated successfully using left molar approach.

  8. A cholestatic syndrome may be a surprising cause of medical error

    Directory of Open Access Journals (Sweden)

    M. Pătrășescu

    2015-04-01

    Full Text Available Autoimmune cholangitis defines a spectrum of cholestatic liver diseases that are characterized by inflammation of bile ducts and a reasonable response to immunosuppressive therapy. The two most common diseases associated with this term in the literature are: an overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis and a form of hyper IgG4 syndrome (currently associated with autoimmune pancreatitis. Liver biopsy is mandatory for the diagnosis. There are, whatsoever, in clinical practice, many cases that do not meet current diagnostic criteria but that have a good response to corticosteroid treatment.

  9. Compound heterozygous PNPLA6 mutations cause Boucher-Neuhäuser syndrome with late-onset ataxia.

    Science.gov (United States)

    Deik, A; Johannes, B; Rucker, J C; Sánchez, E; Brodie, S E; Deegan, E; Landy, K; Kajiwara, Y; Scelsa, S; Saunders-Pullman, R; Paisán-Ruiz, C

    2014-12-01

    PNPLA6 mutations, known to be associated with the development of motor neuron phenotypes, have recently been identified in families with Boucher-Neuhäuser syndrome. Boucher-Neuhäuser is a rare autosomal recessive syndrome characterized by the co-occurrence of cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. Gait ataxia in Boucher-Neuhäuser usually manifests before early adulthood, although onset in the third or fourth decade has also been reported. However, given the recent identification of PNPLA6 mutations as the cause of this condition, the determining factors of age of symptom onset still need to be established. Here, we have identified a sporadic Boucher-Neuhäuser case with late-onset gait ataxia and relatively milder retinal changes due to compound heterozygous PNPLA6 mutations. Compound heterozygosity was confirmed by cloning and sequencing the patient's genomic DNA from coding exons 26-29. Furthermore, both mutations (one novel and one known) fell in the phospholipase esterase domain, where most pathogenic mutations seem to cluster. Taken together, we herein confirm PNPLA6 mutations as the leading cause of Boucher-Neuhäuser syndrome and suggest inquiring about a history of hypogonadism or visual changes in patients presenting with late-onset gait ataxia. We also advocate for neuroophthalmologic evaluation in suspected cases.

  10. LTBP2 mutations cause Weill-Marchesani and Weill-Marchesani-like syndrome and affect disruptions in the extracellular matrix.

    Science.gov (United States)

    Haji-Seyed-Javadi, Ramona; Jelodari-Mamaghani, Sahar; Paylakhi, Seyed Hassan; Yazdani, Shahin; Nilforushan, Naveed; Fan, Jian-Bing; Klotzle, Brandy; Mahmoudi, Mohammad Jafar; Ebrahimian, Mohammad Jafar; Chelich, Noori; Taghiabadi, Ehsan; Kamyab, Kambiz; Boileau, Catherine; Paisan-Ruiz, Coro; Ronaghi, Mostafa; Elahi, Elahe

    2012-08-01

    Latent transforming growth factor (TGF) beta-binding protein 2 (LTBP2) is an extracellular matrix (ECM) protein that associates with fibrillin-1 containing microfibrils. Various factors prompted considering LTBP2 in the etiology of isolated ectopia lentis and associated conditions such as Weill-Marchesani syndrome (WMS) and Marfan syndrome (MFS). LTBP2 was screened in 30 unrelated Iranian patients. Mutations were found only in one WMS proband and one MFS proband. Homozygous c.3529G>A (p.Val1177Met) was shown to cause autosomal recessive WMS or WM-like syndrome by several approaches, including homozygosity mapping. Light, fluorescent, and electron microscopy evidenced disruptions of the microfibrillar network in the ECM of the proband's skin. In conjunction with recent findings regarding other ECM proteins, the results presented strongly support the contention that anomalies in WMS patients are due to disruptions in the ECM. Heterozygous c.1642C >T (p.Arg548*) possibly contributed to MFS-related phenotypes, including ocular manifestations, mitral valve prolapse, and pectus excavatum, but was not cause of MFS.

  11. The frequency of a disease-causing point mutation in the gene coding for medium-chain acyl-CoA dehydrogenase in sudden infant death syndrome

    DEFF Research Database (Denmark)

    Banner, Jytte; Gregersen, N; Kølvraa, S

    1993-01-01

    syndrome is still a matter of controversy. The present study investigated 120 well-defined cases of sudden infant death syndrome in order to detect the frequency of the most common disease-causing point mutation in the gene coding for medium-chain acyl-CoA dehydrogenase (G985) compared with the frequency...

  12. Hepatic Rupture Caused by Hemolysis, Elevated Liver Enzyme, and Low Platelet Count Syndrome: A Case Report with Computed Tomographic and Conventional Angiographic Findings

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Cheong Bok; Ahn, Jae Hong; Choi, Soo Jung; Lee, Jong Hyeog; Park, Man Soo; Jung, Seung Mun; Ryu, Dae Sik [Dept. of Radiology, Asan Foundation, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung (Korea, Republic of)

    2013-03-15

    The authors recently obtained successful clinical outcome after embolization of the hepatic artery and right inferior phrenic artery in a pregnant patient with hemolysis, elevated liver enzyme, and low platelet count (HELLP) syndrome causing hepatic rupture. We report the computed tomographic and conventional angiographic findings in a case of HELLP syndrome, resulting in hepatic infarction and rupture with active bleeding.

  13. A RARE CASE OF GRISCELLI’S SYNDROME WITH REVIEW OF LITERATURE

    Directory of Open Access Journals (Sweden)

    Narayan Reddy

    2014-06-01

    Full Text Available INTRODUCTION: Griscelli syndrome is a rare autosomal recessive disorder characterized by partial albinism and immunodeficiency. The characteristic features include silver hair due to clumped melanosomes in hair shaft. Other features include hepatospleenomegaly, hepatitis, pancytopenia and immune abnormalities. CASE REPORT: A seven years old male child presented with partial albinic features and history of recurrent respiratory tract infection. The child had fever since 2months along with hepatospleenomegaly, pancytopenia and thrombocytopenic purpura. These rare clinical manifestations were diagnosed as GS which was confirmed by bone marrow biopsy and light microscopy of hair shaft. The mean patient age of survival is 5years. As early diagnosis can improve the outcome in such cases, a finding of partial albinism should alert the diagnosis of Griscelli’s syndrome. CONCLUSION: We report a rare case of GS with characteristic manifestation surviving beyond the mean age of reported survival.

  14. Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome.

    NARCIS (Netherlands)

    Dauwerse, J.G.; Dixon, J.; Seland, S.; Ruivenkamp, C.A.; Haeringen, A. van; Hoefsloot, L.H.; Peters, D.J.; Boers, A.C.; Daumer-Haas, C.; Maiwald, R.; Zweier, C.; Kerr, B.; Cobo, A.M.; Toral, J.F.; Hoogeboom, A.J.M.; Lohmann, D.R.; Hehr, U.; Dixon, M.J.; Breuning, M.H.; Wieczorek, D.

    2011-01-01

    We identified a deletion of a gene encoding a subunit of RNA polymerases I and III, POLR1D, in an individual with Treacher Collins syndrome (TCS). Subsequently, we detected 20 additional heterozygous mutations of POLR1D in 252 individuals with TCS. Furthermore, we discovered mutations in both allele

  15. Ramsay Hunt Syndrome : Clinical Characterization of Progressive Myoclonus Ataxia Caused by GOSR2 Mutation

    NARCIS (Netherlands)

    van Egmond, Martje E.; Verschuuren - Bemelmans, Cornelia; Nibbeling, Esther A.; Elting, Jan Willem J.; Sival, Deborah A.; Brouwer, Oebele F.; de Vries, Jeroen J.; Kremer, Hubertus P.; Sinke, Richard J.; Tijssen, Marina A.; de Koning, Tom J.

    2014-01-01

    BACKGROUND: Ramsay Hunt syndrome (progressive myoclonus ataxia) is a descriptive diagnosis characterized by myoclonus, ataxia, and infrequent seizures. Often the etiology cannot be determined. Recently, a mutation in the GOSR2 gene (c.430G>T, p.Gly144Trp) was reported in 6 patients with childhood-on

  16. Giant pseudomeningocele causing urinary obstruction in a patient with Marfan syndrome.

    Science.gov (United States)

    Stone, Jeremy G; Bergmann, Liisa L; Takamori, Ryan; Donovan, Daniel J

    2015-07-01

    Defective collagen biosynthesis in Marfan syndrome predisposes to dural defects such as dural ectasia, meningocele, and pseudomeningocele; thus, an increased index of suspicion for these conditions should be present in the clinical setting of Marfan syndrome. The authors describe a young woman with Marfan syndrome who was being treated with anticoagulants for a prosthetic heart valve and who presented with a spontaneous retroperitoneal hemorrhage requiring surgical evacuation. No CSF leak was encountered at surgery, but she developed progressively more severe positional headaches over the following year. She then experienced the sudden onset of acute urinary obstruction, at which time CT revealed a 17 × 15 × 13-cm presacral pseudomeningocele communicating with the thecal sac through a sacral bone defect. An anterior surgical approach was used for drainage of the pseudomeningocele as well as for primary closure of the dural defect with a bovine pericardial patch and autologous subcutaneous fat graft. After a short period of lumbar subarachnoid drainage of the CSF, the patient was able to resume normal activity without recurrent symptoms. To the authors' knowledge, such a pseudomeningocele in a patient with Marfan syndrome has been reported only twice, and this case features the largest pseudomeningocele to date. They also review the pertinent literature regarding presentation, diagnosis, and management of these lesions.

  17. Rapid onset of severe twin-twin transfusion syndrome caused by placental venous thrombosis

    NARCIS (Netherlands)

    Nikkels, PGJ; van Gemert, MJC; Sollie-Szarynska, KM; Molendijk, H; Timmer, B; Machin, GA

    2002-01-01

    We report a case of rapid onset of severe twin-twin transfusion syndrome (TTTS) at 25 weeks gestation in a monochorionic twin pregnancy that was uneventful before that time. Thrombosis of a main venous branch draining several arteriovenous (AV) anastomoses to the donor changed the previous hemodynam

  18. Blue rubber bleb naevus syndrome: A rare cause of gastrointestinal bleeding in an African child

    Directory of Open Access Journals (Sweden)

    Walter C

    2010-01-01

    Full Text Available Blue rubber bleb naevus syndrome (BRBNS is characterised by vascular malformations of the skin and gastrointestinal tract. We present the rare case of BRBNS in an African child. She presented with large-volume gastrointestinal bleeding and was managed by on-table colonoscopic identification and surgical excision, of all her enteric, vascular malformations.

  19. Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome

    NARCIS (Netherlands)

    Van Houdt, Jeroen K. J.; Nowakowska, Beata Anna; Sousa, Sergio B.; van Schaik, Barbera D. C.; Seuntjens, Eve; Avonce, Nelson; Sifrim, Alejandro; Abdul-Rahman, Omar A.; van den Boogaard, Marie-Jose H.; Bottani, Armand; Castori, Marco; Cormier-Daire, Valerie; Deardorff, Matthew A.; Filges, Isabel; Fryer, Alan; Fryns, Jean-Pierre; Gana, Simone; Garavelli, Livia; Gillessen-Kaesbach, Gabriele; Hall, Bryan D.; Horn, Denise; Huylebroeck, Danny; Klapecki, Jakub; Krajewska-Walasek, Malgorzata; Kuechler, Alma; Lines, Matthew A.; Maas, Saskia; MacDermot, Kay D.; McKee, Shane; Magee, Alex; de Man, Stella A.; Moreau, Yves; Morice-Picard, Fanny; Obersztyn, Ewa; Pilch, Jacek; Rosser, Elizabeth; Shannon, Nora; Stolte-Dijkstra, Irene; Van Dijck, Patrick; Vilain, Catheline; Vogels, Annick; Wakeling, Emma; Wieczorek, Dagmar; Wilson, Louise; Zuffardi, Orsetta; van Kampen, Antoine H. C.; Devriendt, Koenraad; Hennekam, Raoul; Vermeesch, Joris Robert

    2012-01-01

    Nicolaides-Baraitser syndrome (NBS) is characterized by sparse hair, distinctive facial morphology, distal-limb anomalies and intellectual disability. We sequenced the exomes of ten individuals with NBS and identified heterozygous variants in SMARCA2 in eight of them. Extended molecular screening id

  20. A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome

    DEFF Research Database (Denmark)

    Clendenning, Mark; Senter, Leigha; Hampel, Heather;

    2008-01-01

    on immunohistochemical analysis. RESULTS: We have identified a frequently occurring frame-shift mutation (c.736_741del6ins11) in 12 ostensibly unrelated Lynch syndrome patients (20% of patients we have identified with a deleterious mutation in PMS2, n=61). These individuals all display the rare allele (population...

  1. Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome

    DEFF Research Database (Denmark)

    Aligianis, Irene A; Johnson, Colin A; Gissen, Paul;

    2005-01-01

    Warburg Micro syndrome (WARBM1) is a severe autosomal recessive disorder characterized by developmental abnormalities of the eye and central nervous system and by microgenitalia. We identified homozygous inactivating mutations in RAB3GAP, encoding RAB3 GTPase activating protein, a key regulator...

  2. Mutations in the human TBX4 gene cause small patella syndrome.

    NARCIS (Netherlands)

    Bongers, M.H.F.; Duijf, P.H.; Beersum, S.E.C. van; Schoots, J.; Kampen, A. van; Burckhardt, A.; Hamel, B.C.J.; Losan, F.; Hoefsloot, L.H.; Yntema, H.G.; Knoers, N.V.A.M.; Bokhoven, J.H.L.M. van

    2004-01-01

    Small patella syndrome (SPS) is an autosomal-dominant skeletal dysplasia characterized by patellar aplasia or hypoplasia and by anomalies of the pelvis and feet, including disrupted ossification of the ischia and inferior pubic rami. We identified an SPS critical region of 5.6 cM on chromosome 17q22

  3. Two Causes of Underachievement--The Scapegoat Phenomenon and the Peter Pan Syndrome. Part II.

    Science.gov (United States)

    Grau, Phyllis Nelson

    1986-01-01

    Two profiles of underachievement are described: the Peter Pan Syndrome, characterized by irresponsibility, anxiety, loneliness, sex role conflict, and narcissism, and the scapegoating phenomenon, in which children acquire negative self-images from victimization experiences. Prognoses and recommendations for each are offered. (Author/CL)

  4. The pathogenic mechanism of the diarrheal syndrome caused by Bacillus cereus

    NARCIS (Netherlands)

    Wijnands LM; Dufrenne JB; Leusden FM van; MGB

    2002-01-01

    As a contaminant of food commodities, Bacillus cereus may produce several enterotoxins that are responsible for the development of a diarrhaeal syndrome. Although four enterotoxins -haemolysin BL (HBL), non-haemolytic enterotoxin (NHE), enterotoxin-T, and cytotoxin-K- have been described as possibly

  5. Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome

    NARCIS (Netherlands)

    Aligianis, IA; Johnson, CA; Gissen, P; Chen, DR; Hampshire, D; Hoffmann, K; Maina, EN; Morgan, NV; Tee, L; Morton, J; Ainsworth, [No Value; Horn, D; Rosser, E; Cole, TRP; Stolte-Dijkstra, [No Value; Fieggen, K; Clayton-Smith, J; Megarbane, A; Shield, JP; Newbury-Ecob, R; Dobyns, WB; Graham, JM; Kjaer, KW; Warburg, M; Bond, J; Trembath, RC; Harris, LW; Takai, Y; Mundlos, S; Tannahill, D; Woods, CG; Maher, ER

    2005-01-01

    Warburg Micro syndrome (WARBM1) is a severe autosomal recessive disorder characterized by developmental abnormalities of the eye and central nervous system and by microgenitalia. We identified homozygous inactivating mutations in RAB3GAP, encoding RAB3 GTPase activating protein, a key regulator of t

  6. Treatment of Guillain-Barré syndrome and causes and treatment of residual fatigue

    NARCIS (Netherlands)

    M.P.J. Garssen (Marcel)

    2005-01-01

    textabstractChapter 1 is the general introduction of this thesis, in which di.erent aspects of the Guillain-Barré syndrome (GBS) are described. GBS is an acute post-infectious polyneuropathy, in which the immune system plays an important role. Insight in pathogenesis, clinical and electrophysiologic

  7. DOES GROWTH-HORMONE TREATMENT OF PATIENTS WITH TURNERS SYNDROME CAUSE AN ABNORMAL BODY SHAPE

    NARCIS (Netherlands)

    GERVER, WJM; DRAYER, NM; VANES, A

    1992-01-01

    The effect of human growth hormone on the body shape of 51 patients with Turner's syndrome (aged 6-19 years) was evaluated. Biosynthetic growth hormone was given in a dose of 24 IU/m2 body surface/week for two years. Karyotype analysis on peripheral blood was performed. Patients older than 12 years

  8. Middle aortic syndrome as a cause of heart failure in children and its management.

    OpenAIRE

    S. Gupta; B. Goswami; Ghosh, D C; Sen Gupta, A N

    1981-01-01

    Two cases of middle aortic syndrome in children are described along with two other cases reported earlier. In childhood, this disease may present as incipient or overt cardiac failure. Surgical treatment should be undertaken based on an objective assessment of the severity of the stricture and after taking into account the future growth of the child.

  9. Anterior Nutcracker syndrome as a rare cause of hematuria in an 8 year old boy: A case report

    Directory of Open Access Journals (Sweden)

    Prashant S Patil

    2016-09-01

    Full Text Available Nutcracker syndrome is caused by a compression of the left renal vein between the aorta and the superior mesenteric artery. It results in left renal venous hypertension, and the subsequent development of venous varicosities of the renal pelvis, ureter, and gonadal vein. We report a rare case in an 8-year-old boy who presented with a history of intermittent episodes of hematuria leading to anemia and left flank pain. Ultrasound examination of abdomen revealed bulky left kidney and features of subacute medical renal disease. Computed tomography of abdomen showed compressed left renal vein between aorta and superior mesenteric artery. Authors report the successful operative management of this rare syndrome in a pediatric patient.

  10. Further insight into the phenotype associated with a mutation in the ORC6 gene, causing Meier-Gorlin syndrome 3.

    Science.gov (United States)

    Shalev, Stavit Allon; Khayat, Morad; Etty, Daniel-Spiegl; Elpeleg, Orly

    2015-03-01

    Mutations in genes encoding the origin recognition complex subunits cause Meier-Gorlin syndrome. The disease manifests a triad of short stature, small ears, and small and/or absent patellae with variable expressivity. We report on the identification of a homozygous deleterious mutation in the ORC6 gene in previously described fetuses at the severe end of the Meier-Gorlin spectrum. The phenotype included severe intrauterine growth retardation, dislocation of knees, gracile bones, clubfeet, and small mandible and chest. To date, the clinical presentation of ORC6-associated Meier-Gorlin syndrome has been mild compared to other the phenotype associated with other loci. The present report expands the clinical phenotype associated with ORC6 mutations to include severely abnormal embryological development suggesting a possible genotype-phenotype correlation.

  11. A very rare cause of dyspnea with a unique presentation on a computed tomography scan of the chest: macrophage activation syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Brandao-Neto, Rodrigo Antonio [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Clinical Emergency Dept.; Santana, Alfredo Nicodemos Cruz; Danilovic, Debora Lucia Seguro; Mendonca, Berenice Bilharinho de [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina]. E-mail: alfredonicodemos@hotmail.com; Bernardi, Fabiola Del Carlo [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Dept. of Pathology; Barbas, Carmen Silvia Valente [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Dept. of Pulmonology

    2008-02-15

    Macrophage activation syndrome is a rare and potentially life-threatening disease. It occurs due to immune dysregulation manifested as excessive macrophage proliferation, typically causing hepatosplenomegaly, pancytopenia and hepatic dysfunction. Here, we report an unusual case of macrophage activation syndrome presenting as dyspnea, as well as (reported here for the first time) high resolution computed tomography findings of an excavated nodule, diffuse ground glass opacities and consolidations (mimicking severe pneumonia or alveolar hemorrhage). The patient was successfully treated with human immunoglobulin. We recommend that macrophage activation syndrome be considered in the differential diagnosis of respiratory failure. Rapid diagnosis and treatment are essential to achieving favorable outcomes in patients with this syndrome. (author)

  12. Missense mutations in FBN1 exons 41 and 42 cause Weill-Marchesani syndrome with thoracic aortic disease and Marfan syndrome.

    Science.gov (United States)

    Cecchi, Alana; Ogawa, Naomi; Martinez, Hugo R; Carlson, Alicia; Fan, Yuxin; Penny, Daniel J; Guo, Dong-chuan; Eisenberg, Steven; Safi, Hazim; Estrera, Anthony; Lewis, Richard A; Meyers, Deborah; Milewicz, Dianna M

    2013-09-01

    Mutations in FBN1 cause a range of overlapping but distinct conditions including Marfan syndrome (MFS), Weill-Marchesani syndrome (WMS), familial thoracic aortic aneurysms/dissections (FTAAD), acromicric dysplasia (AD), and geleophysic dysplasia (GD). Two forms of acromelic dysplasia, AD and GD, characterized by short stature, brachydactyly, reduced joint mobility, and characteristic facies, result from heterozygous missense mutations occurring in exons 41 and 42 of FBN1; missense mutations in these exons have not been reported to cause MFS or other syndromes. Here we report on probands with MFS and WMS who have heterozygous FBN1 missense mutations in exons 41 and 42, respectively. The proband with WMS has ectopia lentis, short stature, thickened pinnae, tight skin, striae atrophicae, reduced extension of the elbows, contractures of the fingers and toes, and brachydactyly and has a missense mutation in exon 42 of FBN1 (c.5242T>C; p.C1748R). He also experienced a previously unreported complication of WMS, an acute thoracic aortic dissection. The second proband displays classic characteristics of MFS, including ectopia lentis, skeletal features, and aortic root dilatation, and has a missense mutation in exon 41 of FBN1 (c.5084G>A; p.C1695Y). These phenotypes provide evidence that missense mutations in exons 41 and 42 of FBN1 lead to MFS and WMS in addition to AD and GD and also suggest that all individuals with pathogenic FBN1 mutations in these exons should be assessed for thoracic aortic disease and ectopia lentis. Further studies are necessary to elucidate the factors responsible for the different phenotypes associated with missense mutations in these exons of FBN1.

  13. Specific deletion of NaV1.1 sodium channels in inhibitory interneurons causes seizures and premature death in a mouse model of Dravet syndrome

    OpenAIRE

    Cheah, Christine S.; Yu, Frank H.; Westenbroek, Ruth E.; Kalume, Franck K.; Oakley, John C; Potter, Gregory B.; Rubenstein, John L.; Catterall, William A.

    2012-01-01

    Heterozygous loss-of-function mutations in the brain sodium channel NaV1.1 cause Dravet syndrome (DS), a pharmacoresistant infantile-onset epilepsy syndrome with comorbidities of cognitive impairment and premature death. Previous studies using a mouse model of DS revealed reduced sodium currents and impaired excitability in GABAergic interneurons in the hippocampus, leading to the hypothesis that impaired excitability of GABAergic inhibitory neurons is the cause of epilepsy and premature deat...

  14. Ehlers-Danlos Syndrome Type VIII: A Rare Cause of Leg Ulcers in Young Patients

    Science.gov (United States)

    Lucas, Antoine; Piérard, Gérald E.; Hermanns-Lê, Trinh; De Paepe, Anne; Dupuy, Alain

    2013-01-01

    Ehlers-Danlos syndrome type VIII (EDS-VIII) is a very rare autosomal dominant disease characterized by early-onset periodontitis associated with features of Ehlers-Danlos syndrome. We report a 32-year-old man whose chronic leg ulcer led to the diagnosis of EDS-VIII. He had severe periodontitis with complete loss of permanent teeth and skin fragility with thin skin, atrophic scars, and brownish atrophic pretibial plaques. Leg ulcer is not a prominent feature of EDS-VIII. We suggest adding EDS-VIII to the list of rare diseases accounting for chronic leg ulcers, if this case report prompts others to report leg ulcers associated with EDS-VIII. PMID:24198978

  15. Gorlin-Goltz Syndrome: An Uncommon Cause of Facial Pain and Asymmetry.

    Science.gov (United States)

    Pickrell, Brent B; Nguyen, Harrison P; Buchanan, Edward P

    2015-10-01

    Gorlin-Goltz syndrome is an underdiagnosed autosomal dominant disorder with variable expressivity that is characterized by an increased predisposition to tumorigenesis of multiple types. The major clinical features include multiple basal cell carcinomas (BCCs) appearing in early childhood, palmar and plantar pits, odontogenic keratocysts of the oral cavity, skeletal defects, craniofacial dysmorphism, and ectopic intracranial calcification. The authors present the clinical course of a 12-year-old girl presenting with facial asymmetry and pain because of previously undiagnosed Gorlin-Goltz syndrome. Early diagnosis and attentive management by a multidisciplinary team are paramount to improving outcomes in patients with this disorder, and this report serves as a paradigm for maintaining a high clinical suspicion, which must be accompanied by an appropriate radiologic workup.

  16. Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) gene.

    Science.gov (United States)

    Tassabehji, M; Newton, V E; Read, A P

    1994-11-01

    Waardenburg syndrome type 2 (WS2) is a dominantly inherited syndrome of hearing loss and pigmentary disturbances. We recently mapped a WS2 gene to chromosome 3p12.3-p14.1 and proposed as a candidate gene MITF, the human homologue of the mouse microphthalmia (mi) gene. This encodes a putative basic-helix-loop-helix-leucine zipper transcription factor expressed in adult skin and in embryonic retina, otic vesicle and hair follicles. Mice carrying mi mutations show reduced pigmentation of the eyes and coat, and with some alleles, microphthalmia, hearing loss, osteopetrosis and mast cell defects. Here we show that affected individuals in two WS2 families have mutations affecting splice sites in the MITF gene.

  17. Pallister-Killian syndrome caused by mosaicism for a supernumerary ring chromosome 12p.

    Science.gov (United States)

    Yeung, Alison; Francis, David; Giouzeppos, Olivia; Amor, David J

    2009-03-01

    Pallister-Killian syndrome (PKS) is a rare but distinctive chromosomal syndrome distinguished by severe intellectual impairment, characteristic facial features, and variable structural anomalies. The characteristic cytogenetic abnormality in PKS is a supernumerary isochromosome 12p that confers mosaic tetrasomy. We describe a female child with PKS in whom tetrasomy 12p resulted from a supernumerary ring chromosome containing two copies of chromosome 12cen --> p13, a novel cytogenetic finding. The ring chromosome exhibited tissue-limited mosaicism, being absent in blood but detected in 38% of buccal mucosa cells and 41% of skin fibroblasts. Our patient demonstrated the typical dysmorphic characteristics of PKS, but her development was relatively advanced in comparison to children with isochromosome PKS. Her milder developmental phenotype may be attributable to differences in the mosaic distribution or the genomic content of the ring chromosome compared to mosaic isochromosome 12p.

  18. Sympathetic nervous activation in obesity and the metabolic syndrome--causes, consequences and therapeutic implications.

    Science.gov (United States)

    Lambert, Gavin W; Straznicky, Nora E; Lambert, Elisabeth A; Dixon, John B; Schlaich, Markus P

    2010-05-01

    The world wide prevalence of obesity and the metabolic syndrome is escalating. Contrary to earlier experimental evidence, human obesity is characterised by sympathetic nervous activation, with the outflows to both the kidney and skeletal muscle being activated. While the mechanisms responsible for initiating the sympathetic activation remain to be unequivocally elucidated, hyperinsulinemia, obstructive sleep apnoea, increased circulating adipokines, stress and beta adrenergic receptor polymorphisms are implicated. The pattern of sympathetic activation may be the pathophysiological mechanism underpinning much obesity-related illnesses with the consequences including, amongst others, the development of hypertension, insulin resistance, diastolic dysfunction and renal impairment. While diet and exercise are the first line therapy for the treatment of obesity and the metabolic syndrome, pharmacological interventions targeting the sympathetic nervous system, either directly or indirectly are also likely to be of benefit. Importantly, the benefit may not necessarily be weight related but may be associated with a reduction in end organ damage.

  19. Neuroleptic Malignant Syndrome: A Rare Cause of Fever 1 in the Emergency Department

    Directory of Open Access Journals (Sweden)

    Hayriye Gonullu

    2013-10-01

    Full Text Available    Neuroleptic malignant syndrome (NMS is a rare and life threatening complication of antipsychotic therapy. It presents with fever, altered mental status, autonomic instability and muscle rigidity. Differential diagnosis consist many conditions. NMS is a diagnosis of exclusion. NMS is in the differential diagnosis of patients presenting with fever to emergency department, where careful history and previous medication use is essential for diagnosing and treating this phenomenon.

  20. Treatment of Guillain-Barré syndrome and causes and treatment of residual fatigue

    OpenAIRE

    Garssen, Marcel

    2005-01-01

    textabstractChapter 1 is the general introduction of this thesis, in which di.erent aspects of the Guillain-Barré syndrome (GBS) are described. GBS is an acute post-infectious polyneuropathy, in which the immune system plays an important role. Insight in pathogenesis, clinical and electrophysiological features, functional outcome, and residual complaints is increasing. To date, fatigue is considered one of the most disabling residual symptoms, seriously a.ecting quality of life. The considera...

  1. Molasses as a possible cause of an ''endocrine disruptive syndrome'' in calves

    Directory of Open Access Journals (Sweden)

    M.S. Masgoret

    2009-09-01

    Full Text Available During the mid 1990s a potentially serious, chronic syndrome was reported in well-managed beef and dairy herds from unrelated parts of South Africa. Farmers reported that it manifested as various combinations of decreased production, decreased weaning masses, apparent immune breakdown in previously immunocompetent animals, increased reproductive disorders, various mineral imbalances in non-deficient areas and goitre, noticeable as enlarged thyroid glands. The farmers associated this syndrome with certain batches of sugar cane molasses and molasses-based products. The syndrome was reminiscent of an ''endocrine disruptive syndrome''. The objective of this study was to evaluate the suspected endocrine disruptive effect of molasses included in cattle feed. Using existing in vitro assays, four batches of molasses syrup were screened for possible inclusion in a calf feeding trial. Two batches were selected for the trial. Thirty-two, 4- to 6-week-old, weaned Holstein bull calves were included in the single phase, three treatment, parallel design experiment. In two of the groups of calves, two different batches of molasses were included in their rations respectively. The control group was fed a ration to which no molasses was added, but which was balanced for energy and mineral content. The mass gain of the calves was recorded over the 6-month study period. The calves were clinically examined every week and clinical pathology parameters, immune responses and endocrine effects were regularly evaluated. Even though endocrine disrupting effects were detected with the in vitro screening assays, these could not be reproduced in the calves in the experiment. The two batches of molasses utilized in the calf feeding trial did not induce major differences in any of the parameters measured, with the exception of a lower mass gain in one of the molasses-fed groups (Group 1, which tended towards significance. The results of the study indicate that the two batches

  2. Singleton Merten Syndrome: A Rare Cause of Early Onset Aortic Stenosis

    Science.gov (United States)

    Mungee, Sudhir

    2017-01-01

    Singleton Merten syndrome (SMS) is a rare autosomal dominant genetic disorder with variable expression. Its characteristic features include abnormal aortic calcification, abnormal ossification of extremities, and dental anomalies. We present a young man with dyspnea who was noted to have aortic stenosis in the background of glaucoma, psoriasis, dental anomalies, hand and foot deformities, Achilles tendinitis, osteopenia, and nephrolithiasis. The conglomeration of features led to the diagnosis of SMS. His mother had a very similar phenotype. PMID:28321341

  3. Singleton Merten Syndrome: A Rare Cause of Early Onset Aortic Stenosis

    Directory of Open Access Journals (Sweden)

    Harshavardhan Ghadiam

    2017-01-01

    Full Text Available Singleton Merten syndrome (SMS is a rare autosomal dominant genetic disorder with variable expression. Its characteristic features include abnormal aortic calcification, abnormal ossification of extremities, and dental anomalies. We present a young man with dyspnea who was noted to have aortic stenosis in the background of glaucoma, psoriasis, dental anomalies, hand and foot deformities, Achilles tendinitis, osteopenia, and nephrolithiasis. The conglomeration of features led to the diagnosis of SMS. His mother had a very similar phenotype.

  4. A rare cause of cystic lung disease - Birt-Hogg-Dubé syndrome.

    Science.gov (United States)

    Minnis, P; Riddell, P; Keane, M P

    2016-01-01

    Birt-Hogg-Dubé syndrome, initially described in 1977, is an autosomal dominant inherited condition characterised by basal pulmonary cysts often resulting in pneumothorax, renal tumours and cutaneous involvement. Lung cysts have been described in up to 90% of patients with a corresponding risk of pneumothorax of 50 times greater than the normal population. We describe here a case of Birt-Hogg-Dubé diagnosed in the 9th decade of life and discuss the radiological findings and clinical implications.

  5. Marfan Syndrome

    Science.gov (United States)

    Marfan syndrome is a disorder that affects connective tissue. Connective tissues are proteins that support skin, bones, ... fibrillin. A problem with the fibrillin gene causes Marfan syndrome. Marfan syndrome can be mild to severe, ...

  6. Williams syndrome

    Science.gov (United States)

    Williams-Beuren syndrome ... Williams syndrome is caused by not having a copy of several genes. Parents may not have any family history of the condition. However, people with Williams syndrome have a 50% chance of passing the ...

  7. DE ANQUIN SYNDROME-RARE CAUSE OF LOW BACK PAIN: A CASE REPORT WITH REVIEW OF LITERATURE

    Directory of Open Access Journals (Sweden)

    Spasov Marko

    2016-07-01

    Full Text Available Introduction: Low back pain is common medical disorder that can be caused by different etiologies, some of them being very rare. During the past decades, much of the etiology and pato-mechanics of low back pain has been clarified. However, defining precise cause of low back pain in a small subset of patients is still challenging. Case presentation: We are presenting a case of long lasting low back pain caused by impingement of the enlarged spinous process of the fifth lumbar spine into the spina bifida of the first sacral segment, so called De Anquin syndrome. We delineated the precise morphology of the anomaly using CT scans, and since the patient was symptomatic, the resection of the enlarged spinous process was undertaken. During the follow up period, the patient remained completely symptom free. Discussion and Literature review: We undertook literature review and small number of studies describing De Anquin syndrome were found. The most remarkable finding of the case presented is the immediate and complete release of pain. Conclusion: We do recommend seeking for the exact etiology in the patients with long lasting low back pain.

  8. Fibrillin-1 mutations causing Weill-Marchesani syndrome and acromicric and geleophysic dysplasias disrupt heparan sulfate interactions.

    Directory of Open Access Journals (Sweden)

    Stuart A Cain

    Full Text Available The extracellular glycoprotein fibrillin-1 forms microfibrils that act as the template for elastic fibers. Most mutations in fibrillin-1 cause Marfan syndrome with severe cardiovascular and ocular symptoms, and tall stature. This is in contrast to mutations within a heparin-binding TB domain (TB5, which is downstream of the arg-gly-asp cell adhesion domain, which can cause Weill-Marchesani syndrome (WMS or Acromicric (AD and Geleophysic Dysplasias (GD. WMS is characterized by short limbs, joint stiffness and ocular defects, whilst fibrillin-1 AD and GD have severe short stature, joint defects and thickened skin. We previously showed that TB5 binds heparin. Here, we show that the corresponding region of fibrillin-2 binds heparin very poorly, highlighting a novel functional difference between the two isoforms. This finding enabled us to map heparin/heparan sulfate binding to two sites on fibrillin-1 TB5 using a mutagenesis approach. Once these sites were mapped, we were able to investigate whether disease-causing mutations in this domain disrupt binding to HS. We show that a WMS deletion mutant, and five AD and GD point mutants all have disrupted heparin binding to TB5. These data provide insights into the biology of fibrillins and the pathologies of WMS, AD and GD.

  9. Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome.

    Science.gov (United States)

    Mollet, Géraldine; Ratelade, Julien; Boyer, Olivia; Muda, Andrea Onetti; Morisset, Ludivine; Lavin, Tiphaine Aguirre; Kitzis, David; Dallman, Margaret J; Bugeon, Laurence; Hubner, Norbert; Gubler, Marie-Claire; Antignac, Corinne; Esquivel, Ernie L

    2009-10-01

    Podocin is a critical component of the glomerular slit diaphragm, and genetic mutations lead to both familial and sporadic forms of steroid-resistant nephrotic syndrome. In mice, constitutive absence of podocin leads to rapidly progressive renal disease characterized by mesangiolysis and/or mesangial sclerosis and nephrotic syndrome. Using established Cre-loxP technology, we inactivated podocin in the adult mouse kidney in a podocyte-specific manner. Progressive loss of podocin in the glomerulus recapitulated albuminuria, hypercholesterolemia, hypertension, and renal failure seen in nephrotic syndrome in humans. Lesions of FSGS appeared after 4 wk, with subsequent development of diffuse glomerulosclerosis and tubulointerstitial damage. Interestingly, conditional inactivation of podocin at birth resulted in a gradient of glomerular lesions, including mesangial proliferation, demonstrating a developmental stage dependence of renal histologic patterns of injury. The development of significant albuminuria in this model occurred only after early and focal foot process effacement had progressed to diffuse involvement, with complete absence of podocin immunolabeling at the slit diaphragm. Finally, we identified novel potential mediators and perturbed molecular pathways, including cellular proliferation, in the course of progression of renal disease leading to glomerulosclerosis, using global gene expression profiling.

  10. Podocin Inactivation in Mature Kidneys Causes Focal Segmental Glomerulosclerosis and Nephrotic Syndrome

    Science.gov (United States)

    Mollet, Géraldine; Ratelade, Julien; Boyer, Olivia; Muda, Andrea Onetti; Morisset, Ludivine; Lavin, Tiphaine Aguirre; Kitzis, David; Dallman, Margaret J.; Bugeon, Laurence; Hubner, Norbert; Gubler, Marie-Claire; Esquivel, Ernie L.

    2009-01-01

    Podocin is a critical component of the glomerular slit diaphragm, and genetic mutations lead to both familial and sporadic forms of steroid-resistant nephrotic syndrome. In mice, constitutive absence of podocin leads to rapidly progressive renal disease characterized by mesangiolysis and/or mesangial sclerosis and nephrotic syndrome. Using established Cre-loxP technology, we inactivated podocin in the adult mouse kidney in a podocyte-specific manner. Progressive loss of podocin in the glomerulus recapitulated albuminuria, hypercholesterolemia, hypertension, and renal failure seen in nephrotic syndrome in humans. Lesions of FSGS appeared after 4 wk, with subsequent development of diffuse glomerulosclerosis and tubulointerstitial damage. Interestingly, conditional inactivation of podocin at birth resulted in a gradient of glomerular lesions, including mesangial proliferation, demonstrating a developmental stage dependence of renal histologic patterns of injury. The development of significant albuminuria in this model occurred only after early and focal foot process effacement had progressed to diffuse involvement, with complete absence of podocin immunolabeling at the slit diaphragm. Finally, we identified novel potential mediators and perturbed molecular pathways, including cellular proliferation, in the course of progression of renal disease leading to glomerulosclerosis, using global gene expression profiling. PMID:19713307

  11. Endoscopically assisted resection of a scapular osteochondroma causing snapping scapula syndrome

    Directory of Open Access Journals (Sweden)

    Futani Hiroyuki

    2007-03-01

    Full Text Available Abstract Background Osteochondroma is the most common benign bone tumor in the scapula. This condition might lead to snapping scapula syndrome, which is characterized by painful, audible, and/or palpable abnormal scapulothoracic motion. In the present case, this syndrome was successfully treated by use of endoscopically assisted resection of the osteochondroma. Case presentation A 41-year-old man had a tolerable pain in his scapular region over a 10 years' period. The pain developed gradually with shoulder motion, in particular with golf swing since he was aiming a professional golf player career. On physical examination, "clunking" was noted once from 90 degrees of abduction to 180 degrees of shoulder motion. A trans-scapular roentgenogram and computed tomography images revealed an osteochondroma located at the anterior and inferior aspect of the scapula. Removal of the tumor was performed by the use of endoscopically assisted resection. One portal was made at the lateral border of the scapula to introduce a 2.7-mm-diameter, 30 degrees Hopkins telescope. The tumor was resected in a piece-by-piece manner by the use of graspers through the same portal. Immediately after the operation pain relief was obtained, and the "clunking" disappeared. CT images showed complete tumor resection. The patient could start playing golf one week after the surgery. Conclusion Endoscopically assisted resection of osteochondroma of the scapula provides a feasible technique to treat snapping scapula syndrome and obtain early functional recovery with a short hospital stay and cosmetic advantage.

  12. Meier-Gorlin syndrome mutations disrupt an Orc1 CDK inhibitory domain and cause centrosome reduplication.

    Science.gov (United States)

    Hossain, Manzar; Stillman, Bruce

    2012-08-15

    Like DNA replication, centrosomes are licensed to duplicate once per cell division cycle to ensure genetic stability. In addition to regulating DNA replication, the Orc1 subunit of the human origin recognition complex controls centriole and centrosome copy number. Here we report that Orc1 harbors a PACT centrosome-targeting domain and a separate domain that differentially inhibits the protein kinase activities of Cyclin E-CDK2 and Cyclin A-CDK2. A cyclin-binding motif (Cy motif) is required for Orc1 to bind Cyclin A and inhibit Cyclin A-CDK2 kinase activity but has no effect on Cyclin E-CDK2 kinase activity. In contrast, Orc1 inhibition of Cyclin E-CDK2 kinase activity occurs by a different mechanism that is affected by Orc1 mutations identified in Meier-Gorlin syndrome patients. The cyclin/CDK2 kinase inhibitory domain of Orc1, when tethered to the PACT domain, localizes to centrosomes and blocks centrosome reduplication. Meier-Gorlin syndrome mutations that disrupt Cyclin E-CDK2 kinase inhibition also allow centrosome reduplication. Thus, Orc1 contains distinct domains that control centrosome copy number and DNA replication. We suggest that the Orc1 mutations present in some Meier-Gorlin syndrome patients contribute to the pronounced microcephaly and dwarfism observed in these individuals by altering centrosome duplication in addition to DNA replication defects.

  13. Haemolytic uraemic syndrome and accumulation of haemoglobin-haptoglobin complexes in plasma in serum sickness caused by penicillin drugs.

    Science.gov (United States)

    Brandslund, I; Petersen, P H; Strunge, P; Hole, P; Worth, V

    1980-01-01

    2 patients treated with penicillin and ampicillin, respectively, suffered from haemorrhagic diathesis, haemolysis, cerebral symptoms and renal insufficiency, resembling a haemolytic-uraemic syndrome. Their plasma was red due to the presence during several days of haemoglobin-haptoglobin complexes, the P-haemoglobin being 2.8 and 1.6 g/l, respectively. Coagulation tests showed an unusual pattern with prolonged activated partial thromboplastin times, an extremely long thrombin time and very high levels of fibrinogen degradation products. Repeated transfusion had no effect. The patients were considered to have developed a drug-induced serum sickness associated with insufficient function of the reticuloendothelial system, and secondary to this an accumulation of haemoglobin-haptoglobin complexes in plasma. When the penicillin drugs were discontinued, all measured variables rapidly normalised and the patients recovered completely. Thus, the haemolyticuraemic syndrome seemed to be caused by the serum sickness, possibly via circulating or cell-associated immune complexes. The possibility of a type III allergic reaction should be considered in patients with haemolytic-uraemic-like syndromes.

  14. Causes of death in patients ≥75 years of age with non-ST-segment elevation acute coronary syndrome.

    Science.gov (United States)

    Morici, Nuccia; Savonitto, Stefano; Murena, Ernesto; Antonicelli, Roberto; Piovaccari, Giancarlo; Tucci, Daniele; Tamburino, Corrado; Fontanelli, Alessandro; Bolognese, Leonardo; Menozzi, Mila; Cavallini, Claudio; Petronio, Anna Sonia; Ambrosio, Giuseppe; Piscione, Federico; Steffenino, Giuseppe; De Servi, Stefano

    2013-07-01

    The causes of death within 1 year of hospital admission in patients with non-ST-segment elevation acute coronary syndromes are ill defined, particularly in patients aged ≥75 years. From January 2008 through May 2010, we enrolled 645 patients aged ≥75 years with non-ST-segment elevation acute coronary syndromes: 313 in a randomized trial comparing an early aggressive versus an initially conservative approach, and 332, excluded from the trial for specific reasons, in a parallel registry. Each death occurring during 1 year of follow-up was adjudicated by an independent committee. The mean age was 82 years in both study cohorts, and 53% were men. By the end of the follow-up period (median 369 days, interquartile range 345 to 391), 120 patients (18.6%) had died. The mortality was significantly greater in the registry (23.8% vs 13.1%, p = 0.001). The deaths were classified as cardiac in 94% of the cases during the index admission and 68% of the cases during the follow-up period. Eighty-six percent of the cardiac deaths were of ischemic origin. In a multivariate logistic regression model that included the variables present on admission in the whole study population, the ejection fraction (hazard ratio 0.95, 95% confidence interval 0.94 to 0.97; p segment elevation acute coronary syndromes, most deaths in patients aged ≥75 years have a cardiac origin, mostly owing to myocardial ischemia.

  15. The mitochondrial DNA 10197 G > A mutation causes MELAS/Leigh overlap syndrome presenting with acute auditory agnosia.

    Science.gov (United States)

    Leng, Yinglin; Liu, Yuhe; Fang, Xiaojing; Li, Yao; Yu, Lei; Yuan, Yun; Wang, Zhaoxia

    2015-04-01

    Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes/Leigh (MELAS/LS) overlap syndrome is a mitochondrial disorder subtype with clinical and magnetic resonance imaging (MRI) features that are characteristic of both MELAS and Leigh syndrome (LS). Here, we report an MELAS/LS case presenting with cortical deafness and seizures. Cranial MRI revealed multiple lesions involving bilateral temporal lobes, the basal ganglia and the brainstem, which conformed to neuroimaging features of both MELAS and LS. Whole mitochondrial DNA (mtDNA) sequencing and PCR-RFLP revealed a de novo heteroplasmic m.10197 G > A mutation in the NADH dehydrogenase subunit 3 gene (ND3), which was predicted to cause an alanine to threonine substitution at amino acid 47. Although the mtDNA m.10197 G > A mutation has been reported in association with LS, Leber hereditary optic neuropathy and dystonia, it has never been linked with MELAS/LS overlap syndrome. Our patient therefore expands the phenotypic spectrum of the mtDNA m.10197 G > A mutation.

  16. Excess functional copy of allele at chromosomal region 11p15 may cause Wiedemann-Beckwith (EMG) syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kubota, T.; Saitoh, S.; Jinno, Y.; Niikawa, N.; Matsumoto, T. [Nagasaki Univ. School of Medicine (Japan); Narahara, K. [Okayama Univ. School of Medicine, Okayama (Japan); Fukushima, Y. [Saitama Children`s Hospital, Iwatsuki (Japan)

    1994-02-15

    Wiedemann-Beckwith syndrome (WBS) is a genetic disorder with overgrowth and predisposition to Wilms` tumor. The putative locus of the gene responsible for this syndrome is assigned to chromosome region 11p15.5, and genomic imprinting in this region has been proposed: the paternally derived gene(s) at 11p15.5 is selectively expressed, while the maternally transmitted gene(s) is inactive. The authors examined 18 patients for the parental origin of their 11p15 regions. DNA polymorphism analyses using 6 loci on chromosome 11 showed that 2 patients with duplications of 11p15 regions from their respective fathers and one from the mother, indicating the transmission of an excessive paternal gene at 11p15 to each patient. The result, together with the previous findings in karyotypically normal or abnormal patients and in overgrowth mouse experiments, are consistent with imprinting hypothesis that overexpression of paternally derived gene(s) at 11p15.5, probably the human insulin-like growth factor II (IFG-II) gene, may cause the phenotype. Total constitutional uniparental paternal disomy (UPD) or segmental UPD for the 6 loci examined of chromosome 11 was not observed in our 12 sporadic patients. In order to explain completely the inheritance of this syndrome in patients with various chromosomal constitutions, the authors propose an alternative imprinting mechanism involving the other locus that may be paternally imprinted and may suppress the expression of this gene. 28 refs., 3 figs., 1 tab.

  17. Deletion at chromosome 16p13. 3 as a cause of Rubinstein-Taybi syndrome: Clinical aspects

    Energy Technology Data Exchange (ETDEWEB)

    Hennekam, R.C.M.; Tilanus, M.; Boogaard, M.J.H. van den (State Univ., Utrecht (Netherlands)); Hamel, B.C.J.; Voshart-van Heeren, H.; Mariman, E.C.M.; Beersum, S.E.C. van (University Hospital, Nijmegen (Netherlands)); Breuning, M.H. (Clinical Genetics Center, Rotterdam (Netherlands))

    1993-02-01

    In the accompanying paper, a chromosomal localization of the Rubinstein-Taybi syndrome by cytogenetic investigations with fluorescence in situ hybridization techniques at chromosome 16p13.3 is described. The authors investigated 19 of these patients and their parents (a) to ascertain the parental origin of the chromosome with the deletion in families where such a deletion was detected, (b) to disclose whether uniparental disomy plays a role in etiology, and (c) to compare clinical features in patients with a deletion to those in individuals in whom deletions were not detectable. Molecular studies showed a copy of chromosome 16 from each parent in all 19 patients. Uniparental disomy was also excluded for five other chromosome arms known to be imprinted in mice. None of the probes used for determining the origin of the deleted chromosome proved to be informative. The clinical features were essentially the same in patients with and without visible deletion, with a possible exception for the incidence of microcephaly, angulation of thumbs and halluces, and partial duplication of the halluces. A small deletion at 16p13.3 may be found in some patients with Rubinstein-Taybi syndrome. Cytogenetically undetectable deletions, point mutations, mosaicism, heterogeneity, or phenocopy by a nongenetic cause are the most probable explanations for the absence of cytogenetic or molecular abnormalities in other patients with Rubinstein-Taybi syndrome. 26 refs., 3 tabs., 2 figs.

  18. Defects in the IFT-B component IFT172 cause Jeune and Mainzer-Saldino syndromes in humans.

    Science.gov (United States)

    Halbritter, Jan; Bizet, Albane A; Schmidts, Miriam; Porath, Jonathan D; Braun, Daniela A; Gee, Heon Yung; McInerney-Leo, Aideen M; Krug, Pauline; Filhol, Emilie; Davis, Erica E; Airik, Rannar; Czarnecki, Peter G; Lehman, Anna M; Trnka, Peter; Nitschké, Patrick; Bole-Feysot, Christine; Schueler, Markus; Knebelmann, Bertrand; Burtey, Stéphane; Szabó, Attila J; Tory, Kálmán; Leo, Paul J; Gardiner, Brooke; McKenzie, Fiona A; Zankl, Andreas; Brown, Matthew A; Hartley, Jane L; Maher, Eamonn R; Li, Chunmei; Leroux, Michel R; Scambler, Peter J; Zhan, Shing H; Jones, Steven J; Kayserili, Hülya; Tuysuz, Beyhan; Moorani, Khemchand N; Constantinescu, Alexandru; Krantz, Ian D; Kaplan, Bernard S; Shah, Jagesh V; Hurd, Toby W; Doherty, Dan; Katsanis, Nicholas; Duncan, Emma L; Otto, Edgar A; Beales, Philip L; Mitchison, Hannah M; Saunier, Sophie; Hildebrandt, Friedhelm

    2013-11-01

    Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease. To identify additional IFT-B components defective in ciliopathies, we independently performed different mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in 1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome resequencing in 63 individuals with ATD. We thereby detected biallelic mutations in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals displayed abnormalities of the thorax and/or long bones, as well as renal, hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS. Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert syndrome was present in 2 out of 12 families. Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. Knockdown of ift172 in zebrafish recapitulated the human phenotype and demonstrated a genetic interaction between ift172 and ift80. In summary, we have identified defects in IFT172 as a cause of complex ATD and MZSDS. Our findings link the group of skeletal ciliopathies to an additional IFT-B component, IFT172, similar to what has been shown for IFT-A.

  19. Minimal Change Nephrotic Syndrome Which Was Most Likely Caused by Chronic Sinusitis.

    Science.gov (United States)

    Iwatani, Hirotsugu; Mori, Daisuke; Yamamoto, Satoko; Nakano, Chikako; Yamamoto, Ryohei; Masumura, Chisako; Shikina, Takashi; Imai, Takao; Inohara, Hidenori; Rakugi, Hiromi; Isaka, Yoshitaka

    2015-01-01

    A 33-year-old Japanese man was admitted with severe edema, and a renal biopsy confirmed minimal change nephrotic syndrome (MCNS). CT revealed his severe chronic sinusitis, and he first received antimicrobial therapy, which resulted in decreased proteinuria. The surgical operation for sinusitis resulted in the complete disappearance of proteinuria without corticosteroid or immunosuppressant therapy within one week. MCNS may be triggered by infection, but there are no previously reported cases of MCNS that is completely remitted by infection control alone. Therefore, we herein report the first case of MCNS that attained complete remission following therapy for chronic sinusitis alone, which suggests a strong etiology of chronic sinusitis for MCNS.

  20. Skin lesions simulating blue toe syndrome caused by prolonged contact with a millipede

    Directory of Open Access Journals (Sweden)

    Augusto Scardazan Heeren Neto

    2014-04-01

    Full Text Available Venomous animals are those that, by means of a hunting and defense mechanism, are able to inject their prey with a toxic substance produced in their bodies, directly from specialized glands (e.g., tooth, sting, spur through which the poison passes. Millipedes are poisonous animals; they can be harmful to humans, and their effects usually manifest as erythematous, purpuric, and cyanotic lesions; local pain; and paresthesia. Here, we report a case of skin contact with a millipede for 6h resulting in skin lesions similar to blue toe syndrome.

  1. Hypereosinophilic syndrome as a cause of fatal thrombosis: two case reports with histological study.

    Science.gov (United States)

    Fujita, Kumi; Ishimaru, Hiroyasu; Hatta, Kazuhiro; Kobashi, Yoichiro

    2015-08-01

    Herein we present two cases of hypereosinophilic syndrome with a unique clinical presentation. One patient showed severe systemic thrombosis with splenic rupture and the other patient showed finger gangrene with various systemic symptoms. Both patients were examined histologically, and several characteristics were noted. First, fresh or organized thrombosis with marked eosinophilic infiltration was observed in the cavity and walls of the thrombosed vessels. Second, many eosinophils showed degranulation and were positive for eosinophilic cationic protein on immunohistological examination. Third, the structures of thrombosed vessels were well preserved, which is not observed in systemic vasculitis. These patients exhibited no neoplastic features and were treated with prednisolone with excellent therapeutic results.

  2. Life Threatening, Allopurinol-related Dress Syndrome as a Rare Cause of Fever of Unknown Origin.

    Science.gov (United States)

    Civardi, Giuseppe; Zanlari, Luca; Bassi, Emanuele; Zangrandi, Adriano; Maria Cesinaro, Anna; Nosseir, Sofia; De Maria, Nicola

    2015-01-01

    Drug reaction eosinophilia with systemic symptoms (DRESS) syndrome is a potentially life threatening condition secondary to the usage of a wide type of drugs. A 38-year-old woman under allopurinol therapy for hyperuricemia was admitted in our department with fever and a diffuse cutaneous erythematous eruption. A few days after admission she developed rapidly progressive signs of acute liver and kidney failure. Subsequently, her clinical conditions shortly improved. The histologic findings obtained from skin and liver biopsies were consistent with a toxic drug reaction. The patient completely recovered and has been healthy for five years.

  3. Life-Threatening Obstructive Sleep Apnea Caused by Adenoid Hypertrophy in an Infant with Noonan Syndrome

    Directory of Open Access Journals (Sweden)

    Sonia Khirani

    2012-01-01

    Full Text Available Adenoidectomy is a commonly performed surgery in children, even though its effectiveness is still under investigation. However, in children with risk factors such as age under 3 years old, associated comorbidities, or severe obstructive sleep apneas, a high postoperative respiratory morbidity is possible. We report the case of a 15-month-old boy with Noonan syndrome and a complex clinical history, who presented with a life-threatening obstructive sleep apnea due to hypertrophy of the adenoids which resolved completely after adenoidectomy.

  4. Truncating variants in the majority of the cytoplasmic domain of PCDH15 are unlikely to cause Usher syndrome 1F.

    Science.gov (United States)

    Perreault-Micale, Cynthia; Frieden, Alexander; Kennedy, Caleb J; Neitzel, Dana; Sullivan, Jessica; Faulkner, Nicole; Hallam, Stephanie; Greger, Valerie

    2014-11-01

    Loss of function variants in the PCDH15 gene can cause Usher syndrome type 1F, an autosomal recessive disease associated with profound congenital hearing loss, vestibular dysfunction, and retinitis pigmentosa. The Ashkenazi Jewish population has an increased incidence of Usher syndrome type 1F (founder variant p.Arg245X accounts for 75% of alleles), yet the variant spectrum in a panethnic population remains undetermined. We sequenced the coding region and intron-exon borders of PCDH15 using next-generation DNA sequencing technology in approximately 14,000 patients from fertility clinics. More than 600 unique PCDH15 variants (single nucleotide changes and small indels) were identified, including previously described pathogenic variants p.Arg3X, p.Arg245X (five patients), p.Arg643X, p.Arg929X, and p.Arg1106X. Novel truncating variants were also found, including one in the N-terminal extracellular domain (p.Leu877X), but all other novel truncating variants clustered in the exon 33 encoded C-terminal cytoplasmic domain (52 patients, 14 variants). One variant was observed predominantly in African Americans (carrier frequency of 2.3%). The high incidence of truncating exon 33 variants indicates that they are unlikely to cause Usher syndrome type 1F even though many remove a large portion of the gene. They may be tolerated because PCDH15 has several alternate cytoplasmic domain exons and differentially spliced isoforms may function redundantly. Effects of some PCDH15 truncating variants were addressed by deep sequencing of a panethnic population.

  5. A case's root cause analysis of osteofascial compartment syndrome induced by radial artery puncture and its defensive strategy

    Institute of Scientific and Technical Information of China (English)

    Feng-Ying Kang; Yang Yang; Yu-Ping Tong; Ya-Li Hu; Ning-Ning Xue

    2016-01-01

    Objective: The objective of this study was to reduce or avoid the occurrence of the cases of osteofascial compartment syndrome induced by a radial artery puncture for arterial blood gas analysis. Methods: We analyzed an adverse event using cheese model analysis, “fish bone” analysis, root cause analysis, and other methods. Results: There are three root causes leading to an adverse event:operation technique, assessment of the disease, and informing patient families. However, there are many reasons to promote the occurrence and development of the event. Conclusions: We should analyze and manage the adverse events in patients from the point of view of a system. Developing the measures of a system defense can enhance patient safety and create a good safety culture.

  6. An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs.

    Science.gov (United States)

    Fyfe, John C; Hemker, Shelby L; Venta, Patrick J; Fitzgerald, Caitlin A; Outerbridge, Catherine A; Myers, Sherry L; Giger, Urs

    2013-08-01

    Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malabsorption and proteinuria comprising CUBN ligands were demonstrated by radiolabeled cobalamin uptake studies and SDS-PAGE, respectively. CUBN mRNA and protein expression were reduced ~10 fold and ~20 fold, respectively, in both ileum and kidney of affected dogs. DNA sequencing demonstrated a single base deletion in exon 53 predicting a translational frameshift and early termination codon likely triggering nonsense mediated mRNA decay. The mutant allele segregated with the disease in the border collie kindred. The border collie disorder indicates that a CUBN mutation far C-terminal from the intrinsic factor-cobalamin binding site can abrogate receptor expression and cause Imerslund-Gräsbeck syndrome.

  7. A twin sibling with Prader-Willi syndrome caused by uniparental disomy conceived after in vitro fertilization.

    Science.gov (United States)

    Atik, T; Aykut, A; Karaca, E; Onay, H; Ozkinay, F; Cogulu, O

    2014-01-01

    The use of assisted reproductive technologies (ART) has increased gradually in the treatment of infertility worldwide. On the other hand ART has been found to be associated with an increased risk of congenital malformations including imprinting defects as well. Although a number of imprinting syndromes have been reported to be related with ART, no case with uniparental disomy (UPD) caused Prader-Willi syndrome (PWS) [OMIM ID: 176270] has been reported in the literature. Here we present a dizygotic twin in which one of them was born with maternal UPD15 following ART. The proband was a 2-year-old boy who had feeding difficulties, generalized hypotonia, frontal bossing, broad forehead, small hands and feet. Laboratory investigations revealed minimal dilatation in 3rd and 4th ventricles and corpus callosum hypoplasia in magnetic resonance imaging, supravalvular pulmonary stenosis in echocardiography and pelvicaliectasia in the USG examinations. Methylation and microsatellite markers analyses showed maternal UPD for chromosome 15. Here we report, for the first time UPD caused PWS patient born after ART.

  8. Improved husbandry to control an outbreak of rainbow trout fry syndrome caused by infection with Flavobacterium psychrophilum

    Science.gov (United States)

    Bebak, J.A.; Welch, T.J.; Starliper, C.E.; Baya, A.M.; Garner, M.M.

    2007-01-01

    Case Description - A cohort of 35,200, 13-week-old, female rainbow trout at a fish farm was evaluated because of a 2-week history of anorexia and lethargy and a mortality rate of approximately 100 fish/d. Clinical Findings - Affected fish were lethargic and thin and had disequilibrium, bilateral exophthalmia, pale red gills and kidneys, red-tinged coelomic fluid, and pale brown livers. Some fish were differentially pigmented bilaterally. The presumptive diagnosis was bacterial or viral septicemia. The definitive diagnosis was rainbow trout fry syndrome caused by infection with Flavobacterium psychrophilum. Treatment and Outcome - A strategy for controlling the outbreak based on reducing pathogen numbers in affected tanks and reducing pathogen spread among tanks was developed. The option of treating with antimicrobial-medicated feed was discussed with the farmer, but was declined. After changes were made, mortality rate declined quickly, with no more deaths within 10 days after the initial farm visit. Clinical Relevance - Bacterial coldwater disease is the most common manifestation of infection with F psychrophilum in fingerling and adult rainbow trout. However, the organism can also cause rainbow trout fry syndrome. This condition should be included on a list of differential diagnoses for septicemia in hatchery-reared rainbow trout fry.

  9. Free-thiamine is a potential biomarker of thiamine transporter-2 deficiency: a treatable cause of Leigh syndrome.

    Science.gov (United States)

    Ortigoza-Escobar, Juan Darío; Molero-Luis, Marta; Arias, Angela; Oyarzabal, Alfonso; Darín, Niklas; Serrano, Mercedes; Garcia-Cazorla, Angels; Tondo, Mireia; Hernández, María; Garcia-Villoria, Judit; Casado, Mercedes; Gort, Laura; Mayr, Johannes A; Rodríguez-Pombo, Pilar; Ribes, Antonia; Artuch, Rafael; Pérez-Dueñas, Belén

    2016-01-01

    Thiamine transporter-2 deficiency is caused by mutations in the SLC19A3 gene. As opposed to other causes of Leigh syndrome, early administration of thiamine and biotin has a dramatic and immediate clinical effect. New biochemical markers are needed to aid in early diagnosis and timely therapeutic intervention. Thiamine derivatives were analysed by high performance liquid chromatography in 106 whole blood and 38 cerebrospinal fluid samples from paediatric controls, 16 cerebrospinal fluid samples from patients with Leigh syndrome, six of whom harboured mutations in the SLC19A3 gene, and 49 patients with other neurological disorders. Free-thiamine was remarkably reduced in the cerebrospinal fluid of five SLC19A3 patients before treatment. In contrast, free-thiamine was slightly decreased in 15.2% of patients with other neurological conditions, and above the reference range in one SLC19A3 patient on thiamine supplementation. We also observed a severe deficiency of free-thiamine and low levels of thiamine diphosphate in fibroblasts from SLC19A3 patients. Surprisingly, pyruvate dehydrogenase activity and mitochondrial substrate oxidation rates were within the control range. Thiamine derivatives normalized after the addition of thiamine to the culture medium. In conclusion, we found a profound deficiency of free-thiamine in the CSF and fibroblasts of patients with thiamine transporter-2 deficiency. Thiamine supplementation led to clinical improvement in patients early treated and restored thiamine values in fibroblasts and cerebrospinal fluid.

  10. A case report of a pregnancy-related death caused by primary antiphospholipid antibody syndrome

    Directory of Open Access Journals (Sweden)

    Sun Y

    2014-11-01

    Full Text Available Yingjian Sun,1 Manhua Cui,1 Wanan Zhu,2 Weiling Xu,2 Na Li2 1Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, Jilin, People's Republic of China; 2Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China Abstract: Primary antiphospholipid antibody syndrome (APS is a rare clinical event in the People's Republic of China. As APS is easily neglected or misdiagnosed, a delayed treatment can result. The patient reported here was a 32-year-old female who died by systemic venous thrombosis on day 11 after a cesarean section delivery. Luckily, the baby survived. A blood test demonstrated that the patient's platelets were decreased at 19 weeks of gestation. Anti-cardolipin antibody and antiß2GP1 (anti-ß2-glycoprotein-I antibody were positive at 36 weeks and 2 days of gestation. This patient was diagnosed with APS. Unfortunately, as physicians, we could not provide proper treatment as the patient's relatives were concerned that the proposed treatment would have negative effects on the infant's health. This clinical case strongly suggests that physicians need to appreciate that APS is a very serious condition, especially for pregnant women, and that proper treatment should be provided as early as possible to avoid a bad outcome, despite the fact that a cure for this disease is not currently available. Keywords: APS, thrombosis, Hughes syndrome

  11. [A case of AKI-caused minimal change nephrotic syndrome with concomitant pleuritis].

    Science.gov (United States)

    Watanabe, Renya; Abe, Yasuhiro; Sasaki, Masaru; Hamauchi, Aki; Yasunaga, Tomoe; Kurata, Satoshi; Yasuno, Tetsuhiko; Ito, Kenji; Sasatomi, Yoshie; Hisano, Satoshi; Nakashima, Hitoshi

    2016-01-01

    A twenty-year-old man complaining of chest pain was diagnosed as nephrotic syndrome complicated with pleural effusion and ascites. Despite treatment with antibiotics, his fever and high inflammatory reaction persisted. After hospitalization, his urine volume decreased and renal function had deteriorated. As he was suffering from dyspnea, hemodialysis was performed together with chest drainage. His pleural effusion was exudative, and IVIG treatment was added to the antibiotic treatment. He was diagnosed as suspected developed minimal change nephrotic syndrome (MCNS) and administered prednisolone intravenously. His renal function ameliorated as a result of this treatment, enabling him to withdraw from hemodialysis. Inflammatory reaction gradually decreased and his general condition improved. The result of a renal biopsy examination carried out after the hemodialysis treatment confirmed MCNS, which suggested that MCNS had induced acute kidney injury (AKI) atypically in this case. Generally AKI is not induced by MCNS in youth, but it may occur under severe inflammatory conditions. Physicians should be aware that MCNS in young patients may lead to the development of AKI requiring hemodialysis treatment.

  12. [Primary pigmented nodular adrenocortical disease as cause of Cushing's syndrome associated with Carney complex].

    Science.gov (United States)

    Dumić, Miroslav; Janjanin, Nevena; Uroić, Anita Spehar; Ille, Jasenka; Skegro, Mate; Kusec, Vesna; Marjanac, Igor; Matić, Toni; Jelasić, Drazen

    2006-01-01

    We report a 11-year-old girl and two 14-year-old boys with Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). In these patients, hypercortisolism is a consequence of autonomous cortisol secretion from adrenal glands and is ACTH-independent. Besides PPNAD, the girl had lentigines, spotty pigmentation on her bucal mucosa and lips and she also had schwannoma. One of the reported boys had prolactinoma. Considering this, those two patients fulfill the criteria for Carney complex which is a type of multiple endocrine neoplasia syndromes inherited in an autosomal dominant trait. The other boy had PPNAD but no other obvious signs of Carney complex were noticed. Family study didn't reveal any clinical or laboratory signs of Carney complex in our patients' first relatives. All of our patients underwent bilateral adrenalectomy (in one of the boys laparoscopic surgery was performed). Glucocorticoid and mineralocorticoid substitution has been started. Adrenal glands were macroscopically normal but pathohistological analysis confirmed the diagnosis of PPNAD.

  13. Oxidative Stress and Metabolic Syndrome: Cause or Consequence of Alzheimer's Disease?

    Directory of Open Access Journals (Sweden)

    Diana Luque-Contreras

    2014-01-01

    Full Text Available Alzheimer’s disease (AD is a major neurodegenerative disease affecting the elderly. Clinically, it is characterized by a progressive loss of memory and cognitive function. Neuropathologically, it is characterized by the presence of extracellular β-amyloid (Aβ deposited as neuritic plaques (NP and neurofibrillary tangles (NFT made of abnormal and hyperphosphorylated tau protein. These lesions are capable of generating the neuronal damage that leads to cell death and cognitive failure through the generation of reactive oxygen species (ROS. Evidence indicates the critical role of Aβ metabolism in prompting the oxidative stress observed in AD patients. However, it has also been proposed that oxidative damage precedes the onset of clinical and pathological AD symptoms, including amyloid-β deposition, neurofibrillary tangle formation, vascular malfunction, metabolic syndrome, and cognitive decline. This paper provides a brief description of the three main proteins associated with the development of the disease (Aβ, tau, and ApoE and describes their role in the generation of oxidative stress. Finally, we describe the mitochondrial alterations that are generated by Aβ and examine the relationship of vascular damage which is a potential prognostic tool of metabolic syndrome. In addition, new therapeutic approaches targeting ROS sources and metabolic support were reported.

  14. Corticotropin-independent Cushing's syndrome caused by an ectopic adrenal adenoma.

    Science.gov (United States)

    Ayala, A R; Basaria, S; Udelsman, R; Westra, W H; Wand, G S

    2000-08-01

    Although nonsecreting suprarenal embryonic remnants are frequently found in the urogenital tract, adenomatous transformation resulting in glucocorticoid excess is a rare phenomenon. We report a case of a 63-yr-old woman that presented with new-onset hirsutism, facial plethora, hypertension, centripetal obesity, and a proximal myopathy. The 24-h urinary free cortisol excretion rate was elevated, and the serum ACTH level was suppressed. The patient failed an overnight and low dose dexamethasone suppression test and did not respond to CRH stimulation. In light of the undetectable baseline morning ACTH levels and the blunt response to CRH, the diagnosis of corticotropin-independent Cushing's syndrome was made. Imaging studies revealed normal adrenal glands and enlargement of a left pararenal nodule incidentally observed 4 yr before the onset of symptoms. Dramatic resolution of symptoms was observed after surgical removal of the 3.5-cm mass. Pathological exam confirmed adrenocortical adenoma in ectopic adrenal tissue. The case reported here represents the unusual circumstance in which the development of adenomatous transformation of ectopic adrenal tissue has been prospectively observed with imaging studies. It illustrates the importance of considering ectopic corticosteroid-secreting tumors in the context of corticotropin-independent Cushing's syndrome.

  15. 5q14.3 deletion neurocutaneous syndrome: Contiguous gene syndrome caused by simultaneous deletion of RASA1 and MEF2C: A progressive disease.

    Science.gov (United States)

    Ilari, Rita; Agosta, Guillermo; Bacino, Carlos

    2016-03-01

    We report the case of a young girl who was presented with complex clinical symptoms caused by the deletion of contiguous genes: RASA1 and MEF2C, located on chromosome 5q14.3. Specifically, the diagnosis of her skin disorder and vascular malformations involving central nervous system is consistent with a RASopathy. The child's neurological manifestations are observed in most patients suffering from 5q14.3 by deletion or mutation of the MEF2C gene. A review of the literature allowed us to conclude that the contiguous deletion of genes RASA1 and MEF2C fulfills the criteria for the diagnosis of a Neurocutaneous syndrome as proposed by Carr et al. [2011]. We also assessed the penetrance of RASA1 and clinical manifestations of MEF2C according to the type of deletion. This child described presents the complete symptomatology of both deleted genes. We would also like to highlight the progression of the disorder.

  16. Occipital horn syndrome and classical Menkes syndrome caused by deep intronic mutations, leading to the activation of ATP7A pseudo-exon

    DEFF Research Database (Denmark)

    Yasmeen, Saiqa; Lund, Katrine; De Paepe, Anne

    2014-01-01

    Menkes disease is an X-linked disorder of copper metabolism caused by mutations in the ATP7A gene. Whereas most of the patients exhibit a severe classical form, about 9% of the patients exhibit a milder form of Menkes disease. The mildest form is called occipital horn syndrome (OHS). Mutations...... patients: two patients with OHS and one patient with classical Menkes disease. The pseudo-exons were inserted between exons 10 and 11, between exons 16 and 17 and between exons 14 and 15 in the three patients, as a result of deep intronic mutations. This is the first time the activation of pseudo...... mechanism, which has hitherto been overlooked.European Journal of Human Genetics advance online publication, 4 September 2013; doi:10.1038/ejhg.2013.191....

  17. A Rare Cause of Acromegaly: Short Review of McCune Albright Syndrome

    Directory of Open Access Journals (Sweden)

    Yusuf Aydın

    2009-06-01

    Full Text Available McCune-Albright syndrome (MAS is characterized by a triad of poly/monostotic fibrous dysplasia, café-au-lait macules, and hyperfunctioning endocrinopathies, including growth hormone (GH excess. Acromegaly, as a manifestation of endocrine hyperfunction with MAS is uncommon. We report a 34-year-old man with MAS and acromegaly, in whom surgical removal of the pituitary tumour has been technically difficult because of bone deformities. A combination of a long-acting somatostatin analogue (Sandostatin LAR and external irradiation were therefore used as treatment. Acromegaly associated with MAS is very rarely seen, and has been the subject of approximately 70 published reports. We present a case of acromegaly associated with MAS and a brief survey of relevant literature. Turk Jem 2009; 13: 13-5

  18. Severe acute respiratory distress syndrome caused by unintentional sewing machine lubricant ingestion: A case report

    Directory of Open Access Journals (Sweden)

    Sunil Kishore

    2016-01-01

    Full Text Available Sewing machine oil ingestion is rare but is possible due to its availability at home. Chemically, it belongs to hydrocarbon family which is toxic if aspirated, owing to their physical properties such as high volatility and low viscosity. On the contrary, sewing machine lubricant has high viscosity and low volatility which makes it aspiration less likely. The main danger of hydrocarbon ingestion is chemical pneumonitis which may be as severe as acute respiratory distress syndrome (ARDS. We report a case of a 5-year-old girl with accidental ingestion of sewing machine lubricant oil, who subsequently developed ARDS refractory to mechanical ventilation. There was much improvement with airway pressure release ventilation mode of ventilation, but the child succumbed to death due to pulmonary hemorrhage.

  19. The Tourette International Collaborative Genetics (TIC Genetics) study, finding the genes causing Tourette syndrome

    DEFF Research Database (Denmark)

    Dietrich, Andrea; Fernandez, Thomas V; King, Robert A

    2015-01-01

    Tourette syndrome (TS) is a neuropsychiatric disorder characterized by recurrent motor and vocal tics, often accompanied by obsessive-compulsive disorder and/or attention-deficit/hyperactivity disorder. While the evidence for a genetic contribution is strong, its exact nature has yet...... to be clarified fully. There is now mounting evidence that the genetic risks for TS include both common and rare variants and may involve complex multigenic inheritance or, in rare cases, a single major gene. Based on recent progress in many other common disorders with apparently similar genetic architectures...... discovery effort, focusing both on familial genetic variants with large effects within multiply affected pedigrees and on de novo mutations ascertained through the analysis of apparently simplex parent-child trios with non-familial tics. The clinical data and biomaterials (DNA, transformed cell lines, RNA...

  20. A Review of Novel Coronavirus, cause of Middle East Respiratory Syndrome

    Directory of Open Access Journals (Sweden)

    Katayoun Vahdat

    2014-01-01

    Full Text Available Abstract Background: Isolation of a novel virus belonging to coronavirdae family in September 2012, from patients in Middle East who had died of an acute respiratory illness & renal failure lead to researches on this new virus. Here, a brief review to summarize the events of scientific findings of this new emerging virus. Material and Methods: This review is based on a comprehensive search of three databases (Pubmed, Embase and Cochrane and WHO reports. The searched keywords were new coronavirus, Middle East, acute respieratory distress syndrom & Saudi Arabia. Results: Due to novelty of virus only limited papers exist on searched databases, so only 50 papers were identified which after omitting repeated case reports, papers related to SARS and updated WHO reports, 30 papers were finally reviewed. Conclusion: WHO recommendation is evaluation of all patients with acute respiratory illness and history of travel to Saudi Arabia or other countries where this novel virus is epidemic.

  1. Mutation of fibulin-1 causes a novel syndrome involving the central nervous system and connective tissues.

    Science.gov (United States)

    Bohlega, Saeed; Al-Ajlan, Huda; Al-Saif, Amr

    2014-05-01

    Fibulin-1 is an extracellular matrix protein that has an important role in the structure of elastic fibers and basement membranes of various tissues. Using homozygosity mapping and exome sequencing, we discovered a missense mutation, p.(Cys397Phe), in fibulin-1 in three patients from a consanguineous family presented with a novel syndrome of syndactyly, undescended testes, delayed motor milestones, mental retardation and signs of brain atrophy. The mutation discovered segregated with the phenotype and was not found in 374 population-matched alleles. The affected cysteine is highly conserved across vertebrates and its mutation is predicted to abolish a disulfide bond that defines the tertiary structure of fibulin-1. Our findings emphasize the crucial role fibulin-1 has in development of the central nervous system and various connective tissues.

  2. Von Hippel Lindau disease with metastatic pancreatic neuroendocrine tumor causing ectopic Cushing's syndrome.

    Science.gov (United States)

    Hatipoglu, Esra; Kepicoglu, Hasan; Rusen, Elif; Kabasakal, Levent; Gundogdu, Sadi; Kadioglu, Pinar

    2013-01-01

    We present a 39-year-old woman who was previously diagnosed with Von Hippel Lindau Disease (VHLD). She had surgery and radiotherapy for cranial hemangioblastoma (HA) 11 years ago and had unilateral adrenalectomy for pheochromocytoma in another hospital 6 month prior to her admission to our center. Moon face, buffalo hump, central obesity, progressive weight gain and menstrual irregularities persisted after adrenalectomy. Her laboratory results were consistent with ectopic Cushing's syndrome (ECS). A pancreatic solid mass with a nodule on the left lung were revealed upon computed tomography. In addition, Gallium-68 Somatostatin Receptor PET confirmed the pancreatic involvement and demonstrated additional lesions on the left lung and in the aortocaval lymphatic system on the right side, suggesting metastatic pancreatic neuroendocrine tumor (PNET). Peptide receptor radionuclide therapy (PRRT) with [177Lutetium-DOTA0,Tyr3] octreotate was performed on the patient, with no side effects observed. She was discharged from the hospital 10 days after the first cycle.

  3. SHOX Haploinsufficiency as a Cause of Syndromic and Nonsyndromic Short Stature.

    Science.gov (United States)

    Fukami, Maki; Seki, Atsuhito; Ogata, Tsutomu

    2016-04-01

    SHOX in the short arm pseudoautosomal region (PAR1) of sex chromosomes is one of the major growth genes in humans. SHOX haploinsufficiency results in idiopathic short stature and Léri-Weill dyschondrosteosis and is associated with the short stature of patients with Turner syndrome. The SHOX protein likely controls chondrocyte apoptosis by regulating multiple target genes including BNP,Fgfr3, Agc1, and Ctgf. SHOX haploinsufficiency frequently results from deletions and duplications in PAR1 involving SHOX exons and/or the cis-acting enhancers, while exonic point mutations account for a small percentage of cases. The clinical severity of SHOX haploinsufficiency reflects hormonal conditions rather than mutation types. Growth hormone treatment seems to be beneficial for cases with SHOX haploinsufficiency, although the long-term outcomes of this therapy require confirmation. Future challenges in SHOX research include elucidating its precise function in the developing limbs, identifying additional cis-acting enhancers, and determining optimal therapeutic strategies for patients.

  4. Paternal isodisomy for chromosome 2 as the cause of Crigler-Najjar type I syndrome.

    Science.gov (United States)

    Petit, François M; Gajdos, Vincent; Parisot, Frédéric; Capel, Liliane; Aboura, Azzedine; Lachaux, Alain; Tachdjian, Gérard; Poüs, Christian; Labrune, Philippe

    2005-03-01

    Crigler-Najjar syndrome type I (CN-I) is a rare and severe autosomal recessive metabolic disease due to a total deficiency of bilirubin uridine diphosphate glucuronosyltransferase located on chromosome 2. We report on a child with CN-I due to a phenylalanine residue deletion inherited only from the father carrying this deletion at the heterozygous state. Cytogenetic analyses showed no deletion of the chromosomal 2q37 region. Microsatellite analysis of the child and his parents was consistent with paternal isodisomy for chromosome 2 in the child. This report demonstrates that uniparental disomy may be at the origin of very rare diseases transmitted as autosomal recessive traits and emphasizes the need for parental DNA analysis in such cases.

  5. A Case of Central Pontine Myelinolysis Caused by Hypophosphatemia Secondary to Refeeding Syndrome.

    Science.gov (United States)

    Yamashita, Chikara; Shigeto, Hiroshi; Maeda, Norihisa; Torii, Takako; Ohyagi, Yasumasa; Kira, Jun-Ichi

    2015-01-01

    Central pontine myelinolysis (CPM), which was originally considered to be the result of rapid correction of chronic hyponatremia, is not necessarily accompanied by hyponatremia or drastic changes in serum sodium level. Here, we report a case of an anorexic 55-year-old male with a history of pharyngo-laryngo-esophagogastrectomy, initially hospitalized with status epilepticus. Although his consciousness gradually recovered as we were controlling his convulsion, it deteriorated again with new onset of anisocoria, and magnetic resonance imaging (MRI) at this point revealed CPM. Rapid change of serum sodium or osmolarity, which is often associated with CPM, had not been apparent throughout his hospitalization. Instead, a review of the serum biochemistry test results showed that serum phosphate had drastically declined the day before the MRI first detected CPM. In this case, we suspect that hypophosphatemia induced by refeeding syndrome greatly contributed to the occurrence of CPM.

  6. A Case of Central Pontine Myelinolysis Caused by Hypophosphatemia Secondary to Refeeding Syndrome

    Directory of Open Access Journals (Sweden)

    Chikara Yamashita

    2015-10-01

    Full Text Available Central pontine myelinolysis (CPM, which was originally considered to be the result of rapid correction of chronic hyponatremia, is not necessarily accompanied by hyponatremia or drastic changes in serum sodium level. Here, we report a case of an anorexic 55-year-old male with a history of pharyngo-laryngo-esophagogastrectomy, initially hospitalized with status epilepticus. Although his consciousness gradually recovered as we were controlling his convulsion, it deteriorated again with new onset of anisocoria, and magnetic resonance imaging (MRI at this point revealed CPM. Rapid change of serum sodium or osmolarity, which is often associated with CPM, had not been apparent throughout his hospitalization. Instead, a review of the serum biochemistry test results showed that serum phosphate had drastically declined the day before the MRI first detected CPM. In this case, we suspect that hypophosphatemia induced by refeeding syndrome greatly contributed to the occurrence of CPM.

  7. Haemolytic–uraemic syndrome with bacteraemia caused by a new hybrid Escherichia coli pathotype

    Science.gov (United States)

    Mariani-Kurkdjian, P; Lemaître, C; Bidet, P; Perez, D; Boggini, L; Kwon, T; Bonacorsi, S

    2014-01-01

    We describe a new atypical Shiga-toxin-producing Escherichia coli (STEC) responsible for a severe episode of haemolytic–uraemic syndrome in an adult with a relapse associated with bacteraemia. This STECs train of serotype O80:H2 harboured stx2c and stx2d gene subtypes, the rare eae ξ variant and a ColV plasmid with a conserved virulence plasmidic region involved in virulence of human and avian extraintestinal pathogenic E. coli. This atypical hybrid pathotype, which represents a new threat, is a further demonstration that STEC may be a recipient for extraintestinal virulence factors and raises again the question of antibiotic therapy during STEC infection. PMID:25356358

  8. Haemolytic-uraemic syndrome with bacteraemia caused by a new hybrid Escherichia coli pathotype

    Directory of Open Access Journals (Sweden)

    P. Mariani-Kurkdjian

    2014-07-01

    Full Text Available We describe a new atypical Shiga-toxin-producing Escherichia coli (STEC responsible for a severe episode of haemolytic–uraemic syndrome in an adult with a relapse associated with bacteraemia. This STECs train of serotype O80:H2 harboured stx2c and stx2d gene subtypes, the rare eae ɛ variant and a ColV plasmid with a conserved virulence plasmidic region involved in virulence of human and avian extraintestinal pathogenic E. coli. This atypical hybrid pathotype, which represents a new threat, is a further demonstration that STEC may be a recipient for extraintestinal virulence factors and raises again the question of antibiotic therapy during STEC infection.

  9. Judgments of cause and blame: sensitivity to intentionality in Asperger's syndrome.

    Science.gov (United States)

    Channon, Shelley; Lagnado, David; Fitzpatrick, Sian; Drury, Helena; Taylor, Isabelle

    2011-11-01

    Sensitivity to intentionality in people with Asperger's syndrome (AS) and matched controls was investigated using two scenario-based tasks. The first compared intentional and unintentional human actions and physical events leading to the same negative outcomes. The second compared intentional actions that varied in their subjective and objective likelihood of bringing about a negative outcome. Whilst adults with AS did not differ from controls in their judgments of causality, or in their blame judgments in relation to non-mentalistic factors, they showed heightened sensitivity to mentalistic considerations in their attributions of blame. They made greater differentiation than controls between intentional and unintentional actions, and also between actions that the protagonists believed to be likely versus unlikely to lead to negative consequences.

  10. Suppurative dacroadenitis causing ocular sicca syndrome in classic Wegener′s granulomatosis

    Directory of Open Access Journals (Sweden)

    Khanna Dhanita

    2011-01-01

    Full Text Available Wegener′s granulomatosis (WG is a multisystem vasculitic disorder which can commonly afflict various components of the eye. Here we describe some unusual ocular manifestations of the disease in one patient. A young male with history of upper respiratory tract symptoms including epistaxis, nasal stuffiness and maxillary sinus pain presented with bilateral lacrimal gland abscess and ptosis. Lacrimal gland biopsy revealed granulomatous vasculitis. Lung cavities, positive cytoplasmic-antineutrophil cytoplasmic antibodies and high titers of serine proteinase-3 antibodies confirmed the diagnosis of WG. The patient developed dry eyes after a month of first presentation. There was no dryness of mouth, suggesting the absence of salivary gland involvement, and antinuclear antibodies as well as antibodies against Ro and La antigens classical of primary Sjogren′s syndrome were absent. Granulomatous vasculitis of lacrimal gland leading to abscess formation and dryness of eyes has not been described in WG and reflects the aggressive nature of inflammatory process in this disease.

  11. Lung Transplantation in Acute Respiratory Distress Syndrome Caused by Influenza Pneumonia

    Directory of Open Access Journals (Sweden)

    Youjin Chang

    2015-08-01

    Full Text Available Severe acute respiratory distress syndrome (ARDS is a life-threatening disease with a high mortality rate. Although many therapeutic trials have been performed for improving the mortality of severe ARDS, limited strategies have demonstrated better outcomes. Recently, advanced rescue therapies such as extracorporeal membrane oxygenation (ECMO made it possible to consider lung transplantation (LTPL in patients with ARDS, but data is insufficient. We report a 62-year-old man who underwent LTPL due to ARDS with no underlying lung disease. He was admitted to the hospital due to influenza A pneumonia-induced ARDS. Although he was supported by ECMO, he progressively deteriorated. We judged that his lungs were irreversibly damaged and decided he needed to undergo LTPL. Finally, bilateral sequential double-lung transplantation was successfully performed. He has since been alive for three years. Conclusively, we demonstrate that LTPL can be a therapeutic option in patients with severe ARDS refractory to conventional therapies.

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

    Science.gov (United States)

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

    2015-01-01

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

  13. Mutations in c12orf57 cause a syndromic form of colobomatous microphthalmia.

    Science.gov (United States)

    Zahrani, Fatema; Aldahmesh, Mohammed A; Alshammari, Muneera J; Al-Hazzaa, Selwa A F; Alkuraya, Fowzan S

    2013-03-01

    Microphthalmia is an important developmental eye disorder. Although mutations in several genes have been linked to this condition, they only account for a minority of cases. We performed autozygome analysis and exome sequencing on a multiplex consanguineous family in which colobomatous microphthalmia is associated with profound global developmental delay, intractable seizures, and corpus callosum abnormalities, and we identified a homozygous truncating mutation in C12orf57 [c.1A>G; p.Met1?]. In a simplex case with a similar phenotype, we identified compound heterozygosity for the same mutation and another missense mutation [c.152T>A; p.Leu51Gln]. Little is known about C12orf57 but we show that it is expressed in several mouse tissues, including the eye and brain. Our data strongly implicate mutations in C12orf57 in the pathogenesis of a clinically distinct autosomal-recessive syndromic form of colobomatous microphthalmia.

  14. Cronkhite-Canada Syndrome: A Rare Cause of Chronic Diarrhoea in a Young Man

    Directory of Open Access Journals (Sweden)

    Dhrubajyoti Bandyopadhyay

    2016-01-01

    Full Text Available A young Indian man presented with nine-month history of chronic diarrhea, occasionally mixed with blood and intermittent colicky abdominal pain. He also complained of generalized body swelling for the last three months. On examination, he had diffuse hyperpigmentation of the skin and dystrophic nail changes. Upper and lower gastrointestinal endoscopy revealed multiple sessile polyps in the stomach, small bowel, and colon and rectum. Biopsy of polyps showed adenomatous changes with stromal edema and dilated glands. Cronkhite-Canada syndrome (CCS was diagnosed and treated with glucocorticoids and enteral nutritional supplementation. There was an associated small intestinal bacterial overgrowth (SIBO and stool was positive for clostridium difficile toxin. After 12 weeks of treatment, the patient achieved remission. Close correlation with clinical findings, including pertinent ectodermal abnormalities, endoscopic studies, and careful examination of biopsies will ensure a timely and correct diagnosis of CCS.

  15. Mutations in SH3PXD2B cause Borrone dermato-cardio-skeletal syndrome.

    Science.gov (United States)

    Wilson, Gabrielle R; Sunley, Jasmine; Smith, Katherine R; Pope, Kate; Bromhead, Catherine J; Fitzpatrick, Elizabeth; Di Rocco, Maja; van Steensel, Maurice; Coman, David J; Leventer, Richard J; Delatycki, Martin B; Amor, David J; Bahlo, Melanie; Lockhart, Paul J

    2014-06-01

    Borrone Dermato-Cardio-Skeletal (BDCS) syndrome is a severe progressive autosomal recessive disorder characterized by coarse facies, thick skin, acne conglobata, dysmorphic facies, vertebral abnormalities and mitral valve prolapse. We identified a consanguineous kindred with a child clinically diagnosed with BDCS. Linkage analysis of this family (BDCS1) identified five regions homozygous by descent with a maximum LOD score of 1.75. Linkage analysis of the family that originally defined BDCS (BDCS3) identified an overlapping linkage peak at chromosome 5q35.1. Sequence analysis identified two different homozygous mutations in BDCS1 and BDCS3, affecting the gene encoding the protein SH3 and PX domains 2B (SH3PXD2B), which localizes to 5q35.1. Western blot analysis of patient fibroblasts derived from affected individuals in both families demonstrated complete loss of SH3PXD2B. Homozygosity mapping and sequence analysis in a second published BDCS family (BDCS2) excluded SH3PXD2B. SH3PXD2B is required for the formation of functional podosomes, and loss-of-function mutations in SH3PXD2B have recently been shown to underlie 7 of 13 families with Frank-Ter Haar syndrome (FTHS). FTHS and BDCS share some overlapping clinical features; therefore, our results demonstrate that a proportion of BDCS and FTHS cases are allelic. Mutations in other gene(s) functioning in podosome formation and regulation are likely to underlie the SH3PXD2B-mutation-negative BDSC/FTHS patients.

  16. [Nicolau syndrome caused by penicillin preparations: review of the literature in search for potential risk factors].

    Science.gov (United States)

    Saputo, V; Bruni, G

    1998-01-01

    The Authors, who in 1977 published the first Italian case report of the Nicolau syndrome (N.S.) from penicillin preparations in the pediatric field, accomplished a thorough search for similar reports in the world literature finding a total of 102 cases, of whom 80 were less than 12-year old. They made a detailed analysis of each case in that series in order to identify or better define potential risk factors or predisposing circumstances worth being taken in consideration for preventive purposes. Indeed, the possible occurrence of N.S., which may include devastating complications such as limb gangrene, paraplegia, or death and have medico-legal implications, is still largely underrated or unrecognised by both physicians and nurses. It is unfortunate in particular that no acknowledgement of that syndrome is available in the teaching programs and textbooks used in professional nurse schools; in addition physicians are not enough zealous in discouraging unqualified lified people as well as patient's relatives from performing intramuscular injections, mainly using certain kinds of drugs such as crystalline suspensions. On the basis of the findings of their analysis as well as of an overall review of the relevant literature the Authors conclude their paper by making a series of specific recommendations and/or proposals addressed to the various operators involved in the matter (prescribing physicians, managers of nursing schools, nurses, pharmaceutical companies, Regulatory Health Authority), with special emphasis on the precautionary measures to be taken in doing intramuscular injection of long-acting penicillins or other drugs in crystalline suspension.

  17. Loss of MAFB Function in Humans and Mice Causes Duane Syndrome, Aberrant Extraocular Muscle Innervation, and Inner-Ear Defects.

    Science.gov (United States)

    Park, Jong G; Tischfield, Max A; Nugent, Alicia A; Cheng, Long; Di Gioia, Silvio Alessandro; Chan, Wai-Man; Maconachie, Gail; Bosley, Thomas M; Summers, C Gail; Hunter, David G; Robson, Caroline D; Gottlob, Irene; Engle, Elizabeth C

    2016-06-02

    Duane retraction syndrome (DRS) is a congenital eye-movement disorder defined by limited outward gaze and retraction of the eye on attempted inward gaze. Here, we report on three heterozygous loss-of-function MAFB mutations causing DRS and a dominant-negative MAFB mutation causing DRS and deafness. Using genotype-phenotype correlations in humans and Mafb-knockout mice, we propose a threshold model for variable loss of MAFB function. Postmortem studies of DRS have reported abducens nerve hypoplasia and aberrant innervation of the lateral rectus muscle by the oculomotor nerve. Our studies in mice now confirm this human DRS pathology. Moreover, we demonstrate that selectively disrupting abducens nerve development is sufficient to cause secondary innervation of the lateral rectus muscle by aberrant oculomotor nerve branches, which form at developmental decision regions close to target extraocular muscles. Thus, we present evidence that the primary cause of DRS is failure of the abducens nerve to fully innervate the lateral rectus muscle in early development.

  18. Novel A CTG1 mutation causing autosomal dominant non-syndromic hearing impairment in a Chinese family

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Theγ-actin(ACTG1)gene is a cytoplasmic nonmuscle actin gene,which encodes a major cytoskeletal protein in the sensory hair cells of the cochlea.Mutations in ACTG1 were found to cause autosomal dominant,progressive,sensorineural hearing loss linked to the DFNA 20/26 locus on chromosome 17q25.3 in European and American families,respectively.In this study,a novel missense mutation (c.364A>G;p.I122V)co-segregated with the affected individuals in the family and did not exist in the unaffected family members and 150 unrelated normal controls.The alteration of residue I1e122 was predicted to damage its interaction with actin-binding proteins,which may cause disruption of hair cell organization and function.These findings strongly suggested that the I122V mutation in ACTG1 caused autosomal dominant non-syndromic hearing impairment in a Chinese family and expanded the spectrum of ACTG1 mutations causing hearing loss.

  19. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These ... doctors agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  20. Angelman Syndrome

    Science.gov (United States)

    ... this syndrome often display hyperactivity, small head size, sleep disorders, and movement and balance disorders that can cause ... this syndrome often display hyperactivity, small head size, sleep disorders, and movement and balance disorders that can cause ...

  1. Cushing's Syndrome

    Science.gov (United States)

    Cushing's syndrome is a hormonal disorder. The cause is long-term exposure to too much cortisol, a hormone ... cause your body to make too much cortisol. Cushing's syndrome is rare. Some symptoms are Upper body obesity ...

  2. Carcinoma of two parathyroid glands caused by a novel MEN1 gene mutation - a rare feature of the MEN 1 syndrome.

    Science.gov (United States)

    Juodelė, Linas; Serapinas, Danielius; Sabaliauskas, Gintaras; Krasauskienė, Aurelija; Krasauskas, Virgilijus; Verkauskienė, Rasa; Barkauskienė, Diana; Juozaitytė, Elona

    2011-01-01

    Multiple endocrine neoplasia type 1 (MEN 1) is a rare syndrome inherited in an autosomal dominant pattern, characterized by combinations of tumors of the parathyroid glands, pituitary gland, and pancreatic islet cells and more rare tumors of endocrine organs and nonendocrine tissues. Germline mutations in the MEN1 gene are responsible for the MEN 1 syndrome, leading to an inactive form of menin protein. Benign lesions of the parathyroid glands are characteristic in patients with the MEN 1 syndrome; however, patients can develop parathyroid carcinomas very rarely. This report presents a clinical case of the MEN 1 syndrome: a 39-year-old woman underwent surgery for carcinoma of two parathyroid glands as well as was treated for pituitary prolactinoma, which caused infertility, and malignant insulinoma; the patient had multiple subcutaneous lipomas as well. Genetic analysis revealed a novel germline mutation in the MEN1 gene - a nucleotide insertion at codon 43 in exon 2 (c.129insA), which caused the occurrence of the MEN1 syndrome. The clinical case of the MEN 1 syndrome presented here is relevant in gathering the data on etiopathogenesis of not only MEN 1 syndrome, but an extremely rare pathology - parathyroid carcinoma - as well.

  3. Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems.

    Science.gov (United States)

    Williams, Stephen R; Aldred, Micheala A; Der Kaloustian, Vazken M; Halal, Fahed; Gowans, Gordon; McLeod, D Ross; Zondag, Sara; Toriello, Helga V; Magenis, R Ellen; Elsea, Sarah H

    2010-08-13

    Brachydactyly mental retardation syndrome (BDMR) is associated with a deletion involving chromosome 2q37. BDMR presents with a range of features, including intellectual disabilities, developmental delays, behavioral abnormalities, sleep disturbance, craniofacial and skeletal abnormalities (including brachydactyly type E), and autism spectrum disorder. To date, only large deletions of 2q37 have been reported, making delineation of a critical region and subsequent identification of candidate genes difficult. We present clinical and molecular analysis of six individuals with overlapping deletions involving 2q37.3 that refine the critical region, reducing the candidate genes from >20 to a single gene, histone deacetylase 4 (HDAC4). Driven by the distinct hand and foot anomalies and similar cognitive features, we identified other cases with clinical findings consistent with BDMR but without a 2q37 deletion, and sequencing of HDAC4 identified de novo mutations, including one intragenic deletion probably disrupting normal splicing and one intragenic insertion that results in a frameshift and premature stop codon. HDAC4 is a histone deacetylase that regulates genes important in bone, muscle, neurological, and cardiac development. Reportedly, Hdac4(-/-) mice have severe bone malformations resulting from premature ossification of developing bones. Data presented here show that deletion or mutation of HDAC4 results in reduced expression of RAI1, which causes Smith-Magenis syndrome when haploinsufficient, providing a link to the overlapping findings in these disorders. Considering the known molecular function of HDAC4 and the mouse knockout phenotype, taken together with deletion or mutation of HDAC4 in multiple subjects with BDMR, we conclude that haploinsufficiency of HDAC4 results in brachydactyly mental retardation syndrome.

  4. Locked-in syndrome in a patient with acute obstructive hydrocephalus, caused by large unruptured aneurysm of the basilar artery (BA).

    Science.gov (United States)

    Kolić, Zlatko; Kukuljan, Melita; Vukas, Duje; Bonifačić, David; Vrbanec, Kristina; Franić, Ivana Karla

    2016-09-15

    We describe a case of acute obstructive hydrocephalus as a consequence of compression of the brainstem by a large aneurysm of the basilar artery (BA) in a 62-year-old male. After the insertion of the ventriculoperitoneal shunt (VPS), we encountered the "locked-in syndrome" clinical condition. "Locked-in syndrome" is a clinical state characterized by quadriplegia and anarthria with preserved consciousness, most commonly caused by ischemia in the ventral part of pons.

  5. Hyperactive neuroendocrine secretion causes size, feeding, and metabolic defects of C. elegans Bardet-Biedl syndrome mutants.

    Directory of Open Access Journals (Sweden)

    Brian H Lee

    2011-12-01

    Full Text Available Bardet-Biedl syndrome, BBS, is a rare autosomal recessive disorder with clinical presentations including polydactyly, retinopathy, hyperphagia, obesity, short stature, cognitive impairment, and developmental delays. Disruptions of BBS proteins in a variety of organisms impair cilia formation and function and the multi-organ defects of BBS have been attributed to deficiencies in various cilia-associated signaling pathways. In C. elegans, bbs genes are expressed exclusively in the sixty ciliated sensory neurons of these animals and bbs mutants exhibit sensory defects as well as body size, feeding, and metabolic abnormalities. Here we show that in contrast to many other cilia-defective mutants, C. elegans bbs mutants exhibit increased release of dense-core vesicles and organism-wide phenotypes associated with enhanced activities of insulin, neuropeptide, and biogenic amine signaling pathways. We show that the altered body size, feeding, and metabolic abnormalities of bbs mutants can be corrected to wild-type levels by abrogating the enhanced secretion of dense-core vesicles without concomitant correction of ciliary defects. These findings expand the role of BBS proteins to the regulation of dense-core-vesicle exocytosis and suggest that some features of Bardet-Biedl Syndrome may be caused by excessive neuroendocrine secretion.

  6. Streptococcal toxic shock syndrome from necrotizing soft-tissue infection of the breast caused by a mucoid type strain.

    Science.gov (United States)

    Kohayagawa, Yoshitaka; Ishitobi, Natsuko; Yamamori, Yuji; Wakuri, Miho; Sano, Chiaki; Tominaga, Kiyoshi; Ikebe, Tadayoshi

    2015-02-01

    Streptococcal toxic shock syndrome is a severe infectious disease. We report a Japanese case of Streptococcal toxic shock syndrome caused by a highly mucoid strain of Streptococcus pyogenes. A 31-year old female with shock vital sign presented at a tertiary medical center. Her left breast was necrotizing and S. pyogenes was detected by Immunochromatographic rapid diagnostic kits. Intensive care, including administration of antibiotics and skin debridement, was performed. After 53 days in our hospital, she was discharged. The blood cultures and skin swab cultures all grew S. pyogenes which displayed a highly mucoid morphology on culture media. In her course of the disease, the Streptococcus strain had infected two other family members. All of the strains possessed the T1 and M1 antigens, as well as the emm1.0 gene. As for fever genes, the strains were all positive for speA, speB, and speF, but negative for speC. All of the strains exhibited and the same pattern in PFGE with the SfiI restriction enzyme. The strain might have spread in the local area by the data from the Japanese Infectious Disease Surveillance Center. Immunochromatographic rapid diagnostic kits are very useful for detecting S. pyogenes. However, they can not be used to diagnose severe streptococcul disease by highly mucoid strain alone. Careful observation of patients and colony morphology are useful methods for diagnosing severe streptococcal disease by highly mucoid strain.

  7. Follow-up after acute respiratory distress syndrome caused by influenza a (H1N1 virus infection

    Directory of Open Access Journals (Sweden)

    Carlos Toufen Jr.

    2011-01-01

    Full Text Available BACKGROUND: There are no reports on the long-term follow-up of patients with swine-origin influenza A virus infection that progressed to acute respiratory distress syndrome. METHODS: Four patients were prospectively followed up with pulmonary function tests and high-resolution computed tomography for six months after admission to an intensive care unit. RESULTS: Pulmonary function test results assessed two months after admission to the intensive care unit showed reduced forced vital capacity in all patients and low diffusion capacity for carbon monoxide in two patients. At six months, pulmonary function test results were available for three patients. Two patients continued to have a restrictive pattern, and none of the patients presented with abnormal diffusion capacity for carbon monoxide. All of them had a diffuse ground-glass pattern on high-resolution computed tomography that improved after six months. CONCLUSIONS: Despite the marked severity of lung disease at admission, patients with acute respiratory distress syndrome caused by swine-origin influenza A virus infection presented a late but substantial recovery over six months of follow-up.

  8. ICF syndrome mutations cause a broad spectrum of biochemical defects in DNMT3B-mediated de novo DNA methylation.

    Science.gov (United States)

    Moarefi, Amir H; Chédin, Frédéric

    2011-06-24

    The DNMT3B de novo DNA methyltransferase (DNMT) plays a major role in establishing DNA methylation patterns in early mammalian development, but its catalytic mechanism remains poorly characterized. Here, we provide a comprehensive biochemical analysis of human DNMT3B function through the characterization of a series of site-directed DNMT3B variants associated with immunodeficiency, centromere instability, and facial anomalies (ICF) syndrome. Our data reveal several novel and important aspects of DNMT3B function. First, DNMT3B, unlike DNMT3A, requires a DNA cofactor in order to stably bind to S-adenosyl-l-methionine (SAM), suggesting that it proceeds according to an ordered catalytic scheme. Second, ICF mutations cause a broad spectrum of biochemical defects in DNMT3B function, including defects in homo-oligomerization, SAM binding, SAM utilization, and DNA binding. Third, all tested ICF mutations, including the A766P and R840Q variants, result in altered catalytic properties without interfering with DNMT3L-mediated stimulation; this indicates that DNMT3L is not involved in the pathogenesis of ICF syndrome. Finally, our study reveals a novel level of coupling between substrate binding, oligomerization, and catalysis that is likely conserved within the DNMT3 family of enzymes.

  9. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early onset autoinflammatory syndrome

    Science.gov (United States)

    Zhou, Qing; Wang, Hongying; Schwartz, Daniella M.; Stoffels, Monique; Park, Yong Hwan; Zhang, Yuan; Yang, Dan; Demirkaya, Erkan; Takeuchi, Masaki; Tsai, Wanxia Li; Lyons, Jonathan J.; Yu, Xiaomin; Ouyang, Claudia; Chen, Celeste; Chin, David T.; Zaal, Kristien; Chandrasekharappa, Settara C.; Hanson, Eric P.; Yu, Zhen; Mullikin, James C.; Hasni, Sarfaraz A.; Wertz, Ingrid; Ombrello, Amanda K.; Stone, Deborah L.; Hoffmann, Patrycja; Jones, Anne; Barham, Beverly K.; Leavis, Helen L.; van Royen-Kerkof, Annet; Sibley, Cailin; Batu, Ezgi D.; Gül, Ahmet; Siegel, Richard M.; Boehm, Manfred; Milner, Joshua D.; Ozen, Seza; Gadina, Massimo; Chae, JaeJin; Laxer, Ronald M.; Kastner, Daniel L.; Aksentijevich, Ivona

    2016-01-01

    Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity1. Herein we describe a new syndrome caused by high penetrance heterozygous germline mutations in the NFκB regulatory protein TNFAIP3 (A20) in six unrelated families with early onset systemic inflammation. The syndrome resembles Behçet’s disease (BD), which is typically considered a polygenic disorder with onset in early adulthood2. A20 is a potent inhibitor of the NFκB signaling pathway3. TNFAIP3 mutant truncated proteins are likely to act by haploinsufficiency since they do not exert a dominant-negative effect in overexpression experiments. Patients’ cells show increased degradation of IκBα and nuclear translocation of NFκB p65, and increased expression of NFκB-mediated proinflammatory cytokines. A20 restricts NFκB signals via deubiquitinating (DUB) activity. In cells expressing the mutant A20 protein, there is defective removal of K63-linked ubiquitin from TRAF6, NEMO, and RIP1 after TNF stimulation. NFκB-dependent pro-inflammatory cytokines are potential therapeutic targets for these patients. PMID:26642243

  10. Papillorenal syndrome-causing missense mutations in PAX2/Pax2 result in hypomorphic alleles in mouse and human.

    Directory of Open Access Journals (Sweden)

    Ramakrishna P Alur

    2010-03-01

    Full Text Available Papillorenal syndrome (PRS, also known as renal-coloboma syndrome is an autosomal dominant disease characterized by potentially-blinding congenital optic nerve excavation and congenital kidney abnormalities. Many patients with PRS have mutations in the paired box transcription factor gene, PAX2. Although most mutations in PAX2 are predicted to result in complete loss of one allele's function, three missense mutations have been reported, raising the possibility that more subtle alterations in PAX2 function may be disease-causing. To date, the molecular behaviors of these mutations have not been explored. We describe a novel mouse model of PRS due to a missense mutation in a highly-conserved threonine residue in the paired domain of Pax2 (p.T74A that recapitulates the ocular and kidney findings of patients. This mutation is in the Pax2 paired domain at the same location as two human missense mutations. We show that all three missense mutations disrupt potentially critical hydrogen bonds in atomic models and result in reduced Pax2 transactivation, but do not affect nuclear localization, steady state mRNA levels, or the ability of Pax2 to bind its DNA consensus sequence. Moreover, these mutations show reduced steady-state levels of Pax2 protein in vitro and (for p.T74A in vivo, likely by reducing protein stability. These results suggest that hypomorphic alleles of PAX2/Pax2 can lead to significant disease in humans and mice.

  11. Heimler Syndrome Is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6

    Science.gov (United States)

    Ratbi, Ilham; Falkenberg, Kim D.; Sommen, Manou; Al-Sheqaih, Nada; Guaoua, Soukaina; Vandeweyer, Geert; Urquhart, Jill E.; Chandler, Kate E.; Williams, Simon G.; Roberts, Neil A.; El Alloussi, Mustapha; Black, Graeme C.; Ferdinandusse, Sacha; Ramdi, Hind; Heimler, Audrey; Fryer, Alan; Lynch, Sally-Ann; Cooper, Nicola; Ong, Kai Ren; Smith, Claire E.L.; Inglehearn, Christopher F.; Mighell, Alan J.; Elcock, Claire; Poulter, James A.; Tischkowitz, Marc; Davies, Sally J.; Sefiani, Abdelaziz; Mironov, Aleksandr A.; Newman, William G.; Waterham, Hans R.; Van Camp, Guy

    2015-01-01

    Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. We ascertained eight families affected by HS and, by using a whole-exome sequencing approach, identified biallelic mutations in PEX1 or PEX6 in six of them. Loss-of-function mutations in both genes are known causes of a spectrum of autosomal-recessive peroxisome-biogenesis disorders (PBDs), including Zellweger syndrome. PBDs are characterized by leukodystrophy, hypotonia, SNHL, retinopathy, and skeletal, craniofacial, and liver abnormalities. We demonstrate that each HS-affected family has at least one hypomorphic allele that results in extremely mild peroxisomal dysfunction. Although individuals with HS share some subtle clinical features found in PBDs, the diagnosis was not suggested by routine blood and skin fibroblast analyses used to detect PBDs. In conclusion, our findings define HS as a mild PBD, expanding the pleiotropy of mutations in PEX1 and PEX6. PMID:26387595

  12. Allopurinol inappropriate use in case of asymptomatic hyperuricemic patient causes fatal Allopurinol hypersensitive syndrome: lesson to all

    Directory of Open Access Journals (Sweden)

    Arvind Kumar

    2015-12-01

    Full Text Available Allopurinol is used to treat hyperuricemia (HU in a patient of gout. It is also used to prevent HU in a patient of hematological malignancies who are about to undergo chemotherapy. Allopurinol is usually well-tolerated but it occasionally induces hypersensitivity reactions that manifest after few months of therapy. Cutaneous reactions are pruritic, erythematous, or maculopapular eruptions. Rarely fatal toxic epidermal necrolysis or Stevens-Johnson syndrome may occur. Transient leukopenia or leukocytosis, eosinophilia and elevated transaminases may also occur. HU is not a disease in itself. Its level is highly variable in the general population. Uric acid level is influenced by many factors such as dietary intake of proteins, hypertension, and obesity. Only very rarely patients of AHU may progress to gout and renal stones. Not much data is available that support HU alone in an asymptomatic patient in later life shows the diseases which are associated with HU. Sometimes only lifestyle changes, diet restrictions, alcohol restrictions, and treatment of underlying acquired cause may correct HU. Here, we are presenting a rare case of allopurinol hypersensitivity syndrome in an AHU patient. Our aim is to raise awareness among physicians so that they avoid using unnecessarily allopurinol in AHU patients and also titrate the dose of allopurinol in patients of renal failure. Risk-benefit ratio must be considered in these patients before starting allopurinol. [Int J Basic Clin Pharmacol 2015; 4(6.000: 1302-1304

  13. Endovascular treatment of stenoses in the superior vena cava syndrome caused by non-tumoral lesions

    Energy Technology Data Exchange (ETDEWEB)

    Bornak, A.; Ris, H.-B.; Probst, H.; Corpataux, J.-M. [Department of Thoracic and Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Bugnon 46, 1011 Lausanne (Switzerland); Wicky, S. [Department of Radiodiagnostic and Interventional Radiology, Centre Hospitalier Universitaire Vaudois, Bugnon 46, 1011 Lausanne (Switzerland); Milesi, I. [Department of Angiology, Centre Hospitalier Universitaire Vaudois, Bugnon 46, 1011 Lausanne (Switzerland)

    2003-05-01

    We report our experience in percutaneous treatment of non-tumoral superior vena cava syndrome (SVCS) between December 1998 and July 2001. During a period of 2.5 years, 9 patients (age range 27-84 years, mean age 50 years) were treated percutaneously for significant non-tumoral SVCS. Symptomatic SVCS were due to dialysis catheters (7), central line (1) and radiation therapy (1). In thrombotic occlusions and severe stenosis, a preliminary in situ thrombolysis was achieved before angioplasty. Patients were followed by echo-Doppler, computed tomography angiography (CTA), magnetic resonance angiography (MRA), or phlebography. Complete recanalization of the veins and immediate resolution of symptomatic SVCS were obtained in all patients, with no procedure-related complication. Thirteen stents were placed in 9 patients with a mean clinical follow-up of 9.1 months (range 2-23 months). One hundred percent patency at 6 months was obtained. Two patients recurred twice and were treated with new stent placement. At 12 months the patency was 67% and assisted patency was 100%. Stent placement in benign symptomatic SVCS is a safe and minimally invasive procedure, with no technical and clinical complications in our experience. It allowed immediate relief of symptoms, and in dialysed patients could provide continued use of hemodialysis access. Close clinical surveillance is mandatory to assess stent patency. (orig.)

  14. SHOX Haploinsufficiency as a Cause of Syndromic and Nonsyndromic Short Stature

    Science.gov (United States)

    Fukami, Maki; Seki, Atsuhito; Ogata, Tsutomu

    2016-01-01

    SHOX in the short arm pseudoautosomal region (PAR1) of sex chromosomes is one of the major growth genes in humans. SHOX haploinsufficiency results in idiopathic short stature and Léri-Weill dyschondrosteosis and is associated with the short stature of patients with Turner syndrome. The SHOX protein likely controls chondrocyte apoptosis by regulating multiple target genes including BNP,Fgfr3, Agc1, and Ctgf. SHOX haploinsufficiency frequently results from deletions and duplications in PAR1 involving SHOX exons and/or the cis-acting enhancers, while exonic point mutations account for a small percentage of cases. The clinical severity of SHOX haploinsufficiency reflects hormonal conditions rather than mutation types. Growth hormone treatment seems to be beneficial for cases with SHOX haploinsufficiency, although the long-term outcomes of this therapy require confirmation. Future challenges in SHOX research include elucidating its precise function in the developing limbs, identifying additional cis-acting enhancers, and determining optimal therapeutic strategies for patients. PMID:27194967

  15. A case report of a pregnancy-related death caused by primary antiphospholipid antibody syndrome.

    Science.gov (United States)

    Sun, Yingjian; Cui, Manhua; Zhu, Wanan; Xu, Weiling; Li, Na

    2014-01-01

    Primary antiphospholipid antibody syndrome (APS) is a rare clinical event in the People's Republic of China. As APS is easily neglected or misdiagnosed, a delayed treatment can result. The patient reported here was a 32-year-old female who died by systemic venous thrombosis on day 11 after a cesarean section delivery. Luckily, the baby survived. A blood test demonstrated that the patient's platelets were decreased at 19 weeks of gestation. Anti-cardolipin antibody and antiβ2GP1 (anti-β2-glycoprotein-I antibody) were positive at 36 weeks and 2 days of gestation. This patient was diagnosed with APS. Unfortunately, as physicians, we could not provide proper treatment as the patient's relatives were concerned that the proposed treatment would have negative effects on the infant's health. This clinical case strongly suggests that physicians need to appreciate that APS is a very serious condition, especially for pregnant women, and that proper treatment should be provided as early as possible to avoid a bad outcome, despite the fact that a cure for this disease is not currently available.

  16. Autoimmune lymphoproliferative syndrome (ALPS) caused by Fas (CD95) mutation mimicking sarcoidosis.

    Science.gov (United States)

    Müllauer, Leonhard; Emhofer, Josef; Wohlfart, Sabine; Pichlhöfer, Bettina; Stary, Susanne; Ebetsberger, Georg; Mannhalter, Christine; Chott, Andreas

    2008-02-01

    Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder associated with defects in apoptosis, characterized by childhood onset of lymphadenopathy, splenomegaly, hyperimmunoglobulinemia, and autoimmune disease. ALPS is most frequently associated with a mutation in the cell death receptor Fas (CD95). Very rarely a mutation in caspase 10 is present. An increase of CD4/CD8 double negative T cells in the peripheral blood and lymph nodes is a feature characteristic of ALPS. Additionally, histiocytic proliferations resembling sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) were reported recently in patients with ALPS. In the rare cases with a caspase 10 mutation an accumulation of dendritic cells in lymphoid organs was noted. We describe a different, sarcoidosislike, histiocytic infiltration of lymph nodes that persisted for years in a girl, that was initially supposed to suffer from sarcoidosis, but was eventually diagnosed as ALPS, associated with a missense mutation in the intracellular death domain of Fas. This sarcoidosislike histologic picture extends the spectrum of histiocytic lymph node alterations observed in ALPS and alerts of a potential diagnostic pitfall.

  17. Laguna Negra Virus Infection Causes Hantavirus Pulmonary Syndrome in Turkish Hamsters (Mesocricetus brandti).

    Science.gov (United States)

    Hardcastle, K; Scott, D; Safronetz, D; Brining, D L; Ebihara, H; Feldmann, H; LaCasse, R A

    2016-01-01

    Laguna Negra virus (LNV) is a New World hantavirus associated with severe and often fatal cardiopulmonary disease in humans, known as hantavirus pulmonary syndrome (HPS). Five hamster species were evaluated for clinical and serologic responses following inoculation with 4 hantaviruses. Of the 5 hamster species, only Turkish hamsters infected with LNV demonstrated signs consistent with HPS and a fatality rate of 43%. Clinical manifestations in infected animals that succumbed to disease included severe and rapid onset of dyspnea, weight loss, leukopenia, and reduced thrombocyte numbers as compared to uninfected controls. Histopathologic examination revealed lung lesions that resemble the hallmarks of HPS in humans, including interstitial pneumonia and pulmonary edema, as well as generalized infection of endothelial cells and macrophages in major organ tissues. Histologic lesions corresponded to the presence of viral antigen in affected tissues. To date, there have been no small animal models available to study LNV infection and pathogenesis. The Turkish hamster model of LNV infection may be important in the study of LNV-induced HPS pathogenesis and development of disease treatment and prevention strategies.

  18. Untethering an unusual cause of kidney injury in a teenager with Down syndrome.

    Science.gov (United States)

    Yen, Elizabeth; Miele, Niel F; Barone, Joseph G; Tyagi, Rachana; Weiss, Lynne S

    2014-11-01

    Acute kidney injury (AKI) is characterized by the acute nature and the inability of kidneys to maintain fluid homeostasis as well as adequate electrolyte and acid-base balance, resulting in an accumulation of nitrogenous waste and elevation of serum blood urea nitrogen and creatinine values. Acute kidney injury may be a single isolated event, yet oftentimes, it results from an acute chronic kidney disease. It is critical to seek out the etiology of AKI and to promptly manage the underlying chronic kidney disease to prevent comorbidities and mortality that may ensue. We described a case of a 16-year-old adolescent girl with Down syndrome who presented with AKI and electrolyte aberrance.Abdominal and renal ultrasounds demonstrated a significantly dilated bladder as well as frank hydronephrosis and hydroureter bilaterally. Foley catheter was successful in relieving the obstruction and improving her renal function. However, a magnetic resonance imaging was pursued in light of her chronic constipation and back pain, and it revealed a structural defect (tethered cord) that underlies a chronic process that was highly likely contributory to her AKI. She was managed accordingly with a guarded result and required long-term and close monitoring.

  19. Germline PRKACA amplification leads to Cushing syndrome caused by 3 adrenocortical pathologic phenotypes.

    Science.gov (United States)

    Carney, J Aidan; Lyssikatos, Charalampos; Lodish, Maya B; Stratakis, Constantine A

    2015-01-01

    We describe the pathology of 5 patients with germline PRKACA copy number gain and Cushing syndrome: 4 males and 1 female, aged 2 to 43 years, including a mother and son. Imaging showed normal or slightly enlarged adrenal glands in 4 patients and a unilateral mass in the fifth. Biochemically, the patients had corticotropin-independent hypercortisolism. Four underwent bilateral adrenalectomy; unilateral adrenalectomy was performed in the patient with the adrenal mass. Pathologically, 3 patients, including the 1 with the tumor (adenoma), had primary pigmented nodular adrenocortical disease with extranodular cortical atrophy and mild intracapsular and extracapsular extension of cortical cells. The other 2 patients had cortical hyperplasia and prominent capsular and extracapsular micronodular cortical hyperplasia. Immunoperoxidase staining revealed differences for synaptophysin, inhibin-A, and Ki-67 (nuclei) in the atrophic cortices (patients 1, 2, and 3) and hyperplastic cortices (patients 4 and 5) and for Ki-67 (nuclei) and vimentin in the extracortical nodules in the 2 groups of patients. β-Catenin stained the cell membrane, cytoplasm, and nuclei of the adenoma. The patients were well at follow-up (1-23 years); 24-hour urinary cortisol excretion was elevated in the patient who had unilateral adrenalectomy.

  20. Frameshift mutation in the PTCH2 gene can cause nevoid basal cell carcinoma syndrome.

    Science.gov (United States)

    Fujii, Katsunori; Ohashi, Hirofumi; Suzuki, Maiko; Hatsuse, Hiromi; Shiohama, Tadashi; Uchikawa, Hideki; Miyashita, Toshiyuki

    2013-12-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis. The gene responsible for NBCCS is PTCH1, encoding a receptor for the secreted protein, sonic hedgehog. Recently, a Chinese family with NBCCS carrying a missense mutation in PTCH2, a close homolog of PTCH1, was reported. However, the pathological significance of missense mutations should be discussed cautiously. Here, we report a 13-year-old girl diagnosed with NBCCS based on multiple keratocystic odontogenic tumors and rib anomalies carrying a frameshift mutation in the PTCH2 gene (c.1172_1173delCT). Considering the deleterious nature of the frameshift mutation, our study further confirmed a causative role for the PTCH2 mutation in NBCCS. The absence of typical phenotypes in this case such as palmar/plantar pits, macrocephaly, falx calcification, hypertelorism and coarse face, together with previously reported cases, suggested that individuals with NBCCS carrying a PTCH2 mutation may have a milder phenotype than those with a PTCH1 mutation.

  1. EDNRB mutations cause Waardenburg syndrome type II in the heterozygous state.

    Science.gov (United States)

    Issa, Sarah; Bondurand, Nadege; Faubert, Emmanuelle; Poisson, Sylvain; Lecerf, Laure; Nitschke, Patrick; Deggouj, Naima; Loundon, Natalie; Jonard, Laurence; David, Albert; Sznajer, Yves; Blanchet, Patricia; Marlin, Sandrine; Pingault, Veronique

    2017-02-24

    Waardenburg syndrome (WS) is a genetic disorder characterized by sensorineural hearing loss and pigmentation anomalies. The clinical definition of four WS types is based on additional features due to defects in structures mostly arising from the neural crest, with type I and type II being the most frequent. While type I is tightly associated to PAX3 mutations, WS type II (WS2) remains partly enigmatic with mutations in known genes (MITF, SOX10) accounting for only 30% of the cases. We performed exome sequencing in a WS2 index case and identified a heterozygous missense variation in EDNRB. Interestingly, homozygous (and very rare heterozygous) EDNRB mutations are already described in type IV WS (that is, in association with Hirschsprung disease) and heterozygous mutations in isolated Hirschsprung disease. Screening of a WS2 cohort led to the identification of an overall of 6 heterozygous EDNRB variations. Clinical phenotypes, pedigrees and molecular segregation investigations unraveled a dominant mode of inheritance with incomplete penetrance. In parallel, cellular and functional studies showed that each of the mutations impairs the subcellular localization of the receptor or induces a defective downstream signaling pathway. Based on our results, we now estimate EDNRB mutations to be responsible for 5-6% of WS2. This article is protected by copyright. All rights reserved.

  2. Dominant beta-catenin mutations cause intellectual disability with recognizable syndromic features

    NARCIS (Netherlands)

    Tucci, V.; Kleefstra, T.; Hardy, A.; Heise, I.; Maggi, S.; Willemsen, M.H.; Hilton, H.; Esapa, C.; Simon, M.; Buenavista, M.T.; McGuffin, L.J.; Vizor, L.; Dodero, L.; Tsaftaris, S.; Romero, R.; Nillesen, W.N.; Vissers, L.E.L.M.; Kempers, M.J.E.; Silfhout, A.T. van; Iqbal, Z.; Orlando, M.; Maccione, A.; Lassi, G.; Farisello, P.; Contestabile, A.; Tinarelli, F.; Nieus, T.; Raimondi, A.; Greco, B.; Cantatore, D.; Gasparini, L.; Berdondini, L.; Bifone, A.; Gozzi, A.; Wells, S.; Nolan, P.M.

    2014-01-01

    The recent identification of multiple dominant mutations in the gene encoding beta-catenin in both humans and mice has enabled exploration of the molecular and cellular basis of beta-catenin function in cognitive impairment. In humans, beta-catenin mutations that cause a spectrum of neurodevelopment

  3. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes

    DEFF Research Database (Denmark)

    Schubert, J.; Siekierska, A.; Langlois, M.

    2014-01-01

    Febrile seizures affect 2-4% of all children(1) and have a strong genetic component(2). Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2)(3-5) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encodi...

  4. Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature.

    Science.gov (United States)

    Rice, Gillian I; Kasher, Paul R; Forte, Gabriella M A; Mannion, Niamh M; Greenwood, Sam M; Szynkiewicz, Marcin; Dickerson, Jonathan E; Bhaskar, Sanjeev S; Zampini, Massimiliano; Briggs, Tracy A; Jenkinson, Emma M; Bacino, Carlos A; Battini, Roberta; Bertini, Enrico; Brogan, Paul A; Brueton, Louise A; Carpanelli, Marialuisa; De Laet, Corinne; de Lonlay, Pascale; del Toro, Mireia; Desguerre, Isabelle; Fazzi, Elisa; Garcia-Cazorla, Angels; Heiberg, Arvid; Kawaguchi, Masakazu; Kumar, Ram; Lin, Jean-Pierre S-M; Lourenco, Charles M; Male, Alison M; Marques, Wilson; Mignot, Cyril; Olivieri, Ivana; Orcesi, Simona; Prabhakar, Prab; Rasmussen, Magnhild; Robinson, Robert A; Rozenberg, Flore; Schmidt, Johanna L; Steindl, Katharina; Tan, Tiong Y; van der Merwe, William G; Vanderver, Adeline; Vassallo, Grace; Wakeling, Emma L; Wassmer, Evangeline; Whittaker, Elizabeth; Livingston, John H; Lebon, Pierre; Suzuki, Tamio; McLaughlin, Paul J; Keegan, Liam P; O'Connell, Mary A; Lovell, Simon C; Crow, Yanick J

    2012-11-01

    Adenosine deaminases acting on RNA (ADARs) catalyze the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) and thereby potentially alter the information content and structure of cellular RNAs. Notably, although the overwhelming majority of such editing events occur in transcripts derived from Alu repeat elements, the biological function of non-coding RNA editing remains uncertain. Here, we show that mutations in ADAR1 (also known as ADAR) cause the autoimmune disorder Aicardi-Goutières syndrome (AGS). As in Adar1-null mice, the human disease state is associated with upregulation of interferon-stimulated genes, indicating a possible role for ADAR1 as a suppressor of type I interferon signaling. Considering recent insights derived from the study of other AGS-related proteins, we speculate that ADAR1 may limit the cytoplasmic accumulation of the dsRNA generated from genomic repetitive elements.

  5. Inflammatory peeling skin syndrome caused by homozygous genomic deletion in the PSORS1 region encompassing the CDSN gene.

    Science.gov (United States)

    Ishida-Yamamoto, Akemi; Furio, Laetitia; Igawa, Satomi; Honma, Masaru; Tron, Elodie; Malan, Valerie; Murakami, Masamoto; Hovnanian, Alain

    2014-01-01

    Peeling skin syndrome (PSS) type B is a rare recessive genodermatosis characterized by lifelong widespread, reddish peeling of the skin with pruritus. The disease is caused by small-scale mutations in the Corneodesmosin gene (CDSN) leading to premature termination codons. We report for the first time a Japanese case resulting from complete deletion of CDSN. Corneodesmosin was undetectable in the epidermis, and CDSN was unamplifiable by PCR. QMPSF analysis demonstrated deletion of CDSN exons inherited from each parent. Deletion mapping using microsatellite haplotyping, CGH array and PCR analysis established that the genomic deletion spanned 49-72 kb between HCG22 and TCF19, removing CDSN as well as five other genes within the psoriasis susceptibility region 1 (PSORS1) on 6p21.33. This observation widens the spectrum of molecular defects underlying PSS type B and shows that loss of these five genes from the PSORS1 region does not result in an additional cutaneous phenotype.

  6. A review of the factors causing paralysis in wild birds: Implications for the paralytic syndrome observed in the Baltic Sea.

    Science.gov (United States)

    Sonne, Christian; Alstrup, Aage Kristian Olsen; Therkildsen, Ole Roland

    2012-02-01

    We reviewed paralysis in wild birds with a special focus on the Baltic Sea paralytic syndrome recently described by Balk et al. (2009) by assessing multiple causative factors. The review showed that paralysis may occur in various species and that the aetiology can be divided into biotoxins, nutritional deficiencies, environmental contaminants and infectious diseases. The review also showed that the symptoms are influenced by age, sex and species of the affected individual. It seemed that paralysis may be treated or relieved by e.g. thiamine injections or additives. Due to a lack of extensive diagnostic studies, the potentially negative effects of paralysis at the population level of wild birds remain unsolved. We recommend that when investigating paralysis in wild birds, a holistic study approach including multiple factors are undertaken in order to pinpoint cause-and-effect relationships as well as the potential impacts on wild bird populations including those in the Baltic Sea.

  7. Epizootic ulcerative syndrome caused by Aphanomyces invadans in captive bullseye snakehead Channa marulius collected from south Florida, USA

    Energy Technology Data Exchange (ETDEWEB)

    Saylor, Ryan [University of West Florida; Miller, Debra [University of Georgia; Vandersea, Mark [National Oceanic and Atmospheric Admin; Bevelhimer, Mark S [ORNL; Schofield, Pamela [U.S. Geological Survey; Bennett, Wayne [University of West Florida

    2010-02-01

    Epizootic ulcerative syndrome (EUS) caused by the oomycete Aphanomyces invadans is an invasive, opportunistic disease of both freshwater and estuarine fishes. Originally documented as the cause of mycotic granulomatosis of ornamental fishes in Japan and as the cause of EUS of fishes in southeast Asia and Australia, this pathogen is also present in estuaries and freshwater bodies of the Atlantic and gulf coasts of the USA. We describe a mass mortality event of 343 captive juvenile bullseye snakehead Channa marulius collected from freshwater canals in Miami-Dade County, Florida. Clinical signs appeared within the first 2 d of captivity and included petechiae, ulceration, erratic swimming, and inappetence. Histological examination revealed hyphae invading from the skin lesions deep into the musculature and internal organs. Species identification was confirmed using a species-specific PCR assay. Despite therapeutic attempts, 100% mortality occurred. This represents the first documented case of EUS in bullseye snakehead fish collected from waters in the USA. Future investigation of the distribution and prevalence of A. invadans within the bullseye snakehead range in south Florida may give insight into this pathogen-host system.

  8. Epizootic ulcerative syndrome caused by Aphanomyces invadans in captive bullseye snakehead Channa marulius collected from south Florida, USA.

    Science.gov (United States)

    Saylor, Ryan K; Miller, Debra L; Vandersea, Mark W; Bevelhimer, Mark S; Schofield, Pamela J; Bennett, Wayne A

    2010-01-25

    Epizootic ulcerative syndrome (EUS) caused by the oomycete Aphanomyces invadans is an invasive, opportunistic disease of both freshwater and estuarine fishes. Originally documented as the cause of mycotic granulomatosis of ornamental fishes in Japan and as the cause of EUS of fishes in southeast Asia and Australia, this pathogen is also present in estuaries and freshwater bodies of the Atlantic and gulf coasts of the USA. We describe a mass mortality event of 343 captive juvenile bullseye snakehead Channa marulius collected from freshwater canals in Miami-Dade County, Florida. Clinical signs appeared within the first 2 d of captivity and included petechiae, ulceration, erratic swimming, and inappetence. Histological examination revealed hyphae invading from the skin lesions deep into the musculature and internal organs. Species identification was confirmed using a species-specific PCR assay. Despite therapeutic attempts, 100% mortality occurred. This represents the first documented case of EUS in bullseye snakehead fish collected from waters in the USA. Future investigation of the distribution and prevalence of A. invadans within the bullseye snakehead range in south Florida may give insight into this pathogen-host system.

  9. GABAergic Neuron-Specific Loss of Ube3a Causes Angelman Syndrome-Like EEG Abnormalities and Enhances Seizure Susceptibility.

    Science.gov (United States)

    Judson, Matthew C; Wallace, Michael L; Sidorov, Michael S; Burette, Alain C; Gu, Bin; van Woerden, Geeske M; King, Ian F; Han, Ji Eun; Zylka, Mark J; Elgersma, Ype; Weinberg, Richard J; Philpot, Benjamin D

    2016-04-01

    Loss of maternal UBE3A causes Angelman syndrome (AS), a neurodevelopmental disorder associated with severe epilepsy. We previously implicated GABAergic deficits onto layer (L) 2/3 pyramidal neurons in the pathogenesis of neocortical hyperexcitability, and perhaps epilepsy, in AS model mice. Here we investigate consequences of selective Ube3a loss from either GABAergic or glutamatergic neurons, focusing on the development of hyperexcitability within L2/3 neocortex and in broader circuit and behavioral contexts. We find that GABAergic Ube3a loss causes AS-like increases in neocortical EEG delta power, enhances seizure susceptibility, and leads to presynaptic accumulation of clathrin-coated vesicles (CCVs)-all without decreasing GABAergic inhibition onto L2/3 pyramidal neurons. Conversely, glutamatergic Ube3a loss fails to yield EEG abnormalities, seizures, or associated CCV phenotypes, despite impairing tonic inhibition onto L2/3 pyramidal neurons. These results substantiate GABAergic Ube3a loss as the principal cause of circuit hyperexcitability in AS mice, lending insight into ictogenic mechanisms in AS.

  10. Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease.

    Science.gov (United States)

    Roelfsema, Jeroen H; White, Stefan J; Ariyürek, Yavuz; Bartholdi, Deborah; Niedrist, Dunja; Papadia, Francesco; Bacino, Carlos A; den Dunnen, Johan T; van Ommen, Gert-Jan B; Breuning, Martijn H; Hennekam, Raoul C; Peters, Dorien J M

    2005-04-01

    CREB-binding protein and p300 function as transcriptional coactivators in the regulation of gene expression through various signal-transduction pathways. Both are potent histone acetyl transferases. A certain level of CREB-binding protein is essential for normal development, since inactivation of one allele causes Rubinstein-Taybi syndrome (RSTS). There is a direct link between loss of acetyl transferase activity and RSTS, which indicates that the disorder is caused by aberrant chromatin regulation. We screened the entire CREB-binding protein gene (CBP) for mutations in patients with RSTS by using methods that find point mutations and larger rearrangements. In 92 patients, we were able to identify a total of 36 mutations in CBP. By using multiple ligation-dependent probe amplification, we found not only several deletions but also the first reported intragenic duplication in a patient with RSTS. We extended the search for mutations to the EP300 gene and showed that mutations in EP300 also cause this disorder. These are the first mutations identified in EP300 for a congenital disorder.

  11. Short beak and dwarfism syndrome of mule duck is caused by a distinct lineage of goose parvovirus.

    Science.gov (United States)

    Palya, Vilmos; Zolnai, Anna; Benyeda, Zsófia; Kovács, Edit; Kardi, Veronika; Mató, Tamás

    2009-04-01

    From the early 1970s to the present, numerous cases of short beak and dwarfism syndrome (SBDS) have been reported in mule ducks from France. The animals showed strong growth retardation with smaller beak and tarsus. It was suggested that the syndrome was caused by goose parvovirus on the basis of serological investigation, but the causative agent has not been isolated and the disease has not so far been reproduced by experimental infection. The aim of the present study was to characterize the virus strains isolated from field cases of SBDS, and to reproduce the disease experimentally. Phylogenetic analysis proved that the parvovirus isolates obtained from SBDS of mule duck belonged to a distinct lineage of goose parvovirus-related group of waterfowl parvoviruses. The authors carried out experimental infections of 1-day-old, 2-week-old and 3-week-old mule ducks by the oral route with three different parvovirus strains: strain D17/99 of goose parvovirus from Derzsy's disease, strain FM of Muscovy duck parvovirus from the parvovirus disease of Muscovy ducks, and strain D176/02 isolated from SBDS of mule duck. The symptoms of SBDS of the mule duck could only be reproduced with the mule duck isolate (strain D176/02) following 1-day-old inoculation. Infection with a genetically different strain of goose parvovirus isolated from classical Derzsy's disease (D17/99) or with the Muscovy duck parvovirus strain (FM) did not cause any clinical symptoms or pathological lesions in mule ducks.

  12. Metabolic causes and prevention of ventricular fibrillation during acute coronary syndromes.

    Science.gov (United States)

    Oliver, Michael F

    2002-03-01

    The mechanisms leading to ventricular fibrillation that occur during acute myocardial ischemia are ill understood. Whether primary ventricular fibrillation is due to a transient imbalance of electrolytes, an alteration of membrane permeability, electrical re-entry phenomena, or other factors, one overriding influence is the development of regional myocardial energy crises. Acute alteration in the balance of substrate supply may lead, during greatly reduced blood flow, to instability of myocardial electrical conduction with the development of re-entry circuits. An immediate response to the angor animi and initial symptoms of an acute coronary syndrome is a rapid and marked increase in catecholamine release, which leads to adipose tissue lipolysis with an acute increase in plasma free fatty acid concentrations, suppression of insulin activity, and a reduction in glucose uptake by the myocardium. The utilization of free fatty acids instead of glucose by the ischemic myocardium could precipitate regional oxygen or energy crises. Prevention therefore should focus on minimizing the catecholamine response and providing the myocardium with an optimum supply of energy substrates. Since catecholamines are inotropic, the aim should be to redress the imbalance of substrate availability by controlling adipose lipolysis with reduction of plasma free fatty acid concentrations, increasing the availability of glucose, or both. Other approaches include inhibition of acylcarnitine transport and manipulation of fatty acid intermediaries. To combat primary ventricular fibrillation, preventive treatment must be established within 6 to 10 hours of the onset of ischemia. There is already experimental and clinical evidence that antilipolytic drugs decrease the incidence of ventricular fibrillation, but their potential has not been explored extensively.

  13. Rules for distinguishing toxicants that cause type I and type II narcosis syndromes.

    OpenAIRE

    Veith, G D; Broderius, S J

    1990-01-01

    Narcosis is a nonspecific reversible state of arrested activity of protoplasmic structures caused by a wide variety of organic chemicals. The vast majority of industrial organic chemicals can be characterized by a baseline structure-toxicity relationship as developed for diverse aquatic organisms, using only the n-octanol/water partition coefficient as a descriptor. There are, however, many apparent narcotic chemicals that are more toxic than baseline narcosis predicts. Some of these chemical...

  14. Coeliac disease as the cause of resistant sideropenic anaemia in children with Down's syndrome: Case report

    Directory of Open Access Journals (Sweden)

    Pavlović Momčilo

    2010-01-01

    Full Text Available Introduction. Coeliac disease (CD is a permanent intolerance of gluten, i.e. of gliadin and related proteins found in the endosperm of wheat, rye and barley. It is characterized by polygenic predisposition, autoimmune nature, predominantly asymptomatic or atypical clinical course, as well as by high prevalence in patients with Down's syndrome (DS and some other diseases. Outline of Cases. We are presenting a girl and two boys, aged 6-7 (X=6.33 years with DS and CD recognized under the feature of sideropenic anaemia resistant to oral therapy with iron. Beside mental retardation, low stature and the morphological features characteristic of DS, two patients had a congenital heart disease; one ventricular septal defect and the other atrioventricular canal. In two patients, trisomy on the 21st chromosome pair (trisomy 21 was disclosed in all cells, while one had a mosaic karyotype. All three patients had classical laboratory parameters of sideropenic anaemia: blood Hb 77-89 g/l (X=81.67, HCT 0.26-0.29% (X=0.28, MCV 69-80 fl (X=73, MCH 24.3-30 pg (X=26.77 and serum iron 2-5 μmol/L (X=4.0. Beside anaemia and in one patient a mild isolated hypertransaminasemia (AST 67 U/l, ALT 62 U/l, other indicators of CD were not registered in any of the children. In addition, in all three patients, we also detected an increased level of antibodies to tissue transglutaminase (atTG of IgA class (45-88 U/l so that we performed endoscopic enterobiopsy in order to reliably confirm the diagnosis of CD. In all three patients, the pathohistological finding of the duodenal mucosa specimen showed mild to moderate destructive enteropathy associated with high intraepithelial lymphocyte infiltration, cryptic hyperplasia and lympho-plasmocytic infiltration of the stroma. In all three patients, the treatment with a strict gluten-free diet and iron therapy applied orally for 3-4 months resulted in blood count normalization and the correction of sideropenia. Serum level of the at

  15. SLC30A9 mutation affecting intracellular zinc homeostasis causes a novel cerebro-renal syndrome.

    Science.gov (United States)

    Perez, Yonatan; Shorer, Zamir; Liani-Leibson, Keren; Chabosseau, Pauline; Kadir, Rotem; Volodarsky, Michael; Halperin, Daniel; Barber-Zucker, Shiran; Shalev, Hanna; Schreiber, Ruth; Gradstein, Libe; Gurevich, Evgenia; Zarivach, Raz; Rutter, Guy A; Landau, Daniel; Birk, Ohad S

    2017-02-09

    A novel autosomal recessive cerebro-renal syndrome was identified in consanguineous Bedouin kindred: neurological deterioration was evident as of early age, progressing into severe intellectual disability, profound ataxia, camptocormia and oculomotor apraxia. Brain MRI was normal. Four of the six affected individuals also had early-onset nephropathy with features of tubulo-interstitial nephritis, hypertension and tendency for hyperkalemia, though none had rapid deterioration of renal function. Genome wide linkage analysis identified an ∼18 Mb disease-associated locus on chromosome 4 (maximal logarithm of odds score 4.4 at D4S2971; θ = 0). Whole exome sequencing identified a single mutation in SLC30A9 within this locus, segregating as expected within the kindred and not found in a homozygous state in 300 Bedouin controls. We showed that SLC30A9 (solute carrier family 30 member 9; also known as ZnT-9) is ubiquitously expressed with high levels in cerebellum, skeletal muscle, thymus and kidney. Confocal analysis of SH-SY5Y cells overexpressing SLC30A9 fused to enhanced green fluorescent protein demonstrated vesicular cytosolic localization associated with the endoplasmic reticulum, not co-localizing with endosomal or Golgi markers. SLC30A9 encodes a putative zinc transporter (by similarity) previously associated with Wnt signalling. However, using dual-luciferase reporter assay in SH-SY5Y cells we showed that Wnt signalling was not affected by the mutation. Based on protein modelling, the identified mutation is expected to affect SLC30A9's highly conserved cation efflux domain, putatively disrupting its transmembrane helix structure. Cytosolic Zn2+ measurements in HEK293 cells overexpressing wild-type and mutant SLC30A9 showed lower zinc concentration within mutant rather than wild-type SLC30A9 cells. This suggests that SLC30A9 has zinc transport properties affecting intracellular zinc homeostasis, and that the molecular mechanism of the disease is through

  16. Mutations in the DNA methyltransferase gene DNMT3A cause an overgrowth syndrome with intellectual disability

    DEFF Research Database (Denmark)

    Tatton-Brown, Katrina; Seal, Sheila; Ruark, Elise

    2014-01-01

    Overgrowth disorders are a heterogeneous group of conditions characterized by increased growth parameters and other variable clinical features such as intellectual disability and facial dysmorphism. To identify new causes of human overgrowth, we performed exome sequencing in ten proband...... and histone binding. Similar mutations were not present in 1,000 UK population controls (13/152 cases versus 0/1,000 controls; P ... methylation during embryogenesis and is commonly somatically mutated in acute myeloid leukemia. Thus, DNMT3A joins an emerging group of epigenetic DNA- and histone-modifying genes associated with both developmental growth disorders and hematological malignancies....

  17. Ortner's Syndrome: Secondary Laryngeal Paralysis Caused by a Great Thoracic Aorta Aneurysm

    Directory of Open Access Journals (Sweden)

    Zangirolami, Ana Claudia Alves

    2015-01-01

    Full Text Available Introduction Recurrent laryngeal nerve injury caused by cardiovascular disease is a rare condition, and often it is the only prominent sign of an imminent break of an aortic artery aneurysm. Objective To report left laryngeal paralysis caused by a great aortic arch aneurysm and to highlight the importance of an otorhinolaryngologic evaluation along with a thoracic radiologic study. Resumed Report A 42-year-old man complained of thickness of his voice and dysphagia for 3 months, but no thoracic pain or other relevant complaints. Video laryngoscopy revealed immobility of his left vocal fold in the paramedian position. Imaging was obtained for investigation, including magnetic resonance imaging of his thorax, which showed a fusiform aneurysm in the aortic arch, leading to recurrent compression of the left laryngeal nerve. The patient was successfully treated with endovascular repair of the aneurysm. At 2-month follow-up, there was still no recovery of the laryngeal mobility. Conclusion An aortic artery aneurysm can suddenly break, requiring emergency heart surgery, and the results can be fatal in many cases. We suggest routine exam of the vocal folds in all patients with a heart condition, and we review the literature and suggest the use of imaging to reduce the number of emergency procedures.

  18. Disruption of PCP signaling causes limb morphogenesis and skeletal defects and may underlie Robinow syndrome and brachydactyly type B.

    Science.gov (United States)

    Wang, Bing; Sinha, Tanvi; Jiao, Kai; Serra, Rosa; Wang, Jianbo

    2011-01-15

    Brachydactyly type B (BDB1) and Robinow syndrome (RRS) are two skeletal disorders caused by mutations in ROR2, a co-receptor of Wnt5a. Wnt5a/Ror2 can activate multiple branches of non-canonical Wnt signaling, but it is unclear which branch(es) mediates Wnt5a/Ror2 function in limb skeletal development. Here, we provide evidence implicating the planar cell polarity (PCP) pathway as the downstream component of Wnt5a in the limb. We show that a mutation in the mouse PCP gene Vangl2 causes digit defects resembling the clinical phenotypes in BDB1, including loss of phalanges. Halving the dosage of Wnt5a in Vangl2 mutants enhances the severity and penetrance of the digit defects and causes long bone defects reminiscent of RRS, suggesting that Wnt5a and Vangl2 function in the same pathway and disruption of PCP signaling may underlie both BDB1 and RRS. Consistent with a role for PCP signaling in tissue morphogenesis, mutation of Vangl2 alters the shape and dimensions of early limb buds: the width and thickness are increased, whereas the length is decreased. The digit pre-chondrogenic condensates also become wider, thicker and shorter. Interestingly, altered limb bud dimensions in Vangl2 mutants also affect limb growth by perturbing the signaling network that regulates the balance between Fgf and Bmp signaling. Halving the dosage of Bmp4 partially suppresses the loss of phalanges in Vangl2 mutants, supporting the hypothesis that an aberrant increase in Bmp signaling is the cause of the brachydactyly defect. These findings provide novel insight into the signaling mechanisms of Wnt5a/Ror2 and the pathogenesis in BDB1 and RRS.

  19. Peripheral primitive neuroectodermal tumor causing cauda equina syndrome with destruction of L5 vertebra

    Directory of Open Access Journals (Sweden)

    Dhatt Sarvdeep

    2010-01-01

    Full Text Available A 24-year-old male patient presented with cauda equina lesion symptoms. His clinicoradiological examination including X-rays, CT scan and MRI revealed destruction of L 5 vertebral body, pedicle and a mass extending to lateral recess and left intervertebral foramina causing pressure over the thecal sac. A CT guided FNAC was inconclusive. Open biopsy and hemilaminectomy of L 5 vertebra was performed. Histopathology and immunocytochemical analysis revealed it to be primitive neuroectodermal tumor. Patient was given chemotherapy and radiation therapy. His lower limb power improved by grade I post operatively and at 2 years follow-up bowel/bladder recovery was noticed. Patient died after 2.5 years of surgery because of pulmonary metastasis.

  20. Renal leishmaniasis as unusual cause of nephrotic syndrome in an HIV patient.

    Science.gov (United States)

    Amann, Kerstin; Bogdan, Christian; Harrer, Thomas; Rech, Juergen

    2012-04-01

    Renal involvement is a rare complication in HIV-1-infected patients leading to various pathologies and clinical symptoms. In addition to the classic HIV-1-associated nephropathy with collapsing-type focal segmental glomerulosclerosis and characteristic tubulocystic changes, which is more common in Afro-American than in Caucasian HIV-1 patients, immune complex GNs such as membranous GN and membranoproliferative GN are particularly common renal manifestations. Besides HIV-1 itself, a number of opportunistic infections may cause renal disease in HIV-1-infected patients. In this study, we report an unusual case of HIV-1 infection with a severe renal manifestation of systemic leishmaniasis that developed years after repeated visits to Mediterranean countries. The case presents several remarkable clinical, pathologic, and therapeutic aspects that may be important for daily clinical practice.

  1. [A rare cause of compartment syndrome of the forearm and hand following snake bite injury].

    Science.gov (United States)

    Schnecker, K

    1990-06-01

    With the intention to commit suicide a 25 year old patient was bitten by his own rattle snake. At the time of the admission the skin of the right forearm was dark, a hemorrhagic necrotizing colour, and the patient was in shock. He was immediately taken to the intensive care unit and the shock symptoms were treated there. Parasthesias in the area of the nervus medianus were also noticed. The treatment included an antiserum and the release of the tourniquet which caused a further increase of the swelling of the forearm. The lesion led to a hemorrhagic necrotizing inflammation. The surgical incision of the loge of Guyon, the carpal channel, the forearm and proximal of the lacertus fibrosus was persuaded. The circulation improved immediately and after three weeks the nerval function had recovered. The skin defect was covered 14 days after the first operation with meshgraft.

  2. Extreme fatigue and malaise--a syndrome caused by badly cleaned wall-to-wall carpets?

    Science.gov (United States)

    Nexø, E; Skov, P G; Gravesen, S

    1983-01-01

    Complaints connected with the indoor climate are often vague and a cause-effect relationship is difficult to demonstrate. The present paper describes two patients suffering from symptoms in the form of extreme fatigue and malaise. The patients connected their problems to the poorly cleaned working place. We found the working place to be covered with badly cleaned wall-to-wall carpet. Examination of 12 employees showed five to have symptoms related to the working place. Four of the five had precipitating antibodies against extracts of dust collected from the carpets and two of the five had a positive prick test to the same extract. After removal of the carpets all symptoms disappeared. We conclude that vague symptoms related to the indoor climate may be induced by accumulation of organic dust.

  3. De novo MEIS2 mutation causes syndromic developmental delay with persistent gastro-esophageal reflux.

    Science.gov (United States)

    Fujita, Atsushi; Isidor, Bertrand; Piloquet, Hugues; Corre, Pierre; Okamoto, Nobuhiko; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Miyake, Noriko; Matsumoto, Naomichi

    2016-09-01

    MEIS2 aberrations are considered to be the cause of intellectual disability, cleft palate and cardiac septal defect, as MEIS2 copy number variation is often observed with these phenotypes. To our knowledge, only one nucleotide-level change-specifically, an in-frame MEIS2 deletion-has so far been reported. Here, we report a female patient with a de novo nonsense mutation (c.611C>G, p.Ser204*) in MEIS2. She showed severe intellectual disability, moderate motor/verbal developmental delay, cleft palate, cardiac septal defect, hypermetropia, severe feeding difficulties with gastro-esophageal reflux and constipation. By reviewing this patient and previous patients with MEIS2 point mutations, we found that feeding difficulty with gastro-esophageal reflux appears to be one of the core clinical features of MEIS2 haploinsufficiency, in addition to intellectual disability, cleft palate and cardiac septal defect.

  4. The insulin autoimmune syndrome (IAS) as a cause of hypoglycaemia: an update on the pathophysiology, biochemical investigations and diagnosis.

    Science.gov (United States)

    Ismail, Adel A A

    2016-11-01

    Insulin autoimmune syndrome (IAS) is considered to be very rare in Caucasians. Understanding its pathophysiology is paramount in (a) appreciating its potential impact on analyses of pancreatic hormones and (b) explaining its highly variable clinical manifestations in non-diabetic, non-acutely ill patients with indeterminate hypoglycaemia. The underlying aetiology of IAS is the presence of variable affinity/avidity endogenous insulin antibodies in significant amounts. The two types of insulin antibodies namely antibodies which bind insulin and/or proinsulin(s) and receptor antibodies (insulin mimetic) will be discussed. Their biochemical and immunological roles in causing hypoglycaemia will be highlighted. Clinical manifestations of IAS can vary from mild and transient to spontaneous, severe and protracted hypoglycaemia necessitating in extreme cases plasmapheresis for glycaemic control. Antibodies of IAS can interfere in pancreatic immunoassay tests causing erroneous and potentially misleading results. Thorough testing for endogenous insulin antibodies must be considered in the investigations of non-diabetic, non-acutely ill patients with indeterminate and/or unexplained hypoglycaemia.

  5. The fungus Trichophyton redellii sp. nov. causes skin infections that resemble white-nose syndrome of hibernating bats

    Science.gov (United States)

    Lorch, Jeffrey M.; Minnis, Andrew M.; Meteyer, Carol U.; Redell, Jennifer A.; White, J. Paul; Kaarakka, Heather M.; Muller, Laura K.; Lindner, David L.; Verant, Michelle L.; Shearn-Bochsler, Valerie I.; Blehert, David S.

    2014-01-01

    Before the discovery of white-nose syndrome (WNS), a fungal disease caused by Pseudogymnoascus destructans, there were no reports of fungal skin infections in bats during hibernation. In 2011, bats with grossly visible fungal skin infections similar in appearance to WNS were reported from multiple sites in Wisconsin, USA, a state outside the known range of P. destructans and WNS at that time. Tape impressions or swab samples were collected from affected areas of skin from bats with these fungal infections in 2012 and analyzed by microscopy, culture, or direct DNA amplification and sequencing of the fungal internal transcribed spacer region (ITS). A psychrophilic species ofTrichophyton was isolated in culture, detected by direct DNA amplification and sequencing, and observed on tape impressions. Deoxyribonucleic acid indicative of the same fungus was also detected on three of five bat carcasses collected in 2011 and 2012 from Wisconsin, Indiana, and Texas, USA. Superficial fungal skin infections caused by Trichophyton sp. were observed in histopathology for all three bats. Sequencing of the ITS of Trichophyton sp., along with its inability to grow at 25 C, indicated that it represented a previously unknown species, described herein as Trichophyton redellii sp. nov. Genetic diversity present within T. redellii suggests it is native to North America but that it had been overlooked before enhanced efforts to study fungi associated with bats in response to the emergence of WNS.

  6. Loss of the smallest subunit of cytochrome c oxidase, COX8A, causes Leigh-like syndrome and epilepsy.

    Science.gov (United States)

    Hallmann, Kerstin; Kudin, Alexei P; Zsurka, Gábor; Kornblum, Cornelia; Reimann, Jens; Stüve, Burkhard; Waltz, Stephan; Hattingen, Elke; Thiele, Holger; Nürnberg, Peter; Rüb, Cornelia; Voos, Wolfgang; Kopatz, Jens; Neumann, Harald; Kunz, Wolfram S

    2016-02-01

    Isolated cytochrome c oxidase (complex IV) deficiency is one of the most frequent respiratory chain defects in humans and is usually caused by mutations in proteins required for assembly of the complex. Mutations in nuclear-encoded structural subunits are very rare. In a patient with Leigh-like syndrome presenting with leukodystrophy and severe epilepsy, we identified a homozygous splice site mutation in COX8A, which codes for the ubiquitously expressed isoform of subunit VIII, the smallest nuclear-encoded subunit of complex IV. The mutation, affecting the last nucleotide of intron 1, leads to aberrant splicing, a frame-shift in the highly conserved exon 2, and decreased amount of the COX8A transcript. The loss of the wild-type COX8A protein severely impairs the stability of the entire cytochrome c oxidase enzyme complex and manifests in isolated complex IV deficiency in skeletal muscle and fibroblasts, similar to the frequent c.845_846delCT mutation in the assembly factor SURF1 gene. Stability and activity of complex IV could be rescued in the patient's fibroblasts by lentiviral expression of wild-type COX8A. Our findings demonstrate that COX8A is indispensable for function of human complex IV and its mutation causes human disease.

  7. Trisomy 15 with loss of the paternal 15 as a cause of Prader-Willi syndrome due to maternal disomy

    Energy Technology Data Exchange (ETDEWEB)

    Cassidy, S.B.; Lai, Li-Wen; Erickson, R.P. (Univ. of Arizona College of Medicine, Tucson, AZ (United States)); Magnuson, L.; Thomas, E.; Herrmann, J. (Great Lakes Genetics, Milwaukee, AZ (United States)); Gendron, R. (Great Lakes Genetics, Kingsport, TN (United States))

    1992-10-01

    Uniparental disomy has recently been recognized to cause human disorders, including Prader-Willi syndrome (PWS). The authors describe a particularly instructive case which raises important issues concerning the mechanisms producing uniparental disomy and whose evaluation provides evidence that trisomy may precede uniparental disomy in a fetus. Chorionic villus sampling performed for advanced maternal age revealed trisomy 15 in all direct and cultured cells, though the fetus appeared normal. Chromosome analysis of amniocytes obtained at 15 wk was normal in over 100 cells studied. The child was hypotonic at birth, and high-resolution banding failed to reveal the deletion of 15q11-13, a deletion which is found in 50%-70% of patients with PWS. Over time, typical features of PWS developed. Molecular genetic analysis using probes for chromosome 15 revealed maternal disomy. Maternal nondisjunction with fertilization of a disomic egg by a normal sperm, followed by loss of the paternal 15, is a likely cause of confined placental mosaicism and uniparental disomy in this case of PWS, and advanced maternal age may be a predisposing factor. 38 refs., 3 figs., 2 tabs.

  8. A high calorie diet causes memory loss, metabolic syndrome and oxidative stress into hippocampus and temporal cortex of rats.

    Science.gov (United States)

    Treviño, Samuel; Aguilar-Alonso, Patrícia; Flores Hernandez, Jose Angel; Brambila, Eduardo; Guevara, Jorge; Flores, Gonzalo; Lopez-Lopez, Gustavo; Muñoz-Arenas, Guadalupe; Morales-Medina, Julio Cesar; Toxqui, Veronica; Venegas, Berenice; Diaz, Alfonso

    2015-09-01

    A high calorie intake can induce the appearance of the metabolic syndrome (MS), which is a serious public health problem because it affects glucose levels and triglycerides in the blood. Recently, it has been suggested that MS can cause complications in the brain, since chronic hyperglycemia and insulin resistance are risk factors for triggering neuronal death by inducing a state of oxidative stress and inflammatory response that affect cognitive processes. This process, however, is not clear. In this study, we evaluated the effect of the consumption of a high-calorie diet (HCD) on both neurodegeneration and spatial memory impairment in rats. Our results demonstrated that HCD (90 day consumption) induces an alteration of the main energy metabolism markers, indicating the development of MS in rats. Moreover, an impairment of spatial memory was observed. Subsequently, the brains of these animals showed activation of an inflammatory response (increase in reactive astrocytes and interleukin1-β as well as tumor necrosis factor-α) and oxidative stress (reactive oxygen species and lipid peroxidation), causing a reduction in the number of neurons in the temporal cortex and hippocampus. Altogether, these results suggest that a HCD promotes the development of MS and contributes to the development of a neurodegenerative process and cognitive failure. In this regard, it is important to understand the relationship between MS and neuronal damage in order to prevent the onset of neurodegenerative disorders.

  9. TP53 intron 1 hotspot rearrangements are specific to sporadic osteosarcoma and can cause Li-Fraumeni syndrome.

    Science.gov (United States)

    Ribi, Sebastian; Baumhoer, Daniel; Lee, Kristy; Edison; Teo, Audrey S M; Madan, Babita; Zhang, Kang; Kohlmann, Wendy K; Yao, Fei; Lee, Wah Heng; Hoi, Qiangze; Cai, Shaojiang; Woo, Xing Yi; Tan, Patrick; Jundt, Gernot; Smida, Jan; Nathrath, Michaela; Sung, Wing-Kin; Schiffman, Joshua D; Virshup, David M; Hillmer, Axel M

    2015-04-10

    Somatic mutations of TP53 are among the most common in cancer and germline mutations of TP53 (usually missense) can cause Li-Fraumeni syndrome (LFS). Recently, recurrent genomic rearrangements in intron 1 of TP53 have been described in osteosarcoma (OS), a highly malignant neoplasm of bone belonging to the spectrum of LFS tumors. Using whole-genome sequencing of OS, we found features of TP53 intron 1 rearrangements suggesting a unique mechanism correlated with transcription. Screening of 288 OS and 1,090 tumors of other types revealed evidence for TP53 rearrangements in 46 (16%) OS, while none were detected in other tumor types, indicating this rearrangement to be highly specific to OS. We revisited a four-generation LFS family where no TP53 mutation had been identified and found a 445 kb inversion spanning from the TP53 intron 1 towards the centromere. The inversion segregated with tumors in the LFS family. Cancers in this family had loss of heterozygosity, retaining the rearranged allele and resulting in TP53 expression loss. In conclusion, intron 1 rearrangements cause p53-driven malignancies by both germline and somatic mechanisms and provide an important mechanism of TP53 inactivation in LFS, which might in part explain the diagnostic gap of formerly classified "TP53 wild-type" LFS.

  10. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females.

    Science.gov (United States)

    Depienne, Christel; Bouteiller, Delphine; Keren, Boris; Cheuret, Emmanuel; Poirier, Karine; Trouillard, Oriane; Benyahia, Baya; Quelin, Chloé; Carpentier, Wassila; Julia, Sophie; Afenjar, Alexandra; Gautier, Agnès; Rivier, François; Meyer, Sophie; Berquin, Patrick; Hélias, Marie; Py, Isabelle; Rivera, Serge; Bahi-Buisson, Nadia; Gourfinkel-An, Isabelle; Cazeneuve, Cécile; Ruberg, Merle; Brice, Alexis; Nabbout, Rima; Leguern, Eric

    2009-02-01

    Dravet syndrome (DS) is a genetically determined epileptic encephalopathy mainly caused by de novo mutations in the SCN1A gene. Since 2003, we have performed molecular analyses in a large series of patients with DS, 27% of whom were negative for mutations or rearrangements in SCN1A. In order to identify new genes responsible for the disorder in the SCN1A-negative patients, 41 probands were screened for micro-rearrangements with Illumina high-density SNP microarrays. A hemizygous deletion on chromosome Xq22.1, encompassing the PCDH19 gene, was found in one male patient. To confirm that PCDH19 is responsible for a Dravet-like syndrome, we sequenced its coding region in 73 additional SCN1A-negative patients. Nine different point mutations (four missense and five truncating mutations) were identified in 11 unrelated female patients. In addition, we demonstrated that the fibroblasts of our male patient were mosaic for the PCDH19 deletion. Patients with PCDH19 and SCN1A mutations had very similar clinical features including the association of early febrile and afebrile seizures, seizures occurring in clusters, developmental and language delays, behavioural disturbances, and cognitive regression. There were, however, slight but constant differences in the evolution of the patients, including fewer polymorphic seizures (in particular rare myoclonic jerks and atypical absences) in those with PCDH19 mutations. These results suggest that PCDH19 plays a major role in epileptic encephalopathies, with a clinical spectrum overlapping that of DS. This disorder mainly affects females. The identification of an affected mosaic male strongly supports the hypothesis that cellular interference is the pathogenic mechanism.

  11. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females.

    Directory of Open Access Journals (Sweden)

    Christel Depienne

    2009-02-01

    Full Text Available Dravet syndrome (DS is a genetically determined epileptic encephalopathy mainly caused by de novo mutations in the SCN1A gene. Since 2003, we have performed molecular analyses in a large series of patients with DS, 27% of whom were negative for mutations or rearrangements in SCN1A. In order to identify new genes responsible for the disorder in the SCN1A-negative patients, 41 probands were screened for micro-rearrangements with Illumina high-density SNP microarrays. A hemizygous deletion on chromosome Xq22.1, encompassing the PCDH19 gene, was found in one male patient. To confirm that PCDH19 is responsible for a Dravet-like syndrome, we sequenced its coding region in 73 additional SCN1A-negative patients. Nine different point mutations (four missense and five truncating mutations were identified in 11 unrelated female patients. In addition, we demonstrated that the fibroblasts of our male patient were mosaic for the PCDH19 deletion. Patients with PCDH19 and SCN1A mutations had very similar clinical features including the association of early febrile and afebrile seizures, seizures occurring in clusters, developmental and language delays, behavioural disturbances, and cognitive regression. There were, however, slight but constant differences in the evolution of the patients, including fewer polymorphic seizures (in particular rare myoclonic jerks and atypical absences in those with PCDH19 mutations. These results suggest that PCDH19 plays a major role in epileptic encephalopathies, with a clinical spectrum overlapping that of DS. This disorder mainly affects females. The identification of an affected mosaic male strongly supports the hypothesis that cellular interference is the pathogenic mechanism.

  12. What is Metabolic Syndrome?

    Science.gov (United States)

    ... from the NHLBI on Twitter. What Is Metabolic Syndrome? Metabolic syndrome is the name for a group of ... that may play a role in causing metabolic syndrome. Outlook Metabolic syndrome is becoming more common due to a ...

  13. Two family members with a syndrome of headache and rash caused by human parvovirus B19

    Directory of Open Access Journals (Sweden)

    Antonio Carlos M. Pereira

    2001-02-01

    Full Text Available Human parvovirus B19 infection can cause erythema infectiosum (EI and several other clinical presentations. Central nervous system (CNS involvement is rare, and only a few reports of encephalitis and aseptic meningitis have been published. Here, we describe 2 cases of B19 infection in a family presenting different clinical features. A 30 year old female with a 7-day history of headache, malaise, myalgias, joint pains, and rash was seen. Physical examination revealed a maculopapular rash on the patient's body, and arthritis of the hands. She completely recovered in 1 week. Two days before, her 6 year old son had been admitted to a clinic with a 1-day history of fever, headache, abdominal pain and vomiting. On admission, he was alert, and physical examination revealed neck stiffness, Kerning and Brudzinski signs, and a petechial rash on his trunk and extremities. Cerebrospinal fluid analysis was normal. He completely recovered in 5 days. Acute and convalescent sera of both patients were positive for specific IgM antibody to B19. Human parvovirus B19 should be considered in the differential diagnosis of aseptic meningitis, particularly during outbreaks of erythema infectiosum. The disease may mimic meningococcemia and bacterial meningitis.

  14. Self-leveling mortar as a possible cause of symptoms associated with "sick building syndrome".

    Science.gov (United States)

    Lundholm, M; Lavrell, G; Mathiasson, L

    1990-01-01

    In newly constructed houses and buildings in which self-leveling mortar containing casein has been used, residents and office employees have noted a bad odor and have complained of headache, eye and throat irritation, and tiredness. These problems were suspected to result from the degradation products emitted from the mortar. Samples obtained from dry mortar powder and from mortar in buildings where casein was used and from control buildings were found to contain microorganisms (mean of 10(2) culture forming units/g). Environmental species were predominantly found, e.g., Bacillus, Clostridium, Micrococcus, and Propionibacterium. Fungi were found occasionally; no evidence of bacterial degradation was found. Headspace and gas chromatographic-mass spectrometric analysis of air from the newly constructed houses and from hydroxide-degraded casein revealed the presence of amines in the 0.003-0.013 ppm range and the presence of ammonia and sulfhydryl compounds, all of which in low concentrations can cause the symptoms observed. These substances, however, were not detected in control buildings.

  15. An unusual infection of cervicofacial area caused by dental pathology: flesh-eating syndrome.

    Science.gov (United States)

    Ozdinc, Serife; Unlu, Ebru; Oruc, Oya; User, Nese Nur; Karakaya, Zeynep

    2015-10-01

    Necrotizing fasciitis (NF) of the cervicofacial area is highly rare, but physicians should be familiar with the presentation of this situation owing to the suddenness of its beginning, the rapidness of its spread, and ending with high mortality and morbidity. In this article, 5 patients with NF admitted to emergency department with dental pathology history were discussed with a review of the literature. The purpose of this case series is to raise awareness about NF of the cervicofacial area caused by dental pathologies. Five patients admitted to our emergency department between January 2012 and March 2015 and diagnosed as having cervicofacial NF were identified. All patients had dental pathologies. The parameters of the study were patients' age, sex, complaints, self- and family histories, physical examinations' findings, routine laboratory-computed tomographic findings, treatment, and complications. Two of the patients were older than 70 years. One of the patients was healthy but he lost time because of an inappropriate treatment. These 3 patients died. The remaining patients were discharged at the end of the prolonged and intensive treatment. Necrotizing fasciitis should always be remembered in the diagnosis of the infection of the cervicofacial area. Because of difficulty in its diagnosis, a delay in the treatment may result in a horrific outcome.

  16. Mutations in PAX3 that cause Waardenburg syndrome type I: Ten new mutations and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Baldwin, C.T.; Hoth, C.F.; Milunsky, A. [Boston Univ. School of Medicine, MA (United States)] [and others

    1995-08-28

    Waardenburg syndrome (WS) is an autosomal-dominant disorder characterized by sensorineural hearing loss, dystopia canthorum, and pigmentary disturbances, and it represents the most common form of inherited deafness in infants. WS type I is characterized by the presence of dystopia canthorum, while individuals with WS type II have normally-located canthi. WS type III is similar to WS type I but is also characterized by musculoskeletal abnormalities. Defects in the PAX3 gene, a transcription factor expressed during embryonic development, have been shown to cause WS types I and III in several families. In contrast, mutations in PAX3 do not cause WS type II, and linkage of the disease to other chromosomal regions has been demonstrated. We describe 10 additional mutations in the PAX3 gene in families with WS type I. Eight of these mutations are in the region of PAX3, where only one mutation has been previously described. These mutations, together with those previously reported, cover essentially the entire PAX3 gene and represent a wide spectrum of mutations that can cause WS type I. Thus far, all but one of the mutations are private; only one mutation has been reported in two apparently unrelated families. Our analysis thus far demonstrates little correlation between genotype and phenotype; deletions of the entire PAX3 gene result in phenotypes indistinguishable from those associated with single-base substitutions in the paired domain or homeodomain of PAX3. Moreover, two similar mutations in close proximity can result in significantly different phenotypes, WS type I in one family and WS type III in another. 47 refs., 3 figs., 5 tabs.

  17. Homozygosity mapping and whole exome sequencing reveal a novel homozygous COL18A1 mutation causing Knobloch syndrome.

    Directory of Open Access Journals (Sweden)

    Alireza Haghighi

    Full Text Available The aim of this study was to identify the genetic basis of a chorioretinal dystrophy with high myopia of unknown origin in a child of a consanguineous marriage. The proband and ten family members of Iranian ancestry participated in this study. Linkage analysis was carried out with DNA samples of the proband and her parents by using the Human SNP Array 6.0. Whole exome sequencing (WES was performed with the patients' DNA. Specific sequence alterations within the homozygous regions identified by whole exome sequencing were verified by Sanger sequencing. Upon genetic analysis, a novel homozygous frameshift mutation was found in exon 42 of the COL18A1 gene in the patient. Both parents were heterozygous for this sequence variation. Mutations in COL18A1 are known to cause Knobloch syndrome (KS. Retrospective analysis of clinical records of the patient revealed surgical removal of a meningocele present at birth. The clinical features shown by our patient were typical of KS with the exception of chorioretinal degeneration which is a rare manifestation. This is the first case of KS reported in a family of Iranian ancestry. We identified a novel disease-causing (deletion mutation in the COL18A1 gene leading to a frameshift and premature stop codon in the last exon. The mutation was not present in SNP databases and was also not found in 192 control individuals. Its localization within the endostatin domain implicates a functional relevance of endostatin in KS. A combined approach of linkage analysis and WES led to a rapid identification of the disease-causing mutation even though the clinical description was not completely clear at the beginning.

  18. The CHRNE 470del20 mutation causing congenital myasthenic syndrome in South African Brahman cattle: Prevalence, origin, and association with performance traits.

    NARCIS (Netherlands)

    Thompson, P.N.; Werf, van der J.H.J.; Heesterbeek, J.A.P.; Arendonk, van J.A.M.

    2007-01-01

    Genotyping of the South African, registered, Brahman cattle population for the 470del20 mutation in the CHRNE gene causing congenital myasthenic syndrome (CMS) was carried out in 1,453 animals. Overall prevalence of carriers was 0.97% (0.50 to 1.68%, 95% confidence interval). Carrier prevalence amon

  19. Pre-eclampsia and the HELLP syndrome still cause maternal mortality in the Netherlands and other developed countries; can we reduce it?

    NARCIS (Netherlands)

    Onrust, S; Santema, JG; Aarnoudse, JG

    1999-01-01

    Maternal mortality in developed countries does not seem to have decreased during the past decade, despite good prenatal care. Hypertensive disorders of pregnancy are the main cause of maternal mortality in most countries. In more than half of these cases, the HELLP syndrome is involved. In this arti

  20. Bacteria-associated haemophagocytic syndrome and septic pulmonary embolism caused by Burkholderia cepacia complex in a woman with chronic granulomatous disease.

    Science.gov (United States)

    Hisano, Michi; Sugawara, Kana; Tatsuzawa, Osamu; Kitagawa, Michihiro; Murashima, Atsuko; Yamaguchi, Koushi

    2007-05-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent infections with certain types of bacteria and fungi. Presented herein is the case of a 29 year old woman with CGD who suffered from bacteria-associated haemophagocytic syndrome and a septic pulmonary embolism following a uterine infection and sepsis, caused by Burkholderia cepacia complex.