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  1. Loeys-Dietz Syndrome

    MedlinePlus

    ... syndrome is a genetic disorder of the body’s connective tissue. It has some features in common with Marfan ... a mutation, growth and development of the body’s connective tissue and other body systems is disrupted, leading to ...

  2. Genetics Home Reference: Loeys-Dietz syndrome

    MedlinePlus

    ... a bulge in the blood vessel wall ( an aneurysm ). Stretching of the aorta may also lead to ... People with Loeys-Dietz syndrome can also have aneurysms or dissections in arteries throughout the body and ...

  3. LOEYS-DIETZ SYNDROME: PERIOPERATIVE ANESTHESIA CONSIDERATIONS.

    PubMed

    Johnson, Judy G; Bray, Jacob P; Risher, William H; Kaye, Alan David

    2016-06-01

    Loeys-Dietz syndrome (LDS) is a rare autosomal dominant disease related to genetic mutations in receptors for the cytokine transforming growth factor-receptor type 1 (TGFB-R1) or 2 gene (TGFB-R2) on the cell surface. LDS results in abnormal protein synthesis and dysfunctional connective tissue, which can result in unique cardiovascular anesthesia challenges related to perioperative management. Patients with LDS may manifest hypertelorism, bifid uvula or cleft palate, and arterial tortuosity. Virtually all LDS patients show some type of abnormal skin findings and bleeding tendency. These patients may show a rapid progression of aortic dilation, regurgitation, and a propensity towards rupture and/or dissection at a much earlier age and smaller aneurysm size. LDS patients who require surgical intervention require meticulous vigilance from the anesthesiologist. We describe a 26 year old patient with documented LDS type 1 who presented for repair of an ascending/root aneurysm in this case report. Recognition of LDS and intra-operative management of the cardiovascular manifestations of this disease is paramount in ensuring successful surgical outcome and to limit morbidity and mortality. PMID:27487644

  4. High Prevalence of Cervical Deformity and Instability Requires Surveillance in Loeys-Dietz Syndrome

    PubMed Central

    Fuhrhop, Sara K.; McElroy, Mark J.; Dietz, Harry C.; MacCarrick, Gretchen L.; Sponseller, Paul D.

    2015-01-01

    Background: Loeys-Dietz syndrome is a connective tissue disorder characterized by vascular, craniofacial, and musculoskeletal malformation. Our goal was to report the manifestations, surgical treatment, and complications in the cervical spine in patients with Loeys-Dietz syndrome. Methods: We reviewed the clinical and cervical spine imaging data of eighty patients with Loeys-Dietz syndrome who were seen at our institution from January 2005 through January 2014. Their mean age at presentation was 17.3 years (range, three months to seventy-five years). We tested associations with use of the Fisher exact test (type of TGF-βR [transforming growth factor-beta receptor] mutation and cervical abnormalities) and the Student t test (age at presentation and type of TGF-βR mutation) (significance, p = 0.05). Results: Vertebral anomalies and cervical instability were common; we found no significant association of TGF-βR-type with cervical abnormalities or age at presentation. Twenty-eight patients had atlas defects (anterior and/or posterior arch defects or hypoplasia), fifty-three had axis malformations (elongation, apex-anterior dens angulation, or spondylolysis), and twelve had focal kyphosis. Ten patients had hypoplastic subaxial vertebrae, leading to focal kyphosis (eight) and subaxial instability (nine). Eight patients had atlantoaxial instability. Of the thirteen patients with cervical instability, nine were treated surgically: fusion (eight patients) and halo application (one) (mean age, four years; range, three months to twelve years). Postoperative complications (seven patients) were pseudarthrosis, failure of fixation, junctional kyphosis or instability, and development of occipital-cervical instability. Conclusions: Cervical midline defects (most often C1-C3) are common in Loeys-Dietz syndrome. Patients have a high prevalence of cervical instability, particularly a pattern of instability at C2-C3 associated with C3 vertebral body hypoplasia and C2-C3 focal

  5. [Two Surgical Cases of Loeys-Dietz Syndrome in Childhood].

    PubMed

    Sugawara, Masaaki; Oguma, Fumiaki; Hirahara, Hiroyuki

    2016-08-01

    Loeys-Dietz syndrome( LDS) is a recently recognized autosomal dominant connective tissue disorder. Mutations in the genes encoding transforming growth factor-beta( TGF-β) receptor 1 and (2 TGFBR1, TGFBR2)have been associated with LDS. We report here 2 cases of LDS in childhood. Case 1 was a 10-year-old man, who had aneurysm of both the pulmonary trunk and the ascending aorta, associated with pulmonary and aortic valve insufficiency. Surgical repair was performed successfully at the age of 17. The aortic valve was replaced with a mechanical valve. The aneurysmal ascending aorta was replaced with a Dacron graft. Pulmonary valvuloplasty and pulmonary arterioplasty was performed. Case 2 was a 3-month-old female infant, who had a patent ductus arteriosus( PDA) and aortic root dilation. A detailed physical examination revealed hypertelorism, bifid uvula, retrognathia, talipes equinovarus, and camptodactyly. Computed tomography and echocardiography demonstrated PDA, Valsalva sinus dilation, and arterial tortuosity. These findings were consistent with the clinical manifestations of LDS. Surgical ligation and clipping of the PDA was performed with good results. A molecular genetic analysis subsequently demonstrated a heterozygous missense mutation of the TGFBR2. Since aortic dissection occurs at smaller aortic diameters, early diagnosis and close monitoring are important for patients with LDS. PMID:27476563

  6. Further delineation of Loeys-Dietz syndrome type 4 in a family with mild vascular involvement and a TGFB2 splicing mutation

    PubMed Central

    2014-01-01

    Background The Loeys-Dietz syndrome (LDS) is a rare autosomal dominant disorder characterized by thoracic aortic aneurysm and dissection and widespread systemic connective tissue involvement. LDS type 1 to 4 are caused by mutations in genes of the TGF-β signaling pathway: TGFBR1 and TGFBR2 encoding the TGF-β receptor (LDS1 and LDS2), SMAD3 encoding the TGF-β receptor cytoplasmic effector (LDS3), and TGFB2 encoding the TGF-β2 ligand (LDS4). LDS4 represents the mildest end of the LDS spectrum, since aneurysms are usually observed in fourth decade and the progression of the disease is slower than in the other forms. Case presentation We report the clinical and molecular findings of an LDS4 Italian family. Genetic testing included TGFBR1, TGFBR2, SMAD3, and TGFB2 analysis by Sanger sequencing. In order to verify the effect of the identified splice mutation, RT-PCR analysis was performed. The proband, a 57-year-old woman, showed high palate, hypoplasic uvula, easy bruising, joint hypermobility, chronic pain, scoliosis, multiple relapsing hernias, dural ectasia, and mitral valve prolapse. Magnetic resonance angiography revealed tortuosity and ectasia of carotid, vertebral, cerebral, and segmental pulmonary arteries. Arterial aneurysm and dissection never occurred. Her 39- and 34-year-old daughters presented with a variable degree of musculoskeletal involvement. Molecular analysis disclosed the novel c.839-1G>A splice site mutation in the TGFB2 gene. This mutation activates a cryptic splice acceptor site in exon 6 leading to frameshift, premature termination codon and haploinsufficiency (p.Gly280Aspfs*41). Conclusions Our data confirm that loss-of-function mutations in TGFB2 gene do not always lead to aggressive vascular phenotypes and that articular and skeletal signs are prevalent, therefore suggesting that LDS4 must be considered in patients with sparse signs of LDS and related disorders also in the absence of vascular events. PMID:25163805

  7. Aortic and Pulmonary Root Aneurysms in a Child With Loeys-Dietz Syndrome.

    PubMed

    Rizzo, Stefania; Stellin, Giovanni; Milanesi, Ornella; Padalino, Massimo; Vricella, Luca A; Thiene, Gaetano; Cameron, Duke E; Basso, Cristina; Vida, Vladimiro L

    2016-03-01

    We report the case of an 11-year-old boy with Loeys-Dietz syndrome, with both aortic and pulmonary aneurysms requiring cardiac operation because of progressive valve incompetence resulting from loss of coaptation of the cusps. Arterial medial changes, consisting of disarray of elastic fibers and increased collagen deposition, were observed in surgical specimens from both the aorta and the pulmonary artery of our patient, and the strong pSmad2 nuclear staining of smooth muscle cells of both aortic and pulmonary tunica media are the best evidence of transforming growth factor-β pathway activation in Loeys-Dietz syndrome. PMID:26897209

  8. Pregnancy after aortic root replacement in Loeys-Dietz syndrome: High risk of aortic dissection.

    PubMed

    Braverman, Alan C; Moon, Marc R; Geraghty, Patrick; Willing, Marcia; Bach, Christopher; Kouchoukos, Nicholas T

    2016-08-01

    Loeys-Dietz syndrome due to mutations in TGFBR1 and 2 is associated with early and aggressive aortic aneurysm and branch vessel disease. There are reports of uncomplicated pregnancy in this condition, but there is an increased risk of aortic dissection and uterine rupture. Women with underlying aortic root aneurysm are cautioned about the risk of pregnancy-related aortic dissection. Prophylactic aortic root replacement is recommended in women with aortopathy and aortic root dilatation to lessen the risk of pregnancy. There is limited information in the literature about the outcomes of pregnancy after root replacement in Loeys-Dietz syndrome. We present a case series of three women with Loeys-Dietz syndrome who underwent elective aortic root replacement for aneurysm disease and subsequently became pregnant and underwent Cesarean section delivery. Each of these women were treated with beta blockers throughout pregnancy. Surveillance echocardiograms and noncontrast MRA studies during pregnancy remained stable demonstrating no evidence for aortic enlargement. Despite the normal aortic imaging and careful observation, two of the three women suffered acute aortic dissection in the postpartum period. These cases highlight the high risk of pregnancy following aortic root replacement in Loeys-Dietz syndrome. Women with this disorder are recommended to be counseled accordingly. © 2016 Wiley Periodicals, Inc. PMID:27125181

  9. Pathophysiology and Management of Cardiovascular Manifestations in Marfan and Loeys-Dietz Syndromes.

    PubMed

    Takeda, Norifumi; Yagi, Hiroki; Hara, Hironori; Fujiwara, Takayuki; Fujita, Daishi; Nawata, Kan; Inuzuka, Ryo; Taniguchi, Yuki; Harada, Mutsuo; Toko, Haruhiro; Akazawa, Hiroshi; Komuro, Issei

    2016-05-25

    Marfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue that affects the cardiovascular, skeletal, ocular, pulmonary, and nervous systems and is usually caused by mutations in the FBN1 gene, which encodes fibrillin-1. MFS is traditionally considered to result from the structural weakness of connective tissue. However, recent investigations on molecular mechanisms indicate that increased transforming growth factor-β (TGF-β) activity plays a crucial role in the pathogenesis of MFS and related disorders, such as Loeys-Dietz syndrome (LDS), which is caused by mutation in TGF-β signaling-related genes. In addition, recent studies show that angiotensin II type 1 receptor (AT1R) signaling enhances cardiovascular pathologies in MFS, and the angiotensin II receptor blocker losartan has the potential to inhibit aortic aneurysm formation. However, the relationship between TGF-β and AT1R signaling pathways remains poorly characterized. In this review, we discuss the recent studies on the molecular mechanisms underlying cardiovascular manifestations of MFS and LDS and the ensuing strategies for management. PMID:27181042

  10. [Loeys-Dietz syndrome (TGFβR2 mutation) in a 4-year-old child with thoracic aortic aneurysm].

    PubMed

    De Potter, M-J; Edouard, T; Amadieu, R; Plaisancié, J; Julia, S; Hadeed, K; Hascoët, S; Acar, P; Dulac, Y

    2016-05-01

    Loeys-Dietz syndrome is a rare form of connective tissue disorder, whose clinical features can resemble those of Marfan syndrome, but with a more unpolished appearance. Recently brought out, this pathology remains little known; however, its consequences may be dramatic. We report on the case of a 4-year-old girl followed for a congenital hip dislocation, in which a systematic exam found increased cutaneous elasticity and a bifid uvula, suggesting a connective tissue disorder. Symptoms were unpolished, as the child's height was normal, without any positive cardiac, rheumatological, or ophthalmological family history. Cardiovascular tests found a thoracic aortic aneurysm at the Valsalva sinus (26mm, Z-score=+4.24). A genetic investigation found a TGFβR2 gene mutation, leading to the diagnosis of Loeys-Dietz syndrome type 2. Skeletal damage associated with bifid uvula and/or hypertelorism and an aneurysm of the ascending aorta should guide the genetic investigation to the search for TGF-β vasculopathy such as Loeys-Dietz syndrome. PMID:27017362

  11. A patient with Loeys-Dietz syndrome treated with chemoradiotherapy for an oropharyngeal carcinoma.

    PubMed

    Chan, Andrew K; Teoh, Daren; Matthews, Paul; Fresco, Lydia

    2013-01-01

    We present the first published case of a patient with Loeys-Dietz syndrome (LDS) who was treated with radical chemoradiotherapy for an oropharyngeal carcinoma. In view of this newly recognised connective tissue disease, the uncertainty of severe toxicity from chemoradiotherapy to treat a potentially curative cancer posed a management challenge. The patient was treated with chemoradiotherapy and remains well with no evidence of recurrence at 3 years. Furthermore, we have observed minimal late effects secondary to chemoradiotherapy at 3 years following the completion of treatment suggesting that the underlying pathogenesis of LDS may provide an interesting human model to further elucidate the complex interactions of transforming growth factor β1 (TGF-β1) and tissue fibrosis secondary to chemoradiotherapy. A review of LDS as well as the association of TGF-β1 expression and tissue fibrosis is presented. PMID:24045763

  12. Single-Stage Total Arch Replacement Including Resection of Kommerell Diverticulum in a Patient With Loeys-Dietz Syndrome.

    PubMed

    Ong, Chin Siang; Kasai, Yuhei; Fukushima, Souta; Hibino, Narutoshi; Magruder, Trent; Suarez-Pierre, Alejandro; Cameron, Duke; Vricella, Luca

    2016-09-01

    Loeys-Dietz syndrome (LDS) is an autosomal dominant genetic connective tissue disorder associated with aortic aneurysmal disease. Kommerell diverticulum (KD) is a rare aortic diverticulum, for which the indication for surgery and the surgical techniques remain subjects of debate. We describe our experience with a successful total aortic arch replacement including KD resection through a median sternotomy for a pediatric patient with LDS. PMID:27521346

  13. Duplication of the TGFBR1 gene causes features of Loeys-Dietz syndrome.

    PubMed

    Breckpot, Jeroen; Budts, Werner; De Zegher, Francis; Vermeesch, Joris R; Devriendt, Koenraad

    2010-01-01

    Loeys-Dietz syndrome (LDS; OMIM:609192) is an autosomal dominant disorder characterized by hypertelorism, bifid uvula or cleft palate, and arterial tortuosity with widespread vascular aneurysms and a high risk of aortic dissection at an early age. LDS results from mutations in the transforming growth factor beta-receptor I and II (TGFBR1 and TGFBR2) genes, altering the transmission of the subcellular TGF-β signal, mediated by increased activation of Smad2. We report on a 17-year-old boy with pubertas tarda, a bifid uvula, camptodactyly and facial dysmorphic features, suggestive of LDS. Mutation analysis of TGFBR1 and TGFBR2 was normal. By means of molecular karyotyping two previously unreported chromosomal imbalances were detected: a 120 kb deletion on chromosome 22q13.31q13.32, inherited from an unaffected parent, and a de novo 14.6 Mb duplication on chromosome 9q22.32q31.3, comprising TGFBR1. We hypothesize that copy number gain of TGFBR1 contributes to the phenotype. PMID:20813212

  14. Dural ectasia in Loeys-Dietz syndrome: comprehensive study of 30 patients with a TGFBR1 or TGFBR2 mutation.

    PubMed

    Sheikhzadeh, S; Brockstaedt, L; Habermann, C R; Sondermann, C; Bannas, P; Mir, T S; Staebler, A; Seidel, H; Keyser, B; Arslan-Kirchner, M; Kutsche, K; Berger, J; Blankenberg, S; von Kodolitsch, Y

    2014-12-01

    The purpose of this study was to assess the frequency, severity, and clinical associations of dural ectasia (DE) in Loeys-Dietz syndrome (LDS). Database analysis of three German metropolitan regions identified 30 patients with LDS and TGFBR1 mutation in 6 and a TGFBR2 mutation in 24 individuals (17 men; mean age: 31 ± 19 years), as well as 60 age and sex-matched control patients with Marfan syndrome carrying a FBN1 mutation. DE was present in 22 patients with LDS (73%), and it related to skeletal score points (p = 0.008), non-skeletal score points (p < 0.001), and to the presence of ≥7 systemic score points (p = 0.010). Similarly, the severity of DE was related to body height (p = 0.010) and non-skeletal score points (p = 0.004). Frequency (p = 0.131) and severity of DE (p = 0.567) was similar in LDS and Marfan syndrome. DE is a manifestation of LDS that occurs with similar frequency and severity as in Marfan syndrome. Severity of DE may serve as a marker of the overall connective tissue disease severity. LDS may be considered in patients with DE. PMID:24344637

  15. Long noncoding RNA AK056155 involved in the development of Loeys-Dietz syndrome through AKT/PI3K signaling pathway

    PubMed Central

    Yu, Bo; Liu, Long; Sun, Huan; Chen, Yu

    2015-01-01

    Loeys-Dietz syndrome (LDS) is an autosomal dominant genetic connective tissue disorder, and most of LDS patients will develop into aortic aneurysm. Unfortunately, there is no known cure, and a high risk of death from aortic aneurysm rupture. However the detailed mechanism is still unknown. In order to explore the mechanism, we firstly used bioinformatics to predict, and then verified with biology methods. Firstly, we found that LncRNA AK056155 was differentially expressed in peripheral blood circulating endothelial cells between normal patients and LDS patients by bioinformatics. Then we further verified that AK056155 was also overexpressed in aortic aneurysm patients by RT-PCR. Moreover, we demonstrated that the expression of AK056155 can be enhanced by TGF-β1 in a concentration or time depended manner in HUVECs by RT-PCR. Furthermore, the expression of AK056155 was reduced with treatment of PI3K inhibitor (LY294002) or AKT inhibitor (GDC-0068) in combination with TGF-β1. These results indicate that AK056155 involved in the development of Loeys-Dietz syndrome through AKT/PI3K signaling pathway, it may provide a promising target gene to prevent LDS develop in to aortic aneurysm. PMID:26617788

  16. Severe eczema and Hyper-IgE in Loeys-Dietz-syndrome - contribution to new findings of immune dysregulation in connective tissue disorders.

    PubMed

    Felgentreff, Kerstin; Siepe, Matthias; Kotthoff, Stefan; von Kodolitsch, Yskert; Schachtrup, Kristina; Notarangelo, Luigi D; Walter, Jolan E; Ehl, Stephan

    2014-01-01

    Loeys-Dietz syndrome (LDS) is a connective tissue disorder caused by monoallelic mutations in TGFBR1 and TGFBR2, which encode for subunits of the transforming growth factor beta (TGFβ) receptor. Affected patients are identified by vascular aneurysms with tortuosity and distinct morphological presentations similar to Marfan syndrome; however, an additional predisposition towards asthma and allergy has recently been found. We describe two patients with a novel missense mutation in TGFBR1 presenting with highly elevated levels of IgE and severe eczema similar to autosomal-dominant Hyper-IgE syndrome (HIES). Mild allergic manifestations with normal up to moderately increased IgE were observed in 3 out of 6 additional LDS patients. A comparison of this cohort with 4 HIES patients illustrates the significant overlap of both syndromes including eczema and elevated IgE as well as skeletal and connective tissue manifestations. PMID:24333532

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

    PubMed Central

    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

  18. When flexibility is not necessarily a virtue: a review of hypermobility syndromes and chronic or recurrent musculoskeletal pain in children.

    PubMed

    Cattalini, Marco; Khubchandani, Raju; Cimaz, Rolando

    2015-01-01

    Chronic or recurrent musculoskeletal pain is a common complaint in children. Among the most common causes for this problem are different conditions associated with hypermobility. Pediatricians and allied professionals should be well aware of the characteristics of the different syndromes associated with hypermobility and facilitate early recognition and appropriate management. In this review we provide information on Benign Joint Hypermobility Syndrome, Ehlers-Danlos Syndrome, Marfan Syndrome, Loeys-Dietz syndrome and Stickler syndrome, and discuss their characteristics and clinical management. PMID:26444669

  19. Skeletal overgrowth syndrome caused by overexpression of C-type natriuretic peptide in a girl with balanced chromosomal translocation, t(1;2)(q41;q37.1).

    PubMed

    Ko, Jung Min; Bae, Jun-Seok; Choi, Jin Sun; Miura, Kohji; Lee, Hye Ran; Kim, Ok-Hwa; Kim, Nayoung K D; Oh, Sun Kyung; Ozono, Keiichi; Lee, Choon-Ki; Choi, In Ho; Park, Woong-Yang; Cho, Tae-Joon

    2015-05-01

    Chromosomal translocation of 2q37.1 just distal to the NPPC gene coding for C-type natriuretic peptide (CNP) and subsequent overproduction of CNP have been reported to cause a skeletal overgrowth syndrome. Loeys-Dietz syndrome (LDS) is one of marfanoid overgrowth syndromes, of which subtype IV is caused by haploinsufficiency of transforming growth factor beta 2 (TGFB2). We report on a girl with clinical phenotypes of overgrowth syndrome, including long and slim body habitus, macrodactyly of the big toe, scoliosis, ankle valgus deformity, coxa valga, slipped capital femoral epiphysis, and aortic root dilatation. Karyotyping revealed a balanced chromosomal translocation between 1q41 and 2q37.1, and the breakpoints could be mapped by targeted resequencing analysis. On chromosome 2q37.1, the translocation took place 200,365 bp downstream of NPPC, and serum level of the amino terminal of CNP was elevated. The contralateral site of translocation on chromosome 1q41 disrupted TGFB2 gene, presumed to cause its haploinsufficiency. This case supports the concept that NPPC is overexpressed because of the loss of a specific negative regulatory control in the normal chromosomal location, and demonstrates the effectiveness of targeted resequencing in the mapping of breakpoints. PMID:25728306

  20. Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/ehlers-danlos syndrome hypermobility type compared to other heritable connective tissue disorders.

    PubMed

    Colombi, Marina; Dordoni, Chiara; Chiarelli, Nicola; Ritelli, Marco

    2015-03-01

    Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is an evolving and protean disorder mostly recognized by generalized joint hypermobility and without a defined molecular basis. JHS/EDS-HT also presents with other connective tissue features affecting a variety of structures and organs, such as skin, eye, bone, and internal organs. However, most of these signs are present in variable combinations and severity in many other heritable connective tissue disorders. Accordingly, JHS/EDS-HT is an "exclusion" diagnosis which needs the absence of any consistent feature indicative of other partially overlapping connective tissue disorders. While both Villefranche and Brighton criteria include such an exclusion as a mandatory item, a systematic approach for reaching a stringent clinical diagnosis of JHS/EDS-HT is still lacking. The absence of a consensus on the diagnostic approach to JHS/EDS-HT concerning its clinical boundaries with similar conditions contribute to limit our actual understanding of the pathologic and molecular bases of this disorder. In this review, we revise the differential diagnosis of JHS/EDS-HT with those heritable connective tissue disorders which show a significant overlap with the former and mostly include EDS classic, vascular and kyphoscoliotic types, osteogenesis imperfecta, Marfan syndrome, Loeys-Dietz syndrome, arterial tortuosity syndrome, and lateral meningocele syndrome. A diagnostic flow chart is also offered with the attempt to support the less experienced clinician in stringently recognizing JHS/EDS-HT and stimulate the debate in the scientific community for both management and research purposes. PMID:25821090

  1. Analysis of TFGBR1*6A variant in individuals evaluated for Marfan syndrome.

    PubMed

    Somers, Allyson E; Hinton, Robert B; Pilipenko, Valentina; Miller, Erin; Ware, Stephanie M

    2016-07-01

    Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS) are genetic disorders that affect connective tissue as a result of dysregulated TGF-β signaling. MFS is most frequently caused by mutations in FBN1 whereas Loeys-Dietz syndrome results from mutations in TGFBR1 or TGFBR2. There is substantial inter- and intra-familial phenotypic variability among these disorders, suggesting the presence of genetic modifiers. Previously, a polymorphism in the TGFβR1 protein termed the TFGBR1*6A allele was found to be overrepresented in patients with MFS and was identified as a low penetrance allele with suggestion as a possible modifier. To further investigate the importance of this variant, a retrospective review of genetic and phenotypic findings was conducted for 335 patients evaluated for suspicion of MFS or related disorders. In patients with a diagnosis of MFS, the presence of the TFGBR1*6A allele was not associated with phenotypic differences. Similarly, careful phenotyping of patients who carried the TFGBR1*6A allele but did not have MFS did not identify an altered frequency of specific connective tissue features. In this small cohort, the results did not reach significance to identify the TFGBR1*6A allele as a major modifier for aortic dilation, ectopia lentis, or systemic features associated with MFS or other connective tissue disorders. © 2016 Wiley Periodicals, Inc. PMID:27112580

  2. Vascular manifestations of syndromic aortopathies: role of current and emerging imaging techniques.

    PubMed

    Westerland, O; Frigiola, A; Robert, L; Shaw, A; Blakeway, L; Katsanos, K; Kiesewetter, C; Chung, N; Karunanithy, N

    2015-12-01

    Patients with connective tissue diseases such as Marfan's syndrome, Loeys-Dietz syndrome, and vascular Ehlers-Danlos syndrome comprise a small but important group of patients who present early with acute aortic syndrome comprising aneurysmal dilation, rupture, or aortic dissection. Cardiovascular pathologies are an important yet treatable cause of morbidity and mortality in these patients. Imaging plays an important role in initial diagnosis, surveillance, and identification of complications. Furthermore, these patients are prone to developing complications in other vascular territories. Effective screening and surveillance will allow early diagnosis and elective treatment thus reducing the morbidity and mortality associated with presentation with acute complications. In this article, we will provide an overview of the role of magnetic resonance and computed tomography angiography in the management of syndromic aortopathies. PMID:26388241

  3. What Are Related Disorders?

    MedlinePlus

    ... Dietz syndrome, Ehlers-Danlos syndrome, and Familial Thoracic Aortic Aneurysm and Dissection. Disorders related to Marfan syndrome can ... Loeys-Dietz Syndrome Ehlers-Danlos Syndrome Familial Thoracic Aortic Aneurysm and Dissection MASS Phenotype Ectopia Lentis Syndrome Beals ...

  4. Severe inflammatory bowel disease associated with congenital alteration of transforming growth factor beta signaling.

    PubMed

    Naviglio, Samuele; Arrigo, Serena; Martelossi, Stefano; Villanacci, Vincenzo; Tommasini, Alberto; Loganes, Claudia; Fabretto, Antonella; Vignola, Silvia; Lonardi, Silvia; Ventura, Alessandro

    2014-08-01

    Transforming growth factor beta is a pleiotropic cytokine which plays a central role in the homeostasis of the immune system. A complex dysregulation of its signaling occurs in Loeys-Dietz syndrome, a monogenic disorder caused by mutations of transforming growth factor beta receptors type 1 or type 2, characterized by skeletal involvement, craniofacial abnormalities, and arterial tortuosity with a strong predisposition for aneurysm and dissection. In addition, several immunologic abnormalities have been described in these patients, including an increased risk of allergic disorders as well as eosinophilic gastrointestinal disorders. The occurrence of inflammatory bowel disorders has been also reported, but it is poorly documented. We describe two unrelated children with Loeys-Dietz syndrome affected by severe chronic inflammatory colitis appearing at an early age. The intestinal disease presented similar features in both patients, including a histopathological picture of non-eosinophilic chronic ulcerative colitis, striking elevation of inflammatory markers, and a distinctly severe clinical course leading to failure to thrive, with resistance to multiple immunosuppressive treatments. One of the patients also presented autoimmune thyroiditis. Our report confirms that chronic ulcerative colitis may be associated with Loeys-Dietz syndrome. This finding suggests that an alteration of transforming growth factor beta signaling may by itself predispose to inflammatory colitis in humans, and represent an invaluable model to understand inflammatory bowel diseases. PMID:24486179

  5. Hyperactive transforming growth factor-β1 signaling potentiates skeletal defects in a neurofibromatosis type 1 mouse model.

    PubMed

    Rhodes, Steven D; Wu, Xiaohua; He, Yongzheng; Chen, Shi; Yang, Hao; Staser, Karl W; Wang, Jiapeng; Zhang, Ping; Jiang, Chang; Yokota, Hiroki; Dong, Ruizhi; Peng, Xianghong; Yang, Xianlin; Murthy, Sreemala; Azhar, Mohamad; Mohammad, Khalid S; Xu, Mingjiang; Guise, Theresa A; Yang, Feng-Chun

    2013-12-01

    Dysregulated transforming growth factor beta (TGF-β) signaling is associated with a spectrum of osseous defects as seen in Loeys-Dietz syndrome, Marfan syndrome, and Camurati-Engelmann disease. Intriguingly, neurofibromatosis type 1 (NF1) patients exhibit many of these characteristic skeletal features, including kyphoscoliosis, osteoporosis, tibial dysplasia, and pseudarthrosis; however, the molecular mechanisms mediating these phenotypes remain unclear. Here, we provide genetic and pharmacologic evidence that hyperactive TGF-β1 signaling pivotally underpins osseous defects in Nf1(flox/-) ;Col2.3Cre mice, a model which closely recapitulates the skeletal abnormalities found in the human disease. Compared to controls, we show that serum TGF-β1 levels are fivefold to sixfold increased both in Nf1(flox/-) ;Col2.3Cre mice and in a cohort of NF1 patients. Nf1-deficient osteoblasts, the principal source of TGF-β1 in bone, overexpress TGF-β1 in a gene dosage-dependent fashion. Moreover, Nf1-deficient osteoblasts and osteoclasts are hyperresponsive to TGF-β1 stimulation, potentiating osteoclast bone resorptive activity while inhibiting osteoblast differentiation. These cellular phenotypes are further accompanied by p21-Ras-dependent hyperactivation of the canonical TGF-β1-Smad pathway. Reexpression of the human, full-length neurofibromin guanosine triphosphatase (GTPase)-activating protein (GAP)-related domain (NF1 GRD) in primary Nf1-deficient osteoblast progenitors, attenuated TGF-β1 expression levels and reduced Smad phosphorylation in response to TGF-β1 stimulation. As an in vivo proof of principle, we demonstrate that administration of the TGF-β receptor 1 (TβRI) kinase inhibitor, SD-208, can rescue bone mass deficits and prevent tibial fracture nonunion in Nf1(flox/-) ;Col2.3Cre mice. In sum, these data demonstrate a pivotal role for hyperactive TGF-β1 signaling in the pathogenesis of NF1-associated osteoporosis and pseudarthrosis, thus implicating the TGF

  6. Marfan Syndrome and Related Disorders: 25 Years of Gene Discovery.

    PubMed

    Verstraeten, Aline; Alaerts, Maaike; Van Laer, Lut; Loeys, Bart

    2016-06-01

    Marfan syndrome (MFS) is a rare, autosomal-dominant, multisystem disorder, presenting with skeletal, ocular, skin, and cardiovascular symptoms. Significant clinical overlap with other systemic connective tissue diseases, including Loeys-Dietz syndrome (LDS), Shprintzen-Goldberg syndrome (SGS), and the MASS phenotype, has been documented. In MFS and LDS, the cardiovascular manifestations account for the major cause of patient morbidity and mortality, rendering them the main target for therapeutic intervention. Over the past decades, gene identification studies confidently linked the aforementioned syndromes, as well as nonsyndromic aneurysmal disease, to genetic defects in proteins related to the transforming growth factor (TGF)-β pathway, greatly expanding our knowledge on the disease mechanisms and providing us with novel therapeutic targets. As a result, the focus of the developing pharmacological treatment strategies is shifting from hemodynamic stress management to TGF-β antagonism. In this review, we discuss the insights that have been gained in the molecular biology of MFS and related disorders over the past 25 years. PMID:26919284

  7. [The Marfan syndrome and related connective tissue disorders].

    PubMed

    Siepe, Matthias; Löffelbein, Florian

    2009-06-01

    The Marfan syndrome is an inherited disorder of the connective tissue which is mainly caused by a mutation in the fibrillin-1 gene. The defect in the connective tissue protein can lead to several organ dysfunctions. For the life expectancy, the cardiovascular aspect is of paramount importance. Patients with Marfan syndrome may develop aortic aneurysms and valvular heart defects. The risk of aortic aneurysms consists in the development of aortic dissection or rupture with their fatal consequences. Besides the cardiovascular manifestation, the skeletal and ocular system can also be affected. The skeletal manifestation is often characterised by long limbs, arachnodactyly, and abnormal joint flexibility along with other signs. Patients may also have dislocated lenses, ectasia of the dural sac, stretch marks, spontaneous pneumothorax, recurrent hernia, or a family history suspicious for Marfan. During the past years, other related connective tissue disorders with analogous organ manifestation have been described (e.g., Loeys-Dietz syndrome). In this article we present the basic knowledge about these connective tissue disorders, and we mention new insights in the recently explored pathophysiology of the disorder which is a possible target for future medical treatment options. Furthermore, recent new concepts for the prophylactic treatment of the aortic manifestation are explained. PMID:19554831

  8. Modified pediatric Bentall procedure: A novel technique in a rare case

    PubMed Central

    Salve, Gananjay G; Javali, Satish R; Dalvi, Bharat V; Krishnanaik, Shivaprakash

    2016-01-01

    Aneurysms of ascending aorta are rarely seen in pediatric age group. Only few cases with Marfans syndrome have been reported in the literature. Preferred treatment for these children has been the standard Bentall procedure (aortic root replacement with composite graft prosthesis). We report a 4-year-old male child with huge aneurysm of ascending aorta and aortic root dilation with severe aortic regurgitation, having phenotypic features of Loeys-Dietz syndrome type I. He underwent Bentall procedure with a novel modification (medial trap-door technique for coronary reimplantation). Short-term result of this procedure is encouraging and he is asymptomatic for the last 14 months of follow-up.

  9. Differential Diagnosis of Genetic Disorders Associated with Moderate to Severe Refractory Eczema and Elevated Immunoglobulin E.

    PubMed

    Arjona Aguilera, C; Albarrán Planelles, C; Tercedor Sánchez, J

    2016-03-01

    The association of moderate to severe eczema and elevated plasma levels of immunoglobulin E is a characteristic not only of atopic dermatitis but also of various genodermatoses: hyperimmunoglobulin E syndromes, Omenn syndrome, Netherton syndrome, peeling skin syndrome type B, severe dermatitis, multiple allergies, and metabolic wasting syndrome, Wiskott-Aldrich syndrome, prolidase deficiency, Loeys-Dietz syndrome, IPEX syndrome, STAT5B deficiency, and pentasomy X. The clinical presentation of these genodermatoses -typically in children- is consistent with severe atopic dermatitis. Immunoglobulin E is elevated from birth and response to conventional treatments is poor. Diagnosis is further complicated by the fact that these genodermatoses often share other clinical manifestations and laboratory findings. We present practical guidelines for differentiating among these various entities, with the aim of helping physicians decide what type of genetic test should be carried out -and when- in order to establish a definitive diagnosis. PMID:26593686

  10. Genetics Home Reference: otopalatodigital syndrome type 2

    MedlinePlus

    ... Conditions otopalatodigital syndrome type 2 otopalatodigital syndrome type 2 Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Otopalatodigital syndrome type 2 is a disorder involving abnormalities in skeletal development ...

  11. Genetics Home Reference: otopalatodigital syndrome type 1

    MedlinePlus

    ... Conditions otopalatodigital syndrome type 1 otopalatodigital syndrome type 1 Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Otopalatodigital syndrome type 1 is a disorder primarily involving abnormalities in skeletal ...

  12. A rare cause of recurrent aortic dissection.

    PubMed

    Agrawal, Yashwant; Gupta, Vishal

    2016-07-01

    We report the case of a 19-year-old man with a history of Loeys-Dietz syndrome (LDS), which was diagnosed when he had a Stanford type A aortic dissection. He also had multiple aneurysms including ones in the innominate, right common carotid, and right internal mammary arteries. He had had multiple procedures including Bentall's procedure, repeat sternotomy with complete arch and valve replacement, and coil embolization of internal mammary artery aneurysm in the past. His LDS was characterized by gene mutation for transforming growth factor-β receptor 1. He presented to our facility with sudden onset of back pain, radiating to the right shoulder and chest. He was diagnosed with Stanford type B aortic dissection and underwent thoracic aorta endovascular repair for his aortic dissection. This case represents the broad spectrum of pathology associated with LDS where even with regular surveillance and aggressive medical management the patient developed Stanford B aortic dissection. PMID:27358537

  13. National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions

    ClinicalTrials.gov

    2015-12-08

    Marfan Syndrome; Turner Syndrome; Ehlers-Danlos Syndrome; Loeys-Dietz Syndrome; FBN1, TGFBR1, TGFBR2, ACTA2 or MYH11 Genetic Mutation; Bicuspid Aortic Valve Without Known Family History; Bicuspid Aortic Valve With Family History; Bicuspid Aortic Valve With Coarctation; Familial Thoracic Aortic Aneurysm and Dissections; Shprintzen-Goldberg Syndrome; Other Aneur/Diss of Thoracic Aorta Not Due to Trauma, <50yo; Other Congenital Heart Disease

  14. Mucopolysaccharidosis type II, Hunter's syndrome.

    PubMed

    Tylki-Szymańska, Anna

    2014-09-01

    Hunter syndrome is caused by deficiency of the lysososmal enzyme iduronate-2-sulphatase that cleaves O-linked sulphate moieties from dermatan sulphate and heparan sulphate and leads to accumulation of GAGs. The disease is a X-linked condition affecting males and rarely females, clinically divided into severe (2/3) and attenuated types. Children with severe form, diagnosed at 12-36 months, have coarse facial feature, short stature, joint stiffness, short neck, broad chest, large head circumference, watery diarrhea, skeletal changes, progressive and profound mental retardation, retinal degeneration' hearing loss, cardiomyopathy, valvular involvement, with progressive thickening and stiffening of the valve leaflets leading to mitral and aortic regurgitation and stenosis . Recurrent and prolonged rhinitis with persistent nasal discharge are the first symptoms of airway disease that manifests itself as noisy breathing and later sleep apnea. Some patients develop ivory-colored skin lesions on the upper back and sides of the upper arms, pathogenomic of Hunter syndrome. The scalp hair becomes coarse, straight and bristly. Inguinal and umbilical hernias occur caused by the disturbed structure of connective tissue and increased liver and spleen volume. Patients with attenuated form have normal intelligence and a milder phenotype. Physical features diagnosed later are similar but less pronounced but progress to severe disease. Sceening is by quantitative assessment of urinary GAGs excretion. Qualitative assessment of GAG by electrophoresis can distinguish the type of mucopolysaccharidosis. Definitive diagnosis is based on enzyme activity assay in leukocytes, fibroblasts or plasma. Molecular testing is recommended mainly for genetic counseling and carrier detection. Limited experience of Haematopoietic stem cell therapy in MPS II showed progressive neurodegeneration. Recombinant 125 Idursulfase, is indicated for long-term treatment. The response appears to depend on the

  15. Genetics Home Reference: autoimmune polyglandular syndrome, type 1

    MedlinePlus

    ... polyglandular syndrome, type 1 autoimmune polyglandular syndrome, type 1 Enable Javascript to view the expand/collapse boxes. ... All Close All Description Autoimmune polyglandular syndrome, type 1 is an inherited condition that affects many of ...

  16. Kenny-Caffey syndrome type 1

    PubMed Central

    El Jabbour, Tony; Aboursheid, Tarek; Keifo, Mohammad Baraa; Maksoud, Ismael; Alasmar, Diana

    2014-01-01

    Kenny-Caffey syndrome type 1 is a rare hereditary skeletal disorder. We present here a documented case of a 7-month-old girl with the characteristic symptoms of growth retardation, dysmorphic features, and hypoparathyroidism. PMID:24982829

  17. Genetic Risk for Aortic Aneurysm in Adolescent Idiopathic Scoliosis

    PubMed Central

    Haller, Gabe; Alvarado, David M.; Willing, Marcia C.; Braverman, Alan C.; Bridwell, Keith H.; Kelly, Michael; Lenke, Lawrence G.; Luhmann, Scott J.; Gurnett, Christina A.; Dobbs, Matthew B.

    2015-01-01

    Background: Scoliosis is a feature of several genetic disorders that are also associated with aortic aneurysm, including Marfan syndrome, Loeys-Dietz syndrome, and type-IV Ehlers-Danlos syndrome. Life-threatening complications of aortic aneurysm can be decreased through early diagnosis. Genetic screening for mutations in populations at risk, such as patients with adolescent idiopathic scoliosis, may improve recognition of these disorders. Methods: The coding regions of five clinically actionable genes associated with scoliosis (COL3A1, FBN1, TGFBR1, TGFBR2, and SMAD3) and aortic aneurysm were sequenced in 343 adolescent idiopathic scoliosis cases. Gene variants that had minor allele frequencies of <0.0001 or were present in human disease mutation databases were identified. Variants were classified as pathogenic, likely pathogenic, or variants of unknown significance. Results: Pathogenic or likely pathogenic mutations were identified in 0.9% (three) of 343 adolescent idiopathic scoliosis cases. Two patients had pathogenic SMAD3 nonsense mutations consistent with type-III Loeys-Dietz syndrome and one patient had a pathogenic FBN1 mutation with subsequent confirmation of Marfan syndrome. Variants of unknown significance in COL3A1 and FBN1 were identified in 5.0% (seventeen) of 343 adolescent idiopathic scoliosis cases. Six FBN1 variants were previously reported in patients with Marfan syndrome, yet were considered variants of unknown significance based on the level of evidence. Variants of unknown significance occurred most frequently in FBN1 and were associated with greater curve severity, systemic features of Marfan syndrome, and joint hypermobility. Conclusions: Clinically actionable pathogenic mutations in genes associated with adolescent idiopathic scoliosis and aortic aneurysm are rare in patients with adolescent idiopathic scoliosis who are not suspected of having these disorders, although variants of unknown significance are relatively common. Clinical

  18. Fluconazole-Induced Type 1 Kounis Syndrome.

    PubMed

    Singh Mahal, Hardeep

    2016-01-01

    The administration of fluconazole is commonly used in both inpatient and outpatient settings for the management of candidiasis infection. Although it is associated with a relatively safe side effect profile, some patients experience adverse effects associated with increased morbidity. We describe 1 such patient, a 42-year-old woman with a history of severe eczema who developed fluconazole-induced type 1 Kounis syndrome. Review of literature indicates that this as the first case reported of fluconazole-induced type 1 Kounis syndrome. PMID:26938747

  19. Rare case of orofaciodigital syndrome type I

    PubMed Central

    Singh, Abhishek Bahadur; Girhotra, Manish; Goel, Medha; Bhatia, Shilpee

    2013-01-01

    Orofaciodigital syndrome (OFDS) is a group of congenital anomalies which affects the face, oral structures and digits. There are nine subtypes with different modes of inheritance. OFDS type I is an X-linked dominant trait with lethality in the vast majority of affected males. We report a case of OFDS type I in an Indian girl at the age of seven who had most of the typical features of OFDS type I and nephrocalcinosis. PMID:23417374

  20. The neuromuscular differential diagnosis of joint hypermobility.

    PubMed

    Donkervoort, S; Bonnemann, C G; Loeys, B; Jungbluth, H; Voermans, N C

    2015-03-01

    Joint hypermobility is the defining feature of various inherited connective tissue disorders such as Marfan syndrome and various types of Ehlers-Danlos syndrome and these will generally be the first conditions to be considered by geneticists and pediatricians in the differential diagnosis of a patient presenting with such findings. However, several congenital and adult-onset inherited myopathies also present with joint hypermobility in the context of often only mild-to-moderate muscle weakness and should, therefore, be included in the differential diagnosis of joint hypermobility. In fact, on the molecular level disorders within both groups represent different ends of the same spectrum of inherited extracellular matrix (ECM) disorders. In this review we will summarize the measures of joint hypermobility, illustrate molecular mechanisms these groups of disorders have in common, and subsequently discuss the clinical features of: 1) the most common connective tissue disorders with myopathic or other neuromuscular features: Ehlers-Danlos syndrome, Marfan syndrome and Loeys-Dietz syndrome; 2) myopathy and connective tissue overlap disorders (muscle extracellular matrix (ECM) disorders), including collagen VI related dystrophies and FKBP14 related kyphoscoliotic type of Ehlers-Danlos syndrome; and 3) various (congenital) myopathies with prominent joint hypermobility including RYR1- and SEPN1-related myopathy. The aim of this review is to assist clinical geneticists and other clinicians with recognition of these disorders. PMID:25821091

  1. [Waardenburg syndrome type I: case report].

    PubMed

    Silva, Patricia Capua Vieira da; Rangel, Paula; Couto Jr, Abelardo

    2011-01-01

    Waardenburg syndrome (WS) type I is a non-progressive auditory-pigmentary disorder comprising congenital sensorineural hearing loss and pigmentary disturbances of the iris, hair, and skin, along with dystopia canthorum (lateral displacement of the inner canthi). Affected individuals may have higher risk of: neural tube defects, cleft lip and palate, limb abnormalities, and Hirschsprung disease. The diagnosis is clinical and should be considered if the individual has two major or one major plus two minor criteria. PAX3 is the only known gene associated to the syndrome. Nevertheless, its use is mostly for genetic counseling. Regarding different diagnosis, we may list: other causes of non-progressive auditory-pigmentary disorder comprising congenital sensorineural hearing loss, other types of Waardenburg syndrome, piebaldism, albinism, vitiligo and Teitz syndrome. This paper presents a case of an eleven year old boy with deafness and ophthalmologic alterations, based on his files and exams. It reinforced the importance of the ophthalmologist contributing for the diagnosis of this rare systemic disease, as it includes some ophthalmologic alterations. We remind that the early diagnosis allows adequate stimulation for the hearing loss, as well as preventive measures in case of pregnant women affected by genetic counseling. PMID:21915450

  2. Waardenburg Syndrome type 1: A case report.

    PubMed

    Demirci, Gulsen Tukenmez; Atıs, Guldehan; Altunay, Ilknur Kıvanc

    2011-01-01

    Waardenburg Syndrome (WS) is a rare hereditary disorder that is characterized by the clinical manifestations of oculocutaneous anomalies of pigmentation, congenital deafness, dystopia canthorum, and broad nasal root. It demonstrates both genetically and clinically heterogenous characteristics. In this article, we report an 11-month-old boy with WS1, one of four clinicat types of WS. He exhibited white forelock, hypopigmented macules and patches, heterochromia irides, and dystopia canthorum. PMID:22136859

  3. Congenital Nephrotic Syndrome – Finish Type

    PubMed Central

    Spahiu, Lidvana; Merovci, Besart; Jashari, Haki; Këpuska, Arbnore Batalli; Rugova, Blerta Elezi

    2016-01-01

    Introduction: Identification of the NPHS1 gene, which encodes nephrin, was followed by many studies demonstrating its mutation as a frequent cause of congenital nephrotic syndrome (CNS). While this gene is found in 98% of Finnish children with this syndrome, non-Finnish cases have lower level of incidence ranging from 39 to 80%. Case report: This report describes the clinical presentation of a two-week-old neonate who presented with periorbital and lower extremities edema, abdominal distention, heavy proteinuria, serum hypoproteinemia and failure to thrive. Genetic analysis revealed NHPS1 gene mutation leading to CNS-Finnish type diagnosis. Conclusion: Through this case we want to create awareness about diagnosis and treatment challenges in developing countries for rare congenital diseases. PMID:27594755

  4. Cardiorenal Syndrome Type 4: A Review

    PubMed Central

    Clementi, Anna; Virzì, Grazia Maria; Goh, Ching Yan; Cruz, Dinna N.; Granata, Antonio; Vescovo, Girogio; Ronco, Claudio

    2013-01-01

    There is a bidirectional and complex relationship between the heart and kidneys. This interaction is physical, chemical as well as biological and is also reflected in a strong connection between renal and cardiovascular diseases. Cardiorenal syndrome type 4 (CRS type 4) is characterized by primary chronic kidney disease (CKD) leading to an impairment of cardiac function, with ventricular hypertrophy, diastolic dysfunction, and/or increased risk of adverse cardiovascular events. The incidence of CKD is increasing, and CRS type 4 is becoming a major public health problem associated with a high morbidity and mortality. In this study, we briefly review the epidemiology and pathophysiology of CRS type 4, the role of biomarkers in its early identification, and its management. PMID:23946725

  5. Pregnancy and Thoracic Aortic Disease: Managing the Risks.

    PubMed

    Wanga, Shaynah; Silversides, Candice; Dore, Annie; de Waard, Vivian; Mulder, Barbara

    2016-01-01

    The most common aortopathies in women of childbearing age are bicuspid aortic valve, coarctation of the aorta, Marfan syndrome, Ehlers-Danlos syndrome, Loeys-Dietz syndrome, SMAD3 aortopathy, Turner syndrome, and familial thoracic aneurysm and dissection. The hemodynamic and hormonal changes of pregnancy increase the risk of progressive dilatation or dissection of the aorta in these women. The presence of hypertension increases the risk further. Therefore, appropriate preconception counselling is advised. For women who become pregnant, serial follow-up by a specialized multidisciplinary team throughout pregnancy and postpartum period is required. In this review we discuss risk assessment and management strategies for women with aortopathies. PMID:26604124

  6. Targeted therapy for hereditary cancer syndromes: neurofibromatosis type 1, neurofibromatosis type 2, and Gorlin syndrome.

    PubMed

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2014-12-01

    Hereditary cancer syndromes are well known in the oncology community, typically affecting children, adolescents, and young adults and thereby resulting in great cumulative morbidity and mortality. These syndromes often lag behind their de novo counterparts in the development of approved novel treatment options due to their rarity in the general population. Recent work has allowed the identification of molecular aberrations and associated targeted therapies that may effectively treat these conditions. In this review, we seek to characterize some of the involved aberrations and associated targeted therapies for several germline malignancies, including neurofibromatosis types 1 and 2, and Gorlin syndrome. Though patients with hereditary cancer syndromes may be too rare to effectively include in large clinical trials, by understanding the pathophysiology of these diseases, clinicians can attain insights into the use of targeted therapies in their own practice when treating affected individuals. PMID:25549703

  7. Spontaneous Bilateral Cervical Internal Carotid and Vertebral Artery Dissection in a Japanese Patient without Collagen Vascular Disease with Special Reference to Single-Nucleotide Polymorphisms.

    PubMed

    Abe, Arata; Nito, Chikako; Sakamoto, Yuki; Nogami, Akane; Hokama, Hiroyuki; Takahashi, Shiro; Kirita, Kumiko; Ueda, Masayuki; Ishimaru, Yoshiro; Kimura, Kazumi

    2016-08-01

    Spontaneous cervical artery dissection (sCAD) is a major cause of ischemic stroke in young adults. Frequently, sCAD involves multiple neck arteries, accounting for 13%-28% of the total sCAD cases. However, little is known about factors related to multiple sCAD. In this case, a 52-year-old man was admitted due to headache without aura. There was a personal history of migraine with aura and a family history of similar symptoms. The patient's younger brother had a left vertebral artery (VA) dissecting aneurysm and underwent endovascular occlusion of his parent artery at the age of 48. Magnetic resonance imaging of our admitted patient showed hyperintensities in the right internal carotid artery (ICA) without acute infarction, and magnetic resonance angiography revealed a narrowing of the right ICA. Angiography was then performed, which showed a trace of dissection of the left ICA and both VAs as well as the right ICA. The patient did not fulfill any major criteria of collagen vascular disease such as Ehlers-Danlos syndrome type IV or Loeys-Dietz syndrome. The data in our patient are quite similar to those reported in patients with single-nucleotide polymorphism (SNP) of PHACTR1. Obtaining the patient's informed consent, we analyzed a common SNP variation in the rs9349379[G] allele (PHACTR1), which has been reported to be associated with a lower risk of sCAD. PMID:27216377

  8. Nephrocalcinosis as adult presentation of Bartter syndrome type II.

    PubMed

    Huang, L; Luiken, G P M; van Riemsdijk, I C; Petrij, F; Zandbergen, A A M; Dees, A

    2014-02-01

    Bartter syndrome consists a group of rare autosomal-recessive renal tubulopathies characterised by renal salt wasting, hypokalaemic metabolic alkalosis, hypercalciuria and hyperreninaemic hyperaldosteronism. It is classified into five types. Mutations in the KCNJ1 gene (classified as type II) usually cause the neonatal form of Bartter syndrome. We describe an adult patient with a homozygous KCNJ1 mutation resulting in a remarkably mild phenotype of neonatal type Bartter syndrome. PMID:24659592

  9. Epidemiology of paediatric metabolic syndrome and type 2 diabetes mellitus.

    PubMed

    De Ferranti, Sarah D; Osganian, Stavroula K

    2007-12-01

    The epidemic in childhood obesity is a driving force behind the increase in paediatric metabolic syndrome, a collection of abnormalities that is associated in adults with increased risk for cardiovascular disease and type 2 diabetes mellitus. Although there is no clear consensus about the paediatric definition for metabolic syndrome, the prevalence of this syndrome is clearly rising. Children with metabolic syndrome are at increased risk for metabolic syndrome in adulthood. A late consequence of metabolic syndrome is type 2 diabetes, which increasingly affects adolescents. The rise in metabolic syndrome and type 2 diabetes in children is almost sure to lead to an increase in associated complications in young adulthood, including early cardiovascular disease. This epidemic will bear fruit in forthcoming decades, putting further stress on the healthcare system and probably leading to increased morbidity and a shorter lifespan for future generations. PMID:18158698

  10. Modulation of lipid metabolic defects rescues cleft palate in Tgfbr2 mutant mice.

    PubMed

    Iwata, Junichi; Suzuki, Akiko; Pelikan, Richard C; Ho, Thach-Vu; Sanchez-Lara, Pedro A; Chai, Yang

    2014-01-01

    Mutations in transforming growth factor beta (TGFβ) receptor type II (TGFBR2) cause Loeys-Dietz syndrome, characterized by craniofacial and cardiovascular abnormalities. Mice with a deletion of Tgfbr2 in cranial neural crest cells (Tgfbr2(fl/fl);Wnt1-Cre mice) develop cleft palate as the result of abnormal TGFβ signaling activation. However, little is known about metabolic processes downstream of TGFβ signaling during palatogenesis. Here, we show that Tgfbr2 mutant palatal mesenchymal cells spontaneously accumulate lipid droplets, resulting from reduced lipolysis activity. Tgfbr2 mutant palatal mesenchymal cells failed to respond to the cell proliferation stimulator sonic hedgehog, derived from the palatal epithelium. Treatment with p38 mitogen-activated protein kinase (MAPK) inhibitor or telmisartan, a modulator of p38 MAPK activation and lipid metabolism, blocked abnormal TGFβ-mediated p38 MAPK activation, restoring lipid metabolism and cell proliferation activity both in vitro and in vivo. Our results highlight the influence of alternative TGFβ signaling on lipid metabolic activities, as well as how lipid metabolic defects can affect cell proliferation and adversely impact palatogenesis. This discovery has broader implications for the understanding of metabolic defects and potential prevention of congenital birth defects. PMID:23975680

  11. Autoimmune polyglandular syndrome type 3 with anorexia.

    PubMed

    Kahara, Toshio; Wakakuri, Hitomi; Takatsuji, Juri; Motoo, Iori; Shima, Kosuke R; Ishikura, Kazuhide; Usuda, Rika; Noda, Yatsugi

    2012-01-01

    A 71-year-old man with diabetes mellitus visited our hospital with complaints of anorexia and weight loss (12 kg/3 months). He had megaloblastic anemia, cobalamin level was low, and autoantibody to intrinsic factor was positive. He was treated with intramuscular cyanocobalamin, and he was able to consume meals. GAD autoantibody and ICA were positive, and he was diagnosed with slowly progressive type 1 diabetes mellitus (SPIDDM). Thyroid autoantibodies were positive. According to these findings, he was diagnosed with autoimmune polyglandular syndrome type 3 with SPIDDM, pernicious anemia, and Hashimoto's thyroiditis. Extended periods of cobalamin deficiency can cause serious complications such as ataxia and dementia, and these complications may not be reversible if replacement therapy with cobalamin is delayed. Although type 1 diabetes mellitus with coexisting pernicious anemia is very rare in Japan, physicians should consider the possibility of pernicious anemia when patients with diabetes mellitus have cryptogenic anorexia with the finding of significant macrocytosis (MCV > 100 fL). PMID:23304573

  12. Histopathological types in adult nephrotic syndrome.

    PubMed

    Yusuf, Md Ghulam; Das, Bidhu Bhushan; Shaha, Amaresh Chandra; Hossain, Md Zakir

    2016-01-01

    In Bangladesh, there are very few studies about biopsy proven adult Nephrotic syndrome (NS) with histological types and their clinical findings. To determine the histological types of glomerulonephritis (GN) in adult NS and correlate them with the clinical presentations and biochemical parameters, we studied 100 biopsies in 87 patients who underwent ultrasonography- guided renal biopsy in Rangpur Medical College and Hospital from July 2010 to June 2012. The mean age of the patients was 32.8 ± 13.2 years; male was preponderance (72.4%) and most of the patients (67.8%) came from rural areas. Membranoproliferative GN (MPGN) was the most common underlying cause that was found in 32 (36.8%) patients followed by mesangial prolife- rative GN in 27 (31%) patients, membranous GN in 16 (18.4%) cases, minimal change disease in four (4.6%) patients, diffuse proliferative GN in four (4.6%) patients, focal segmental GN, and focal proliferative GN in two (2.4%) patients each. High proteinuria level was found in minimal change disease, which was 7.59 ± 0.24 g/24 h (mean ± standard deviation). The most common symptoms were oliguria (92%) and edema (86.2%) followed by hematuria (dark urine) (72.4%) and hypertension (35.6%). MPGN was the most common histological type of adult NS in Rangpur. PMID:27215253

  13. Waardenburg syndrome type 2: an orthodontic perspective.

    PubMed

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

    2015-01-01

    Waardenburg syndrome is a rare form of neurocristopathy. It is a disorder in the development of neural crest cells, caused by an altered cellular migration during the embryonic phase. That alteration causes an association of different abnormalities such as pigmentary disturbances of the hair, iris, skin, stria vascularis of the cochlea, dystopia canthorum and sensorineural hearing loss. We report a case of a 14-year-old Romanian male, with a family history of Waardenburg syndrome (mother) and Usher syndrome (father - congenitally sensorineural hearing loss and retinal degeneration). The case particularities are: the correlation between malocclusion and Waardenburg syndrome due to hypoplastic alae nasi and also factors that produced hearing loss, which could be Waardenburg syndrome, Usher syndrome or the presence of the connexin 26 (W24X) gene mutation. PMID:26429191

  14. Cholesterol and Alzheimer Type Dementia among Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Buckley, Frank

    2008-01-01

    This article reports a summary of research by Warren Zigman and colleagues investigating the link between cholesterol levels and Alzheimer type dementia among adults with Down syndrome. Warren Zigman and colleagues followed 123 adults with Down syndrome between May 1998 and April 2006. The participants were aged between 41 and 78 years at the…

  15. The risk for type B aortic dissection in Marfan syndrome.

    PubMed

    Setacci, C; Galzerano, G; Setacci, F; Mazzitelli, G; de Donato, G; Ricci, C

    2015-12-01

    Marfan syndrome is the most prevalent connective tissue disorder, with an autosomal dominant inheritance with variable penetrance. This paper aims to summarize epidemiology and treatment for type B dissection in Marfan patients. PMID:26350976

  16. Gait Strategy in Patients with Ehlers-Danlos Syndrome Hypermobility Type and Down Syndrome

    ERIC Educational Resources Information Center

    Rigoldi, Chiara; Galli, Manuela; Cimolin, Veronica; Camerota, Filippo; Celletti, Claudia; Tenore, Nunzio; Albertini, Giorgio

    2012-01-01

    People suffering from Ehlers-Danlos syndrome (EDS) hypermobility type present a severe ligament laxity that results in difficulties in muscle force transmission. The same condition is present in people suffering from Down syndrome (DS) even if their clumsy movements are due to cerebral and cognitive impairments. The aim of this study was to…

  17. Type VI Aplasia Cutis Congenita: Bart's Syndrome

    PubMed Central

    Kulalı, Ferit; Bas, Ahmet Yagmur; Kale, Yusuf; Celik, Istemi Han; Demirel, Nihal; Apaydın, Sema

    2015-01-01

    Bart's syndrome is characterized by aplasia cutis congenita and epidermolysis bullosa. We present the case of a newborn male who developed blisters on the mucous membranes and the skin following congenital localized absence of skin. Bart's syndrome (BS) is diagnosed clinically based on the disorder's unique signs and symptoms but histologic evaluation of the skin can help to confirm the final diagnosis. The patient was managed conservatively with topical antibacterial ointment and wet gauze dressing. Periodic follow-up examinations showed complete healing. We emphasized that it is important to use relatively simple methods for optimal healing without the need for complex surgical interventions. PMID:26609453

  18. Nevus comedonicus in oral-facial-digital syndrome type 1: a new finding or overlapping syndromes?

    PubMed

    Baker, Lauren A; Agim, Nnenna G

    2014-01-01

    We report a patient with oral-facial-digital syndrome type 1 (OFDS1) who exhibited features overlapping those of nevus comedonicus syndrome, an unusual presentation that may potentially represent a new variant of OFDS1. OFDS1 and nevus comedonicus syndrome represent two rare syndromes with numerous overlapping features that have yet to be described in relation to one another. The features present in our patient led us to propose the possibility of a new variant of OFDS1 in which nevus comedonicus represents a cutaneous manifestation of the syndrome. Knowledge of this potential relationship is important for identification and management of the syndromes' accompanying manifestations in affected patients and may offer further insight into crossroads of pathogenesis. PMID:24517846

  19. Burning mouth syndrome due to herpes simplex virus type 1.

    PubMed

    Nagel, Maria A; Choe, Alexander; Traktinskiy, Igor; Gilden, Don

    2015-01-01

    Burning mouth syndrome is characterised by chronic orofacial burning pain. No dental or medical cause has been found. We present a case of burning mouth syndrome of 6 months duration in a healthy 65-year-old woman, which was associated with high copy numbers of herpes simplex virus type 1 (HSV-1) DNA in the saliva. Her pain resolved completely after antiviral treatment with a corresponding absence of salivary HSV-1 DNA 4 weeks and 6 months later. PMID:25833911

  20. Cardio-renal syndrome type 5: epidemiology, pathophysiology, and treatment.

    PubMed

    Soni, Sachin S; Ronco, Claudio; Pophale, Rupesh; Bhansali, Ashish S; Nagarik, Amit P; Barnela, Shriganesh R; Saboo, Sonali S; Raman, Anuradha

    2012-01-01

    The cardio-renal syndromes (CRS) recently were defined systematically as disorders of the heart or kidney whereby dysfunction of one organ leads to dysfunction of another. Five types of CRS are defined. The first four types describe acute or chronic cardio-renal or renocardiac syndromes. Type 5 CRS refers to secondary cardio-renal syndrome or cardio-renal involvement in systemic conditions. It is a clinical and pathophysiological entity to describe the concomitant presence of renal and cardiovascular dysfunction. Type 5 CRS can be acute or chronic and it does not strictly satisfy the definition of CRS. However, it encompasses many conditions in which combined heart and kidney dysfunction is observed. Because this entity has been described only recently there is limited information about the epidemiology, clinical course, and treatment of this condition. PMID:22365162

  1. Type 2 leprosy reaction with Sweet's syndrome-like presentation*

    PubMed Central

    Chiaratti, Francielle Chiavelli; Daxbacher, Egon Luiz Rodrigues; Neumann, Antonielle Borges Faria; Jeunon, Thiago

    2016-01-01

    Leprosy is a chronic disease characterized by manifestations in the peripheral nerves and skin. The course of the disease may be interrupted by acute phenomena called reactions. This article reports a peculiar case of type 2 leprosy reaction with Sweet's syndrome-like features as the first clinical manifestation of leprosy, resulting in a delay in the diagnosis due to unusual clinical presentation. The patient had clinical and histopathological features reminiscent of Sweet's syndrome associated with clusters of vacuolated histiocytes containing acid-fast bacilli isolated or forming globi. Herein, it is discussed how to recognize type 2 leprosy reaction with Sweet's syndrome features, the differential diagnosis with type 1 leprosy reaction and the treatment options. When this kind of reaction is the first clinical presentation of leprosy, the correct diagnosis might be not suspected clinically, and established only with histopathologic evaluation. PMID:27438203

  2. Evidence for a fourth locus in Usher syndrome type I.

    PubMed Central

    Gerber, S; Larget-Piet, D; Rozet, J M; Bonneau, D; Mathieu, M; Der Kaloustian, V; Munnich, A; Kaplan, J

    1996-01-01

    Usher syndrome type I (US1) is an autosomal recessive condition in which three different genes have been already localised (USH1A, USH1B, and USH1C on chromosomes 14q32, 11q13, and 11p15 respectively). The genetic heterogeneity of US1 has been confirmed in a previous study by linkage analysis of 20 French pedigrees. Here, we report the genetic exclusion of the three previously reported loci in two large multiplex families of Moroccan and Pakistani origin, suggesting the existence of at least a fourth locus in Usher syndrome type I. PMID:8825055

  3. Mammary-type myofibroblastoma with the nephrotic syndrome

    PubMed Central

    Vankawala, Preksha; Kuperman, Michael B.; Mennel, Robert G.

    2016-01-01

    We describe a 23-year-old white man who presented with anasarca and a new periumbilical mass. He had preserved kidney function and laboratory findings consistent with nephrotic syndrome, including 9.7 g/day albuminuria. Serum serologies were positive for anti-SSa and anti-SSb and low complements but were negative for antinuclear antibody. Pathologic findings of the abdominal mass showed a mammary-type myofibroblastoma. A kidney biopsy revealed a diffuse proliferative and membranous immune-mediated glomerulonephritis with 10% interstitial fibrosis. This is a novel case of mammary-type myofibroblastoma associated with nephrotic syndrome mimicking a proliferative lupus pattern. PMID:27365885

  4. Complex regional pain syndrome after thromboendarterectomy: which type is it?

    PubMed

    Baillet, Georges; Planchon, Claude Alain; Tamgac, Feyzi; Thomassin, Martine; Foult, Jean-Marc

    2002-09-01

    The authors describe a complex regional pain syndrome (CRPS) and discuss its type according to the presence or absence of nerve injury. A patient underwent thromboendarterectomy of the right popliteal artery. Subsequently, right lower limb reflex sympathetic dystrophy developed, which was confirmed by scintigraphy and responded well to calcitonin treatment. Typing according to the new classification of CRPS type I or II with possible nerve injury is discussed, and a short review of the literature is included. PMID:12192276

  5. Ehlers-danlos syndrome-hypermobility type and hemorrhoids.

    PubMed

    Plackett, Timothy P; Kwon, Edward; Gagliano, Ronald A; Oh, Robert C

    2014-01-01

    Ehlers-Danlos syndrome-hypermobility type (EDS-HT) is a connective tissue disorder associated with chronic musculoskeletal pain. The diagnosis is based on simple clinical examination, although it is easily overlooked. Herein we present a case of EDS-HT associated with hemorrhoids and suggest that there may be an association between the two conditions. PMID:24839575

  6. Free flap transfer for complex regional pain syndrome type II

    PubMed Central

    Matsuda, Ken; Kikuchi, Mamoru; Murase, Tsuyoshi; Hosokawa, Ko; Shibata, Minoru

    2014-01-01

    Abstract A patient with complex regional pain syndrome type II was successfully treated using free anterolateral thigh flap transfer with digital nerve coaptation to the cutaneous nerve of the flap. Release of the scarred tissue and soft tissue coverage with targeted sensory nerve coaptation were useful in relieving severe pain.

  7. Bilateral Horner's syndrome in cluster type headaches.

    PubMed

    Khurana, R K

    1993-09-01

    A patient with cluster type headaches demonstrated bilateral and alternating ocular sympathetic dysfunction during a spontaneous as well as a nitroglycerin-induced attack. Biochemical evaluation revealed postganglionic pupillary dysfunction on the symptomatic side and preganglionic pupillary dysfunction contralaterally. These findings defy a simple explanation regarding a central or peripheral origin of the oculocephalic sympathetic dysfunction. PMID:8262788

  8. Management of pregnancy in Crigler Najjar syndrome type 2

    PubMed Central

    Chaubal, Alisha Nitin; Patel, Ruchir; Choksi, Dhaval; Shah, Kaivan; Ingle, Meghraj; Sawant, Prabha

    2016-01-01

    Crigler Najjar syndrome is associated with indirect hyperbilirubinemia due to a deficiency of enzyme Uridine Di Phospho Glucoronosyl Transferase (UDPGT). Presented here is a case of a female in the first trimester of pregnancy, who was diagnosed to have type 2 Crigler Najjar syndrome. We also discuss the management of this rare disease especially in pregnancy. Unconjugated bilirubin can cross the placental barrier causing neurological damage in the newborn. Patient was carefully monitored during pregnancy and treatment with phenobarbitone in low doses was adjusted such that the serum bilirubin levels were below 10 mg/dL. Crigler Najjar syndrome being rare needs to be diagnosed early in pregnancy to avoid adverse fetal outcomes. Phenobarbitone being an inducer of enzyme UDPGT is used as the first line of treatment and is not teratogenic in the low doses used. Treatment protocol followed was on the basis of previous reported cases and successful perinatal outcome was achieved. PMID:27099654

  9. Adult presentation of Bartter syndrome type IV with erythrocytosis

    PubMed Central

    Heilberg, Ita Pfeferman; Tótoli, Cláudia; Calado, Joaquim Tomaz

    2015-01-01

    Abstract Bartter syndrome comprises a group of rare autosomal-recessive salt-losing disorders with distinct phenotypes, but one unifying pathophysiology consisting of severe reductions of sodium reabsorption caused by mutations in five genes expressed in the thick ascending limb of Henle, coupled with increased urinary excretion of potassium and hydrogen, which leads to hypokalemic alkalosis. Bartter syndrome type IV, caused by loss-of-function mutations in barttin, a subunit of chloride channel CLC-Kb expressed in the kidney and inner ear, usually occurs in the antenatal-neonatal period. We report an unusual case of late onset presentation of Bartter syndrome IV and mild phenotype in a 20 years-old man who had hypokalemia, deafness, secondary hyperparathyroidism and erythrocytosis. PMID:26537508

  10. Occurrence of Parkinson's syndrome in type I Gaucher disease.

    PubMed

    Neudorfer, O; Giladi, N; Elstein, D; Abrahamov, A; Turezkite, T; Aghai, E; Reches, A; Bembi, B; Zimran, A

    1996-09-01

    Gaucher disease, the most prevalent glycolipid storage disorder, is classically subdivided into types according to the presence or absence of neurological involvement. Type I has hitherto been considered non-neuronopathic. We present six cases and a review of the literature of Parkinsonian symptoms in type I Gaucher disease patients. The hallmark of this atypical Parkinsonian syndrome is a relatively severe clinical course with early appearance of neurological signs in the 4th to 6th decade of life, aggressive progression of the signs and refractoriness to conventional anti-Parkinson therapy. We discuss the implications of these findings in the light of enzyme replacement therapy for Gaucher disease. PMID:8917744

  11. Eosinophilia associated with disorders of immune deficiency or immune dysregulation

    PubMed Central

    Williams, Kelli W.; Milner, Joshua D.; Freeman, Alexandra F.

    2015-01-01

    Synopsis Elevated serum eosinophil levels have been associated with multiple disorders of immune deficiency or immune dysregulation. Although primary immunodeficiency diseases (PIDD) are rare, it is important to consider these in the differential diagnosis of patients with eosinophilia. This review discusses the clinical features, laboratory findings, diagnosis, and genetic basis of disease of several disorders of immune deficiency or dysregulation – all which have documented eosinophilia as part of the syndrome. The article includes autosomal dominant hyper IgE syndrome, DOCK8 deficiency, PGM3 deficiency, ADA-SCID, Omenn syndrome, Wiskott-Aldrich syndrome, Loeys-Dietz syndrome, autoimmune lymphoproliferative syndrome, immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, Comel-Netherton syndrome, and severe dermatitis, multiple allergies, and metabolic wasting syndrome (SAM). PMID:26209898

  12. Eosinophilia Associated with Disorders of Immune Deficiency or Immune Dysregulation.

    PubMed

    Williams, Kelli W; Milner, Joshua D; Freeman, Alexandra F

    2015-08-01

    Increased serum eosinophil levels have been associated with multiple disorders of immune deficiency or immune dysregulation. Although primary immunodeficiency diseases are rare, it is important to consider these in the differential diagnosis of patients with eosinophilia. In this review, the clinical features, laboratory findings, diagnosis, and genetic basis of disease of several disorders of immune deficiency or dysregulation are discussed. The article includes autosomal dominant hyper IgE syndrome, DOCK8 deficiency, phosphoglucomutase 3 deficiency, ADA-SCID, Omenn syndrome, Wiskott-Aldrich syndrome, Loeys-Dietz syndrome, autoimmune lymphoproliferative syndrome, immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, Comel-Netherton syndrome, and severe dermatitis, multiple allergies, and metabolic wasting syndrome. PMID:26209898

  13. DRESS syndrome associated with type 2 diabetes in a child

    PubMed Central

    Erdem, Semiha Bahceci; Bag, Ozlem; Karkiner, Canan Sule Unsal; Korkmaz, Huseyin Anil; Can, Demet

    2016-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon, life-threatening drug reaction. The basic findings are skin rash, multiorgan involvement, and eosinophilia. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital and carbamazepine can induce DRESS. Herein we report a 14-year-old patient with DRESS syndrome related to carbamazepine use. The patient presented with signs of involvement of the skin, lungs, liver, and microscopic hematuria. Carbamazepine treatment was discontinued; antihistamines and steroids were started. Hyperglycemia, commencing on the first dose of the steroid given, persisted even after the discontinuation of steroids and improvement of other signs. There were no signs of pancreatitis or type 1 diabetes clinically in laboratory tests. Her blood glucose levels were regulated at first with insulin and later with metformin. Within 1 year of follow-up, still regulated with oral antidiabetics, she has been diagnosed with type 2 diabetes. Formerly, long-term sequelae related to “drug rash with eosinophilia and systemic symptoms syndrome” such as hepatic and renal failure, type 1 diabetes mellitus, Grave's disease, autoimmune hemolytic anemia, and lupus have also been reported. However, up to date, no cases with type 2 diabetes have been reported as long-term sequelae. To our knowledge, this is the first case in the literature presenting with type 2 diabetes as long-term sequelae. PMID:26862317

  14. Polyglandular autoimmune syndrome type I among Iranian Jews.

    PubMed Central

    Zlotogora, J; Shapiro, M S

    1992-01-01

    Polyglandular autoimmune syndrome (PAS) has been well characterised and the accepted criteria for diagnosis are the presence of at least two of the three major components: hypoparathyroidism (HPT), candidiasis, and adrenal insufficiency (AI). HPT may, however, be the only manifestation of the syndrome. Iranian Jews, having a high rate of consanguinity, appear to be a community in which PAS type I is frequent. We report on 19 families of patients with HPT from the Iranian Jewish community assuming that they are in fact affected with PAS type I. In the 19 families, 23 patients were affected, including 11 males and 12 females. All the patients but one had HPT (96%), and most were diagnosed by the age of 20 years (91%). AI was diagnosed in five of our patients; in all cases but one it appeared after HPT. Mild oral candidiasis was present in four patients and six of the patients (three males and three females) had hypogonadism. Other features of the syndrome found in some of our patients were pernicious anaemia, hypothyroidism, and alopecia. The disease is autosomal recessive and the calculated prevalence among the Iranian Jews is 1:6500 to 1:9000. The disease is also found with a very high incidence among Finns. A comparison of the symptoms between the two groups showed clinical differences including the relative rarity of candidiasis and absence of keratopathy among the Iranian Jews. PMID:1453436

  15. Acrocephalopolysyndactyly type II--Carpenter syndrome: clinical spectrum and an attempt at unification with Goodman and Summit syndromes.

    PubMed

    Cohen, D M; Green, J G; Miller, J; Gorlin, R J; Reed, J A

    1987-10-01

    Carpenter syndrome (ACPS type II) was first described by Carpenter in 1901. The syndrome consists of acrocephaly, soft tissue syndactyly, brachy- or agenesis mesophalangy of the hands and feet, preaxial polydactyly, congenital heart disease, mental retardation, hypogenitalism, obesity, and umbilical hernia. Here we review the literature on Carpenter syndrome and add 2 affected sibs with marked intrafamilial variability. This review showed that 2 reported variations of Carpenter syndrome, Goodman and Summitt syndromes, actually fall within the clinical spectrum of this disorder. This confirms earlier suggestions of Gorlin (personal communication 1982) and Hall et al [Am J Med Genet 5:423-434, 1980]. PMID:3322002

  16. Respiratory complications of Ehlers-Danlos syndrome type IV.

    PubMed

    Hatake, Katsuhiko; Morimura, Yoshifumi; Kudo, Risa; Kawashima, Wataru; Kasuda, Shogo; Kuniyasu, Hiroki

    2013-01-01

    We describe a case of Ehlers-Danlos syndrome (EDS) type IV in a male in early half in his twenties, who experienced recurrent and eventually fatal pulmonary hemorrhage. EDS type IV is a rare disorder of type III collagen synthesis that is characterized by unusual facies, thin translucent skin with a venous vascular pattern, easy bruising, and hypermobility of the small joints. Autopsy findings showed hypermobility of the joints and distensibility of the skin. Microscopically, the abdominal skin showed substantially decreased dermal thickness. Moreover, the reticular dermis showed fine collagen bundles and large interstitial spaces compared with the skin from a normal control that showed large collagen bundles. Individual elastic fibers were also thicker than those observed in the skin of a normal control. The thoracic aorta showed thin adventitia and a relative increase in elastic fibers. The parenchyma of both the lungs showed markedly diffuse hemorrhage with hemosiderin-laden alveolar macrophages or old thrombi and organized thrombi in the small bronchi. Furthermore, both sections of the lung showed multiple fibrous nodules containing benign metaplastic bone. Vascular wall disruption and tearing of the vessel walls in the lung parenchyma were also observed. We concluded that EDS type IV led to the patient's death because of pulmonary hemorrhage. Because this syndrome resulted in the patient's death from arterial and bowel rupture, it is important to consider EDS as a potential cause of sudden death. PMID:22940417

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

    PubMed

    Rajyalakshmi, R; Chakrapani, R N B

    2016-01-01

    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. PMID:26960655

  18. Advances in the Pathogenesis of Cardiorenal Syndrome Type 3

    PubMed Central

    Clementi, Anna; Virzì, Grazia Maria; Brocca, Alessandra; de Cal, Massimo; Pastori, Silvia; Clementi, Maurizio; Granata, Antonio; Vescovo, Giorgio; Ronco, Claudio

    2015-01-01

    Cardiorenal syndrome (CRS) type 3 is a subclassification of the CRS whereby an episode of acute kidney injury (AKI) leads to the development of acute cardiac injury or dysfunction. In general, there is limited understanding of the pathophysiologic mechanisms involved in CRS type 3. An episode of AKI may have effects that depend on the severity and duration of AKI and that both directly and indirectly predispose to an acute cardiac event. Experimental data suggest that cardiac dysfunction may be related to immune system activation, inflammatory mediators release, oxidative stress, and cellular apoptosis which are well documented in the setting of AKI. Moreover, significant derangements, such as fluid and electrolyte imbalance, metabolic acidosis, and uremia, which are typical features of acute kidney injury, may impair cardiac function. In this review, we will focus on multiple factors possibly involved in the pathogenesis issues regarding CRS type 3. PMID:25821551

  19. Ehlers-Danlos Syndrome Type IV with Bilateral Pneumothorax.

    PubMed

    Nakagawa, Hiroaki; Wada, Hiroshi; Hajiro, Takashi; Nagao, Taishi; Ogawa, Emiko; Hatamochi, Atsushi; Tanaka, Toshihiro; Nakano, Yasutaka

    2015-01-01

    A 17-year-old teen was hospitalized with bilateral pneumothorax. After the bilateral lungs were expanded using catheter tubes, he fully recovered and he was discharged from our hospital. He had a history of colon perforation. Ehlers-Danlos syndrome (EDS) was suspected due to the combination of colon perforation and pneumothorax, and EDS type IV was confirmed after a genetic study identified a c.1511g>a mutation in the COL3A1 gene. This is the first report of bilateral pneumothorax caused by EDS type IV. Clinicians should consider EDS type IV in the differential diagnosis for bilateral pneumothorax in conjunction with distinct previous histories and radiological findings. PMID:26666608

  20. Thoracic aortic aneurysms and pregnancy.

    PubMed

    Coulon, Capucine

    2015-11-01

    Half of acute aortic dissection in women under the age of 40 occurs during pregnancy or peripartum period. Marfan syndrome is the most common syndromic presentation of ascending aortic aneurysm, but other syndromes such as vascular Ehlers-Danlos syndrome, Loeys-Dietz syndrome and Turner syndrome also have ascending aortic aneurysms and the associated cardiovascular risk of aortic dissection and rupture. Management of aortic root aneurysm has been established in recent recommendations, even if levels of evidence are weak. Pregnancy and postpartum period should be followed very closely and determined to be at high risk. Guidelines suggest that women with aortopathy should be counseled against the risk of pregnancy and about the heritable nature of the disease prior to pregnancy. PMID:26454306

  1. The Expanding Clinical Spectrum of Extracardiovascular and Cardiovascular Manifestations of Heritable Thoracic Aortic Aneurysm and Dissection.

    PubMed

    Bradley, Timothy J; Bowdin, Sarah C; Morel, Chantal F J; Pyeritz, Reed E

    2016-01-01

    More than 30 heritable conditions are associated with thoracic aortic aneurysm and dissection (TAAD). Heritable syndromic conditions, such as Marfan syndrome, Loeys-Dietz syndrome, and vascular Ehlers-Danlos syndrome, have somewhat overlapping systemic features, but careful clinical assessment usually enables a diagnosis that can be validated with genetic testing. Nonsyndromic FTAAD can also occur and in 20%-25% of these probands mutations exist in genes that encode elements of the extracellular matrix, signalling pathways (especially involving transforming growth factor-β), and vascular smooth muscle cytoskeletal and contractile processes. Affected individuals with either a syndromic presentation or isolated TAAD can have mutations in the same gene. In this review we focus on the genes currently known to have causal mutations for syndromic and isolated FTAAD and outline the range of associated extracardiovascular and cardiovascular manifestations with each. PMID:26724513

  2. Type 1 diabetes and polyglandular autoimmune syndrome: A review

    PubMed Central

    Hansen, Martin P; Matheis, Nina; Kahaly, George J

    2015-01-01

    Type 1 diabetes (T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well described. In addition, the putative susceptibility genes for T1D as a monoglandular disease and the relation to polyglandular autoimmune syndrome (PAS) have also been well explored. The incidence of T1D has steadily increased in most parts of the world, especially in industrialized nations. T1D is frequently associated with autoimmune endocrine and non-endocrine diseases and patients with T1D are at a higher risk for developing several glandular autoimmune diseases. Familial clustering is observed, which suggests that there is a genetic predisposition. Various hypotheses pertaining to viral- and bacterial-induced pancreatic autoimmunity have been proposed, however a definitive delineation of the autoimmune pathomechanism is still lacking. In patients with PAS, pancreatic and endocrine autoantigens either colocalize on one antigen-presenting cell or are expressed on two/various target cells sharing a common amino acid, which facilitates binding to and activation of T cells. The most prevalent PAS phenotype is the adult type 3 variant or PAS type III, which encompasses T1D and autoimmune thyroid disease. This review discusses the findings of recent studies showing noticeable differences in the genetic background and clinical phenotype of T1D either as an isolated autoimmune endocrinopathy or within the scope of polyglandular autoimmune syndrome. PMID:25685279

  3. Clinical findings in obligate carriers of type I Usher syndrome

    SciTech Connect

    Wagenaar, M.; Rahe, B. ter; Aarem, A. van; Huygen, P.; Admiraal, R.

    1995-11-20

    Seventeen obligate carriers from nine families with autosomal recessive Usher syndrome type I underwent otological, audiological, vestibular, and ophthalmological examination in order to identify possible manifestations of heterozygosity. Linkage studies were performed and six families showed linkage to chromosome region 11q13.5 while 3 families have so far failed to show linkage to the candidate regions. Eight obligate carriers had an abnormal puretone audiogram. Two different audiometric patterns could be distinguished when hearing loss was corrected for age and sex. Four carriers (24%) had significant sensorineural hearing loss (SNHL) which increased at higher frequencies. The other 13 carriers had SNHL of about 10 dB at 0.25 and 0.5 kHz, but less at higher frequencies. Vestibular findings were generally normal. Electrooculography demonstrated a significant lower mean light peak/dark trough ratio in Usher type I carriers compared to normal control individuals. The methods used in this study were found not to be specific enough to clinically identify carriers of Usher type I syndrome. Nevertheless it is remarkable that a number of obligate carriers showed significant audiological and ophthalmological abnormalities. 29 refs., 1 fig., 3 tabs.

  4. Paradoxical hypertension and salt wasting in Type II Bartter syndrome.

    PubMed

    Chan, Winnie Kwai-Yu; To, Ka Fai; Tong, Joanna H M; Law, Chi Wai

    2012-06-01

    Ante/neonatal Bartter syndrome (BS) is a rare hereditary disorder. It is characterized by renal salt wasting, hypokalaemic metabolic alkalosis, high renin and aldosterone but normal blood pressure. We report a low birth weight newborn baby who presented with repeated apnoea shortly after birth as well as hyponatraemia, hypochloraemia, hyperkalaemia and metabolic acidosis. Her biochemical features mimicked pseudohypoaldosteronism but with initial hypertension, which had not been described in BS. Her subsequent genetic study confirmed two novel heterozygous mutations in the Exon 5 of KCNJ1 compatible with Type II BS. PMID:26069767

  5. Skeletal abnormalities of tricho-rhino-phalangeal syndrome type I.

    PubMed

    de Barros, Guilherme Monteiro; Kakehasi, Adriana Maria

    2016-01-01

    The tricho-rhino-phalangeal syndrome (TRPS) type I is a rare genetic disorder related to the TRPS1 gene mutation in chromosome 8, characterized by craniofacial abnormalities and disturbances in formation and maturation of bone matrix. The hallmarks are sparse and brittle hair, tendency to premature baldness, bulbous nose called pear-shaped, long and flat filter and low ear implantation. The most noticeable skeletal changes are clinodactyly, phalangeal epiphyses of the hands appearing as cone-shaped, short stature and hip joint malformations. We report a case of a teenager boy diagnosed with TRPS and referred for rheumatologic evaluation due to joint complaints. PMID:27267340

  6. Difficulty eating and significant weight loss in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

    PubMed

    Baeza-Velasco, Carolina; Van den Bossche, Thomas; Grossin, Daniel; Hamonet, Claude

    2016-06-01

    Joint Hypermobility Syndrome, also known as Ehlers-Danlos Syndrome Hypermobility Type (JHS/EDS-HT), is a heritable disorder of connective tissue, common but poorly known by the medical community. Although generalized joint hypermobility and fragility of tissues have been described as core features, recent research highlights the multisystemic nature of JHS/EDS-HT, which presents with a wide range of articular and extra-articular symptoms. Among these, gastrointestinal problems, temporomandibular disorders, and smell and taste abnormalities are common among those affected, having significant implications for eating. The present work reviews the literature linking JHS/EDS-HT and eating problems. Two illustrative case reports, in which JHS/EDS-HT manifestations contribute to developing and maintaining disturbed eating behaviors and significant weight loss, are presented. PMID:26506923

  7. A neurodystrophic syndrome resembling carbohydrate-deficient glycoprotein syndrome type III.

    PubMed

    Stibler, H; Gylje, H; Uller, A

    1999-04-01

    A 10-month old girl is described with a serum transferrin isoform abnormality of the same kind as in two previously reported girls with carbohydrate-deficient glycoprotein syndrome type III. This patient presented with joint abnormalities and rapidly developing hypsarrhythmia, hypotonia, psychomotor delay and growth retardation. Fingers, toes, nails and local skin were dysmorphic. She had pale optic discs, thoracic syringomyelia and frontal lobe atrophy at three months. The CDT value in serum was greatly elevated. Several carbohydrate-deficient isoforms were found in transferrin (four), alpha1-antitrypsin (three), antithrombin (two) and thyroxine-binding globulin (four). Mutations in the CDGS 1-gene were excluded. The CDGS III glycoprotein abnormality most probably represents a distinct disorder of glycoprotein metabolism, and needs to be considered in unclear hypsarrhythmia with developmental delay. Dysmorphic features may be added to this syndrome. PMID:10401691

  8. Ehlers-Danlos Syndrome Type IV: A Case Report.

    PubMed

    Soo-Hoo, Sarah; Porten, Brandon R; Engstrom, Bjorn I; Skeik, Nedaa

    2016-04-01

    Ehlers-Danlos syndrome (EDS) encompasses a group of rare genetic connective tissue disorders. The vascular type (type IV) poses the most serious risk to patients. Diagnosis is usually difficult, especially if patients lack a family history. Life-threatening vascular emergency such as dissection or rupture can be the first presenting symptom. Management of the disease can pose a clinical challenge due to the emergency of presentation, tissue friability, and lack of clear management recommendations. We report a unique case of a 40-year-old man who presented with a ruptured celiac artery and a strong family history of EDS. This case highlights the difficulties and complications associated with treating this uncommon and serious disease. PMID:26975607

  9. Anisometropic amblyopia in a case of type 2 Waardenburg syndrome.

    PubMed

    Akal, Ali; Göncü, Tugba; Boyaci, Nurefsan; Yılmaz, Ömer Faruk

    2013-01-01

    This study presents a case of an 8-year-old boy with iris heterochromia and anisometropic amblyopia who was diagnosed with Waardenburg syndrome (WS) type 2. An ophthalmic examination revealed iris heterochromia and anisometropic amblyopia in our patient. In the systemic examination, a white forelock and vitiligo on the arms and body were observed and neurosensory hearing loss was revealed, for which the patient used hearing aids. Identification and typing of patients with WS is crucial to address neurosensory hearing loss, glaucoma and fundus changes. While it might be challenging to communicate with a patient with speech and hearing problems, visual acuity should be examined carefully and probable amblyopia should be identified. Anterior segment changes and signs of glaucoma should also be evaluated in detail. PMID:24351514

  10. Generalized joint hypermobility, joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type.

    PubMed

    Castori, Marco; Colombi, Marina

    2015-03-01

    This issue of the American Journal of Medical Genetics Seminar Series Part C is dedicated to generalized joint hypermobility (gJHM), joint hypermobility syndrome (JHS), and Ehlers-Danlos syndrome, hypermobility type (EDS-HT). gJHM is the best known clinical manifestation of inherited defects of the connective tissue. On the other side, JHS and EDS-HT are actually considered one and the same from a clinical perspective by most practitioners and researchers (i.e., JHS/EDS-HT), and their molecular basis remains unknown. For decades, "non-syndromic" gJHM and JHS/EDS-HT have been thought to be simple clinical curiosities or an asset for the "affected" individual. In recent years, the attention on these partially overlapping phenotypes has increased, as they are now recognized risk factors for a series of non-communicable diseases and long-term disabilities. This series consists of 10 papers focused on three main topics, namely (i) assessment and differential diagnosis of children and adults with gJHM, (ii) systematic presentation of selected key non-articular manifestations of JHS/EDS-HT and actual perception of physiotherapy as the best therapeutic resource for this condition, and (iii) exploration of the available knowledge relating "congenital laxity of tissues" to various dysfunctions of the nervous system during development and adulthood. The contributors hope that this collection raises attention to this fascinating field of knowledge, which seems to have ramifications in virtually all medical disciplines. PMID:25821089

  11. Relationship between fatigue and gait abnormality in joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type.

    PubMed

    Celletti, Claudia; Galli, Manuela; Cimolin, Veronica; Castori, Marco; Albertini, Giorgio; Camerota, Filippo

    2012-01-01

    Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterised by joint hypermobility, skin hyperextensibility and tissue fragility. It has recently been shown that muscle weakness occurs frequently in EDS, and that fatigue is a common and clinically important symptom. The aim of this study was to investigate the relationship between fatigue severity and the gait pattern using 3D Gait Analysis (GA). Eleven individuals with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility type (JHS/EDS-HT) were investigated using muscle strength measured with standardised questionnaire measuring fatigue (Fatigue Severity Scale, FSS) and quantitative 3D GA. Our data showed that FSS value well correlated with the peak of vertical component of ground reaction force (r=-0.66, p<0.05). The negative correlation gives evidence that the higher the fatigue is the more reduced force is during gait. Our results showed that the ground reaction force has been applied as a functional evaluation score for detecting pathology in gait of JHS/EDS-HT participants and the found correlation between vertical force and fatigue demonstrated that muscle fatigue may be associated with a loss of proprioceptive acuity in lower limb muscles. PMID:22819599

  12. Mutations in PIEZO2 Cause Gordon Syndrome, Marden-Walker Syndrome, and Distal Arthrogryposis Type 5

    PubMed Central

    McMillin, Margaret J.; Beck, Anita E.; Chong, Jessica X.; Shively, Kathryn M.; Buckingham, Kati J.; Gildersleeve, Heidi I.S.; Aracena, Mariana I.; Aylsworth, Arthur S.; Bitoun, Pierre; Carey, John C.; Clericuzio, Carol L.; Crow, Yanick J.; Curry, Cynthia J.; Devriendt, Koenraad; Everman, David B.; Fryer, Alan; Gibson, Kate; Giovannucci Uzielli, Maria Luisa; Graham, John M.; Hall, Judith G.; Hecht, Jacqueline T.; Heidenreich, Randall A.; Hurst, Jane A.; Irani, Sarosh; Krapels, Ingrid P.C.; Leroy, Jules G.; Mowat, David; Plant, Gordon T.; Robertson, Stephen P.; Schorry, Elizabeth K.; Scott, Richard H.; Seaver, Laurie H.; Sherr, Elliott; Splitt, Miranda; Stewart, Helen; Stumpel, Constance; Temel, Sehime G.; Weaver, David D.; Whiteford, Margo; Williams, Marc S.; Tabor, Holly K.; Smith, Joshua D.; Shendure, Jay; Nickerson, Deborah A.; Bamshad, Michael J.

    2014-01-01

    Gordon syndrome (GS), or distal arthrogryposis type 3, is a rare, autosomal-dominant disorder characterized by cleft palate and congenital contractures of the hands and feet. Exome sequencing of five GS-affected families identified mutations in piezo-type mechanosensitive ion channel component 2 (PIEZO2) in each family. Sanger sequencing revealed PIEZO2 mutations in five of seven additional families studied (for a total of 10/12 [83%] individuals), and nine families had an identical c.8057G>A (p.Arg2686His) mutation. The phenotype of GS overlaps with distal arthrogryposis type 5 (DA5) and Marden-Walker syndrome (MWS). Using molecular inversion probes for targeted sequencing to screen PIEZO2, we found mutations in 24/29 (82%) DA5-affected families and one of two MWS-affected families. The presence of cleft palate was significantly associated with c.8057G>A (Fisher’s exact test, adjusted p value < 0.0001). Collectively, although GS, DA5, and MWS have traditionally been considered separate disorders, our findings indicate that they are etiologically related and perhaps represent variable expressivity of the same condition. PMID:24726473

  13. Chronic pain in hypermobility syndrome and Ehlers–Danlos syndrome (hypermobility type): it is a challenge

    PubMed Central

    Scheper, Mark C; de Vries, Janneke E; Verbunt, Jeanine; Engelbert, Raoul HH

    2015-01-01

    Generalized joint hypermobility (GJH) is highly prevalent among patients diagnosed with chronic pain. When GJH is accompanied by pain in ≥4 joints over a period ≥3 months in the absence of other conditions that cause chronic pain, the hypermobility syndrome (HMS) may be diagnosed. In addition, GJH is also a clinical sign that is frequently present in hereditary diseases of the connective tissue, such as the Marfan syndrome, osteogenesis imperfecta, and the Ehlers–Danlos syndrome. However, within the Ehlers–Danlos spectrum, a similar subcategory of patients having similar clinical features as HMS but lacking a specific genetic profile was identified: Ehlers–Danlos syndrome hypermobility type (EDS-HT). Researchers and clinicians have struggled for decades with the highly diverse clinical presentation within the HMS and EDS-HT phenotypes (Challenge 1) and the lack of understanding of the pathological mechanisms that underlie the development of pain and its persistence (Challenge 2). In addition, within the HMS/EDS-HT phenotype, there is a high prevalence of psychosocial factors, which again presents a difficult issue that needs to be addressed (Challenge 3). Despite recent scientific advances, many obstacles for clinical care and research still remain. To gain further insight into the phenotype of HMS/EDS-HT and its mechanisms, clearer descriptions of these populations should be made available. Future research and clinical care should revise and create consensus on the diagnostic criteria for HMS/EDS-HT (Solution 1), account for clinical heterogeneity by the classification of subtypes within the HMS/EDS-HT spectrum (Solution 2), and create a clinical core set (Solution 3). PMID:26316810

  14. Chronic pain in hypermobility syndrome and Ehlers-Danlos syndrome (hypermobility type): it is a challenge.

    PubMed

    Scheper, Mark C; de Vries, Janneke E; Verbunt, Jeanine; Engelbert, Raoul Hh

    2015-01-01

    Generalized joint hypermobility (GJH) is highly prevalent among patients diagnosed with chronic pain. When GJH is accompanied by pain in ≥4 joints over a period ≥3 months in the absence of other conditions that cause chronic pain, the hypermobility syndrome (HMS) may be diagnosed. In addition, GJH is also a clinical sign that is frequently present in hereditary diseases of the connective tissue, such as the Marfan syndrome, osteogenesis imperfecta, and the Ehlers-Danlos syndrome. However, within the Ehlers-Danlos spectrum, a similar subcategory of patients having similar clinical features as HMS but lacking a specific genetic profile was identified: Ehlers-Danlos syndrome hypermobility type (EDS-HT). Researchers and clinicians have struggled for decades with the highly diverse clinical presentation within the HMS and EDS-HT phenotypes (Challenge 1) and the lack of understanding of the pathological mechanisms that underlie the development of pain and its persistence (Challenge 2). In addition, within the HMS/EDS-HT phenotype, there is a high prevalence of psychosocial factors, which again presents a difficult issue that needs to be addressed (Challenge 3). Despite recent scientific advances, many obstacles for clinical care and research still remain. To gain further insight into the phenotype of HMS/EDS-HT and its mechanisms, clearer descriptions of these populations should be made available. Future research and clinical care should revise and create consensus on the diagnostic criteria for HMS/EDS-HT (Solution 1), account for clinical heterogeneity by the classification of subtypes within the HMS/EDS-HT spectrum (Solution 2), and create a clinical core set (Solution 3). PMID:26316810

  15. Targeted Exon Sequencing in Usher Syndrome Type I

    PubMed Central

    Bujakowska, Kinga M.; Consugar, Mark; Place, Emily; Harper, Shyana; Lena, Jaclyn; Taub, Daniel G.; White, Joseph; Navarro-Gomez, Daniel; Weigel DiFranco, Carol; Farkas, Michael H.; Gai, Xiaowu; Berson, Eliot L.; Pierce, Eric A.

    2014-01-01

    Purpose. Patients with Usher syndrome type I (USH1) have retinitis pigmentosa, profound congenital hearing loss, and vestibular ataxia. This syndrome is currently thought to be associated with at least six genes, which are encoded by over 180 exons. Here, we present the use of state-of-the-art techniques in the molecular diagnosis of a cohort of 47 USH1 probands. Methods. The cohort was studied with selective exon capture and next-generation sequencing of currently known inherited retinal degeneration genes, comparative genomic hybridization, and Sanger sequencing of new USH1 exons identified by human retinal transcriptome analysis. Results. With this approach, we were able to genetically solve 14 of the 47 probands by confirming the biallelic inheritance of mutations. We detected two likely pathogenic variants in an additional 19 patients, for whom family members were not available for cosegregation analysis to confirm biallelic inheritance. Ten patients, in addition to primary disease–causing mutations, carried rare likely pathogenic USH1 alleles or variants in other genes associated with deaf-blindness, which may influence disease phenotype. Twenty-one of the identified mutations were novel among the 33 definite or likely solved patients. Here, we also present a clinical description of the studied cohort at their initial visits. Conclusions. We found a remarkable genetic heterogeneity in the studied USH1 cohort with multiplicity of mutations, of which many were novel. No obvious influence of genotype on phenotype was found, possibly due to small sample sizes of the genotypes under study. PMID:25468891

  16. Acute Type A Aortic Dissection Missed as Acute Coronary Syndrome

    PubMed Central

    Ansari-Ramandi, Mohammad Mostafa; Firoozi, Ata

    2016-01-01

    Although the aortic dissection is not common, its outcome is frequently fatal, and many patients with aortic dissection die before referral to the hospital or any diagnostic testing. The symptoms of aortic dissection can be similar to myocardial ischemia. A 66-year-old male was referred to our hospital with suspicion of aortic dissection after echocardiography done for evaluating his high blood pressure. He had symptoms of acute coronary syndrome two years before and had done coronary angiography. On presentation to our hospital he had a high blood pressure. On reviewing his past medical history and examining, in the film of coronary angiography, the dissection flap in ascending aorta was identified. Although type A aortic dissection is a catastrophic condition with high mortality and requires prompt surgical treatment but in some cases it may be misdiagnosed as acute coronary syndrome. Sometimes against its high mortality when left untreated, patients survive and are diagnosed later in life incidentally. So it is of great importance to have great clinical suspicion for aortic dissection in patients referring to the hospital with chest pain and the predisposing factors. PMID:27437290

  17. [Otoneurologic symptoms associated with Arnold-Chiari syndrome type I].

    PubMed

    Urban, Irena; Namysłowski, Grzegorz; Morawski, Krzysztof; Wojtacha, Maciej

    2004-01-01

    This study presents two cases of Arnold-Chiari malformation type I. In a 26-year old man, right side deafness and left side sensorineural hearing loss at high frequencies occurred. Another patient, a 48-year old man also complained of sensorineural hearing loss and dizziness, that appeared a year and half ago. In addition, this patient had episodes of vertigo with nausea and vomit that occurred about one year before main symptoms. In both patients ENT examinations were performed as well as an audiological diagnostic battery including tonal- and impedance-audiometry, auditory brainstem responses, distortion product otoacoustic emissions and electroencephalography. Magnetic resonance imaging (MRI) showed pathological changes in the cerebello-pontine angle region that allowed diagnosing Arnold-Chiari malformation in both cases. Additionally, angio-MRI performed in patient with right side deafness revealed cochleovestibular nerve compression syndrome on the same side. Presumably, both anomalies occurring simultaneously in this patient might be responsible for deafness in the right ear, instead of mild or moderate hearing loss and tinnitus usually expected according to the literature. The paper presented two cases of Arnold-Chiari malformation with co-existing cochleovestibular nerve compression syndrome in one case. The importance of both audiological diagnostic battery and MRI in diagnostic procedures of this malformation has been demonstrated. PMID:15307473

  18. Hermansky-Pudlak syndrome type 4 with interstitial pneumonia.

    PubMed

    Sakata, Yoshihiko; Kawamura, Kodai; Ichikado, Kazuya; Suga, Moritaka; Yoshioka, Masakazu

    2013-01-01

    Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, bleeding tendency, and lysosomal accumulation of ceroid-like material, with occasional development of interstitial pneumonia (IP). Nine genetically distinct subtypes of HPS are known in humans; IP develops primarily in types 1 and 4. Most reported cases of HPS with IP are type 1, and there are no published reports of type 4 in Japanese individuals. A 58-year-old man with congenital oculocutaneous albinism and progressive dyspnea for 1 month was admitted to our hospital. We administered high-dose corticosteroids on the basis of a diagnosis of acute exacerbation of interstitial pneumonia. Respiratory symptoms and the findings of high-resolution computed tomography (CT) showed improvement. He was diagnosed with HPS type 4 with interstitial pneumonia on the basis of gene analysis. He has been receiving pirfenidone for 1 year and his condition is stable. This is the first report on the use of pirfenidone for HPS with IP caused by a novel mutation in the HPS4 gene. We conclude that HPS should be suspected in patients with albinism and interstitial pneumonia. High-dose corticosteroid treatment may be useful in cases of acute exacerbation of interstitial pneumonia due to HPS-4, and pirfenidone may be useful and well tolerated in patients with HPS-4. PMID:26029628

  19. Acquired hemophilia complicated by cardiorenal syndrome type 3

    PubMed Central

    Sharma, Rakesh; Dash, Sananta Kumar; Chawla, Rajesh; Kansal, Sudha; Agrawal, Devender Kumar; Dua, Harsh

    2013-01-01

    Development of autoantibodies against coagulation factor VIII (FVIII) leads to a rare condition defined as acquired hemophilia (AH). If not diagnosed and treated early, AH may be associated with high mortality and morbidity. A 65-year-old woman presented with history of macrohematuria, acute renal failure, cardiogenic shock, and acute respiratory failure. Blood investigation revealed azotemia, prolonged activated partial thromboplastin time (aPTT), coagulation FVIII level of <1%, and presence of FVIII inhibitor. Echocardiography showed global hypokinesia and ultrasonography and computed tomography (CT) revealed bilateral hydroureteronephrosis. The final diagnosis was acquired hemophilia A, complicated by acute obstructive renal failure and cardiorenal syndrome (CRS) type 3. Patient was managed with mechanical ventilation, heparin-free hemodialysis, negative fluid balance, recombinant activated factor VII, and prednisolone. Hematuria was relieved, renal function improved, and cardiac function showed improvement on repeat echocardiography. Patient was discharged on prednisolone with subsequent follow ups. PMID:24501492

  20. Ehlers-Danlos Syndrome Type VIIC: A Mexican Case Report.

    PubMed

    Rincón-Sánchez, Ana Rosa; Arce, Irma Elia; Tostado-Rabago, Enrique Alejandro; Vargas, Alberto; Padilla-Gómez, Luis Alfredo; Bolaños, Alejandro; Barrios-Guyot, Selenne; Anguiano-Alvarez, Víctor Manuel; Ledezma-Rodríguez, Víctor Chistian; Islas-Carbajal, María Cristina; Rivas-Estilla, Ana María; Feria-Velasco, Alfredo; Dávalos, Nory Omayra

    2012-01-01

    Ehlers-Danlos syndrome (EDS) is a heterogeneous group of heritable connective tissue disorders whose primary clinical features include soft and extensible skin, articular hypermobility and tissue fragility. EDS type VIIC or 'human dermatosparaxis' is an autosomal recessive disease characterized by severe skin fragility and sagging redundant skin (major criteria) with a soft, doughy texture, easy bruising, premature rupture of fetal membranes and large hernias (minor criteria). Dermatosparaxis (meaning 'tearing of skin'), which has been described in several non-human species, is a disorder of the connective tissue resulting from a deficiency of the enzyme that cleaves the registration peptide off the N-terminal end of collagen after it has been secreted from fibroblasts. We describe a Mexican case from consanguineous parents with all the phenotypical characteristics previously described, plus skeletal abnormalities. PMID:22787447

  1. Hypnosis for postpolio syndrome & Type-A behavior.

    PubMed

    Hammond, D C

    1991-07-01

    Many of the hundreds of thousands of survivors of polio are now developing postpolio syndrome. Symptoms include progressive muscle weakness, fatigue, decreased endurance, joint and muscle pain, weight gain, respiratory difficulties, and sleep disturbance, often precipitated or exacerbated by a Type-A Personality pattern. A postpolio patient with Type-A Personality was taught self-hypnosis as a vital component of treatment. Pre-post testing included the Profile of Mood States, the State-Trait Anxiety Inventory, the State-Trait Anger Inventory, and the Personal Orientation Inventory; the patient's spouse was interviewed during the follow-up. At the 6-month follow-up, improvements were documented in pain level, depression, self-regard, self-acceptance, capacity for intimate contact, time competence (living in the present), confusion, anxiety, insomnia, and in trait and state anger. Only a mild improvement occurred in fatigue, and no improvement was found in weight control. Follow-up at 12 months confirmed the maintenance of improvements. Self-hypnosis training may prove extremely helpful for postpolio patients and may prove helpful in modifying central characteristics of Type-A Personality. PMID:1951142

  2. Gastrointestinal and nutritional issues in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

    PubMed

    Castori, Marco; Morlino, Silvia; Pascolini, Giulia; Blundo, Carlo; Grammatico, Paola

    2015-03-01

    Gastrointestinal involvement is a well known complication of Ehlers-Danlos syndromes (EDSs), mainly in form of abdominal emergencies due to intestinal/abdominal vessels rupture in vascular EDS. In the last decade, a growing number of works investigated the relationship between a wide spectrum of chronic gastrointestinal complaints and various EDS forms, among which the hypermobility type (a.k.a. joint hypermobility syndrome; JHS/EDS-HT) was the most studied. The emerging findings depict a major role for gastrointestinal involvement in the health status and, consequently, management of JHS/EDS-HT patients. Nevertheless, fragmentation of knowledge limits its impact on practice within the boundaries of highly specialized clinics. In this paper, literature review on gastrointestinal manifestations in JHS/EDS-HT was carried out and identified papers categorized as (i) case-control/cohort studies associating (apparently non-syndromic) joint hypermobility and gastrointestinal involvement, (ii) case-control/cohort studies associating JHS/EDS-HT and gastrointestinal involvement, (iii) case reports/series on various gastrointestinal complications in (presumed) JHS/EDS-HT, and (iv) studies reporting gastrointestinal features in heterogeneous EDS patients' cohorts. Gastrointestinal manifestations of JHS/EDS-HT were organized and discussed in two categories, including structural anomalies (i.e., abdominal/diaphragmatic hernias, internal organ/pelvic prolapses, intestinal intussusceptions) and functional features (i.e., dysphagia, gastro-esophageal reflux, dyspepsia, recurrent abdominal pain, constipation/diarrhea), with emphasis on practice and future implications. In the second part of this paper, a summary of possible nutritional interventions in JHS/EDS-HT was presented. Supplementation strategies were borrowed from data available for general population with minor modifications in the light of recent discoveries in the pathogenesis of selected JHS/EDS-HT features. PMID

  3. Neurodevelopmental attributes of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type: Update and perspectives.

    PubMed

    Ghibellini, Giulia; Brancati, Francesco; Castori, Marco

    2015-03-01

    In the last decade, increasing attention has been devoted to the extra-articular and extra-cutaneous manifestations of joint hypermobility syndrome, also termed Ehlers-Danlos syndrome, hypermobility type (i.e., JHS/EDS-HT). Despite the fact that the current diagnostic criteria for both disorders remain focused on joint hypermobility, musculoskeletal pain and skin changes, medical practice and research have started investigating a wide spectrum of visceral, neurological and developmental complications, which represent major burdens for affected individuals. In particular, children with generalized joint hypermobility often present with various neurodevelopmental issues and can be referred for neurological consultation. It is common that investigations in these patients yield negative or inconsistent results, eventually leading to the exclusion of any structural neurological or muscle disorder. In the context of specialized clinics for connective tissue disorders, a clear relationship between generalized joint hypermobility and a characteristic neurodevelopmental profile affecting coordination is emerging. The clinical features of these patients tend to overlap with those of developmental coordination disorder and can be associated with learning and other disabilities. Physical and psychological consequences of these additional difficulties add to the chief manifestations of the pre-existing connective tissue disorder, affecting the well-being and development of children and their families. In this review, particular attention is devoted to the nature of the link between joint hypermobility, coordination difficulties and neurodevelopmental issues in children. Presumed pathogenesis and management issues are explored in order to attract more attention on this association and nurture future clinical research. PMID:25654988

  4. Gait strategy in patients with Ehlers-Danlos syndrome hypermobility type and Down syndrome.

    PubMed

    Rigoldi, Chiara; Galli, Manuela; Cimolin, Veronica; Camerota, Filippo; Celletti, Claudia; Tenore, Nunzio; Albertini, Giorgio

    2012-01-01

    People suffering from Ehlers-Danlos syndrome (EDS) hypermobility type present a severe ligament laxity that results in difficulties in muscle force transmission. The same condition is present in people suffering from Down syndrome (DS) even if their clumsy movements are due to cerebral and cognitive impairments. The aim of this study was to quantify the gait patterns of subjects with EDS and with DS using Gait Analysis (GA). We quantified the gait strategy in 12 EDS individuals and in 16 participants with DS. Both pathological groups were compared to 20 age-matched healthy controls in terms of kinematics and kinetics. Results showed that DS individuals are characterized by a more compromised gait pattern than EDS participants, even if both groups are characterized by joint hypermobility. All the patients showed significant decreased of ankle stiffness probably due to congenital hypotonia and ligament laxity, while different values of hip stiffness. These findings help to elucidate the complex biomechanical changes due to joint hypermobility and may have a major role in the multidimensional evaluation and tailored management of these patients. PMID:22522202

  5. Joint hypermobility syndrome (a.k.a. Ehlers-Danlos Syndrome, Hypermobility Type): an updated critique.

    PubMed

    Castori, M

    2013-02-01

    Joint hypermobility syndrome, alternatively termed Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT), is likely the most common, though the least recognized heritable connective tissue disorder. While its leading clinical features typically affect joints, recent evidence indicates a wider spectrum of satellite symptoms/dysfunctions, involving practically all major systems and organs. Accordingly, clinical research on JHS/EDS-HT is moving from rheumatology and clinical genetics to other disciplines, including neurology, clinical psychology, ophthalmology, cardiology and gynecology/obstetrics. As the skin is one of the most commonly affected and, surely, the easiest to assess body part in heritable connective tissue disorders, it is expected that also the dermatologist should be trained to recognize this condition. In this review, JHS/EDS-HT is presented and discussed in separate sections dedicated to all major aspects of diagnosis, differential diagnosis, clinical features, natural history and principles of management. Particular attention is posed on the role of epidermal, dermal and mucosal assessment in JHS/EDS-HT is order to rise the attention to a series of too neglected, though quite common manifestations of this condition. Management principles are presented with a multidisciplinary approach in mind, covering pharmacologic, physical and occupational therapy, surgical, and nutriceutical aspects, as well as general lifestyle recommendations. Connections with organs and systems other than joints and skin are also discussed. PMID:23407074

  6. Four treatment strategies for complex regional pain syndrome type 1.

    PubMed

    Lee, Sang Ki; Yang, Dae Suk; Lee, Jae Won; Choy, Won Sik

    2012-06-01

    Complex regional pain syndrome (CRPS) poses a dilemma for many clinicians due to its unknown etiology and largely unsuccessful treatment modalities. The purpose of this study was to compare the clinical results of 4 treatment modalities for CRPS type 1. A total of 59 patients were divided into 4 groups based on treatment modality: group A, an oral nonsteroidal anti-inflammatory drug (NSAID) (n=10); group B, oral gabapentin (n=12); group C, intravenous (IV) 10% mannitol and steroid (n=11); group D, a combination of IV 20% mannitol and steroid with oral gabapentin (n=26). The patients remained under medical supervision after discharge and were evaluated either once a month or once every 2 months until final follow-up at a mean of 8 months. Patients in group A showed improvement in pain level, finger range of motion, swelling, and grip strength, without statistical significance (P=.076, P=.062, P=.312, and P=.804, respectively). Patients in group B showed significant improvement in pain level (P<.001), and patients in group C showed improvement in pain, finger range of motion, and swelling (P=.127), which rendered functional impairment unchanged. In comparison, patients in group D showed recovery of grip strength and improvement in pain level, finger range of motion, and (P<.001, P=.016, P=.031, and P=.047, respectively). Based on these results, a protocol including a combination of IV 20% mannitol and steroid with oral gabapentin is an acceptable and effective treatment for CRPS type 1. PMID:22691654

  7. Hearing dysfunction in heterozygous Mitf(Mi-wh) /+ mice, a model for Waardenburg syndrome type 2 and Tietz syndrome.

    PubMed

    Ni, Christina; Zhang, Deming; Beyer, Lisa A; Halsey, Karin E; Fukui, Hideto; Raphael, Yehoash; Dolan, David F; Hornyak, Thomas J

    2013-01-01

    The human deafness-pigmentation syndromes, Waardenburg syndrome (WS) type 2a, and Tietz syndrome are characterized by profound deafness but only partial cutaneous pigmentary abnormalities. Both syndromes are caused by mutations in MITF. To illuminate differences between cutaneous and otic melanocytes in these syndromes, their development and survival in heterozygous Microphthalmia-White (Mitf(Mi-wh) /+) mice were studied and hearing function of these mice characterized. Mitf(Mi-wh) /+ mice have a profound hearing deficit, characterized by elevated auditory brainstem response thresholds, reduced distortion product otoacoustic emissions, absent endocochlear potential, loss of outer hair cells, and stria vascularis abnormalities. Mitf(Mi-wh) /+ embryos have fewer melanoblasts during embryonic development than their wild-type littermates. Although cochlear melanocytes are present at birth, they disappear from the Mitf(Mi-wh) /+ cochlea between P1 and P7. These findings may provide insight into the mechanism of melanocyte and hearing loss in human deafness-pigmentation syndromes such as WS and Tietz syndrome and illustrate differences between otic and follicular melanocytes. PMID:23020089

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

    SciTech Connect

    Veith, G.D.; Broderius, S.J. )

    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.

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

    PubMed

    Veith, G D; Broderius, S J

    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. PMID:2269227

  10. Genetic heterogeneity of usher syndrome type 1 in French families

    SciTech Connect

    Larget-Piet, D.; Gerber, S.; Rozet, J.M. ); Bonneau, D. ); Marc, S.; Weissenbach, J. ); Ghazi, I.; Dufier, J.L. ); David, A. ); Bitoun, P. )

    1994-05-01

    Usher syndrome type 1 (US1) is an autosomal recessive disease characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa, and constant vestibular dysfunction. Three localizations have been described in US1: USH1A, 14q32; USH1B, 11q13.5; and USH1C, 11p15. Studying a series of 33 affected individuals belonging to 20 US1 pedigrees of French ancestry, the authors found that none of the three localizations accounted for all US1 families in the series. However, when the sample was split into two groups according to the geographic origin of the probands' grandparents, they were able to confirm the presence of a gene for US1 on chromosome 14q32 (USH1A) in 9 families originating from the Poitou region in Western France. Moreover, they refined the genetic mapping of USH1A by showing that the disease gene maps to the D14S13 locus, within the genetic interval defined by loci D14S78 and D14S250 (location score in log base 10 = 4.90). Consistent with this, nonsignificant lod score values for linkage to either USH1B or USH1C were found in this group. With regard to US1 families of other geographic origin (Normandy and Northern France, 11 families), nonsignificant lod scores for linkage to chromosome 11q13.5 were observed. However, the HOMOG test suggested that USH1B might account for the disease in 9/11 families in the series (families 10-19), the latter two families possibly being accounted for by USH1C (maximum likelihood for heterogeneity = 7.91 in lnL; heterogeneity versus homogeneity, P = 0.01; heterogeneity versus nonlinkage, P < 0.01). The present study supports the view that Usher syndrome type 1 is a genetically heterogeneous condition that is caused by at least three genes and possibly many more. 16 refs., 4 figs., 3 tabs.

  11. Prevalence of metabolic syndrome in type 2 diabetes mellitus patients

    PubMed Central

    Nsiah, Kwabena; Shang, V Owusua; Boateng, K Agyenim; Mensah, FO

    2015-01-01

    Background: The diabetic condition is influenced by several factors, some of which can accelerate the disease's progression to various complications that aggravate the morbidity. Aims: This study aimed at determining the prevalence of metabolic syndrome (MetS) and its individual components and the most critical predictive risk factors of MetS in type 2 diabetic patients. Materials and Methods: This cross-sectional study involved 150 type 2 diabetes mellitus patients and was conducted at the Diabetes Centre of the Komfo Anokye Teaching Hospital in Kumasi, the Ashanti Region of Ghana, from February, 2013 to April, 2013. The study involved the use of a questionnaire to obtain some information on the diabetics, undertaking anthropometric measurements, as well as collecting blood samples for the measurement of some biochemical parameters; fasting blood glucose and lipid profile. MetS was defined according to the National Cholesterol Education Program/Adult Treatment Panel III criteria. Results: The prevalence of MetS was 58% in the studied Ghanaian population. Hypertension was the commonest risk factor (60%), followed by central obesity (48.67%) and dyslipidemia (37%). Female type 2 diabetics had a higher prevalence of MetS, and carried more components than their male counterparts. Regression analysis showed three factors; femininity, high body mass index and low educational status were the most critical predictive risk factors of MetS, according to this study. Conclusion: With hypertension being the commonest component, future cardiovascular disease prevention strategies should focus attention on its management and prevention, through education. PMID:26097823

  12. Evidence based guidelines for complex regional pain syndrome type 1

    PubMed Central

    2010-01-01

    Background Treatment of complex regional pain syndrome type I (CRPS-I) is subject to discussion. The purpose of this study was to develop multidisciplinary guidelines for treatment of CRPS-I. Method A multidisciplinary task force graded literature evaluating treatment effects for CRPS-I according to their strength of evidence, published between 1980 to June 2005. Treatment recommendations based on the literature findings were formulated and formally approved by all Dutch professional associations involved in CRPS-I treatment. Results For pain treatment, the WHO analgesic ladder is advised with the exception of strong opioids. For neuropathic pain, anticonvulsants and tricyclic antidepressants may be considered. For inflammatory symptoms, free-radical scavengers (dimethylsulphoxide or acetylcysteine) are advised. To promote peripheral blood flow, vasodilatory medication may be considered. Percutaneous sympathetic blockades may be used to increase blood flow in case vasodilatory medication has insufficient effect. To decrease functional limitations, standardised physiotherapy and occupational therapy are advised. To prevent the occurrence of CRPS-I after wrist fractures, vitamin C is recommended. Adequate perioperative analgesia, limitation of operating time, limited use of tourniquet, and use of regional anaesthetic techniques are recommended for secondary prevention of CRPS-I. Conclusions Based on the literature identified and the extent of evidence found for therapeutic interventions for CRPS-I, we conclude that further research is needed into each of the therapeutic modalities discussed in the guidelines. PMID:20356382

  13. Risk of Restless Legs Syndrome Following Tension-Type Headache

    PubMed Central

    Yang, Fu-Chi; Lin, Te-Yu; Chen, Hsuan-Ju; Lee, Jiunn-Tay; Lin, Chun-Chieh; Kao, Chia-Hung

    2015-01-01

    Abstract Migraine and restless legs syndrome (RLS) appear to be associated, but the relationship between tension-type headache (TTH) and RLS is unknown. This nationwide, population-based, retrospective cohort study explored the potential association between TTH and RLS. We identified 15,504 patients with newly diagnosed TTH from 2000 to 2007 and 62,016 individuals without TTH who were selected by frequency matched based on sex, age, and the index year. The study participants were followed until diagnosed with RLS, withdrawal from the NHI program, or the end of 2011. Cox proportional hazard models were used to identify risk factors for RLS in TTH patients. After adjusting for sex, age, comorbidity, and medications, TTH was significantly associated with an increased risk of RLS (hazard ratio [HR] = 1.57, 95% confidence interval [CI] = 1.22–2.02). The risk was most prominent in patients aged 20 to 39 years in the TTH group, which exhibited a 2.60-fold higher risk (95% confidence interval = 1.53–4.42) of RLS compared with the non-TTH group. The TTH group had a higher risk of RLS than that of the non-TTH group regardless of sex. Tension-type headache appears to be associated with an increased risk of developing RLS. This similarity to migraines may indicate that headache and RLS have a coincident pathophysiological mechanism, a possibility requiring further study. Clinicians should be more attentive to RLS as a possible comorbidity in patients with TTH. PMID:26579827

  14. Crooked fingers and sparse hair: an interesting case of trichorhinophalangeal syndrome type 1.

    PubMed

    Narayanan, Ramakrishna; Chennareddy, Srinivasa

    2015-01-01

    Trichorhinophalangeal syndrome type 1 is a rare skeletal dysplasia of autosomal-dominant inheritance due to defects in the TRPS-1 gene. The syndrome is characterised by sparse slow-growing hair, a bulbous pear-shaped nose, cone-shaped epiphyses and deformities of the interphalangeal joints resembling those in rheumatoid arthritis. We present a case of trichorhinophalangeal syndrome in a 23-year-old man who presented with symmetrical painless progressive deformity of the fingers in both hands. PMID:25628322

  15. Mucopolysaccharidosis type I Hurler-Scheie syndrome: A rare case report.

    PubMed

    Tatapudi, Ramesh; Gunashekhar, M; Raju, P Suryanarayana

    2011-01-01

    Mucopolysaccharidosis I (MPS I) is a rare inherited disorder that belongs to a group of clinically progressive disorders and is caused by the deficiency of the lysosomal enzyme, α(1)-iduronidase. MPS I has been recently classified into a severe (Hurler syndrome) and an attenuated type (Hurler-Scheie and Scheie syndromes). The purpose of this article was to describe a rare case of MPS type I, attenuated type (Hurler-Scheie) affecting a 15-year-old Indian child. PMID:22114460

  16. Complex regional pain syndrome type 1 in a pediatric patient: Case report

    PubMed Central

    Demirdal, Ümit Seçil; Bükülmez, Ayşegül; Solak, Özlem

    2014-01-01

    Complex regional pain syndrome type 1 is one of the causes of morbidity of childhood which is also named reflex symphathetic dystrophia. The syndrome is characterized with regional pain and vasomotor, sudomotor and sensory changes in the distal parts of the extremities involved. Complex regional pain syndrome type 1 shows difference in children in terms of clinical picture and imaging methods compared to adults. The most important point is that the prognosis is generally better in children if early diagnosis and treatment is provided. On the other hand, causes including presence of psychological factors or less contribution of imaging methods in children lead to delayed diagnosis or erroneous diagnosis. In this article, a 10 year-old male patient who was diagnosed with complex regional pain syndrome type 1 was described. Thus, we aimed to remind clinicians that this syndrome should also be kept in mind in the differential diagnosis of pain in children. PMID:26078637

  17. Association of a congenital long QT syndrome type 1 with Takotsubo cardiomyopathy.

    PubMed

    El-Battrawy, Ibrahim; Behnes, Michael; Borggrefe, Martin; Akin, Ibrahim

    2016-08-01

    The occurrence of takotsubo cardiomyopathy in a patient with congenital long QT syndrome has rarely been described. This case report discusses the occurrence of a clinically overt takotsubo cardiomyopathy accompanied by congenital long QT syndrome type 1 in a female patient. PMID:27525086

  18. Type 1 diabetes: Syndromes in resource-challenged settings.

    PubMed

    Nagesh, V Sri; Kalra, Sanjay

    2015-06-01

    Type 1 Diabetes is a complex disorder that is made more complex by the myriad of co-morbid conditions associated with it. Mauriac Syndrome is a well-known but nowadays uncommon condition that presents with growth retardation secondary to poor glycaemic control. Limited Joint Mobility is an often-missed association of diabetes. Its importance lies in the fact that it can cause significant impairment of fine movements in T1DM children. It also indicates poor glycaemic control over a long period of time and can be used as a surrogate marker for development of diabetic microvascular complications. Anaemia in T1DM is protean and can develop due to a combination of nutritional factors, chronic renal disease, coeliac disease and worm infestation. Management is etiological. Vitamin deficiencies are ubiquitous in T1DM and if left untreated, can lead to neurological, haematological and skeletal dysfunction. The best-known co-morbid conditions are the local site reactions clubbed together under the moniker lipodystrophies. These can be either atrophic or hypertrophic and are usually due to repeated injections at the same site, improper technique and needle re-use. Management is often difficult and they are best prevented by appropriate diabetes education and emphasis on proper injection techniques at the time of T1DM diagnosis, with periodic reinforcement. Amyloidosis is a little known condition that shares a lot of features in common with the lipodystrophies and often needs to be differentiated from lipohypertrophy. T1DM is a disease which is often associated with a poor quality of life and these co-morbid conditions also need to be treated for effective general and psychological well-being. PMID:26060173

  19. Management of patients with complex regional pain syndrome type I.

    PubMed

    Gatti, D; Rossini, M; Adami, S

    2016-08-01

    Complex regional pain syndrome type I (CRPS-I) includes different conditions characterized by regional pain and sensory, motor, sudomotor, vasomotor, and/or trophic findings, affecting a peripheral limb usually after a noxious event, such as a trauma or surgery. The pathophysiology is still poorly understood. Limited data are available on the incidence of CRPS-I, and the disease is underestimated and under-diagnosed. The disease shows a female preponderance approximately 3:1 with a peak age of incidence around the 5th and 6th decade. The available diagnostic criteria for CRPS-I rely on clinical criteria that are unfortunately focused on the signs and symptoms of the chronic and late disease, while little emphasis is given to the typical imaging (X-rays, bone scintigraphy, MRI) findings of the early phase. Over the last decades, several therapies have been proposed but the few studies available are often too small to be conclusive and rarely evolved to randomized controlled trials (RCTs). On the basis of the results of a few RCTs, only short courses of high bisphosphonate doses appear to provide substantial benefits. The best results are seen in patients in the early phase of the disease, often with the persistent remission or complete healing of the conditions. Since the only accredited mechanism of action of bisphosphonates is the suppression of osteoclastic bone resorption, it is likely the initial dramatic bone loss plays a role in the maintenance and evolution of CRPS-I. Short courses of high doses of bisphosphonates should be considered the treatment of choice for patients with CRPS-I. PMID:26928187

  20. Screening of three Usher syndrome type II candidate genes

    SciTech Connect

    Bloemker, B.K.; Swaroop, A.; Kimberling, W.J.

    1994-09-01

    Usher syndrome type II (US2) is an autosomal recessive disorder that results in blindness due to retinitis pigmentosa and congenital hearing loss. The disease affects approximately 1 in 20,000 individuals in the general population and is responsible for over 50% of all cases of deafness with blindness. The underlying US2 defect is unknown. The US2 gene has been localized to the 1q41 region of chromosome 1 by linkage studies. Three genes previously localized to 1q were analyzed to assess their candidacy as the US2 gene. These were evaluated by PCR assays using DNA from a YAC contig spanning the US2 region on chromosome 1. The first gene evaluated was the human choroideremia-like gene (hCHML), which had been mapped to chromosome 1q. The sequence on 1q is a homologue of the human choroideremia gene on chromosome X. Choroideremia is a degenerative disorder causing ocular pathology similar to that observed in US2 patients. Therefore, hCHML is a candidate for the US2 gene. Two cDNAs (A and B) from an enriched human retinal pigment epithelium library have been mapped to 1q41 by in situ hybridization. Both cDNAs are considered good candidates. The hCHML and cDNA A were ruled out as candidates for the US2 gene based on negative results from PCR assays performed on YACs spanning the US2 region. cDNA B could not be ruled out as a candidate for the US2 gene by these assays. Answers to many clinical questions regarding US2 will only be resolved after the gene is identified and characterized. Eventually, understanding the function and expression of the US2 gene will provide a basis for the development of therapy.

  1. Giant bladder diverticulum in Ehlers-Danlos syndrome type I causing outflow obstruction.

    PubMed

    Burrows, N P; Monk, B E; Harrison, J B; Pope, F M

    1998-05-01

    We describe a 16-year-old patient with Ehlers-Danlos syndrome (EDS) type I and recurrent urinary retention caused by giant bladder diverticulum and review the literature on this association. PMID:9861737

  2. The pathogenesis of the clinical features of oral-facial-digital syndrome type I

    PubMed Central

    AlKattan, Wael M.; Al-Qattan, Mohammad M.; Bafaqeeh, Sameer A.

    2015-01-01

    Oral-facial-digital syndrome type I (OFDI) is an X-linked syndrome, which has several craniofacial and limb features; and hence, patients frequently present to craniofacial and plastic surgeons. Oral-facial-digital syndrome type I is caused by mutations in the CXORF5 gene. The gene product is one of the basal body proteins of a slim microtubule-based organelle called the “primary cilium”. Most of the clinical features of OFDI patients are related to dysfunctions of the primary cilium leading to abnormal Hedgehog signal transduction, depressed planar cell polarity pathway, and errors in cell cycle control. PMID:26593159

  3. Semen analysis in the Usher syndrome type 2A.

    PubMed

    van Aarem, A; Wagenaar, M; Tonnaer, E; Pieke Dahl, S; Bisseling, J; Janssen, H; Bastiaans, B; Kimberling, W; Cremers, C

    1999-01-01

    Semen analysis in patients with Usher syndrome suggested that defective connecting cilia axonemes may be involved in the irreversible, progressive loss of photoreceptors in Usher's syndrome. In the framework of clinical genetic research into Usher syndrome, a pilot study was set up to test these findings. The semen of 6 Usher 2A patients was analysed. The fertility status of the study group of Usher 2A patients was evaluated, including semen analysis, supplemented by electron microscopic examination of the spermatozoa. Except for a significantly increased pH value, no abnormalities were found in the functional semen analysis, whereas electron microscopy revealed microtubular tail abnormalities. The latter finding was of little relevance, however, in view of the normal motility of the spermatozoa observed in these patients. There were no fertility problems in our group of Usher 2A patients, nor have any been mentioned in Usher patients in general. Earlier study findings were not supported by our data. PMID:10325550

  4. Type IV Ehlers-Danlos Syndrome: A Surgical Emergency? A Case of Massive Retroperitoneal Hemorrhage.

    PubMed

    Chun, Stephen G; Pedro, Patrick; Yu, Mihae; Takanishi, Danny M

    2011-01-01

    Retroperitoneal hemorrhagic bleeding is a known manifestation of Type-IV Ehlers-Danlos Syndrome that is caused by loss-of-function mutations of the pro-alpha-1 chains of type III pro-collagen (COL3A1) resulting in vascular fragility. A number of previous reports describe futile surgical intervention for retroperitoneal bleeding in Type-IV Ehlers-Danlos Syndrome with high post-operative mortality, although the rarity of retroperitoneal bleeding associated with Type-IV Ehlers-Danlos Syndrome precludes an evidence-based approach to clinical management. We report a 23-year-old male with history of Type-IV Ehlers-Danlos Syndrome who presented with severe abdominal pain and tachycardia following an episode of vomiting. Further work-up of his abdominal pain revealed massive retroperitoneal bleeding by CT-scan of the abdomen. Given numerous cases of catastrophic injury caused by surgical intervention in Type-IV Ehlers-Danlos Syndrome, the patient was treated non-operatively, and the patient made a full recovery. This case suggests that even in cases of large retroperitoneal hemorrhages associated with Ehlers-Danlos Syndrome, it may not truly represent a surgical emergency. PMID:21966332

  5. 15 YEARS OF PARAGANGLIOMA: Clinical manifestations of paraganglioma syndromes types 1–5

    PubMed Central

    Benn, Diana E; Robinson, Bruce G; Clifton-Bligh, Roderick J

    2015-01-01

    The paraganglioma (PGL) syndromes types 1–5 are autosomal dominant disorders characterized by familial predisposition to PGLs, phaeochromocytomas (PCs), renal cell cancers, gastrointestinal stromal tumours and, rarely, pituitary adenomas. Each syndrome is associated with mutation in a gene encoding a particular subunit (or assembly factor) of succinate dehydrogenase (SDHx). The clinical manifestations of these syndromes are protean: patients may present with features of catecholamine excess (including the classic triad of headache, sweating and palpitations), or with symptoms from local tumour mass, or increasingly as an incidental finding on imaging performed for some other purpose. As genetic testing for these syndromes becomes more widespread, presymptomatic diagnosis is also possible, although penetrance of disease in these syndromes is highly variable and tumour development does not clearly follow a predetermined pattern. PGL1 syndrome (SDHD) and PGL2 syndrome (SDHAF2) are notable for high frequency of multifocal tumour development and for parent-of-origin inheritance: disease is almost only ever manifest in subjects inheriting the defective allele from their father. PGL4 syndrome (SDHB) is notable for an increased risk of malignant PGL or PC. PGL3 syndrome (SDHC) and PGL5 syndrome (SDHA) are less common and appear to be associated with lower penetrance of tumour development. Although these syndromes are all associated with SDH deficiency, few genotype–phenotype relationships have yet been established, and indeed it is remarkable that such divergent phenotypes can arise from disruption of a common molecular pathway. This article reviews the clinical presentations of these syndromes, including their component tumours and underlying genetic basis. PMID:26273102

  6. A Critical Evaluation of the Down Syndrome Diagnosis for LB1, Type Specimen of Homo floresiensis.

    PubMed

    Baab, Karen L; Brown, Peter; Falk, Dean; Richtsmeier, Joan T; Hildebolt, Charles F; Smith, Kirk; Jungers, William

    2016-01-01

    The Liang Bua hominins from Flores, Indonesia, have been the subject of intense scrutiny and debate since their initial description and classification in 2004. These remains have been assigned to a new species, Homo floresiensis, with the partial skeleton LB1 as the type specimen. The Liang Bua hominins are notable for their short stature, small endocranial volume, and many features that appear phylogenetically primitive relative to modern humans, despite their late Pleistocene age. Recently, some workers suggested that the remains represent members of a small-bodied island population of modern Austro-Melanesian humans, with LB1 exhibiting clinical signs of Down syndrome. Many classic Down syndrome signs are soft tissue features that could not be assessed in skeletal remains. Moreover, a definitive diagnosis of Down syndrome can only be made by genetic analysis as the phenotypes associated with Down syndrome are variable. Most features that contribute to the Down syndrome phenotype are not restricted to Down syndrome but are seen in other chromosomal disorders and in the general population. Nevertheless, we re-evaluated the presence of those phenotypic features used to support this classification by comparing LB1 to samples of modern humans diagnosed with Down syndrome and euploid modern humans using comparative morphometric analyses. We present new data regarding neurocranial, brain, and symphyseal shape in Down syndrome, additional estimates of stature for LB1, and analyses of inter- and intralimb proportions. The presence of cranial sinuses is addressed using CT images of LB1. We found minimal congruence between the LB1 phenotype and clinical descriptions of Down syndrome. We present important differences between the phenotypes of LB1 and individuals with Down syndrome, and quantitative data that characterize LB1 as an outlier compared with Down syndrome and non-Down syndrome groups. Homo floresiensis remains a phenotypically unique, valid species with its roots

  7. A Critical Evaluation of the Down Syndrome Diagnosis for LB1, Type Specimen of Homo floresiensis

    PubMed Central

    Baab, Karen L.; Brown, Peter; Falk, Dean; Richtsmeier, Joan T.; Hildebolt, Charles F.; Smith, Kirk; Jungers, William

    2016-01-01

    The Liang Bua hominins from Flores, Indonesia, have been the subject of intense scrutiny and debate since their initial description and classification in 2004. These remains have been assigned to a new species, Homo floresiensis, with the partial skeleton LB1 as the type specimen. The Liang Bua hominins are notable for their short stature, small endocranial volume, and many features that appear phylogenetically primitive relative to modern humans, despite their late Pleistocene age. Recently, some workers suggested that the remains represent members of a small-bodied island population of modern Austro-Melanesian humans, with LB1 exhibiting clinical signs of Down syndrome. Many classic Down syndrome signs are soft tissue features that could not be assessed in skeletal remains. Moreover, a definitive diagnosis of Down syndrome can only be made by genetic analysis as the phenotypes associated with Down syndrome are variable. Most features that contribute to the Down syndrome phenotype are not restricted to Down syndrome but are seen in other chromosomal disorders and in the general population. Nevertheless, we re-evaluated the presence of those phenotypic features used to support this classification by comparing LB1 to samples of modern humans diagnosed with Down syndrome and euploid modern humans using comparative morphometric analyses. We present new data regarding neurocranial, brain, and symphyseal shape in Down syndrome, additional estimates of stature for LB1, and analyses of inter- and intralimb proportions. The presence of cranial sinuses is addressed using CT images of LB1. We found minimal congruence between the LB1 phenotype and clinical descriptions of Down syndrome. We present important differences between the phenotypes of LB1 and individuals with Down syndrome, and quantitative data that characterize LB1 as an outlier compared with Down syndrome and non-Down syndrome groups. Homo floresiensis remains a phenotypically unique, valid species with its roots

  8. People with Usher Syndrome, Type II: Issues and Adaptations.

    ERIC Educational Resources Information Center

    Miner, I. D.

    1997-01-01

    Describes the experiences of individuals with Usher Syndrome, discusses the lack of appropriate services and the failure of professionals to provide sufficient information on the condition, and stresses the importance of access to information and the acquisition of new skills before the visual impairment becomes severe. (Author/CR)

  9. X-linked albinism-deafness syndrome and Waardenburg syndrome type II: A hypothesis

    SciTech Connect

    Zlotogora, J.

    1995-11-20

    Margolis reported on a large pedigree with a {open_quotes}new{close_quotes} X-linked syndrome of profound deafness and albinism (MIM 300700, albinism-deafness syndrome). The affected males presented with profound deafness and severe pigmentary abnormalities of the skin. At birth the skin appeared as almost albinotic except for areas of light pigmentation over the gluteal and scrotal areas, and thereafter pigmentation gradually increased over the body. Skin changes ultimately included areas of hypopigmentation and spots of hyperpigmentation. Some of the affected males also had blue irides, heterochromia, or segmental color iris changes. In carrier females, variable hearing impairment was documented without any pigmentary changes. 9 refs., 1 fig.

  10. Surgical treatment for Scheie's syndrome (mucopolysaccharidosis type I-S): report of two cases.

    PubMed

    Minakata, K; Konishi, Y; Matsumoto, M; Miwa, S

    1998-09-01

    Scheie's syndrome (mucopolysaccharidosis type I-S) is a rare genetic lysosomal storage disease affecting mucopolysaccharide metabolism, and is known to include cardiovascular disease. Surgical treatment was carried out in 2 patients with Scheie's syndrome. Patient 1 was a 56-year-old man with triple-vessel coronary artery disease, who successfully underwent coronary artery bypass grafting. Patient 2 was a 52-year-old man with aortic and mitral valve stenosis, who successfully underwent combined aortic and mitral valve replacement. The literature on Scheie's syndrome associated with valvular and coronary artery disease is also reviewed. PMID:9766711

  11. Nonfunctional Metastatic Parathyroid Carcinoma in the Setting of Multiple Endocrine Neoplasia Type 2A Syndrome.

    PubMed

    Posada-González, María; Gómez-Ramírez, Joaquín; Luque-Ramírez, Manuel; Guijarro, Mercedes; Martín-Pérez, Elena; Rodríguez-Sánchez, Ana; García-Sanz, Iñigo; Larrañaga, Eduardo

    2014-01-01

    Parathyroid carcinoma is a very rare malignancy. It has been associated with hyperparathyroidism-jaw tumour syndrome, familial isolated primary hyperparathyroidism, and multiple endocrine neoplasia type 1 (MEN-1) and 2A (MEN-2A) syndromes. We report a 54-year-old man with a MEN-2A which presents with a nonfunctional metastatic parathyroid carcinoma and a pheochromocytoma in the absence of medullary thyroid carcinoma. Only a few cases of parathyroid carcinoma have been reported in the literature associated with this syndrome. PMID:25374962

  12. Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) in the pre-Columbian culture of Colombia

    PubMed Central

    Rodriguez, Carlos Armando

    2014-01-01

    Mucopolysaccharidosis type VI or Maroteaux Lamy syndrome is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B, the clinical features include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities, and facial dysmorphism, with intelligence usually normal. We present evidence of the possible existence of Maroteaux Lamy syndrome in pre-Columbian pottery 2000 years ago, in the Colombo-Ecuadorian Pacific coast of the Tumaco-Tolita culture. PMID:25100895

  13. Waardenburg syndrome type I with heterochromia iridis and circumscribed hypopigmentation of the skin.

    PubMed

    Eigelshoven, Sibylle; Kameda, Gitta; Kortüm, Anne-Katrin; Hübsch, Simone; Angerstein, Wolfgang; Singh, Preeti; Vöhringer, Renate; Goecke, Timm; Mayatepek, Ertan; Ruzicka, Thomas; Wildhardt, Gabriele; Meissner, Thomas; Kruse, Roland

    2009-01-01

    We report a 3-year-old girl with autosomal dominant inherited Waardenburg syndrome type I showing circumscribed hypopigmentation of the skin, heterochromia iridis, sensorineural deafness, and dental aberrations. Clinical diagnosis was confirmed by the identification of an underlying missense mutation (C811T) in the PAX3 gene. Early diagnosis of Waardenburg syndrome among children with pigment anomalies enables a successful interdisciplinary medical care. PMID:20199465

  14. Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) in the pre-Columbian culture of Colombia.

    PubMed

    Pachajoa, Harry; Rodriguez, Carlos Armando

    2014-01-01

    Mucopolysaccharidosis type VI or Maroteaux Lamy syndrome is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B, the clinical features include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities, and facial dysmorphism, with intelligence usually normal. We present evidence of the possible existence of Maroteaux Lamy syndrome in pre-Columbian pottery 2000 years ago, in the Colombo-Ecuadorian Pacific coast of the Tumaco-Tolita culture. PMID:25100895

  15. Perisigmoid Abscess Leading to a Diagnosis of Ehlers-Danlos Syndrome Type IV.

    PubMed

    Normatov, Inessa; Kesavan, Anil; Srikumar, Pillai B; McConnie, Randolph M

    2016-01-01

    The Ehlers-Danlos syndromes (EDS) are a group of connective tissue disorders characterized by triad of joint hypermobility, skin extensibility, and tissue fragility. Ehlers-Danlos syndrome type IV places patients at risk for life-threatening, spontaneous, vascular or visceral rupture due to reduced or abnormal secretion of type III collagen. We present an adolescent male who was found to have a perisigmoid abscess with a fistula connecting to adjacent sigmoid colon secondary to undiagnosed EDS type IV. Conservative management with antibiotics and bowel rest was pursued to allow for elective resection for his acute complicated diverticulitis at a safer time. PMID:26958560

  16. Perisigmoid Abscess Leading to a Diagnosis of Ehlers-Danlos Syndrome Type IV

    PubMed Central

    Kesavan, Anil; Srikumar, Pillai B.; McConnie, Randolph M.

    2016-01-01

    The Ehlers-Danlos syndromes (EDS) are a group of connective tissue disorders characterized by triad of joint hypermobility, skin extensibility, and tissue fragility. Ehlers-Danlos syndrome type IV places patients at risk for life-threatening, spontaneous, vascular or visceral rupture due to reduced or abnormal secretion of type III collagen. We present an adolescent male who was found to have a perisigmoid abscess with a fistula connecting to adjacent sigmoid colon secondary to undiagnosed EDS type IV. Conservative management with antibiotics and bowel rest was pursued to allow for elective resection for his acute complicated diverticulitis at a safer time. PMID:26958560

  17. A study of migraine characteristics in joint hypermobility syndrome a.k.a. Ehlers-Danlos syndrome, hypermobility type.

    PubMed

    Puledda, Francesca; Viganò, Alessandro; Celletti, Claudia; Petolicchio, Barbara; Toscano, Massimiliano; Vicenzini, Edoardo; Castori, Marco; Laudani, Guido; Valente, Donatella; Camerota, Filippo; Di Piero, Vittorio

    2015-08-01

    Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping heritable connective tissue disorders strongly associated with musculoskeletal pain, fatigue and headache. Migraine with or without aura is considered the most common form of headache in JHS/EDS-HT. In this population of chronically ill patients, we investigated whether migraine characteristics were different from those of a control population of migraine patients. The study was carried out on 33 selected JHS/EDS-HT patients, diagnosed according to current criteria. Sixty-six migraine subjects matching age and gender were consecutively selected as controls (MO group) among patients attending our Headache Clinic. JHS/EDS-HT and MO were screened for a series of headache characteristics, such as frequency, intensity, age of onset, level of disability, use of rescue and prophylactic medications. Differences between the two groups were tested by using independent group comparisons. Results showed that in JHS/EDS-HT: (1) migraine has an earlier onset (12.6 vs 17 years of age; p = 0.005); (2) the rate of migraine days/month is higher (15 vs 9.3 days/month; p = 0.01); (3) accompanying symptoms are usually more frequent; (4) HIT-6 and MIDAS scores are higher (p = 0.04 and p = 0.03); (5) efficacy of rescue medication is almost identical, although, total drug consumption is significantly lower (p < 0.04). Joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type patients have a more severe headache syndrome with respect to the MO group, therefore demonstrating that migraine has a very high impact on quality of life in this disease. PMID:25791889

  18. Relationship between Fatigue and Gait Abnormality in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type

    ERIC Educational Resources Information Center

    Celletti, Claudia; Galli, Manuela; Cimolin, Veronica; Castori, Marco; Albertini, Giorgio; Camerota, Filippo

    2012-01-01

    Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterised by joint hypermobility, skin hyperextensibility and tissue fragility. It has recently been shown that muscle weakness occurs frequently in EDS, and that fatigue is a common and clinically important symptom. The…

  19. Sugar-Sweetened Beverages and Risk of Metabolic Syndrome and Type 2 Diabetes

    PubMed Central

    Malik, Vasanti S.; Popkin, Barry M.; Bray, George A.; Després, Jean-Pierre; Willett, Walter C.; Hu, Frank B.

    2010-01-01

    OBJECTIVE Consumption of sugar-sweetened beverages (SSBs), which include soft drinks, fruit drinks, iced tea, and energy and vitamin water drinks has risen across the globe. Regular consumption of SSBs has been associated with weight gain and risk of overweight and obesity, but the role of SSBs in the development of related chronic metabolic diseases, such as metabolic syndrome and type 2 diabetes, has not been quantitatively reviewed. RESEARCH DESIGN AND METHODS We searched the MEDLINE database up to May 2010 for prospective cohort studies of SSB intake and risk of metabolic syndrome and type 2 diabetes. We identified 11 studies (three for metabolic syndrome and eight for type 2 diabetes) for inclusion in a random-effects meta-analysis comparing SSB intake in the highest to lowest quantiles in relation to risk of metabolic syndrome and type 2 diabetes. RESULTS Based on data from these studies, including 310,819 participants and 15,043 cases of type 2 diabetes, individuals in the highest quantile of SSB intake (most often 1–2 servings/day) had a 26% greater risk of developing type 2 diabetes than those in the lowest quantile (none or <1 serving/month) (relative risk [RR] 1.26 [95% CI 1.12–1.41]). Among studies evaluating metabolic syndrome, including 19,431 participants and 5,803 cases, the pooled RR was 1.20 [1.02–1.42]. CONCLUSIONS In addition to weight gain, higher consumption of SSBs is associated with development of metabolic syndrome and type 2 diabetes. These data provide empirical evidence that intake of SSBs should be limited to reduce obesity-related risk of chronic metabolic diseases. PMID:20693348

  20. Electrocardiogram in Andersen-Tawil Syndrome. New Electrocardiographic Criteria for Diagnosis of Type-1 Andersen-Tawil Syndrome

    PubMed Central

    Kukla, Piotr; Biernacka, Elżbieta K; Baranchuk, Adrian; Jastrzębski, Marek; Jagodzińska, Michalina

    2014-01-01

    Andersen - Tawil syndrome (ATS) is an autosomal - dominant or sporadic disorder characterized by ventricular arrhythmias, periodic paralysis, and distinctive facial and skeletal dysmorphism. Mutations in KCNJ2, which encodes the α-subunit of the potassium channel Kir2.1, were identified in patients with ATS. This genotype has been designated as type-1 ATS (ATS1). KCNJ2 mutations are detectable in up to 60 % of patients with ATS. Cardiac manifestations of ATS include frequent premature ventricular contractions (PVC), Q-U interval prolongation, prominent U-waves, and a special type of polymorphic ventricular tachycardia (PMVT) called bidirectional ventricular tachycardia (BiVT). The presence of frequent PVCs at rest are helpful in distinguishing ATS from typical catecholaminergic polymorphic ventricular tachycardia (CPVT). In typical CPVT, rapid PMVT and BiVT usually manifest during or after exercising. Additionally, CPVT or torsade de pointes in LQTS are faster, very symptomatic causing syncope or often deteriorate into VF resulting in sudden cardiac death. PVCs at rest are quite frequent in ATS1 patients, however, in LQTS patients, PVCs and asymptomatic VT are uncommon which also contributes to differentiating them. The article describes the new electrocardiographic criteria proposed for diagnosis of type-1 Andersen-Tawil syndrome. A differential diagnosis between Andersen-Tawil syndrome, the catecholamine polymorphic ventiruclar tachycardia and long QT syndrome is depicted. Special attention is paid on the repolarization abnormalities, QT interval and the pathologic U wave. In this article, we aim to provide five new electrocardiographic clues for the diagnosis of ATS1. PMID:24827800

  1. Demographic and clinical correlates of metabolic syndrome in Native African type-2 diabetic patients.

    PubMed Central

    Isezuo, S. A.; Ezunu, E.

    2005-01-01

    OBJECTIVES: To describe the metabolic syndrome and its demographic and clinical correlates in native African type-2 diabetic patients. METHODS: Cross-sectional analysis of 254 type-2 diabetic indigenous Nigerians consecutively recruited in a teaching hospital. The main outcome measure was metabolic syndrome. Variables of interest included family history/duration of diabetes mellitus and hypertension, gender, socioeconomic class, occupation and place of domicile (urban or rural). Intergroup comparisons were made with Chi-squared tests or t-tests. RESULTS: Patients were aged 35-80 years (mean: 52.0 +/- 11.7 years) and made of 154 (60.6%) males and 100 (39.4%) females. Full-blown metabolic syndrome was noted in 52 patients (20.5%). Metabolic syndrome, as defined by the WHO, was noted in 150 patients (59.1%). About 72.4% of patients were dyslipidemic, 54.3% were hypertensive, 42.5% were obese, 44.9% were microalbuminuric and 32.3% were hyperuricemic. Ischemic heart disease (myocardial infarction) occurred in only 2.4% of patients. Concurrent hypertension and dyslipidemia; obesity and dyslipidemia; and hypertension and obesity occurred in 44.4%, 42.5% and 33.1% of type-2 diabetics, respectively. Compared to the diabetics without metabolic syndrome, those with the syndrome had a significantly higher proportion of patients with a family history of hypertension and diabetes (44% versus 25%; p = 0.003); among the upper/middle socioeconomic class: 52.0% versus 30.8% (p = 0.001); and among the urban dwelling: 68.0% versus 49.0% (p = 0.004). Metabolic syndrome was inversely proportional to the physical activity of an individual (chi2 = 21.69, df = 5, p = 0.001). Blood pressure was significantly higher among patients with metabolic syndrome than those without it (140.6 +/- 22.9/85.2 +/- 12.9 mmHg versus 126.9 +/- 15.4 mmHg; P < 0.01). CONCLUSIONS: The development of metabolic syndrome in African type-2 diabetic patients is influenced by demographic and clinical factors

  2. Mucopolysaccharidosis type-IS presenting with onset of carpal tunnel syndrome at adolescence.

    PubMed

    Bahadir, Cengiz; Kurtulus, Duygu; Cihandide, Ercan

    2009-12-01

    Mucopolysaccharidosis type I (MPS I) results from deficiency of the lysosomal enzyme alpha-L iduronidase. Three subtypes, based on severity of clinical findings, have been described, of which MPS type IS (also called Scheie syndrome) is the mildest form. A woman (age, 30 years) and her little brother (age, 21 years) presented to our clinic complaining of atrophy of the thenar muscles, numbness in both hands, and contractures in the finger joints. Electrophysiologic examination showed severe carpal tunnel syndrome for both patients. Findings of cardiac and ocular involvements and decreased level of alpha-L iduronidase confirmed the diagnosis of Scheie syndrome. Enzyme replacement therapy was initiated for the further prevention of musculoskeletal and other organ complications. Delayed diagnosis of MPS type-IS and the musculoskeletal findings are discussed in these 2 familial patients. PMID:19955999

  3. Cardiovascular pathologies in mucopolysaccharidosis type VII (Sly Syndrome).

    PubMed

    Gniadek, Thomas J; Singer, Nicole; Barker, Norman J; Spevak, Philip J; Crain, Barbara J; Valle, David; Halushka, Marc K

    2015-01-01

    We present the cardiac findings from the autopsy of a 28-year-old male with mucopolysaccharidosis VII (MPS VII), also known as Sly Syndrome, whose diagnosis was confirmed by biochemical testing. The patient died a sudden cardiac death. Autopsy showed thickened and stenotic aortic valve leaflets as well as marked concentric intimal thickening of the aorta and muscular arteries. There was left ventricular hypertrophy as well as mild papillary muscle thickening and fusion. Increased colloid iron staining was seen in the small- and medium-sized arteries of the heart and at the intercalated discs. We discuss the patient's premortem echocardiographic and electrocardiographic studies. In addition, we discuss the pathogenesis of MPS VII and review previous literature on its anatomic and pathologic features. PMID:26141114

  4. First Case Report of Turcot Syndrome Type 1 in Colombia

    PubMed Central

    Dora, Vallejo; Diego, Garnica; Rómulo, Bonilla; Natalia, Olaya

    2012-01-01

    Turcot syndrome is an autosomal recessive disorder clinically characterized by the occurrence of primary tumors of the central nervous system and adenomatous colonic polyps during the first or second decades of life, with a spectrum of clinical features such as “café-au-lait” spots, axillary freckling, and hyperpigmented spots. Currently its prevalence globally and in Colombia remains unknown. We present the case of a 20-year-old male with a clinical presentation of both glioblastoma multiforme and multiple adenomatous colonic polyps. The molecular genetics study revealed a mutation in KrasAsp12 gene and altered expression of HMSH2 and HMSH6 proteins encoded by the DNA mismatch repair genes in two of the colonic polyps. Even though this clinical presentation may suggest a shorter survival rate, this patient is still alive after seven months of treatment. A literature review complements this report. PMID:23320220

  5. Intestinal lymphangiectasia in a patient with autoimmune polyglandular syndrome type III.

    PubMed

    Choudhury, Bipul Kumar; Saiki, Uma Kaimal; Sarm, Dipti; Choudhury, Bikash Narayan; Choudhury, Sarojini Dutta; Saharia, Dhiren; Saikia, Mihir

    2011-11-01

    Autoimmune polyglandular syndromes (APS) comprise a wide clinical spectrum of autoimmune disorders. APS is divided into Type I, Type II, Type I and Type IV depending upon the pattern of disease combination. Ghronic diarrhoea is one of the many manifestations of APS and many aetiological factors have been suggested for it. Apart from the established aetiological factors, intestinal lymphangiectasia may be responsible for chronic diarrhea in some cases.Intestinal lymphangiectasia has been reported in Type I APS. We report a case of Type III APS with hypocalcaemia and hypothyroidism who had chronic diarrhea of long duration and was finally diagnosed to have intestinal lymphangiectasia. PMID:22616341

  6. [Severe type A insulin resistance syndrome due to a mutation in the insulin receptor gene].

    PubMed

    Ros, P; Colino-Alcol, E; Grasso, V; Barbetti, F; Argente, J

    2015-01-01

    Insulin resistance syndromes without lipodystrophy are an infrequent and heterogeneous group of disorders with variable clinical phenotypes, associated with hyperglycemia and hyperinsulinemia. The three conditions related to mutations in the insulin receptor gene are leprechaunism or Donohue syndrome, Rabson-Mendenhall syndrome, and Type A syndrome. A case is presented on a patient diagnosed with type A insulin resistance, defined by the triad of extreme insulin resistance, acanthosis nigricans, and hyperandrogenism, carrying a heterozygous mutation in exon 19 of the insulin receptor gene coding for its tyrosine kinase domain that is crucial for the catalytic activity of the receptor. The molecular basis of the syndrome is reviewed, focusing on the structure-function relationships of the insulin receptor, knowing that the criteria for survival are linked to residual insulin receptor function. It is also pointed out that, although type A insulin resistance appears to represent a somewhat less severe condition, these patients have a high morbidity and their treatment is still unsatisfactory. PMID:25027621

  7. Comparison of Two Commercial Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Modified Live Vaccines against Heterologous Type 1 and Type 2 PRRSV Challenge in Growing Pigs

    PubMed Central

    Kim, Taeyeon; Park, Changhoon; Choi, Kyuhyung; Jeong, Jiwoon; Kang, Ikjae; Park, Su-Jin

    2015-01-01

    The objective of the present study was to compare the efficacy of two commercial type 1 porcine reproductive and respiratory syndrome virus (PRRSV) modified live vaccines against heterologous type 1 and type 2 PRRSV challenge in growing pigs. Vaccination with a type 1 PRRSV vaccine reduced the level of viremia after type 1 PRRSV challenge but did not reduce the level of viremia after the type 2 PRRSV challenge in pigs. Increased levels of interleukin-10 (IL-10) stimulated by type 2 PRRSV coincided with the low numbers of type 2 PRRSV-specific interferon gamma-secreting cells (IFN-γ-SC) in vaccinated pigs after type 2 PRRSV challenge, whereas low levels of IL-10 stimulated by type 1 PRRSV coincided with high numbers of type 1 PRRSV-specific IFN-γ-SC in vaccinated pigs after type 1 PRRSV challenge. Additionally, vaccination with the type 1 PRRSV vaccine effectively reduced the lung lesions and type 1 PRRSV nucleic acids in type 1 PRRSV-challenged pigs but did not reduce lung lesions and type 2 PRRSV nucleic acids in type 2 PRRSV-challenged pigs. There were no significant differences between two commercial type 1 PRRSV vaccines against type 1 and type 2 PRRSV challenge based on virological results, immunological responses, and pathological outcomes. This study demonstrates that vaccinating pigs with the type 1 PRRSV vaccine provides partial protection against respiratory disease with heterologous type 1 PRRSV challenge but no protection with heterologous type 2 PRRSV challenge. PMID:25855554

  8. [Duane's retraction syndrome--overview and diagnosis of clinical types].

    PubMed

    Otradovec, J

    2001-05-01

    The author presents a postgraduate review of the problem. In the introduction he reviews typical features of Duane's retraction syndrome (DS) and its main symptoms and reminds of the main approaches to classification: (1) Malbrane s (Duane I, II and III), (2) Huber's which is based on EMG findings in ZOS and (3) Kaufman's which classifies DS according to the enforced position of the head. The author maintains that even according to the above many atypical rare pictures cannot be classified or explained pathogenetically. Some are mentioned: (1) "Inverse" DS, which was recorded and documented by Chytilová-Divisová (1949) in a girl with congenital paralysis of abduction on both eyes retraction of the bulbus developed and narrowing of the palpebral aperture when attempting abduction (1) of the eye, (2) Bilateral acquired DS in a female patient with a tumour of the brain stem confirmed by EMG records of both horizontal muscles. (3) Unilateral DS in a child from a family with familial incidence of congenital ZOS fibrosis with an obscure ratio of the neurogenic and myogenic and fibrous component of the two pictures. In another member of this family the Marcus Gunn phenomenon was present. The latter findings support the idea that in the development of the fairly uniform picture of DS a combination of neurogenic, myogenic and connective tissue changes participate. PMID:11433591

  9. Glucose Transporter Type 1 Deficiency Syndrome with Carbohydrate-Responsive Symptoms but without Epilepsy

    ERIC Educational Resources Information Center

    Koy, Anne; Assmann, Birgit; Klepper, Joerg; Mayatepek, Ertan

    2011-01-01

    Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is caused by a defect in glucose transport across the blood-brain barrier. The main symptoms are epilepsy, developmental delay, movement disorders, and deceleration of head circumference. A ketogenic diet has been shown to be effective in controlling epilepsy in GLUT1-DS. We report a female…

  10. Phenotype of the fibroblast growth factor receptor 2 Ser351Cys mutation: Pfeiffer syndrome type III.

    PubMed

    Gripp, K W; Stolle, C A; McDonald-McGinn, D M; Markowitz, R I; Bartlett, S P; Katowitz, J A; Muenke, M; Zackai, E H

    1998-07-24

    We present a patient with pansynostosis, hydrocephalus, seizures, extreme proptosis with luxation of the eyes out of the lids, apnea and airway obstruction, intestinal non-rotation, and severe developmental delay. His skeletal abnormalities include bilateral elbow ankylosis, radial head dislocation, and unilateral broad and deviated first toe. The phenotype of this patient is consistent with that previously reported in Pfeiffer syndrome type III, but is unusual for the lack of broad thumbs. Our patient most closely resembles the case described by Kerr et al. [1996: Am J Med Genet 66:138-143] as Pfeiffer syndrome type III with normal thumbs. Mutations in the genes for fibroblast growth factor receptors (FGFR) 1 and 2 have previously been seen in patients with Pfeiffer syndrome type I. The mutation identified in our patient, Ser351Cys in FGFR2, represents the first reported cause of Pfeiffer syndrome type III. An identical mutation was described once previously by Pulleyn et al., in a patient whose brief clinical description included cloverleaf skull, significant developmental delay, and normal hands and feet [Eur. J. Hum. Genet. 4: 283-291, 1996]. In our patient, previously performed single-strand conformation polymorphism analysis failed to detect a band shift; the mutation was identified only after independent sequence analysis. PMID:9714439

  11. Genomic sequence and virulence comparison of four type 2 porcine reproductive and respiratory syndrome virus strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine reproductive and respiratory syndrome virus (PRRSV) is a ubiquitous and costly virus that exhibits substantial sequence and virulence disparity among diverse isolates. In this study, we compared the whole genomic sequence and virulence of 4 North American Type 2 PRRSV isolates. Among the 4 i...

  12. A rare type of congenital Sturge-Weber Syndrome: presenting with history of perinatal asphyxia.

    PubMed

    Ejike, Obuoha; Odume, Calistus; Ekwochi, Uchenna; Ndu, Ikenna; Imanyikwa, Ugochukwu

    2016-08-01

    The presentation of a newborn with perinatal asphyxia and poor developmental milestones in a resource-poor setting. Many a times, obscured, unsuspected, and uncommon etiologies compound well-known causes of failure to thrive; in this case a rare finding of Type III Sturge-Weber Syndrome was revealed by Brain CT scanning. PMID:27525070

  13. Extended phenotypes in a boy and his mother with oto-palato-digital-syndrome type II.

    PubMed

    Kaissi, Ali Al; Kraschl, Raimund; Kaulfersch, Wilhelm; Grill, Franz; Ganger, Rudolf

    2015-09-01

    We describe additional phenotypic features in a boy and his mother. Both manifested the phenotypic/genotypic correlation of oto-palato-digital syndrome type II. The mother's radiographs showed wormian bones of the skull, and paranasal bossing, her feet showed bilateral fusion of the cuboid with the lateral cuneiform bone with subsequent development of metatarsus varus associated with dysplastic distal phalanges. PMID:26401283

  14. Psychosocial Implications of Usher Syndrome, Type I, throughout the Life Cycle.

    ERIC Educational Resources Information Center

    Miner, I. D.

    1995-01-01

    Usher syndrome, Type I, requires multiple adaptations throughout the life cycle because each stage of life has tasks and losses associated with deafness and progressive retinitis pigmentosa. This article examines the issues raised at each stage, using clinical vignettes from persons who have this condition and their families. (Author/DB)

  15. Metachronous Bilateral Posterior Tibial Artery Aneurysms in Ehlers-Danlos Syndrome Type IV

    SciTech Connect

    Hagspiel, Klaus D.; Bonatti, Hugo; Sabri, Saher; Arslan, Bulent; Harthun, Nancy L.

    2011-04-15

    Ehlers-Danlos syndrome type IV is a life-threatening genetic connective tissue disorder. We report a 24-year-old woman with EDS-IV who presented with metachronous bilateral aneurysms/pseudoaneurysms of the posterior tibial arteries 15 months apart. Both were treated successfully with transarterial coil embolization from a distal posterior tibial approach.

  16. Physical and Psychological Health in Persons with Deafblindness that Is due to Usher Syndrome Type II

    ERIC Educational Resources Information Center

    Wahlqvist, Moa; Moller, Claes; Moller, Kerstin; Danermark, Berth

    2013-01-01

    Introduction: The objectives of the study reported here were to describe the physical and psychological health of persons with Usher syndrome Type II (USH2) and to explore any differences in terms of gender. Methods: The participants were recruited from the Swedish Usher database. In the first step, 122 persons received the questionnaire by mail,…

  17. Exploration of Differences in Types of Sleep Disturbance and Severity of Sleep Problems between Individuals with Cri du Chat Syndrome, Down's Syndrome, and Jacobsen Syndrome: A Case Control Study

    ERIC Educational Resources Information Center

    Maas, Anneke P. H. M.; Didden, Robert; Korzilius, Hubert; Curfs, Leopold M. G.

    2012-01-01

    The prevalence of sleep problems in individuals with intellectual disability (ID) seems to vary between genetic syndromes associated with ID. Different types of sleep disturbances may indicate underlying causes of sleep problems and these types of sleep disturbances may vary between different genetic syndromes. We examined and compared five types…

  18. Herpes simplex virus type 1 encephalitis in acquired immunodeficiency syndrome.

    PubMed

    Chrétien, F; Bélec, L; Hilton, D A; Flament-Saillour, M; Guillon, F; Wingertsmann, L; Baudrimont, M; de Truchis, P; Keohane, C; Vital, C; Love, S; Gray, F

    1996-10-01

    Herpes simplex (HSV) infection of the central nervous system is uncommon in AIDS and usually has an atypical topography. This review is centred around the case of a 49-year-old homosexual patient with AIDS who died from diffuse encephalopathy. Neuropathological examination revealed necrotic and haemorrhagic changes involving both temporal lobes, insulae and cingulate gyri. Cowdry type A intranuclear inclusion bodies were abundant but inflammation was minimal. Electron microscopy confirmed characteristic herpes virus particles. Immunocyto-chemistry was positive for HSV type 1 and 2. In situ hybridization and PCR, however, were positive for HSV type 1 but excluded HSV type 2. There was associated cytomegalovirus ventriculitis but clearly separated from HSV encephalitis. There were no histological features of HIV encephalitis and HIV could not be demonstrated by immunocytochemistry or by PCR to demonstrate proviral DNA. Apoptotic neurons were numerous in areas with a severe macrophage reaction. Only two pathological cases with characteristic limbic distribution and necrotic haemorrhagic histologic have been reported previously. The rarity of these reports suggests that in advanced AIDS, the immune reaction causing a typical necrotizing encephalitis cannot be mounted. Distinction between HSV type 1 and 2 infection may be difficult by immunocytochemistry and usually requires in situ hybridization, tissue culture or PCR. In AIDS patients, HSV-1 has been identified as responsible for encephalitis whereas HSV-2 has been more responsible for myelitis. Associated productive HIV infection of the CNS was found in none of the cases. In contrast, cytomegalovirus encephalitis was found in nine of 11 cases of AIDS-associated HSV encephalitis. PMID:8930949

  19. Type 1 diabetes mellitus in a 3 1/2 year-old girl with Turner's syndrome.

    PubMed

    Gonc, E Nazli; Ozon, Alev; Alikasifoglu, Ayfer; Kandemir, Nurgun

    2002-01-01

    Turner's syndrome is associated with autoimmune disorders. Autoimmune endocrinopathy in Turner's syndrome seems to be limited to autoimmune thyroiditis. A small number of patients with Turner's syndrome has also been associated with celiac disease, inflammatory bowel disease and juvenile rheumatoid arthritis. Type 1 diabetes mellitus in Turner's syndrome has been rarely reported. We present here the youngest patient with Turner's syndrome who developed type 1 diabetes mellitus. At the age of 3.5 years she was hospitalized with diabetic ketoacidosis. Anti-islet cell and anti-insulin antibodies were positive and C-peptide level was low. When she was investigated for recurrent urinary tract infections, horseshoe kidney was detected by ultrasonography. Karyotype analysis revealed 45,XO. She has been followed for 2 years with an insulin dose of 0.9 U/kg per day. The prevalence of type 1 diabetes mellitus associated with Turner's syndrome is still unknown. PMID:12387520

  20. Pulmonary Alveolar Type II Epithelial Cells and Adult Respiratory Distress Syndrome

    PubMed Central

    Mason, Robert J.

    1985-01-01

    During the past ten years, functions of alveolar type II cells have been well characterized with isolated cells in vitro. Some of the functions were well known from studies in vivo, but others such as transepithelial sodium transport were unsuspected. A better understanding of this important pulmonary cell type improves our knowledge of the pathophysiology of adult respiratory distress syndrome and may in time lead to new therapeutic strategies. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:3909639

  1. Type B aortic dissection triggered by heart transplantation in a patient with Marfan syndrome.

    PubMed

    Audenaert, Tjorven; De Pauw, Michel; François, Katrien; De Backer, Julie

    2015-01-01

    Heart transplantation in patients with Marfan syndrome is challenging and raises concerns with regards to the haemodynamic and immunosuppressive-induced effects on the inherently fragile aorta. Most aortic events following transplantation reported so far in the literature occurred in patients with pre-existent distal aortic dissection. We report a case of successful orthotopic heart transplantation in a patient with Marfan syndrome that was complicated by late-onset type B dissection in pre-existing mild and stable distal aortic dilation. Serial aortic imaging revealed progressive growth at the level of the descending thoracic aorta. An open thoracoabdominal aortic repair procedure was successfully performed 6 months after the transplantation. PMID:26475875

  2. Increased incidence of neonatal respiratory distress in infants with mucopolysaccharidosis type II (MPS II, Hunter syndrome).

    PubMed

    Dodsworth, Charlotte; Burton, Barbara K

    2014-02-01

    Records were reviewed on all patients with mucopolysaccharidosis type II (Hunter syndrome) seen at a single institution from 1999 to 2013 to identify those with a history of neonatal intensive care. Eleven of 34 patients were in a neonatal intensive care unit and all had respiratory distress with 8 diagnoses of respiratory distress syndrome and 3 of transient tachypnea of the newborn. None of the infants were premature; four were delivered by cesarean section. These findings suggest that respiratory distress is more commonly observed in neonates with MPS II than in the general population. This may reflect airway disease already present in this disorder at the time of birth. PMID:24238892

  3. Familial partial lipodystrophy: two types of an X linked dominant syndrome, lethal in the hemizygous state.

    PubMed Central

    Köbberling, J; Dunnigan, M G

    1986-01-01

    Familial lipodystrophy (referred to in publications as the Köbberling-Dunnigan syndrome) comprises at least two clinical phenotypes which are consistent within each pedigree. In type 1 familial lipodystrophy, loss of subcutaneous fat is confined to the limbs, sparing the face and trunk. In type 2 familial lipodystrophy, the trunk is also affected with the exception of the vulva, giving an appearance of labial hypertrophy. Diabetes mellitus, hyperlipoproteinaemia, and acanthosis nigricans are present to a variable degree in some but not all patients with familial lipodystrophy, and the abnormal distribution of subcutaneous fat is the essential hallmark of the syndrome. In addition to a survey of published reports, new cases with the syndrome are described. Both types of partial lipodystrophy, occurring either as familial disease or as sporadic cases, have only been observed in female patients. Study of the pedigrees of five families with familial lipodystrophy (two Scottish and three German) suggests an X linked dominant mode of transmission, lethal in the hemizygous (XY) state. The two clinical phenotypes with their variably expressive metabolic abnormalities are consistent either with different mutants of the same allele or with two genes on adjacent loci. Other clinical phenotypes of familial lipodystrophy may exist due to further mutations of the same allele or of genes on adjacent loci. The nature of the disorder in patients with familial lipodystrophy usually escapes recognition for many years and the syndrome is almost certainly much commoner than the few families described to date suggest. Images PMID:3712389

  4. Precocious presentation of autoimmune polyglandular syndrome type 2 associated with an AIRE mutation.

    PubMed

    Resende, Eduarda; Gόmez, Gemma Novoa; Nascimento, Marta; Loidi, Lourdes; Saborido Fiaño, Rebeca; Cabanas Rodrίguez, Paloma; Castro-Feijoo, Lidia; Barreiro Conde, Jesús

    2015-01-01

    Autoimmune polyglandular syndrome type 2 (type 2 APS), or Schmidt's syndrome, is defined by the presence of Addison's disease in combination with type 1 diabetes and/or autoimmune thyroid disease. The estimated prevalence of this syndrome is 1.4-4.5 per 100,000 inhabitants and it is more frequent in middle-aged females, whilst it is quite rare in children. Type 2 APS, which shows a pattern of autosomal dominant inheritance with low penetrance, has been associated with HLA specific DR3/DQ2 and DR4/DQ8 haplotypes. However, it has been hypothesized that genetic variability in the AIRE gene, which causing type 1 APS, may play a role in more common organ-specific autoimmune conditions like type 1 diabetes, Hashimoto's disease and type 2 APS, among others. Here we present the case of an 8-year-old girl, with a past medical history of type 1 diabetes diagnosed at the age of 3. She was taken to the Emergency Department because she complained of abdominal pain, nausea and vomiting, and her blood analysis revealed a severe hyponatremia. She also had seizures as a consequence of the hyponatremia and frequent hypoglycemia. She was ultimately found to be suffering from autoimmune primary adrenal insufficiency. The combination of both mentioned conditions, type 1 diabetes and Addison's disease, in the absence of chronic mucocutaneous candidiasis, made a diagnosis of type 2 APS plausible in this girl. The genetic study showed two heterozygous variants: NM_000383.2:C.1411C>T (p. Arg471Cys) in exon 12 and IVS9+6G>A in intron 9 of the AIRE gene. The description of an uncommon case of type 2 APS with precocious presentation associated with an AIRE mutation in a very young girl could help to clarify the role of AIRE in the development of autoimmune diseases. PMID:25402387

  5. Tricho-rhino-phalangeal syndrome type 1 as an outcome of in vitro fertilization?

    PubMed

    Karaer, K; Yüksel, Z

    2014-01-01

    Trichorhinophalangeal syndrome type I [OMIM #190350] is an autosomal dominant disorder. Common features are: Slowly growing sparse hair, laterally thin eyebrows, bulbous tip of the nose, long philtrum, thin upper lip, protruding ears. Common skeletal anomalies include shortening of phalanges and metacarpals causing mild to severe brachydactyly, cone shaped epiphyses, hip dysplasia and short stature. Recently many reports have been published on the use of assisted reproductive technology (ART) and the increased risk of congenital major malformations or syndromes. We present a 6 years old Turkish Trichorhinophalangeal syndrome (TRPS) case of a twin pair after in vitro fertilization (IVF). TRPS with IVF pregnancy has not been reported previously. This new case reported herein will contribute to a better understanding whether ART pregnancy increases congenital malformations. PMID:24783650

  6. Unusual phenotype of glucose transport protein type 1 deficiency syndrome: A case report and literature review

    PubMed Central

    Posar, Annio; Santucci, Margherita

    2014-01-01

    The glucose transport protein type 1 (GLUT1) deficit causes a chronic brain energy failure. The classic phenotype of GLUT1 deficiency syndrome is characterized by: Mild to severe motor delay and mental retardation; infantile-onset epilepsy; head growth deceleration; movement disorders (ataxia, dystonia, spasticity); and non-epileptic paroxysmal events (intermittent ataxia, periodic confusion, recurrent headaches). During last years the classic phenotype of this syndrome, as originally reported, has expanded. We report the atypical phenotype of a boy with GLUT1 deficiency syndrome, characterized by mild mental retardation and drug-resistant absence seizures with onset at the age of 6 years, without movement disorders nor decrease of head circumference. A prompt diagnosis of this disorder is mandatory since the ketogenic diet might represent an effective treatment. PMID:24891901

  7. Scimitar Syndrome and H-type Tracheo-esophageal Fistula in a Newborn Infant.

    PubMed

    Lastinger, Allison; El Yaman, Malek; Gustafson, Robert; Yossuck, Panitan

    2016-06-01

    Scimitar syndrome is a rare congenital anomaly characterized by partial anomalous pulmonary venous drainage of the right lung to the inferior vena cava (IVC) creating a tubular opacity paralleling the right cardiac border on chest radiography which resembles a curved Turkish sword or scimitar. Associated pulmonary and vascular anomalies have been reported in cases of Scimitar syndrome, most commonly hypoplasia of right lung, dextroposition of the heart, hypoplasia of the right pulmonary artery, and aberrant arterial supply from the descending aorta to the affected lobe of the right lung. To the best of our knowledge, this is the first case of Scimitar syndrome with an H-type tracheoesophageal fistula that has ever been reported. PMID:24269859

  8. Unusual phenotype of glucose transport protein type 1 deficiency syndrome: A case report and literature review.

    PubMed

    Posar, Annio; Santucci, Margherita

    2014-01-01

    The glucose transport protein type 1 (GLUT1) deficit causes a chronic brain energy failure. The classic phenotype of GLUT1 deficiency syndrome is characterized by: Mild to severe motor delay and mental retardation; infantile-onset epilepsy; head growth deceleration; movement disorders (ataxia, dystonia, spasticity); and non-epileptic paroxysmal events (intermittent ataxia, periodic confusion, recurrent headaches). During last years the classic phenotype of this syndrome, as originally reported, has expanded. We report the atypical phenotype of a boy with GLUT1 deficiency syndrome, characterized by mild mental retardation and drug-resistant absence seizures with onset at the age of 6 years, without movement disorders nor decrease of head circumference. A prompt diagnosis of this disorder is mandatory since the ketogenic diet might represent an effective treatment. PMID:24891901

  9. Radiographic and Tomographic Analysis in Patients with Stickler Syndrome Type I

    PubMed Central

    Al Kaissi, Ali; Chehida, Farid Ben; Ganger, Rudolf; Kenis, Vladimir; Zandieh, Shahin; Hofstaetter, Jochen G; Klaushofer, Klaus; Grill, Franz

    2013-01-01

    Objective: To further investigate the underlying pathology of axial and appendicular skeletal abnormalities such as painful spine stiffness, gait abnormalities, early onset osteoarthritis and patellar instability in patients with Stickler syndrome type I. Radiographic and tomographic analyses were organized. Methods: From a series of Stickler syndrome patients followed from early life to late childhood. Ten patients (6 boys and four girls of different ethnic origins were consistent with the diagnosis of Stickler syndrome type I ). Phenotypic characterization was the baseline tool applied for all patients and genotypic correlation was performed on four families Results: A constellation of axial abnormalities namely; anterolateral ossification of the anterior longitudinal spinal ligament with subsequent fusion of two cervical vertebrae, early onset Forestier disease (progressive spinal hyperostosis with subsequent vertebral fusion on top of bridging osteophytes and “Bamboo-like spine” resembling ankylosing spondylitis) and severe premature spine degeneration were evident. Appendicular abnormalities in connection with generalized epiphyseal dysplasia were the underlying aetiology in patients with Intoeing gait and femoral anteversion, early onset severe osteoarthritis of the weight bearing joint. Remarkable trochleo-patellar dysplasia secondary to severe osteoarthritis causing effectively the development of patellar instability was additional pathology. Mutation of COL2A1 has been confirmed as the causative gene for Stickler syndrome type I Conclusion: We concluded that conventional radiographs and the molecular determination of a COL2A1 in patients with (Stickler syndrome type I) are insufficient tools to explain the reasons behind the tremendous magnitude of axial and appendicular skeletal abnormalities. We were able to modify the criteria of the clinical phenotype as designated by Rose et al in accordance with the novel axial and appendicular criteria as

  10. Spontaneous rupture of the spleen in type IV Ehlers-Danlos syndrome: report of a case.

    PubMed

    Privitera, Antonio; Milkhu, Chaz; Datta, Vivek; Sayegh, Mazim; Cohen, Richard; Windsor, Alastair

    2009-01-01

    The vascular type of Ehlers-Danlos syndrome, type IV, is associated with severe complications, including arterial rupture and visceral perforation. However, to our knowledge, there has been only one previous report of splenic rupture caused by a spontaneous hemorrhage in type IV Ehlers-Danlos syndrome. We report another case of this uncommon complication, occurring in a 35-year-old woman who presented after the sudden onset of acute abdominal pain. Patients should be stabilized quickly in the intensive care unit and the most timesaving surgical techniques used. Moreover, tissues must be handled with great care intraoperatively in view of their extreme fragility. Despite prompt and appropriate treatment, the prognosis is often dismal. PMID:19132469

  11. C5orf42 is the major gene responsible for OFD syndrome type VI.

    PubMed

    Lopez, Estelle; Thauvin-Robinet, Christel; Reversade, Bruno; Khartoufi, Nadia El; Devisme, Louise; Holder, Muriel; Ansart-Franquet, Hélène; Avila, Magali; Lacombe, Didier; Kleinfinger, Pascale; Kaori, Irahara; Takanashi, Jun-Ichi; Le Merrer, Martine; Martinovic, Jelena; Noël, Catherine; Shboul, Mohammad; Ho, Lena; Güven, Yeliz; Razavi, Ferechté; Burglen, Lydie; Gigot, Nadège; Darmency-Stamboul, Véronique; Thevenon, Julien; Aral, Bernard; Kayserili, Hülya; Huet, Frédéric; Lyonnet, Stanislas; Le Caignec, Cédric; Franco, Brunella; Rivière, Jean-Baptiste; Faivre, Laurence; Attié-Bitach, Tania

    2014-03-01

    Oral-facial-digital syndrome type VI (OFD VI) is a recessive ciliopathy defined by two diagnostic criteria: molar tooth sign (MTS) and one or more of the following: (1) tongue hamartoma (s) and/or additional frenula and/or upper lip notch; (2) mesoaxial polydactyly of one or more hands or feet; (3) hypothalamic hamartoma. Because of the MTS, OFD VI belongs to the "Joubert syndrome related disorders". Its genetic aetiology remains largely unknown although mutations in the TMEM216 gene, responsible for Joubert (JBS2) and Meckel-Gruber (MKS2) syndromes, have been reported in two OFD VI patients. To explore the molecular cause(s) of OFD VI syndrome, we used an exome sequencing strategy in six unrelated families followed by Sanger sequencing. We identified a total of 14 novel mutations in the C5orf42 gene in 9/11 families with positive OFD VI diagnostic criteria including a severe fetal case with microphthalmia, cerebellar hypoplasia, corpus callosum agenesis, polydactyly and skeletal dysplasia. C5orf42 mutations have already been reported in Joubert syndrome confirming that OFD VI and JBS are allelic disorders, thus enhancing our knowledge of the complex, highly heterogeneous nature of ciliopathies. PMID:24178751

  12. Myocardial infarction resulting from coronary artery dissection in an adolescent with Ehlers-Danlos syndrome type IV due to a type III collagen mutation.

    PubMed Central

    Adès, L. C.; Waltham, R. D.; Chiodo, A. A.; Bateman, J. F.

    1995-01-01

    Ehlers-Danlos syndrome encompasses a group of inherited disorders of connective tissue, some of which are characterised by abnormalities of collagen metabolism. The chromosomal location, identified genes and biochemical defects, inheritance pattern, and clinical features for the various known subtypes are outlined. Prenatal diagnosis is possible for types IV, VI, VIIA1, and VIIA2. An unusual presentation of type IV Ehlers-Danlos syndrome in a 16 year old boy with an anterior myocardial infarction resulting from dissection of the left anterior descending coronary artery is reported here. A clinical diagnosis of type IV Ehlers-Danlos syndrome was made subsequently and confirmed by the reduced production, impaired secretion, and abnormally slow electrophoretic migration of type III collagen, indicating an underlying mutation in the COL3A1 gene. This patient represents the first case of type IV Ehlers-Danlos syndrome with symptomatic coronary artery dissection. Images PMID:7546986

  13. Plasma Fibrinogen in Type 2 Diabetic Patients with Metabolic Syndrome and its Relation with Ischemic Heart Disease (IHD) and Retinopathy

    PubMed Central

    Mahendra, J.V.; Anuradha, T.S.; Talikoti, Prashanth; Nagaraj, R.S.; Vishali, V.

    2015-01-01

    Introduction: Metabolic syndrome or Syndrome X is characterized by hyperlipidemia, increased blood pressure, abdominal obesity and hyperglycemia, which increases the risk of cardiovascular complications. In addition to these, it is also associated with nontraditional risk factor like C- reactive protein, Plasminogen activator and fibrinogen. Various studies have documented association of these nontraditional risk factor, in Type 2 diabetes mellitus. Thus patients with diabetes mellitus are higher risk of developing micro and macro vascular complications like ischemic heart disease (IHD) and diabetic retinopathy. Diabetic retinopathy is the leading cause of decreased visual acuity, which is associated with maculopathy and profierative complications of it. Chronic hyperglycemia and its associated nonenzymatic glycation play an important role in the development of microangiopathy. Aims and Objectives: To study the prevalence of the metabolic syndrome in type 2 diabetes mellitus. To study the plasma fibrinogen and its relationship with IHD and retinopathy in type 2 Diabetes mellitus patients with metabolic syndrome. Materials and Methods: Patients of type 2 diabetes Mellitus were recruited based on the inclusion and exclusion criteria. History of IHD and ECG evidence of ischemia was obtained. Retinopathy was diagnosed by direct opthalmoscopy. Fasting glucose, lipid profile and plasma fibrinogen were analyzed. Stastical analysis was carried by Chi square test and student‘t’ test. Results: The prevalence of metabolic syndrome in study population of 100 type 2 diabetic patients is 58% and is significantly associated with duration of the disease (p<0.001). Fifty eight patients have hyperfibrinogenemia and mean fibrinogen level is significantly high in diabetic patients with metabolic syndrome when compared to diabetic patients without metabolic syndrome (p<0.001). Diabetic patient with metabolic syndrome and hyperfibrinogenemia have higher prevalence of IHD and

  14. Inflammatory Cytokine Profile Associated with Metabolic Syndrome in Adult Patients with Type 1 Diabetes

    PubMed Central

    Ferreira-Hermosillo, Aldo; Molina-Ayala, Mario; Ramírez-Rentería, Claudia; Vargas, Guadalupe; Gonzalez, Baldomero; Isibasi, Armando; Archundia-Riveros, Irma; Mendoza, Victoria

    2015-01-01

    Objective. To compare the serum concentration of IL-6, IL-10, TNF, IL-8, resistin, and adiponectin in type 1 diabetic patients with and without metabolic syndrome and to determine the cut-off point of the estimated glucose disposal rate that accurately differentiated these groups. Design. We conducted a cross-sectional evaluation of all patients in our type 1 diabetes clinic from January 2012 to January 2013. Patients were considered to have metabolic syndrome when they fulfilled the joint statement criteria and were evaluated for clinical, biochemical, and immunological features. Methods. We determined serum IL-6, IL-8, IL-10, and TNF with flow cytometry and adiponectin and resistin concentrations with enzyme linked immunosorbent assay in patients with and without metabolic syndrome. We also compared estimated glucose disposal rate between groups. Results. We tested 140 patients. Forty-four percent fulfilled the metabolic syndrome criteria (n = 61), 54% had central obesity, 30% had hypertriglyceridemia, 29% had hypoalphalipoproteinemia, and 19% had hypertension. We observed that resistin concentrations were higher in patients with MS. Conclusion. We found a high prevalence of MS in Mexican patients with T1D. The increased level of resistin may be related to the increased fat mass and could be involved in the development of insulin resistance. PMID:26273680

  15. Knowledge, assessment, and management of adults with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type among Flemish physiotherapists.

    PubMed

    Rombaut, Lies; Deane, Janet; Simmonds, Jane; De Wandele, Inge; De Paepe, Anne; Malfait, Fransiska; Calders, Patrick

    2015-03-01

    Physiotherapy plays a fundamental role in managing adults with the joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT). However, it is a challenge for both the patient and the physiotherapist as the condition is poorly understood and treatment for JHS/EDS-HT is currently undefined. Insight into current practice is, therefore, necessary in order to establish baseline knowledge in this area and in the long term to improve the standard of patient care. Therefore, the purpose of this study was to evaluate current physiotherapists' knowledge of JHS/EDS-HT and to gain insight into current physiotherapy practice with emphasis on assessment, management, and treatment efficacy. Three hundred twenty-five Flemish physiotherapists participated in the study by filling out electronically a modified version of the "Hypermobility and Hypermobility Syndrome Questionnaire" (HHQ), which covered theoretical constructs such as general knowledge, assessment, management, and learning in relation to generalized joint hypermobility and JHS/EDS-HT. The results show that physiotherapists report a low level of confidence with regard to assessment and management of JHS/EDS-HT. Knowledge of hypermobility and JHS/EDS-HT is weak, especially regarding the features associated with JHS/EDS-HT. Many treatment approaches are used by physiotherapists with the majority showing preference for education, reassurance, muscle strengthening, proprioceptive and core stability training. Almost all approaches were perceived as being clinically effective by the physiotherapists, highlighting a lack of consensus. In conclusion, this study in Flemish physiotherapists confirms that JHS/EDS-HT is under-recognized, not well known and deemed difficult to treat. Further education is required and sought by the physiotherapists surveyed, and future research is needed. PMID:25821093

  16. Clinical Presentation of Mucopolysaccharidosis Type II (Hunter's Syndrome)

    PubMed Central

    Chinawa, JM; Adimora, GN; Obu, HA; Tagbo, B; Ujunwa, F; Onubogu, I

    2012-01-01

    We present a rare case of mucopolysaccharidosis (MPS) with a typical presentation of mental retardation and absence of corneal clouding. The purpose of presenting this case report is to highlight the distinctive manifestation of MPS (Hunter's disease) and to provide a concise report of Hunter's disease for medical practitioners with the hope that such information will help identify boys earlier in the course of their disease. This report is of a 7-year-old boy who presented to the children outpatient through a referral with a history of inability to grasp objects, inability to express self, and coarse skin, which started 5 years ago. On examination, he was short statured, with a big head, protruding abdomen, coarse skin, swollen wrist joints, and clubbed fingers. There was mild mental retardation. Investigations revealed mucopolysaccharides in urine ad radiographic findings were in keeping with diagnosis. Based on the clinical features and radiological findings, one can diagnose a case of MPS. However, careful and critical approach is necessary to exactly diagnose the type of MPS as enzymatic studies are not available in most centers. PMID:23209998

  17. Polyglandular endocrinopathy type II (Schmidt's syndrome) in a Dobermann pinscher.

    PubMed

    Cartwright, J A; Stone, J; Rick, M; Dunning, M D

    2016-09-01

    A three-year-old, female neutered, Dobermann pinscher was presented for investigation of lethargy, episodic collapse, ataxia and myxoedema. Primary hypothyroidism and primary cortisol-deficient hypoadrenocorticism were diagnosed based on history, physical examination and compatible hormonal analysis. Increased serum concentrations of thyroglobulin autoantibodies and 21-hydroxylase autoantibodies indicated an immune-mediated aetiology. The case was complicated by lymphadenopathy with hand-mirror lymphocytes, classically identified in lymphoma. A polymerase chain reaction test for antigen receptor rearrangement indicated polyclonality and therefore reactive lymphadenopathy. The dog's clinical signs resolved following introduction of levothyroxine and prednisolone. Prioritising the problem-based approach in this case facilitated the diagnosis of hypoadrenocorticism in addition to hypothyroidism due to the persistence of clinical signs despite thyroxine replacement. Importantly, atypical adrenal gland dysfunction was not misinterpreted as inadequate therapeutic response to thyroxine supplementation. The observation that polyglandular endocrinopathy type II can occur in dogs suggests that in dogs with a suboptimal response to treatment for hypothyroidism or hypoadrenocorticism comorbid endocrinopathies should be investigated. PMID:27487017

  18. The role of narrative medicine in the management of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

    PubMed

    Knight, Isobel

    2015-03-01

    Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is a hereditary connective tissue disorder affecting every bodily system. It is largely underdiagnosed by many practitioners, with the result of a considerable delay in diagnosis and, consequently, in the onset of adequate management schedule and treatment. Patients may also experience to be misbelieved, erroneously considered affected by a psychiatric or psychosomatic disorders, and rejected by the medical profession, which can lead to feelings of anger and resentment. Patient journeys are often long and complicated, but if doctors allowed the patient time to tell the full story, and were more prepared to think holistically, there may be a far more positive outcome. Here, the patients' perspective is presented with a narrative medicine approach, illustrating the tri-dimensional experience of a JHS/EDS-HT patient, who is also a Bowen Practitioner and a medical writer/educator. Narrative medicine would be invaluable in working with JHS/EDS-HT so that the patient can tell the story, and offer the practitioner a whole picture of her/his suffering and, often, the key for understanding the cause(s). Once this has been achieved, it might be possible to build upon a more positive and therapeutic dialogue which would result in better treatment and more effective management. It is also important for doctors to communicate with JHS/EDS-HT experts who will ultimately improve the patient journey and treatment outcomes of such a complex connective tissue disorder. PMID:25821096

  19. Heart rate, conduction and ultrasound abnormalities in adults with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

    PubMed

    Camerota, Filippo; Castori, Marco; Celletti, Claudia; Colotto, Marco; Amato, Silvia; Colella, Alessandra; Curione, Mario; Danese, Chiara

    2014-07-01

    Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping heritable connective tissue disorders strongly associating with pain, fatigue and other secondary aspects. Though not considered a diagnostic criterion for most EDS subtypes, cardiovascular involvement is a well-known complication in EDS. A case-control study was carried out on 28 adults with JHS/EDS-HT diagnosed according to current criteria, compared to 29 healthy subjects evaluating resting electrocardiographic (ECG), 24-h ECG and resting heart ultrasound data. Results obtained in the ECG studies showed a moderate excess in duration of the PR interval and P wave, an excess of heart conduction and rate abnormalities and an increased rate of mitral and tricuspid valve insufficiency often complicating with "true" mitral valve prolapse in the ecocardiographic study. These variable ECG subclinical anomalies reported in our sample may represent the resting surrogate of such a subnormal cardiovascular response to postural changes that are known to be present in patients with JHS/EDS-HT. Our findings indicate the usefulness of a full cardiologic evaluation of adults with JHS/EDS-HT for the correct management. PMID:24752348

  20. Cardiac arrest refractory to standard intervention in atypical Timothy syndrome (LQT8 type 2).

    PubMed

    Philipp, Lucas R; Rodriguez, Fred H

    2016-04-01

    Timothy syndrome (TS) is a rare, multisystem disorder most commonly associated with profound QTc prolongation and cutaneous dysmorphia arising from mutations of the L-type calcium channel. We present a case of a 12-day-old newborn who presented with respiratory distress and cyanosis. Diagnostic workup was notable for multiple cardiac abnormalities, and genetic analysis was consistent with an exon 8 mutation of the CACNA1C gene, which is diagnostic for TS type 2 (atypical TS). This patient presented with a novel constellation of symptoms, without dysmorphic features, and with a more moderate QTc interval. The heterogeneity of phenotypes suggests that this disorder may be characterized by variable expressivity or a spectrum of disease rather than a clearly defined syndrome. PMID:27034553

  1. Rous-associated virus type 7 induces a syndrome in chickens characterized by stunting and obesity.

    PubMed Central

    Carter, J K; Ow, C L; Smith, R E

    1983-01-01

    Infection of 10-day-old chicken embryos with an avian retrovirus. Rous-associated virus type 7, resulted in a disease characterized by stunting and hyperlipidemia. By 20 days after hatch, infected chickens were smaller than hatchmates and developed ataxia and obesity over the next 30 days. Histological examinations of livers from infected chickens revealed a diffuse panlobular fatty infiltrate involving an accumulation of fat in microdroplets. Electron microscopic examinations of livers from infected chickens revealed hepatocytes with swollen mitochondria that lacked cristae. The thyroid and pancreas were infiltrated with lymphoblastoid cells by 1 week after hatch. An examination of the blood revealed a mild anemia, a frank lipemia, and high levels of uric acid. This syndrome induced by Rous-associated virus type 7 in chickens may be useful for elucidating the nature of several diseases, including that found in the fatty liver and kidney syndrome of chickens and that observed in a strain of obese chickens. Images PMID:6295959

  2. Acute respiratory distress syndrome in adenovirus type 4 pneumonia: A case report.

    PubMed

    Narra, R; Bono, P; Zoccoli, A; Orlandi, A; Piconi, S; Grasselli, G; Crotti, S; Girello, A; Piralla, A; Baldanti, F; Lunghi, G

    2016-08-01

    Human adenoviruses (HAdVs) cause a wide spectrum of clinical syndromes, depending on species and types, from mild respiratory infections to deadly pneumonia: in particular, severe infections occur in immunocompromised patients. In this report, we describe the case of a 36 years-old woman admitted to our intensive care unit (ICU) with severe respiratory distress syndrome caused by adenovirus pneumonia, that required invasive respiratory support (mechanical ventilation and extracorporeal membrane oxygenation). Molecular assays detected the virus in respiratory and plasma specimen and sequencing procedure identified HAdV type 4. Patient improved after cidofovir administration. Leukopenia and subsequent bacterial infection occurred, but the patient recovered completely and was discharged from the hospital after 54days. PMID:27354307

  3. Daughter and mother with orofaciodigital syndrome type 1 and glomerulocystic kidney disease.

    PubMed

    Iijima, Takashi; Hoshino, Junichi; Mise, Koki; Sumida, Keiichi; Suwabe, Tatsuya; Hayami, Noriko; Ueno, Toshiharu; Takaichi, Kenmei; Fujii, Takeshi; Ohashi, Kenichi; Morisada, Naoya; Iijima, Kazumoto; Ubara, Yoshifumi

    2016-09-01

    A 35-year-old woman was admitted to our hospital for evaluation of end-stage renal failure. Diagnostic imaging, including ultrasonography and magnetic resonance imaging, showed polycystic kidneys and peribiliary hepatic cysts, but the renal cysts were isointense and her kidneys were smaller than the end-stage kidneys of patients with autosomal dominant polycystic kidney disease. Glomerulocystic kidney disease was diagnosed by renal biopsy. Clinical examination revealed findings such as a missing maxillary canine, lingual anomalies, and brachydactyly. Genetic testing gave a diagnosis of orofaciodigital syndrome type 1 with a 5 nucleotide deletion indicating a frameshift mutation in exon 9. The patient's mother had the same mutation and similar clinical findings. This case is useful for understanding kidney and liver involvement in orofaciodigital syndrome type 1. PMID:27131853

  4. Cardiac arrest refractory to standard intervention in atypical Timothy syndrome (LQT8 type 2)

    PubMed Central

    Rodriguez, Fred H.

    2016-01-01

    Timothy syndrome (TS) is a rare, multisystem disorder most commonly associated with profound QTc prolongation and cutaneous dysmorphia arising from mutations of the L-type calcium channel. We present a case of a 12-day-old newborn who presented with respiratory distress and cyanosis. Diagnostic workup was notable for multiple cardiac abnormalities, and genetic analysis was consistent with an exon 8 mutation of the CACNA1C gene, which is diagnostic for TS type 2 (atypical TS). This patient presented with a novel constellation of symptoms, without dysmorphic features, and with a more moderate QTc interval. The heterogeneity of phenotypes suggests that this disorder may be characterized by variable expressivity or a spectrum of disease rather than a clearly defined syndrome. PMID:27034553

  5. Extended phenotypes in a boy and his mother with oto-palato-digital-syndrome type II

    PubMed Central

    Kaissi, Ali Al; Kraschl, Raimund; Kaulfersch, Wilhelm; Grill, Franz; Ganger, Rudolf

    2015-01-01

    Key Clinical Message We describe additional phenotypic features in a boy and his mother. Both manifested the phenotypic/genotypic correlation of oto-palato-digital syndrome type II. The mother′s radiographs showed wormian bones of the skull, and paranasal bossing, her feet showed bilateral fusion of the cuboid with the lateral cuneiform bone with subsequent development of metatarsus varus associated with dysplastic distal phalanges. PMID:26401283

  6. A novel PAX3 mutation in a Japanese boy with Waardenburg syndrome type 1

    PubMed Central

    Yoshida, Yu; Doi, Rieko; Adachi, Kaori; Nanba, Eiji; Kodani, Isamu; Ryoke, Kazuo

    2016-01-01

    Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant disorder characterized by hair hypopigmentation, abnormal iris pigmentation, and congenital hearing loss. WS1 is caused by mutations in paired box gene 3 (PAX3). We identified a novel PAX3 mutation (c.1107 C>G, p.Ser369Arg) in a Japanese WS1 patient showing abnormal right iris pigmentation, right-sided congenital hearing loss, synophrys, incomplete left cleft lip, and cryptorchidism. PMID:27081571

  7. A novel PAX3 mutation in a Japanese boy with Waardenburg syndrome type 1.

    PubMed

    Yoshida, Yu; Doi, Rieko; Adachi, Kaori; Nanba, Eiji; Kodani, Isamu; Ryoke, Kazuo

    2016-01-01

    Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant disorder characterized by hair hypopigmentation, abnormal iris pigmentation, and congenital hearing loss. WS1 is caused by mutations in paired box gene 3 (PAX3). We identified a novel PAX3 mutation (c.1107 C>G, p.Ser369Arg) in a Japanese WS1 patient showing abnormal right iris pigmentation, right-sided congenital hearing loss, synophrys, incomplete left cleft lip, and cryptorchidism. PMID:27081571

  8. Aromatase excess syndrome presenting with prepubertal gynecomastia in an Egyptian child with type 1 neurofibromatosis

    PubMed Central

    Metwalley, Kotb Abbass; Farghaly, Hekma Saad

    2013-01-01

    A romatase excess syndrome (AEXS) is a rare autosomal dominant disorder characterized by prepubertal gynecomastia, it responds well to medical treatment. In the absence of prompt suspicion, it can expose the patient to the risk of unnecessary surgical intervention. Up to our best knowledge, the association between AEXS and neurofibromatosis type 1 (NF1) was not reported before. Here, we describe a AEXS presenting with prepubertal gynecomastia in an Egyptian child with NF1 that improved with aromatase inhibitors. PMID:24497716

  9. Math Learning Disability and Math LD Subtypes: Evidence from Studies of Turner Syndrome, Fragile X Syndrome, and Neurofibromatosis Type 1.

    ERIC Educational Resources Information Center

    Mazzocco, Michele M. M.

    2001-01-01

    This study examined whether indicators of math learning disability were observed in 35 5- and 6-year-olds with either neurofibromatosis, Turner Syndrome, or fragile X syndrome and compared to controls. Findings indicate that girls with fragile X or Turner syndrome but not neurofibromatosis are significantly more likely to have specific math…

  10. Different impacts of metabolic syndrome components on insulin resistance in type 2 diabetes.

    PubMed

    Hsu, Chung-Hua

    2013-01-01

    Objective. To examine the different impacts of MS components on insulin resistance in type 2 diabetes. Methods. A number of subjects (144) who met the criteria of (1) age between 30 and 75 years, (2) had type 2 diabetes for more than one year, and (3) taking gliclazide and metformin for more than 6 months were enrolled. All subjects were assigned to one of the four HOMA index categories. The HOMA index quartile 4 denotes the highest insulin resistance. The main outcome evaluated is the odds ratios (ORs) of different MS components on HOMA index quartile 4. The characteristics in HOMA index quartiles and groups of nonmetabolic syndrome (NMS; number of components < 2), metabolic syndrome A (MSA; number of components = 2), and metabolic syndrome B (MSB; number of components > 2) were also evaluated. Results. The results showed that both MSA and MSB groups had higher ORs (5.9 and 13.8 times, resp.) than the NMS group; and that subjects with large waist circumference (LWC) and high triglyceride (HTG) level have higher ORs (6.1 and 2.6 times, resp.) in developing higher insulin resistance than normal control subjects. Conclusion. Type 2 diabetic patients with greater number of MS components have higher ORs in developing increased insulin resistance. PMID:23431295

  11. Clinical and molecular characterization of two patients with palmoplantar keratoderma-congenital alopecia syndrome type 2.

    PubMed

    Castori, M; Morlino, S; Sana, M E; Paradisi, M; Tadini, G; Angioni, A; Malacarne, M; Grammatico, P; Iascone, M; Forzano, F

    2016-08-01

    Palmoplantar keratoderma-congenital alopecia (PPKCA) syndrome is a rare genodermatosis, with two clinically recognizable forms: dominant (Type 1) and recessive (Type 2). Reports of only 18 patients have been published to date, and the molecular basis of the condition is unknown. We describe two cases with PPKCA Type 2 (PPKCA2), comprising a novel patient, originally reported as an example of autosomal ichthyosis follicularis-atrichia-photophobia syndrome, and the 6-year follow-up of a previously published case. Extensive molecular studies of both patients excluded mutations in all the known genes associated with PPK and partially overlapping syndromes. The striking similarities between these two patients confirm PPKCA2 as a discrete genodermatosis, of which the main features are congenital and universal alopecia, diffuse keratosis pilaris, facial erythema, and a specific PPK with predominant involvement of the fingertips and borders of the hands and feet, with evolution of sclerodactyly, contractures and constrictions. Clinical follow-up of these patients has demonstrated progressive worsening of the hand involvement and attenuation of facial erythema. PMID:27339777

  12. Latent polyglandular autoimmune syndrome type 2 case diagnosed during a shock manifestation.

    PubMed

    Gürkan, Eren; Çetinarslan, Berrin; Güzelmansur, İsmail; Kocabaş, Beyza

    2016-07-01

    There are many types of polyglandular autoimmune syndrome (PAS). PAS type 2 is the most common type among adults. For PAS type 2 (PAS-2) diagnosis, detection of Addison's disease with autoimmune thyroid disease and/or type 1 diabetes mellitus are required. Premature ovarian insufficiency, pernicious anemia, vitiligo, alopecia, myasthenia gravis, celiac disease and autoimmune diabetes insipidus may be comorbidities of this condition. Contrary to the common belief, latent PAS is more common than the manifest forms. Here, we present a PAS-2 case diagnosed via adrenal crisis. At the time of diagnosis, the case was observed to have thyroid, adrenal and ovarian involvement. Therefore, PAS-2 and possible immunologic disorders were discussed. PMID:26806667

  13. Addison's disease in a patient with hypothyroidism: autoimmune polyglandular syndrome type 2.

    PubMed

    Bain, Anna; Stewart, Munro; Mwamure, Peter; Nirmalaraj, Kingsley

    2015-01-01

    A 57-year-old Caucasian woman with known autoimmune hypothyroidism diagnosed in 2006 presented to hospital with flu-like symptoms and circulatory collapse. She reported weight loss and gradual increase in her skin pigmentation over a 1-year period. Aggressive fluid resuscitation was instituted. Hormonal tests showed primary adrenal insufficiency. Appropriate steroid replacement was started with rapid clinical response. Subsequent antibody tests confirmed the diagnosis of autoimmune polyglandular type 2 (Schmidt's) syndrome. The adrenal crisis had been precipitated by influenza virus type B infection. PMID:26240101

  14. Successful management of complex regional pain syndrome type 1 using single injection interscalene brachial plexus block

    PubMed Central

    Fallatah, Summayah M.A.

    2014-01-01

    Complex regional pain syndrome (CRPS) type 1 of the upper limb is a painful and debilitating condition. Interscalene brachial plexus block (ISB) in conjugation with other modalities was shown to be a feasible therapy with variable success. We reported a case of CRPS type 1 as diagnosed by International Association for the Study of Pain criteria in which pharmacological approaches failed to achieve adequate pain relief and even were associated with progressive dysfunction of the upper extremity. Single injection ISB, in combination with physical therapy and botulinum toxin injection, was successful to alleviate pain with functional restoration. PMID:25422619

  15. Waardenburg syndrome type 4: report of two new cases caused by SOX10 mutations in Spain.

    PubMed

    Fernández, Raquel M; Núñez-Ramos, Raquel; Enguix-Riego, M Valle; Román-Rodríguez, Francisco José; Galán-Gómez, Enrique; Blesa-Sánchez, Emilio; Antiñolo, Guillermo; Núñez-Núñez, Ramón; Borrego, Salud

    2014-02-01

    Shah-Waardenburg syndrome or Waardenburg syndrome type 4 (WS4) is a neurocristopathy characterized by the association of deafness, depigmentation and Hirschsprung disease. Three disease-causing genes have been identified so far for WS4: EDNRB, EDN3, and SOX10. SOX10 mutations, found in 45-55% of WS4 patients, are inherited in autosomal dominant way. In addition, mutations in SOX10 are also responsible for an extended syndrome involving peripheral and central neurological phenotypes, referred to as PCWH (peripheral demyelinating neuropathy, central dysmyelinating leucodystrophy, Waardenburg syndrome, Hirschsprung disease). Such mutations are mostly private, and a high intra- and inter-familial variability exists. In this report, we present a patient with WS4 and a second with PCWH due to SOX10 mutations supporting again the genetic and phenotypic heterogeneity of these syndromes. Interestingly, the WS4 family carries an insertion of 19 nucleotides in exon 5 of SOX10, which results in distinct phenotypes along three different generations: hypopigmentation in the maternal grandmother, hearing loss in the mother, and WS4 in the proband. Since mosaicism cannot explain the three different related-WS features observed in this family, we propose as the most plausible explanation the existence of additional molecular events, acting in an additive or multiplicative fashion, in genes or regulatory regions unidentified so far. On the other hand, the PCWH case was due to a de novo deletion in exon 5 of the gene. Efforts should be devoted to unravel the mechanisms underlying the intrafamilial phenotypic variability observed in the families affected, and to identify new genes responsible for the still unsolved WS4 cases. PMID:24311220

  16. Impact of angiotensin II type 1 receptor gene polymorphism on insulin resistance in polycystic ovary syndrome.

    PubMed

    El-Mesallamy, H; El-Refaie, T; El-Razek, R A

    2013-04-01

    Insulin resistance is allegedly a target pathophysiological mechanism in the pathogenesis of polycystic ovary syndrome. Moreover, this metabolic alteration is possibly genetically determined. In view of the recent evidence implicating genetic variants of the renin-angiotensin system as candidates in several metabolic disorders, we investigated the allele and genotype frequencies of the A1166 C polymorphism of the angiotensin II type 1 receptor in relation with various metabolic and biochemical parameters in affected females trying to asses its role in the pathogenesis of this syndrome. The study was conducted on 83 females of which 39 females served as the control group. The participants were matched for age, body mass index and degree of obesity. For all subjects biochemical parameters were assayed including soluble CD40 ligand together with fasting glucose and insulin which were used for calculation of insulin resistance indices, Genotyping performed using real time polymerase chain reaction revealed that the C allele frequency and the AC genotype were less frequently observed in patients compared to controls, however this difference was not statistically significant (p=0.146). Lack of the C allele was associated with adverse metabolic parameters including higher rate of insulin resistance as well as solubes CD40 ligand in the patients group. Results of the current study support a causative role for the A1166 C polymorphism of the angiotensin II type 1 gene polymorphism in the pathogenesis or phenotypic expression of polycystic ovary syndrome. PMID:23564192

  17. Discovery of a Genetic Metabolic Cause for Mauriac Syndrome in Type 1 Diabetes.

    PubMed

    MacDonald, Michael J; Hasan, Noaman M; Ansari, Israr-Ul H; Longacre, Melissa J; Kendrick, Mindy A; Stoker, Scott W

    2016-07-01

    A mechanistic cause for Mauriac syndrome, a syndrome of growth failure and delayed puberty associated with massive liver enlargement from glycogen deposition in children with poorly controlled type 1 diabetes, is unknown. We discovered a mutation in the catalytic subunit of liver glycogen phosphorylase kinase in a patient with Mauriac syndrome whose liver extended into his pelvis. Glycogen phosphorylase kinase activates glycogen phosphorylase, the enzyme that catalyzes the first step in glycogen breakdown. We show that the mutant subunit acts in a dominant manner to completely inhibit glycogen phosphorylase kinase enzyme activity and that this interferes with glycogenolysis causing increased levels of glycogen in human liver cells. It is known that even normal blood glucose levels physiologically inhibit glycogen phosphorylase to diminish glucose release from the liver when glycogenolysis is not needed. The patient's mother possessed the same mutant glycogen phosphorylase kinase subunit, but did not have diabetes or hepatomegaly. His father had childhood type 1 diabetes in poor glycemic control, but lacked the mutation and had neither hepatomegaly nor growth failure. This case proves that the effect of a mutant enzyme of glycogen metabolism can combine with hyperglycemia to directly hyperinhibit glycogen phosphorylase, in turn blocking glycogenolysis causing the massive liver in Mauriac disease. PMID:27207549

  18. Alu-mediated deletion of SOX10 regulatory elements in Waardenburg syndrome type 4.

    PubMed

    Bondurand, Nadége; Fouquet, Virginie; Baral, Viviane; Lecerf, Laure; Loundon, Natalie; Goossens, Michel; Duriez, Benedicte; Labrune, Philippe; Pingault, Veronique

    2012-09-01

    Waardenburg syndrome type 4 (WS4) is a rare neural crest disorder defined by the combination of Waardenburg syndrome (sensorineural hearing loss and pigmentation defects) and Hirschsprung disease (intestinal aganglionosis). Three genes are known to be involved in this syndrome, that is, EDN3 (endothelin-3), EDNRB (endothelin receptor type B), and SOX10. However, 15-35% of WS4 remains unexplained at the molecular level, suggesting that other genes could be involved and/or that mutations within known genes may have escaped previous screenings. Here, we searched for deletions within recently identified SOX10 regulatory sequences and describe the first characterization of a WS4 patient presenting with a large deletion encompassing three of these enhancers. Analysis of the breakpoint region suggests a complex rearrangement involving three Alu sequences that could be mediated by a FosTes/MMBIR replication mechanism. Taken together with recent reports, our results demonstrate that the disruption of highly conserved non-coding elements located within or at a long distance from the coding sequences of key genes can result in several neurocristopathies. This opens up new routes to the molecular dissection of neural crest disorders. PMID:22378281

  19. Transcriptome-Wide Expression Profiling in Skin Fibroblasts of Patients with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type.

    PubMed

    Chiarelli, Nicola; Carini, Giulia; Zoppi, Nicoletta; Dordoni, Chiara; Ritelli, Marco; Venturini, Marina; Castori, Marco; Colombi, Marina

    2016-01-01

    Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT), is likely the most common systemic heritable connective tissue disorder, and is mostly recognized by generalized joint hypermobility, joint instability complications, minor skin changes and a wide range of satellite features. JHS/EDS-HT is considered an autosomal dominant trait but is still without a defined molecular basis. The absence of (a) causative gene(s) for JHS/EDS-HT is likely attributable to marked genetic heterogeneity and/or interaction of multiple loci. In order to help in deciphering such a complex molecular background, we carried out a comprehensive immunofluorescence analysis and gene expression profiling in cultured skin fibroblasts from five women affected with JHS/EDS-HT. Protein study revealed disarray of several matrix structural components such as fibrillins, tenascins, elastin, collagens, fibronectin, and their integrin receptors. Transcriptome analysis indicated perturbation of different signaling cascades that are required for homeostatic regulation either during development or in adult tissues as well as altered expression of several genes involved in maintenance of extracellular matrix architecture and homeostasis (e.g., SPON2, TGM2, MMP16, GPC4, SULF1), cell-cell adhesion (e.g., CDH2, CHD10, PCDH9, CLDN11, FLG, DSP), immune/inflammatory/pain responses (e.g., CFD, AQP9, COLEC12, KCNQ5, PRLR), and essential for redox balance (e.g., ADH1C, AKR1C2, AKR1C3, MAOB, GSTM5). Our findings provide a picture of the gene expression profile and dysregulated pathways in JHS/EDS-HT skin fibroblasts that correlate well with the systemic phenotype of the patients. PMID:27518164

  20. Transcriptome-Wide Expression Profiling in Skin Fibroblasts of Patients with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type

    PubMed Central

    Chiarelli, Nicola; Carini, Giulia; Zoppi, Nicoletta; Dordoni, Chiara; Ritelli, Marco; Venturini, Marina; Castori, Marco; Colombi, Marina

    2016-01-01

    Joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type (JHS/EDS-HT), is likely the most common systemic heritable connective tissue disorder, and is mostly recognized by generalized joint hypermobility, joint instability complications, minor skin changes and a wide range of satellite features. JHS/EDS-HT is considered an autosomal dominant trait but is still without a defined molecular basis. The absence of (a) causative gene(s) for JHS/EDS-HT is likely attributable to marked genetic heterogeneity and/or interaction of multiple loci. In order to help in deciphering such a complex molecular background, we carried out a comprehensive immunofluorescence analysis and gene expression profiling in cultured skin fibroblasts from five women affected with JHS/EDS-HT. Protein study revealed disarray of several matrix structural components such as fibrillins, tenascins, elastin, collagens, fibronectin, and their integrin receptors. Transcriptome analysis indicated perturbation of different signaling cascades that are required for homeostatic regulation either during development or in adult tissues as well as altered expression of several genes involved in maintenance of extracellular matrix architecture and homeostasis (e.g., SPON2, TGM2, MMP16, GPC4, SULF1), cell-cell adhesion (e.g., CDH2, CHD10, PCDH9, CLDN11, FLG, DSP), immune/inflammatory/pain responses (e.g., CFD, AQP9, COLEC12, KCNQ5, PRLR), and essential for redox balance (e.g., ADH1C, AKR1C2, AKR1C3, MAOB, GSTM5). Our findings provide a picture of the gene expression profile and dysregulated pathways in JHS/EDS-HT skin fibroblasts that correlate well with the systemic phenotype of the patients. PMID:27518164

  1. Unexpected association between joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type and obsessive-compulsive personality disorder.

    PubMed

    Pasquini, Massimo; Celletti, Claudia; Berardelli, Isabella; Roselli, Valentina; Mastroeni, Simona; Castori, Marco; Biondi, Massimo; Camerota, Filippo

    2014-05-01

    Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is a largely unrecognized, heritable connective tissue disorder, mainly characterized by joint instability complications, widespread musculoskeletal pain, and minor skin features. In a case-control study, 47 consecutive JHS/EDS-HT patients were investigated for the prevalence of psychiatric disorders and compared to 45 healthy controls in a single center. The psychiatric evaluation consisted of structured clinical interview for DSM-IV criteria by using the SCID-I and the SCID-II. Symptom severity was assessed using the Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), and the Brief Psychiatric Rating Scale (BPRS). The Global Assessment of Functioning Scale (GAF) was used to assess the overall severity of psychological, social, and occupational functions. JHS/EDS-HT patients had significantly higher mean scores for all questionnaires: HAM-A (6.7 vs. 3.8), HAM-D (6.4 vs. 2.7), GAF (75.0 vs. 86.1), and BPRS (27.5 vs. 25.6). The JHS/EDS-HT group had a 4.3 higher risk of being affected by any psychiatric disorder, and in particular, a 5.8 higher risk of having a personality disorder. In particular, 5 JHS/EDS-HT suffered from obsessive-compulsive personality disorder with an observed prevalence rate of 10.6 % (3.6-23.1). Psychiatric assessment of JHS/EDS-HT patients showed an extremely high prevalence of personality disorders (21 %), and of Axis-I disorders (38 %), mostly depressive. This study did not confirm the previously reported increased rate of panic disorders in JHS/EDS-HT. PMID:24272065

  2. Spectrum of mucocutaneous manifestations in 277 patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

    PubMed

    Castori, Marco; Dordoni, Chiara; Morlino, Silvia; Sperduti, Isabella; Ritelli, Marco; Valiante, Michele; Chiarelli, Nicola; Zanca, Arianna; Celletti, Claudia; Venturini, Marina; Camerota, Filippo; Calzavara-Pinton, Piergiacomo; Grammatico, Paola; Colombi, Marina

    2015-03-01

    Cutaneous manifestations are a diagnostic criterion of Ehlers-Danlos syndrome, hypermobility type (EDS-HT) and joint hypermobility syndrome (JHS). These two conditions, originally considered different disorders, are now accepted as clinically indistinguishable and often segregate as a single-familial trait. EDS-HT and JHS are still exclusion diagnoses not supported by any specific laboratory test. Accuracy of clinical diagnosis is, therefore, crucial for appropriate patients' classification and management, but it is actually hampered by the low consistency of many applied criteria including the cutaneous one. We report on mucocutaneous findings in 277 patients with JHS/EDS-HT with both sexes and various ages. Sixteen objective and five anamnestic items were selected and ascertained in two specialized outpatient clinics. Feature rates were compared by sex and age by a series of statistical tools. Data were also used for a multivariate correspondence analysis with the attempt to identify non-causal associations of features depicting recognizable phenotypic clusters. Our findings identified a few differences between sexes and thus indicated an attenuated sexual dimorphism for mucocutaneous features in JHS/EDS-HT. Ten features showed significantly distinct rates at different ages and this evidence corroborated the concept of an evolving phenotype in JHS/EDS-HT also affecting the skin. Multivariate correspondence analysis identified three relatively discrete phenotypic profiles, which may represent the cutaneous counterparts of the three disease phases previously proposed for JHS/EDS-HT. These findings could be used for revising the cutaneous criterion in a future consensus for the clinical diagnosis of JHS/EDS-HT. PMID:25655071

  3. Changing epidemiology of metabolic syndrome and type 2 diabetes in Chinese youth.

    PubMed

    Fu, JunFen; Prasad, Heranmaye C

    2014-01-01

    China is gradually taking its place as one of the world's economic giants and concurrently learning to understand how to bear the burdens of diseases that are more common in the fully developed world, such as pediatric obesity, metabolic syndrome, and type 2 diabetes mellitus. The purpose of this review is to consolidate the available information regarding these and draw the focus toward their sequential progression and increasing prevalence in Chinese children. Studies were collected in both English and Chinese, and the data were reviewed on the basis of disease prevalence and risk factors that are known from scientific literature that has been published to date. The majority of studies with appropriate content for inclusion here have been conducted within the last 15 years and up to date information from recent local and international research has also been included. Several factors have been implicated for the rise in obesity, most notably, the progressing economic expansion and exposure of local Chinese populations to Western influences. With this, metabolic syndrome has become a growing concern, as it is a precursor to cardiovascular disease and type 2 diabetes, leading to the alarmingly rapid development of deleterious consequences in children. The International Diabetes Federation proposed a definition for metabolic syndrome in 2007 (MS-IDF2007) worldwide, but whether it is also suitable for the Chinese population remains uncertain, so we have created the Chinese definition of metabolic syndrome upon the IDF framework. This MS-CHN2012 definition is based on multicenter studies to simplify and standardize primary care screening methods and is the first of its kind in China. Juvenile type 2 diabetes is the most worrisome result of obesity and metabolic syndrome, and studies have shown that the prevalence has doubled within 5 years-surpassing the prevalence of juvenile type 1 diabetes. Because of the extremely low number of studies currently published on these

  4. Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal

    PubMed Central

    Accurso, Anthony; Bernstein, Richard K; Dahlqvist, Annika; Draznin, Boris; Feinman, Richard D; Fine, Eugene J; Gleed, Amy; Jacobs, David B; Larson, Gabriel; Lustig, Robert H; Manninen, Anssi H; McFarlane, Samy I; Morrison, Katharine; Nielsen, Jørgen Vesti; Ravnskov, Uffe; Roth, Karl S; Silvestre, Ricardo; Sowers, James R; Sundberg, Ralf; Volek, Jeff S; Westman, Eric C; Wood, Richard J; Wortman, Jay; Vernon, Mary C

    2008-01-01

    Current nutritional approaches to metabolic syndrome and type 2 diabetes generally rely on reductions in dietary fat. The success of such approaches has been limited and therapy more generally relies on pharmacology. The argument is made that a re-evaluation of the role of carbohydrate restriction, the historical and intuitive approach to the problem, may provide an alternative and possibly superior dietary strategy. The rationale is that carbohydrate restriction improves glycemic control and reduces insulin fluctuations which are primary targets. Experiments are summarized showing that carbohydrate-restricted diets are at least as effective for weight loss as low-fat diets and that substitution of fat for carbohydrate is generally beneficial for risk of cardiovascular disease. These beneficial effects of carbohydrate restriction do not require weight loss. Finally, the point is reiterated that carbohydrate restriction improves all of the features of metabolic syndrome. PMID:18397522

  5. A Rare Clinical Variant of Oromandibular Limb Hypogenesis Syndrome Type I B.

    PubMed

    Kalaskar, Ritesh Rambharos; Godhane, Alkesh; Kalaskar, Ashita; Demble, Swati

    2016-01-01

    Aglossia is a rare congenital malformation that often occurs as an isolated disorder or is observed in association with other congenital deformities, particularly limb defects. We present a unique case of a 7-year-old girl with aglossia, hypodactyli, rudimentary ears, retrognathic and V-shaped mandible. Her parental history revealed intrauterine exposure of medicines. The patient had problems in difficulty in eating, speech, taste sensation and hearing. The present case does not fit into Hall's classification of oromandibular limb hypogenesis syndrome (OLHS) which best describes hypoglossia and limb deformities. Therefore, the purpose of this article is to document the rare variant of OLHS which can be included in Hall's classification. How to cite this article: Kalaskar RR, Godhane A, Kalaskar A, Demble S. A Rare Clinical Variant of Oromandibular Limb Hypogenesis Syndrome Type I B. Int J Clin Pediatr Dent 2016;9(1):78-81. PMID:27274161

  6. Detection of human papillomavirus type 10 DNA in eccrine syringofibroadenomatosis occurring in Clouston's syndrome.

    PubMed

    Carlson, J A; Rohwedder, A; Daulat, S; Schwartz, J; Schaller, J

    1999-02-01

    Syringofibroadenomatosis is often associated with an underlying condition such as diabetes mellitus or hidrotic ectodermal dysplasia. By reason of these associations, a reactive or hamartomatous cause is suspected. We report a case of a 71-year-old woman with Clouston's syndrome in whom progressive multiple palmoplantar syringofibroadenomas developed over a 10-year period. The syringofibroadenomas formed flat-topped papules simulating verruca plana; the widespread distribution and chronic progressive course resembled epidermodysplasia verruciformis. Contiguous with the syringofibroadenoma's characteristic epithelial-stromal proliferation were epidermal changes of verruca plana. Evidence of human papillomavirus (HPV) infection was verified by immunolabeling with antibodies to bovine papillomavirus type 1 and detection of HPV 10 viral DNA by means of polymerase chain reaction. Rather than a hamartomatous process, these findings suggest that syringofibroadenomas occurring in the setting of Clouston's syndrome could represent an HPV-induced epithelial proliferation. PMID:10025758

  7. Hypocretin Deficiency Associated with Narcolepsy Type 1 and Central Hypoventilation Syndrome in Neurosarcoidosis of the Hypothalamus

    PubMed Central

    Mayo, Mary Catherine; Deng, Jane C.; Albores, Jeffrey; Zeidler, Michelle; Harper, Ronald M.; Avidan, Alon Y.

    2015-01-01

    We report a case of a 53-year-old man presenting with depressed alertness and severe excessive sleepiness in the setting of neurosarcoidosis. Neuroimaging demonstrated hypothalamic destruction due to sarcoidosis with a CSF hypocretin level of 0 pg/mL. The patient also experienced respiratory depression that presumably resulted from hypocretin-mediated hypothalamic dysfunction as a result of extensive diencephalic injury. This is a novel case, demonstrating both hypocretin deficiency syndrome, as well as respiratory dysfunction from destruction of hypocretin neurons and extensive destruction of key diencephalic structures secondary to the underlying neurosarcoidosis. Citation: May MC, Deng JC, Albores J, Zeidler M, Harper RM, Avidan AY. Hypocretin deficiency associated with narcolepsy type 1 and central hypoventilation syndrome in neurosarcoidosis of the hypothalamus. J Clin Sleep Med 2015;11(9):1063–1065. PMID:25979096

  8. Oral-facial-digital syndrome type VI: is C5orf42 really the major gene?

    PubMed

    Romani, Marta; Mancini, Francesca; Micalizzi, Alessia; Poretti, Andrea; Miccinilli, Elide; Accorsi, Patrizia; Avola, Emanuela; Bertini, Enrico; Borgatti, Renato; Romaniello, Romina; Ceylaner, Serdar; Coppola, Giangennaro; D'Arrigo, Stefano; Giordano, Lucio; Janecke, Andreas R; Lituania, Mario; Ludwig, Kathrin; Martorell, Loreto; Mazza, Tommaso; Odent, Sylvie; Pinelli, Lorenzo; Poo, Pilar; Santucci, Margherita; Signorini, Sabrina; Simonati, Alessandro; Spiegel, Ronen; Stanzial, Franco; Steinlin, Maja; Tabarki, Brahim; Wolf, Nicole I; Zibordi, Federica; Boltshauser, Eugen; Valente, Enza Maria

    2015-01-01

    Oral-facial-digital type VI syndrome (OFDVI) is a rare phenotype of Joubert syndrome (JS). Recently, C5orf42 was suggested as the major OFDVI gene, being mutated in 9 of 11 families (82 %). We sequenced C5orf42 in 313 JS probands and identified mutations in 28 (8.9 %), most with a phenotype of pure JS. Only 2 out of 17 OFDVI patients (11.7 %) were mutated. A comparison of mutated vs. non-mutated OFDVI patients showed that preaxial and mesoaxial polydactyly, hypothalamic hamartoma and other congenital defects may predict C5orf42 mutations, while tongue hamartomas are more common in negative patients. PMID:25407461

  9. A Rare Clinical Variant of Oromandibular Limb Hypogenesis Syndrome Type I B

    PubMed Central

    Godhane, Alkesh; Kalaskar, Ashita; Demble, Swati

    2016-01-01

    ABSTRACT Aglossia is a rare congenital malformation that often occurs as an isolated disorder or is observed in association with other congenital deformities, particularly limb defects. We present a unique case of a 7-year-old girl with aglossia, hypodactyli, rudimentary ears, retrognathic and V-shaped mandible. Her parental history revealed intrauterine exposure of medicines. The patient had problems in difficulty in eating, speech, taste sensation and hearing. The present case does not fit into Hall’s classification of oromandibular limb hypogenesis syndrome (OLHS) which best describes hypoglossia and limb deformities. Therefore, the purpose of this article is to document the rare variant of OLHS which can be included in Hall’s classification. How to cite this article: Kalaskar RR, Godhane A, Kalaskar A, Demble S. A Rare Clinical Variant of Oromandibular Limb Hypogenesis Syndrome Type I B. Int J Clin Pediatr Dent 2016;9(1):78-81. PMID:27274161

  10. Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins

    PubMed Central

    Tenenbaum, Alexander; Fisman, Enrique Z; Motro, Michael; Adler, Yehuda

    2006-01-01

    Lowering of low-density lipoprotein cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is clearly efficacious in the treatment and prevention of coronary artery disease. However, despite increasing use of statins, a significant number of coronary events still occur and many of such events take place in patients presenting with type 2 diabetes and metabolic syndrome. More and more attention is being paid now to combined atherogenic dyslipidemia which typically presents in patients with type 2 diabetes and metabolic syndrome. This mixed dyslipidemia (or "lipid quartet"): hypertriglyceridemia, low high-density lipoprotein cholesterol levels, a preponderance of small, dense low-density lipoprotein particles and an accumulation of cholesterol-rich remnant particles (e.g. high levels of apolipoprotein B) – emerged as the greatest "competitor" of low-density lipoprotein-cholesterol among lipid risk factors for cardiovascular disease. Most recent extensions of the fibrates trials (BIP – Bezafibrate Infarction Prevention study, HHS – Helsinki Heart Study, VAHIT – Veterans Affairs High-density lipoprotein cholesterol Intervention Trial and FIELD – Fenofibrate Intervention and Event Lowering in Diabetes) give further support to the hypothesis that patients with insulin-resistant syndromes such as diabetes and/or metabolic syndrome might be the ones to derive the most benefit from therapy with fibrates. However, different fibrates may have a somewhat different spectrum of effects. Other lipid-modifying strategies included using of niacin, ezetimibe, bile acid sequestrants and cholesteryl ester transfer protein inhibition. In addition, bezafibrate as pan-peroxisome proliferator activated receptor activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism and insulin sensitivity. Because fibrates, niacin, ezetimibe and statins each regulate serum lipids by different mechanisms, combination therapy

  11. Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome.

    PubMed

    Meuwissen, Marije E C; Schot, Rachel; Buta, Sofija; Oudesluijs, Grétel; Tinschert, Sigrid; Speer, Scott D; Li, Zhi; van Unen, Leontine; Heijsman, Daphne; Goldmann, Tobias; Lequin, Maarten H; Kros, Johan M; Stam, Wendy; Hermann, Mark; Willemsen, Rob; Brouwer, Rutger W W; Van IJcken, Wilfred F J; Martin-Fernandez, Marta; de Coo, Irenaeus; Dudink, Jeroen; de Vries, Femke A T; Bertoli Avella, Aida; Prinz, Marco; Crow, Yanick J; Verheijen, Frans W; Pellegrini, Sandra; Bogunovic, Dusan; Mancini, Grazia M S

    2016-06-27

    Pseudo-TORCH syndrome (PTS) is characterized by microcephaly, enlarged ventricles, cerebral calcification, and, occasionally, by systemic features at birth resembling the sequelae of congenital infection but in the absence of an infectious agent. Genetic defects resulting in activation of type 1 interferon (IFN) responses have been documented to cause Aicardi-Goutières syndrome, which is a cause of PTS. Ubiquitin-specific peptidase 18 (USP18) is a key negative regulator of type I IFN signaling. In this study, we identified loss-of-function recessive mutations of USP18 in five PTS patients from two unrelated families. Ex vivo brain autopsy material demonstrated innate immune inflammation with calcification and polymicrogyria. In vitro, patient fibroblasts displayed severely enhanced IFN-induced inflammation, which was completely rescued by lentiviral transduction of USP18. These findings add USP18 deficiency to the list of genetic disorders collectively termed type I interferonopathies. Moreover, USP18 deficiency represents the first genetic disorder of PTS caused by dysregulation of the response to type I IFNs. Therapeutically, this places USP18 as a promising target not only for genetic but also acquired IFN-mediated CNS disorders. PMID:27325888

  12. An unfortunate challenge: Ketogenic diet for the treatment of Lennox-Gastaut syndrome in tyrosinemia type 1.

    PubMed

    De Lucia, Silvana; Pichard, Samia; Ilea, Adina; Greneche, Marie-Odile; François, Laurent; Delanoë, Catherine; Schiff, Manuel; Auvin, Stéphane

    2016-07-01

    The ketogenic diet is an evidence-based treatment for resistant epilepsy including Lennox-Gastaut syndrome. This diet is based on low carbohydrate-high fat intakes. Dietary treatment is also therapeutic for inborn errors of metabolism such as aminoacdiopathies. We report a child with both Lennox-Gastaut syndrome and tyrosinemia type 1. This epilepsy syndrome resulted form a porencephalic cyst secondary to brain abscesses that occurred during the management of malnutrition due to untreated tyrosinemia type 1. We used a ketogenic diet as treatment for Lennox-Gastaut syndrome taking into account dietary requirements for tyrosinemia type 1. The patient was transiently responder during a 6-month period. This report illustrates that ketogenic diet remains a therapeutic option even when additional dietary requirements are needed. PMID:27052529

  13. Correlation Between the Type of Acute Coronary Syndrome With the Needs of Hospitalized Patients

    PubMed Central

    Polikandrioti, Maria; Goudevenos, John; Michalis, Lampros K.; Koutelekos, Ioannis; Georgiadi, Elpida; Karakostas, Kostas; Elisaf, Moses

    2016-01-01

    Introduction: Acute Coronary Syndromes (ACS) comprise life-threatening health problems that demand emergency care and immediate intervention. As patients are abruptly transitioning from healthy state into suffering, they consequently experience several needs, mainly attributed to the type of the syndrome including the therapeutic regimen. Objectives: To access the correlation between the type of acute coronary syndrome (ACS) with the needs of hospitalized patients. Methods: A sample of 454 hospitalized patients with ACS, recruited from 4 hospitals in Greece, was enrolled in the study. Data were collected by the completion of questionnaire which apart from socio-demographic and clinical characteristics, it also included the questionnaire “Needs of hospitalized patients with coronary artery disease” which is consisted 6 subscales: a) need for support and guidance, b) need for information from the medical-nursing staff, c) need for being in contact with other patient groups and ensuring communication with relatives, d) need for individualized treatment and for the patient’s personal participation to his/her treatment e) need to meet the emotional and physical needs f) need to trust the medical-nursing staff. Statistical methods used were Kolmogorov-Smirnov test, chi2 test of independence, Kruskal wallis-test and multiple regression. Results: The type of ACS was statistically significant correlated with the place of residence (p=0.002), management of disease (p<0.001) and prior experience of hospitalization (p=0.003). All six needs were statistically significantly correlated with the type of ACS, (p<0.001 for the need for support and guidance, p<0.001 for the need to be informed from the medical and nursing staff, p<0.001 for the need for being in contact with other patient groups, and ensuring communication with relatives, p<0.001 for the need for individualized treatment and for the patient’s personal participation to his/her treatment, p<0.001 for the need

  14. Candidate regions for Waardenburg syndrome type II: Search for a second WS locus

    SciTech Connect

    Nance, W.E.; Pandya, A.; Blanton, S.H.

    1994-09-01

    Waardenburg syndrome is an autosomal dominant disorder characterized by deafness and pigmentary abnormalities such as heterochromia of irides, hypopigmented skin patches, white forlock and premature graying. Clinically the syndrome has been classified into three types. Type II differs from type I in that dystopia canthorum is generally absent, and type III has associated limb anomalies. Recently linkage analysis localized the gene for WSI to chromosome 2q. PAX-3, which is a human analogue of the murine pax-3 locus, maps to this region and mutations in this gene have been found to segregate with WSI. However genetic heterogeneity clearly exists: most if not all WSII families are unlinked to PAX-3 while most if not all WSI cases are linked. We ascertained a four-year-old female child with an interstitial deletion of chromosome 13 who had features of WS including bilateral congenital sensorineural hearing loss, pale blue irides and pinched nostrils as well as hypertelorism microcephaly, bilateral eyelid ptosis, digitalization of thumbs and fifth finger clinodactyly. High resolution chromosomal analysis revealed a de novo interstitial deletion of 13q22-33.2. There was no family history of WS or retardation. A similar deletion in the region of 13q21-32 has been described in a 13-year-old boy with features of WSII. These two cases strongly suggested that this chromosomal region may include a second locus for WS. We have identified eight families with clinical features of WS type I which have been excluded from linkage to the PAX-3 locus. We have typed these families for microsatellite markers spanning chromosome 13. Linkage between WSII and the chromosome 13 markers was excluded in these families. Hirschsprung disease has been associated with WS and it has recently been mapped to chromosome 10q11.2-q21.1. We are currently typing the 8 families for microsatellites in this region.

  15. Cardiorenal Syndrome Type 5: In Vitro Cytotoxicity Effects on Renal Tubular Cells and Inflammatory Profile

    PubMed Central

    Brocca, Alessandra; Virzì, Grazia Maria; Pasqualin, Chiara; Pastori, Silvia; Marcante, Stefano; de Cal, Massimo; Ronco, Claudio

    2015-01-01

    Background. Cardiorenal Syndrome Type 5 (CRS Type 5) reflects concomitant cardiac and renal dysfunctions in the setting of a wide spectrum of systemic disorders. Our aim was to study in vitro effects of CRS Type 5 plasma on renal tubular cells (RTCs), in terms of cellular death and the characterization of inflammatory plasma profile in these patients. Material and Methods. We enrolled 11 CRS Type 5 patients from ICU and 16 healthy controls. Plasma from patients and controls was incubated with renal tubular cells (RTCs) and cell death was evaluated. Plasma cytokines were detected. Results. RTCs incubated with CRS Type 5 plasma showed significantly higher apoptosis and necrosis with respect to controls. Plasma cytokine profile of CRS Type 5 patients was significantly different from controls: we observed the production of pro- and anti-inflammatory mediators in these patients. Caspase-3, caspase-8, and caspase-9 were activated in cells treated with CRS Type 5 plasma compared to controls. Conclusions. Our results underline the cytotoxic effect of CRS Type 5 mediators on RTC viability, probably due to the activation of both intrinsic and extrinsic pathways of apoptosis and to the deregulation of cytokine release. The consequence may be the damage of distant organs which lead to the worsening of condition of patients. PMID:26266085

  16. Frequency of Usher syndrome type 1 in deaf children by massively parallel DNA sequencing

    PubMed Central

    Yoshimura, Hidekane; Miyagawa, Maiko; Kumakawa, Kozo; Nishio, Shin-ya; Usami, Shin-ichi

    2016-01-01

    Usher syndrome type 1 (USH1) is the most severe of the three USH subtypes due to its profound hearing loss, absent vestibular response and retinitis pigmentosa appearing at a prepubescent age. Six causative genes have been identified for USH1, making early diagnosis and therapy possible through DNA testing. Targeted exon sequencing of selected genes using massively parallel DNA sequencing (MPS) technology enables clinicians to systematically tackle previously intractable monogenic disorders and improve molecular diagnosis. Using MPS along with direct sequence analysis, we screened 227 unrelated non-syndromic deaf children and detected recessive mutations in USH1 causative genes in five patients (2.2%): three patients harbored MYO7A mutations and one each carried CDH23 or PCDH15 mutations. As indicated by an earlier genotype–phenotype correlation study of the CDH23 and PCDH15 genes, we considered the latter two patients to have USH1. Based on clinical findings, it was also highly likely that one patient with MYO7A mutations possessed USH1 due to a late onset age of walking. This first report describing the frequency (1.3–2.2%) of USH1 among non-syndromic deaf children highlights the importance of comprehensive genetic testing for early disease diagnosis. PMID:26791358

  17. Herpes simplex virus type 1 colitis in a patient with common variable immunodeficiency syndrome.

    PubMed

    Dray, Xavier; Treton, Xavier; Mazeron, Marie-Christine; Lavergne-Slove, Anne; Joly, Francisca; Mimram, Dora; Attar, Alain; Tobelem, Gérard; Bouhnik, Yoram

    2006-05-01

    We report on a case of herpes simplex virus (HSV) type 1 colitis in a 69-year-old patient with common variable immunodeficiency syndrome. A treatment with polyvalent immunoglobulins was discontinued in April 2001. In March 2004 she developed chronic diarrhoea related to rectosigmoidal and caecal ulcerations. In November 2004, HSV was recovered in tissue culture from colonic biopsies. Valaciclovir was then started, leading the patient to clinical remission at day 4, and continued for a 6-week course (without any secondary antiviral prophylaxis). Colonic biopsies were negative for HSV by tissue culture and PCR within 3 weeks of antiviral treatment. Intravenous polyvalent immunoglobulin infusions were readministered within the third week of antiviral treatment. She has declared no clinical event since this period. Three months after the antiviral treatment was achieved, a rectosigmoidoscopy showed an ad-integrum macroscopic and histological mucosal healing whereas PCR was negative for HSV in the colonic tissue. As a large proportion of patients with common variable immunodeficiency syndrome present not only as a humoral immunodeficiency but also as a defect in the cellular immunity compartment (with T-cell deficits), HSV, as well as cytomegalovirus, should be investigated in patients with common variable immunodeficiency syndrome presenting colitis. PMID:16607152

  18. A Multiparametric Computational Algorithm for Comprehensive Assessment of Genetic Mutations in Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome)

    PubMed Central

    Thomas, Clayton L.; Lee, Shaun W.

    2015-01-01

    Mucopolysaccharidosis type IIIA (MPS-IIIA, Sanfilippo syndrome) is a Lysosomal Storage Disease caused by cellular deficiency of N-sulfoglucosamine sulfohydrolase (SGSH). Given the large heterogeneity of genetic mutations responsible for the disease, a comprehensive understanding of the mechanisms by which these mutations affect enzyme function is needed to guide effective therapies. We developed a multiparametric computational algorithm to assess how patient genetic mutations in SGSH affect overall enzyme biogenesis, stability, and function. 107 patient mutations for the SGSH gene were obtained from the Human Gene Mutation Database representing all of the clinical mutations documented for Sanfilippo syndrome. We assessed each mutation individually using ten distinct parameters to give a comprehensive predictive score of the stability and misfolding capacity of the SGSH enzyme resulting from each of these mutations. The predictive score generated by our multiparametric algorithm yielded a standardized quantitative assessment of the severity of a given SGSH genetic mutation toward overall enzyme activity. Application of our algorithm has identified SGSH mutations in which enzymatic malfunction of the gene product is specifically due to impairments in protein folding. These scores provide an assessment of the degree to which a particular mutation could be treated using approaches such as chaperone therapies. Our multiparametric protein biogenesis algorithm advances a key understanding in the overall biochemical mechanism underlying Sanfilippo syndrome. Importantly, the design of our multiparametric algorithm can be tailored to many other diseases of genetic heterogeneity for which protein misfolding phenotypes may constitute a major component of disease manifestation. PMID:25807448

  19. Scintigraphic portrayal of the syndrome of multiple endocrine neoplasia type-2B

    SciTech Connect

    Yobbagy, J.J.; Levatter, R.; Sisson, J.C.; Shulkin, B.L.; Polley, T.

    1988-06-01

    The scintigraphic appearance of the neoplasms in multiple endocrine neoplasia type 2B (MEN-2B) and the interpretations of the image patterns are described. An 18-year-old male patient with the MEN-2B syndrome underwent TI-201 imaging that showed concentrations of TI-201 in the primary medullary thyroid carcinoma (MTC) tumor and in cervical lymph node metastases. After total thyroidectomy and lymph node dissection, the TI-201 image was normal. Catecholamine levels in the blood and urine were only borderline elevated. Yet, greater than normal concentrations of I-131 metaiodobenzylguanidine (I-131 MIBG) were present in both adrenal glands. Computed tomography of the abdomen showed normal adrenal glands. These results were consistent with the diagnosis of adrenal medullary hyperplasia, a precursor of pheochromocytoma. No operation was indicated to remove the adrenal glands. Imaging with TI-201 appears to be useful in identifying sites of MTC in patients with the MEN-2B syndrome. I-131 MIBG imaging, in conjunction with computed tomography of the adrenal glands and appropriate catecholamine measurements, should be performed in patients with the MEN-2B syndrome to determine the status of the adrenal medullae, which then may be classified as normal, hyperplastic, or tumorous with pheochromocytoma.

  20. Frequency of Usher syndrome type 1 in deaf children by massively parallel DNA sequencing.

    PubMed

    Yoshimura, Hidekane; Miyagawa, Maiko; Kumakawa, Kozo; Nishio, Shin-Ya; Usami, Shin-Ichi

    2016-05-01

    Usher syndrome type 1 (USH1) is the most severe of the three USH subtypes due to its profound hearing loss, absent vestibular response and retinitis pigmentosa appearing at a prepubescent age. Six causative genes have been identified for USH1, making early diagnosis and therapy possible through DNA testing. Targeted exon sequencing of selected genes using massively parallel DNA sequencing (MPS) technology enables clinicians to systematically tackle previously intractable monogenic disorders and improve molecular diagnosis. Using MPS along with direct sequence analysis, we screened 227 unrelated non-syndromic deaf children and detected recessive mutations in USH1 causative genes in five patients (2.2%): three patients harbored MYO7A mutations and one each carried CDH23 or PCDH15 mutations. As indicated by an earlier genotype-phenotype correlation study of the CDH23 and PCDH15 genes, we considered the latter two patients to have USH1. Based on clinical findings, it was also highly likely that one patient with MYO7A mutations possessed USH1 due to a late onset age of walking. This first report describing the frequency (1.3-2.2%) of USH1 among non-syndromic deaf children highlights the importance of comprehensive genetic testing for early disease diagnosis. PMID:26791358

  1. Laparoscopic Treatment of Type III Mirizzi Syndrome by T-Tube Drainage

    PubMed Central

    Yetışır, Fahri; Şarer, Akgün Ebru; Acar, H. Zafer; Polat, Yılmaz; Osmanoglu, Gokhan; Aygar, Muhittin; Ciftciler, A. Erdinc; Parlak, Omer

    2016-01-01

    Mirizzi syndrome (MS) is an impacted stone in the cystic duct or Hartmann's pouch that mechanically obstructs the common bile duct. We would like to report laparoscopic treatment of type III MS. A 75-year-old man was admitted with the complaint of abdominal pain and jaundice. The patient was accepted as MS type III according to radiological imaging and intraoperative view. Laparoscopic subtotal cholecystectomy, extraction of impacted stone by opening anterior surface of dilated cystic duct and choledochus, and repair of this opening by using the remaining part of gallbladder over the T-tube drainage were performed in a patient with type III MS. Application of reinforcement suture over stump was done in light of the checking with oliclinomel N4 injection trough the T-tube. At the 18-month follow-up, he was symptom-free with normal liver function tests. PMID:27293947

  2. Pregnancy and delivery in ehlers-danlos syndrome (hypermobility type): review of the literature.

    PubMed

    Dutta, Indranil; Wilson, Helen; Oteri, Odiri

    2011-01-01

    Ehlers-Danlos syndrome (EDS) is a group of connective tissue disorders which are divided into various distinguishable phenotypes. The type of EDS determines the potential obstetric complications. Due to the spectrum of clinical manifestation and overlap between phenotypes, there are no standardised obstetric management guidelines. Existing literature illustrates different obstetric management in hypermobility type of EDS, including uneventful term vaginal deliveries as well as preterm cesarean section deliveries. This paper discusses obstetric management of a woman with EDS hypermobility type. Cesarean section was deemed the most appropriate delivery method in this patient due to the possible complications including risk of joint dislocation and pain morbidity. No obstetric complications were experienced, and good maternal and neonatal outcomes were achieved. PMID:21765833

  3. Griscelli syndrome types 1 and 3: analysis of four new cases and long-term evaluation of previously diagnosed patients.

    PubMed

    Cağdaş, Deniz; Ozgür, Tuba Turul; Asal, Gülten Türkkanı; Tezcan, Ilhan; Metin, Ayşe; Lambert, Nathalie; de Saint Basile, Geneiveve; Sanal, Ozden

    2012-10-01

    Griscelli syndrome (GS) is a rare autosomal recessive disorder characterized by partial albinism. Three different types are caused by defects in three different genes. Patients with GS type 1 have primary central nervous system dysfunction, type 2 patients commonly develop hemophagocytic lymphohistiocytosis, and type 3 patients have only partial albinism. While hematopoietic stem cell transplantation is life saving in type 2, no specific therapy is required for types 1 and 3. Patients with GS types 1 and 3 are very rare. To date, only 2 patients with type 3 and about 20 GS type 1 patients, including the patients described as Elejalde syndrome, have been reported. The neurological deficits in Elejalde syndrome were reported as severe neurodevelopmental delay, seizures, hypotonia, and ophthalmological problems including nystagmus, diplopia, and retinal problems. However, none of these patients' clinical progresses were reported. We described here our two new type 1 and two type 3 patients along with the progresses of our previously diagnosed patients with GS types 1 and 3. Our previous patient with GS type I is alive at age 21 without any other problems except severe mental and motor retardation, patients with type 3 are healthy at ages 21 and 24 years having only pigmentary dilution; silvery gray hair, eye brows, and eyelashes. Since prognosis, treatment options, and genetic counseling markedly differ among different types, molecular characterization has utmost importance in GS. PMID:22711375

  4. Three novel ZBTB24 mutations identified in Japanese and Cape Verdean type 2 ICF syndrome patients.

    PubMed

    Nitta, Hirohisa; Unoki, Motoko; Ichiyanagi, Kenji; Kosho, Tomoki; Shigemura, Tomonari; Takahashi, Hiroshi; Velasco, Guillaume; Francastel, Claire; Picard, Capucine; Kubota, Takeo; Sasaki, Hiroyuki

    2013-07-01

    Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive disorder that shows DNA hypomethylation at pericentromeric satellite-2 and -3 repeats in chromosomes 1, 9 and 16. ICF syndrome is classified into two groups: type 1 (ICF1) patients have mutations in the DNMT3B gene and about half of type 2 (ICF2) patients have mutations in the ZBTB24 gene. Besides satellite-2 and -3 repeats, α-satellite repeats are also hypomethylated in ICF2. In this study, we report three novel ZBTB24 mutations in ICF2. A Japanese patient was homozygous for a missense mutation (C383Y), and a Cape Verdean patient was compound heterozygous for a nonsense mutation (K263X) and a frame-shift mutation (C327W fsX54). In addition, the second Japanese patient was homozygous for a previously reported nonsense mutation (R320X). The C383Y mutation abolished a C2H2 motif in one of the eight zinc-finger domains, and the other three mutations caused a complete or large loss of the zinc-finger domains. Our immunofluorescence analysis revealed that mouse Zbtb24 proteins possessing a mutation corresponding to either C383Y or R320X are mislocalized from pericentrometic heterochromatin, suggesting the importance of the zinc-finger domains in proper intranuclear localization of this protein. We further revealed that the proper localization of wild-type Zbtb24 protein does not require DNA methylation. PMID:23739126

  5. Glucose transporter type 1 deficiency syndrome effectively treated with modified Atkins diet.

    PubMed

    Haberlandt, Edda; Karall, Daniela; Jud, Veronika; Baumgartner, Sara Sigl; Zotter, Sibylle; Rostasy, Kevin; Baumann, Matthias; Scholl-Buergi, Sabine

    2014-04-01

    This is a report on the successful treatment of a 6-year-old girl with genetically proven glucose transporter type 1 deficiency syndrome (GLUT1-DS) with modified Atkins diet (MAD). GLUT1-DS is an inborn disorder of glucose transport across the blood-brain barrier, which leads to energy deficiency of the brain with a broad spectrum of neurological symptoms including therapy-resistant epilepsy. Usually classical ketogenic diet (KD) is the standard treatment for patients with GLUT1-DS. Treatment with MAD, a variant of KD, for an observation period of 17 months resulted in improvement of seizures, alertness, cognitive abilities, and electroencephalography in this patient. PMID:23888468

  6. Mirror visual feedback for the treatment of complex regional pain syndrome (type 1).

    PubMed

    McCabe, Candida S; Haigh, Richard C; Blake, David R

    2008-04-01

    Mirror visual feedback was originally devised as a therapeutic tool to relieve perceived involuntarily movements and paralysis in the phantom limb. Since this pioneering work was conducted in the mid-1990s, the technique has been applied to relieve pain and enhance movement in other chronic conditions such as stroke and complex regional pain syndrome (CRPS) type 1. This review describes how mirror visual feedback was first developed with amputees, its original application in CRPS, and how further research has demonstrated its potential benefit within graded motor imagery programs. We discuss the potential mechanisms behind this technique and consider the implications for clinical practice. PMID:18474189

  7. Blunt aortic trauma in a patient with the Ehlers-Danlos syndrome type VI.

    PubMed

    Yung, Marco Yat Hang; Murray, Jennifer; Thompson, Errington C

    2016-01-01

    A 24-year-old male with the Ehlers-Danlos syndrome (EDS) type VI (ocular scoliotic) who was kicked in the abdomen presented to the emergency room (ER) with abdominal pain. He was found to have a blunt traumatic aortic injury. The patient was treated nonoperatively. He was stable and discharged home on the eighth day. The patient returned to the ER several days later hypotensive and tachycardic. The patient was taken immediately to the operating room, but vascular repair was not possible. The patient expired. We discuss the challenges of taking care of a patient with EDS and offer suggestions that might improve future patient's outcome. PMID:26956239

  8. Blunt aortic trauma in a patient with the Ehlers–Danlos syndrome type VI

    PubMed Central

    Yung, Marco Yat Hang; Murray, Jennifer; Thompson, Errington C.

    2016-01-01

    A 24-year-old male with the Ehlers–Danlos syndrome (EDS) type VI (ocular scoliotic) who was kicked in the abdomen presented to the emergency room (ER) with abdominal pain. He was found to have a blunt traumatic aortic injury. The patient was treated nonoperatively. He was stable and discharged home on the eighth day. The patient returned to the ER several days later hypotensive and tachycardic. The patient was taken immediately to the operating room, but vascular repair was not possible. The patient expired. We discuss the challenges of taking care of a patient with EDS and offer suggestions that might improve future patient's outcome. PMID:26956239

  9. A gene for Usher syndrome type I (USH1A) maps to chromosome 14q

    SciTech Connect

    Kaplan, J.; Gerber, S.; Rozet, J.M.; Delrieu, O.; Briard, M.L.; Dollfus, H.; Frezal, J.; Munnich, A. ); Bonneau, D. ); Ghazi, I. )

    1992-12-01

    Usher syndrome (US) is an autosomal recessive disease characterized by congenital hearing impairment and retinitis pigmentosa. It is the most frequent cause of deaf-blindness in adults and accounts for 3 to 6% of deaf children. Here, the authors report the genetic mapping of a gene for US type I (USH1A), the most severe form of the disease, to the long arm of chromosome 14, by linkage to probe MLJ14 at the D14S13 locus in 10 families of Western France ancestry ([cflx Z] = 4.13 at [cflx [theta

  10. Renal-type Clear Cell Carcinoma Occurring in the Prostate With Zinner Syndrome

    PubMed Central

    Sato, Yuichi; Kataoka, Masao; Hata, Junya; Akaihata, Hidenori; Ogawa, Soichiro; Kojima, Yoshiyuki

    2016-01-01

    We report a case of clear cell carcinoma occurring in the prostate with Zinner syndrome in a 64-year-old man. Based on the immunohistochemical findings, it was concluded that this tumor represented primary renal-type clear cell carcinoma arising in the prostate. After receiving radical cystoprostatectomy, he was treated with tyrosine kinase inhibitor (TKI) therapy for local recurrence in accordance with the protocol of renal cell carcinoma (RCC) treatment, because microarray cluster analysis using a resected sample demonstrated that the present case belonged to the cluster group of RCC. PMID:26793589

  11. Renal-type Clear Cell Carcinoma Occurring in the Prostate With Zinner Syndrome.

    PubMed

    Sato, Yuichi; Kataoka, Masao; Hata, Junya; Akaihata, Hidenori; Ogawa, Soichiro; Kojima, Yoshiyuki

    2016-03-01

    We report a case of clear cell carcinoma occurring in the prostate with Zinner syndrome in a 64-year-old man. Based on the immunohistochemical findings, it was concluded that this tumor represented primary renal-type clear cell carcinoma arising in the prostate. After receiving radical cystoprostatectomy, he was treated with tyrosine kinase inhibitor (TKI) therapy for local recurrence in accordance with the protocol of renal cell carcinoma (RCC) treatment, because microarray cluster analysis using a resected sample demonstrated that the present case belonged to the cluster group of RCC. PMID:26793589

  12. 'Moya' than meets the eye: neurofibromatosis type 1 associated with Moyamoya syndrome.

    PubMed

    Tan, R M; Chng, S M; Seow, W T; Wong, J; Lim, C C

    2008-04-01

    Moyamoya syndrome (MMS) is an uncommon association of neurofibromatosis type 1 (NF1). We describe a seven-year-old chinese girl with NF1 and unilateral MMS with multiple hyperintensities on T2-weighted magnetic resonance (MR) images. The ischaemic lesions in the ipsilateral white matter were hypointense on fluid attenuated inversion recovery (FLAIR) MR images, in contrast to the hyperintense "unidentified bright objects" (UBOs) of NF1. Neuroradiologists should be aware of associated MMS in NF1 patients, and distinguish the effects of ischaemia from UBOs, especially on FLAIR MR imaging. PMID:18418511

  13. Interstitial type granuloma annulare associated with Sjögren's syndrome.

    PubMed

    Sumikawa, Yasuyuki; Ansai, Shinichi; Kimura, Tetsunori; Nakamura, Junnosuke; Inui, Shigeki; Katayama, Ichiro

    2010-05-01

    We describe a case of granuloma annulare (GA) associated with Sjögren's syndrome (SS) in a 69-year-old woman. She complained of erythematous plaques on the left forearm and neck in addition to dry eyes and mouth. The laboratory and clinical findings also fulfilled the criteria for diagnosis of SS. Histopathological examination revealed the features of interstitial type GA. It is not rare that granulomatous diseases are associated with autoimmune diseases. This case indicated that granulomatous diseases and SS are closely related and that GA should be recognized as a cutaneous manifestation associated with autoimmune diseases, including SS. PMID:20536658

  14. Multiple developmental dental anomalies and hypermobility type Ehlers-Danlos syndrome.

    PubMed

    Yassin, Othman M; Rihani, Farouk B

    2006-01-01

    Concurrent existence of multiple developmental dental anomalies: hypodontia of permanent mandibular incisors, dentin dysplasia, transmigration, root dilaceration, ectopic eruption and delayed eruption combined with systemic abnormalities including joint hyperlaxity and skin hyperextensibility aided in diagnosis of a sporadic case of hypermobility type of Ehlers-Danlos syndrome in a Jordanian Arab male. In dental practice the presence of multiple developmental dental anomalies expressing simultaneous defects in different stages of tooth development should raise suspicion of possible of manifestation of an underlying systemic abnormality. PMID:16937863

  15. Oxidative Stress: Dual Pathway Induction in Cardiorenal Syndrome Type 1 Pathogenesis

    PubMed Central

    Virzì, Grazia Maria; Clementi, Anna; de Cal, Massimo; Brocca, Alessandra; Day, Sonya; Pastori, Silvia; Bolin, Chiara; Vescovo, Giorgio; Ronco, Claudio

    2015-01-01

    Cardiorenal Syndrome Type 1 (Type 1) is a specific condition which is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Even though its pathophysiology is complex and not still completely understood, oxidative stress seems to play a pivotal role. In this study, we examined the putative role of oxidative stress in the pathogenesis of CRS Type 1. Twenty-three patients with acute heart failure (AHF) were included in the study. Subsequently, 11 patients who developed AKI due to AHF were classified as CRS Type 1. Quantitative determinations for IL-6, myeloperoxidase (MPO), nitric oxide (NO), copper/zinc superoxide dismutase (Cu/ZnSOD), and endogenous peroxidase activity (EPA) were performed. CRS Type 1 patients displayed significant augmentation in circulating ROS and RNS, as well as expression of IL-6. Quantitative analysis of all oxidative stress markers showed significantly lower oxidative stress levels in controls and AHF compared to CRS Type 1 patients (P < 0.05). This pilot study demonstrates the significantly heightened presence of dual oxidative stress pathway induction in CRS Type 1 compared to AHF patients. Our findings indicate that oxidative stress is a potential therapeutic target, as it promotes inflammation by ROS/RNS-linked pathogenesis. PMID:25821554

  16. [Complex regional pain syndrome type I (CRPS I). Pathophysiology, diagnostics, and therapy].

    PubMed

    Köck, F X; Borisch, N; Koester, B; Grifka, J

    2003-05-01

    Complex regional pain syndrome type I (CRPS type I)--formerly termed Sudeck's atrophy or reflex sympathetic dystrophy (RSD)--causes chronic, poorly controllable pain, autonomic, sensorimotor disorders,and serious trophic alterations in the later stages. It develops in the distal extremities mostly after minimal trauma or surgical intervention and rarely spontaneously. The severity of symptoms is disproportionate to the causative event. The latest scientific findings show that the previously called reflex sympathetic dystrophy (RSD), which was supposed to be a result of a hyperreactive autonomic nervous system,is a very complex syndrome that occurs on different integration levels of the nervous system. Sympathetically maintained pain (SMP) may be facultatively characteristic, but is not to be misunderstood as an underlying mechanism. A neurogenic inflammation reaction has recently been discussed, just as had been postulated by Paul Sudeck long before. That was the reason why the International Association for the Study of Pain (ISAP) introduced the more descriptive term "complex regional pain syndrome" (CRPS) type I in 1994. Due to the complexity of the process necessitating qualified knowledge, it is important to immediately refer patients to a specialized pain OPD or clinic. The diagnosis of CRPS type I is based upon a carefully taken case history and a clinical examination by an experienced practitioner. Imaging diagnostic tools and laboratory findings are of no or only low predicative value. The question of whether SMP exists after diagnosing CRPS type I is eminent for therapy planning. Therefore, diagnostic regional anesthetics are still important in spite of their uncertain prognostic relevance. Physical therapy, occupational therapy, medical treatment, and psychotherapy play an important role in the primary treatment of CRPS type I as noninvasive procedures. Despite heavy criticism, invasive sympathetic block, subsequent to adequate diagnostics, is an

  17. Importance of Laparoscopic Assessment of the Uterine Adnexa in a Mayer-Rokitansky-Kuster-Hauser Syndrome Type II Case

    PubMed Central

    DRAGUSIN, ROXANA; TUDORACHE, ȘTEFANIA; SURLIN, V.; LICHIARDOPOL, CORINA; ILIESCU, D.G.

    2014-01-01

    In the case reported, diagnosed with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, the presence of normal ovaries proved to be challenging to confirm due to unusual high positioned (ectopic) ovaries. MRKH syndrome is a rare pathological condition characterized by a spectrum of the Mullerian duct abnormalities resulting in congenital aplasia of the uterus and of the upper part (2/3) of the vagina, developed during embryogenesis. At the same time, the mullerian development is interdependent with the Wolffian (mesonephric) duct and this explains the associated renal abnormalities (MRKH type II). Laparoscopic assessment was of great importance in defining the exact anatomic characteristics of MRKH syndrome. PMID:25729598

  18. Bloom's Syndrome

    MedlinePlus

    ... Glycogen Storage Disease, Type 1A Joubert Syndrome Maple Syrup Urine Disease and DLD Mucolipidosis IV (MLIV) Nemaline ... Glycogen Storage Disease, Type 1A Joubert Syndrome Maple Syrup Urine Disease and DLD Mucolipidosis IV (MLIV) Nemaline ...

  19. Usher Syndrome

    MedlinePlus

    Usher syndrome is an inherited disease that causes serious hearing loss and retinitis pigmentosa, an eye disorder ... hearing and vision. There are three types of Usher syndrome: People with type I are deaf from ...

  20. Association of Parental Age and the Type of Down Syndrome on the Territory of Bosnia and Herzegovina

    PubMed Central

    Sotonica, Mia; Mackic-Djurovic, Mirela; Hasic, Sabaheta; Kiseljakovic, Emina; Jadric, Radivoj; Ibrulj, Slavka

    2016-01-01

    Background: Advanced paternal and/or maternal age is a classic risk factor for Down syndrome. The aim of the study was to investigate the frequency of Down syndrome types in children and its association with maternal and paternal age in Bosnia and Herzegovina. Subjects and Methods: The cross sectional, observational study included 127 children, 49 girls and 78 boys, aged 1-180 months suspected to have Down syndrome, admitted to the Centre for Genetics, Faculty of Medicine University of Sarajevo, for cytogenetic analysis and differential diagnosis of Down syndrome during the period from January 2010 to May 2015. Standard method of 72 hours cultivation of peripheral blood lymphocytes has been applied. The accepted level of statistical significance was p<0.05. Study Results: The most common type of Down syndrome was standard trisomy (86.6%), comparing to translocation and mosaicism (7.1%; 6.3%, respectively). The highest frequency of Down syndrome cases was in mother and father’s group from 30-39 years old (57; 57 children, respectively) compared to mother and father’s groups with younger than 30 (44; 29, respectively) and 40 and older (26; 41, respectively). The significant difference was found in maternal age between translocation and mosaicism groups (p=0.036). Difference between parental years and type of Down syndrome was significant when Standard trisomy 21 and translocation (p=0.045), as well as mosaicism and translocation (p=0.036), were compared. Conclusion: The most common type of Down syndrome was standard trisomy 21, with highest occurrence in parents from 30 to 39 years old. Parents were the youngest in translocation group. Obtained results suggest that multidisciplinary approach to identifying the trigger for trisomy appearance and the influence of maternal age is required. PMID:27147778

  1. Abducens Nerve in Patients with Type 3 Duane’s Retraction Syndrome

    PubMed Central

    Hwang, Jeong-Min

    2016-01-01

    Background We have previously reported that the presence of the abducens nerve was variable in patients with type 3 Duane’s retraction syndrome (DRS), being present in 2 of 5 eyes (40%) and absent in 3 (60%) on magnetic resonance imaging (MRI). The previous study included only 5 eyes with unilateral DRS type 3. Objectives To supplement existing scarce pathologic information by evaluating the presence of the abducens nerve using high resolution thin-section MRI system in a larger number of patients with DRS type 3, thus to provide further insight into the pathogenesis of DRS. Data Extraction A retrospective review of medical records on ophthalmologic examination and high resolution thin-section MRI at the brainstem level and orbit was performed. A total of 31 patients who showed the typical signs of DRS type 3, including abduction and adduction deficit, globe retraction, narrowing of fissure on adduction and upshoot and/or downshoot, were included. The abducens nerve and any other extraocular muscle abnormalities discovered by MRI were noted. Results DRS was unilateral in 26 patients (84%) and bilateral in 5 patients (16%). Two out of 5 bilateral patients had DRS type 3 in the right eye and DRS type 1 in the left eye. Of the 34 affected orbits with DRS type 3 in 31 patients, the abducens nerve was absent or hypoplastic in 31 eyes (91%) and present in 3 eyes (9%). Patients with a present abducens nerve showed more limitation in adduction compared to patients with an absent abducens nerve (P = 0.030). Conclusions The abducens nerve is absent or hypoplastic in 91% of DRS type 3. Patients with a present abducens nerve showed more prominent limitation of adduction. As DRS type 3 partly share the same pathophysiology with type 1 and 2 DRS, the classification of DRS may have to be revised according to MRI findings. PMID:27352171

  2. Recovery from alopecia areata in a patient with autoimmune polyglandular syndrome type 3

    PubMed Central

    Uchihashi, Takeshi; Kataoka, Yasuo; Fujiwara, Masayoshi

    2015-01-01

    Summary Recovery from alopecia is rare in autoimmune polyglandular syndrome (APS). A 41-year-old male was admitted to our hospital with hyperglycemia. He developed alopecia areata (AA) 5 months before admission and developed thirst, polyuria, and anorexia in 2 weeks. His plasma glucose level upon admission was 912 mg/dl (50.63 mmol/l) and HbA1c was 13.7%. Although urinary and plasma C-peptide levels showed that insulin secretion was not depleted, anti-insulinoma-associated antigen 2 antibody was present. In addition, measurement of thyroid autoantibodies revealed the presence of Hashimoto's thyroiditis. These findings suggested a diagnosis of APS type 3. The patient has showed signs of improvement with the continuation of insulin therapy. During the successful control of diabetes, he had total hair regrowth within 2–3 months. Human leukocyte antigen typing showed that DRB1*1501-DQB1*0602 and DQB1*0301 were present. Similar cases should be accumulated to clarify the association of APS type 3 with recovery from AA. Learning points Alopecia in diabetic patients is a suspicious manifestation of autoimmune type 1 diabetes.Patients with autoimmune type 1 diabetes specifically manifesting alopecia should be further examined for diagnosis of APS.Insulin-mediated metabolic improvement may be a factor, but not the sole factor, determining a favorable outcome of alopecia in patients with autoimmune type 1 diabetes. PMID:25759758

  3. Macrophage involvement in mitral valve pathology in mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome).

    PubMed

    Brands, Marion; Roelants, Jorine; de Krijger, Ronald; Bogers, Ad; Reuser, Arnold; van der Ploeg, Ans; Helbing, Wim

    2013-10-01

    Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI) is a rare lysosomal storage disorder in which the pathologic storage of glycosaminoglycans in various tissues can lead to severe symptoms, including cardiomyopathy. We report on a child with Maroteaux-Lamy syndrome whose cardiac condition deteriorated and eventually led to cardiac failure at the age of 7 years due to severe mitral regurgitation. She received a mitral valve replacement and tricuspid repair with successful outcome. Histologic examination of the mitral valve showed abundant "clear" cells in both the leaflets and chordae tendineae. In Hurler disease (MPS I), similar cells have been identified as activated valvular interstitial cells (VICs, a myofibroblast like cell type). Here we report that the "clear" cells are CD68 positive, a frequently used marker of macrophage lineage. The "clear" cells remained unstained with the more specific macrophage marker CD14 while persistent staining of other cells demonstrated macrophage infiltration. From these observations, we infer that macrophages are involved in mitral valve pathology in MPS VI. PMID:23949968

  4. Clinical and genetic investigation of families with type II Waardenburg syndrome.

    PubMed

    Chen, Yong; Yang, Fuwei; Zheng, Hexin; Zhou, Jianda; Zhu, Ganghua; Hu, Peng; Wu, Weijing

    2016-03-01

    The present study aimed to investigate the molecular pathology of Waardenburg syndrome type II in three families, in order to provide genetic diagnosis and hereditary counseling for family members. Relevant clinical examinations were conducted on the probands of the three pedigrees. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of paired box 3 (PAX3), microphthalmia‑associated transcription factor (MITF), sex‑determining region Y‑box 10 (SOX10) and snail family zinc finger 2 (SNAI2) were analyzed by polymerase chain reaction and DNA sequencing. The heterozygous mutation, c.649_651delAGA in exon 7 of the MITF gene was detected in the proband and all patients of pedigree 1; however, no pathological mutation of the relevant genes (MITF, SNAI2, SOX10 or PAX3) was detected in pedigrees 2 and 3. The heterozygous mutation c.649_651delAGA in exon 7 of the MITF gene is therefore considered the disease‑causing mutation in pedigree 1. However, there are novel disease‑causing genes in Waardenburg syndrome type II, which require further research. PMID:26781036

  5. Clinical and genetic investigation of families with type II Waardenburg syndrome

    PubMed Central

    CHEN, YONG; YANG, FUWEI; ZHENG, HEXIN; ZHOU, JIANDA; ZHU, GANGHUA; HU, PENG; WU, WEIJING

    2016-01-01

    The present study aimed to investigate the molecular pathology of Waardenburg syndrome type II in three families, in order to provide genetic diagnosis and hereditary counseling for family members. Relevant clinical examinations were conducted on the probands of the three pedigrees. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of paired box 3 (PAX3), microphthalmia-associated transcription factor (MITF), sex-determining region Y-box 10 (SOX10) and snail family zinc finger 2 (SNAI2) were analyzed by polymerase chain reaction and DNA sequencing. The heterozygous mutation, c.649_651delAGA in exon 7 of the MITF gene was detected in the proband and all patients of pedigree 1; however, no pathological mutation of the relevant genes (MITF, SNAI2, SOX10 or PAX3) was detected in pedigrees 2 and 3. The heterozygous mutation c.649_651delAGA in exon 7 of the MITF gene is therefore considered the disease-causing mutation in pedigree 1. However, there are novel disease-causing genes in Waardenburg syndrome type II, which require further research. PMID:26781036

  6. Type III Guyon Syndrome in 'B Boy' Break-Dancer: A Case Report.

    PubMed

    Hu, Soo-Young; Choi, Jin-Gyu; Son, Byung-Chul

    2015-10-01

    Although the musculoskeletal injuries associated with break-dancing which is gaining more popularity among adolescent and young people has been reported, the report regarding a peripheral nerve injury associated with breakdance is scarce. We report a rare case of a young amateur break-dancer, 'b-boy' who suffered from a painful paresthesia in his left hand, later diagnosed as type III Guyon's canal syndrome. A 23-year-old, right handed college man presented with a tenderness over the left hypothenar eminence and painful paresthesia over the ring and little fingers of 3 months duration. He trained himself as an amateur 'b boy' break-dancer for the last 10 months. Conservative management under the diagnosis of wrist sprain before presentation did not improve his hand pain. An magnetic resonance imaging and electrodiagnostic study revealed that painful paresthesia was caused by type III Guyon's canal syndrome, and 4 weeks of corticosteroid treatment was given with resolution of pain and paresthesia. PMID:27169091

  7. Type III Guyon Syndrome in 'B Boy' Break-Dancer: A Case Report

    PubMed Central

    Hu, Soo-young; Choi, Jin-gyu

    2015-01-01

    Although the musculoskeletal injuries associated with break-dancing which is gaining more popularity among adolescent and young people has been reported, the report regarding a peripheral nerve injury associated with breakdance is scarce. We report a rare case of a young amateur break-dancer, 'b-boy' who suffered from a painful paresthesia in his left hand, later diagnosed as type III Guyon's canal syndrome. A 23-year-old, right handed college man presented with a tenderness over the left hypothenar eminence and painful paresthesia over the ring and little fingers of 3 months duration. He trained himself as an amateur 'b boy' break-dancer for the last 10 months. Conservative management under the diagnosis of wrist sprain before presentation did not improve his hand pain. An magnetic resonance imaging and electrodiagnostic study revealed that painful paresthesia was caused by type III Guyon's canal syndrome, and 4 weeks of corticosteroid treatment was given with resolution of pain and paresthesia. PMID:27169091

  8. The multifaceted and complex hypermobility syndrome (a.k.a. Ehlers-Danlos Syndrome Hypermobility Type): evaluation and management through a rehabilitative approach.

    PubMed

    Celletti, C; Camerota, F

    2013-01-01

    Joint hypermobility syndrome (JHS) is a hereditary disorder of connective tissue recently considered the one and the same as the Ehlers-Danlos Syndrome Hypermobility Type (EDS-HT). The JHS/EDS-HT is mainly characterized by joint hypermobility, chronic pain and a variable skin involvement. Clinical manifestations expressed by patients are multiple and varied. The rehabilitative approach may play a fundamental role in the understanding and management of symptoms and clinical manifestation. Aim of this study is to make a literature revision of all the aspects of this not so rare disease. PMID:24045532

  9. [WPW syndrome combined with AV block 2 in an adult with glycogenosis (Type II)].

    PubMed

    Francesconi, M; Auff, E; Ursin, C; Sluga, E

    1982-08-01

    A 31 year-old female with a five year history of muscle weakness, cardiac palpitations and elevation of activity of some serum enzymes of muscular origin, showed signs of the WPW syndrome on ECG, often in combination with grade 2 A-V block. Type II glycogenosis (Pompe's disease) was diagnosed on the basis of the results of physical examination, laboratory findings--especially subtotal deficiency of acid maltase (a-1,4 glucosidase) activity-and morphological aspects of light and electron microscopy of a quadriceps muscle biopsy specimen. To our knowledge the coincidence of such a rarely encountered arrhythmia with glycogenosis type II in an adult has never been reported so far. PMID:6959422

  10. Expanding the spectrum of genetic mutations in antenatal Bartter syndrome type II.

    PubMed

    Fretzayas, Andreas; Gole, Evangelia; Attilakos, Achilleas; Daskalaki, Anna; Nicolaidou, Polyxeni; Papadopoulou, Anna

    2013-06-01

    Bartter syndrome (BS) is a group of genetic disorders characterized by hypokalemic metabolic alkalosis, hyponatremia and elevated renin and aldosterone plasma concentrations. BS type II is caused by mutations in the KCNJ1 gene and usually presents with transient hyperkalemia. We report here a novel KCNJ1 mutation in a male neonate, prematurely born after a pregnancy complicated by polyhydramnios. The infant presented with typical clinical and laboratory findings of BS type II, such as hyponatremia, hypochloremic metabolic alkalosis, severe weight loss, elevated renin and aldosterone levels and transient hyperkalemia in the early postnatal period, which were later normalized. Molecular analysis revealed a compound heterozygous mutation in the KCNJ1 gene, consisting of a novel K76E and an already described V315G mutation, both affecting functional domains of the channel protein. Typical manifestations of antenatal BS in combination with hyperkalemia should prompt the clinician to search for mutations in the KCNJ1 gene first. PMID:23782368