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1.
Yi Chuan ; 41(8): 716-724, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31447422

RESUMO

In order to investigate the genetic variations and the clinical manifestations of a range of congenital ectrodactyly family and to summarize the split hand/foot malformation (SHFM) types and their related pathogenic genes, we conducted phenotypic analyses of patient's limbs by physical and X-ray examination. The haplotypes were analyzed by using the extracted genes from peripheral blood on D10S1709, D10S192, D10S597, D10S1693 and D10S587 loci, and the mutation duplication loci were confirmed by Array-CGH detection. The pathogenic factors and inheritance pattern of SHFM were analyzed based on family investigation and gene analysis. Results demonstrate the proband's phenotype is typically of a congenital SHFM which is manifested by missing bilateral index and middle fingers, short bilateral thumbs, deformed left ring finger with webbing of the skin missing at the middle finger; bilateral big toe with the second and the third toe missing, fourth and fifth toe fusion leading to a deformed toe separated from the first toe by the middle of the foot. The haplotype analyses show that there is a repeat of at least 610 kb in chromosome 10q24.31-10q24.32 region. Array-CGH analysis shows 10q24.31 (102 832 650-103 511 083) ×3. Our results demonstrate that the pathogenic gene variation of ectrodactyly in this family is due to duplication of 10q24.31 (102 832 650~103 511 083). The haplotype 165-251-289-219-102 can be used as a disease marker for detecting 10q24.31~10q24.32 allele for SHFM.


Assuntos
Duplicação Cromossômica , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/genética , Deformidades Congênitas dos Membros/genética , Cromossomos Humanos Par 10/genética , Humanos , Linhagem
2.
Cytogenet Genome Res ; 154(4): 181-186, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29902798

RESUMO

Oculodentodigital dysplasia (ODDD) is a rare condition characterized by a typical facial appearance and variable findings of the eyes, teeth, and fingers. ODDD is caused by mutations in the GJA1 gene in chromosome 6q22 and inherited in an autosomal dominant manner in the majority of the patients. However, in recent clinical reports, autosomal recessive ODDD cases due to by GJA1 mutations were also described. Here, we report on a 14-year-old boy with microphthalmia, microcornea, narrow nasal bridge, hypoplastic alae nasi, prominent columnella, hypodontia, dental caries, and partial syndactyly of the 2nd and 3rd toes. These clinical findings were concordant with the diagnosis of ODDD, and a novel homozygous mutation (c.442C>T, p.Arg148Ter) was determined in the GJA1 gene leading to a premature stop codon. His phenotypically normal parents were found to be carriers of the same mutation. This is the third family in the literature in which ODDD segregates in an autosomal recessive manner.


Assuntos
Anormalidades Craniofaciais/genética , Anormalidades do Olho/genética , Deformidades Congênitas do Pé/genética , Genes Recessivos , Sindactilia/genética , Anormalidades Dentárias/genética , Adolescente , Códon de Terminação/genética , Conexina 43/genética , Homozigoto , Humanos , Masculino , Mutação
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 35(2): 268-271, 2018 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-29653008

RESUMO

OBJECTIVE: To explore the genetic basis for a patient with oculodentodigital dysplasia. METHODS: Genomic DNA was extracted from peripheral blood samples from the patient and his parents. Whole-exome sequencing was carried out for the trio family. Suspected mutation was verified by Sanger sequencing. RESULTS: A de novo c.412G>A mutation of the GJA1 gene was identified in the patient, which was validated by Sanger sequencing. CONCLUSION: The c.412G>A mutation of the GJA1 gene probably underlies the disease in the patient.


Assuntos
Conexina 43/genética , Anormalidades Craniofaciais/genética , Exoma , Anormalidades do Olho/genética , Deformidades Congênitas do Pé/genética , Mutação , Sindactilia/genética , Anormalidades Dentárias/genética , Adulto , Humanos , Masculino , Análise de Sequência de DNA
5.
Int J Pediatr Otorhinolaryngol ; 108: 208-212, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29605356

RESUMO

OBJECTIVE: Evaluation of clinical findings and audiological outcome after surgery in a Danish family with autosomal dominant facio-audio-symphalangism syndrome with stapes fixation, syndactyly and symphalangism. METHODS: Retrospective report on eight affected family members in a Danish family. Clinical investigation included X-ray, audiology and in one case video-recorded surgery. Main outcome measure was audiologic results after stapedectomy. Sanger DNA sequencing of NOG was performed on peripheral blood. RESULTS: Audiologic analysis showed that seven of eight affected family members had bilateral conductive hearing loss. Three patients were treated with stapedectomy, on one or both ears, due to fixation of stapes. All the affected members had syndactyly and symphalangism. A not previously reported mutation in the NOG gene (c.688_699del, p.Cys230_Cys232delins11) was found to segregate with the stapes fixation, syndactyly, and symphalangism. p.Cys230_Cysdelins11 was classified as likely pathogenic according to guidelines from the American College of Medical Genetics and Genomics. CONCLUSION: The clinical presentation of the reported mutation corresponds with previous case reports of families with NOG mutation. In this family, surgery with stapedectomy had lasting effect without renewed fixation of the stapes in a follow up period of 18 months-38 years.


Assuntos
Ossos do Carpo/anormalidades , Proteínas de Transporte/genética , Deformidades Congênitas do Pé/cirurgia , Deformidades Congênitas da Mão/cirurgia , Perda Auditiva Condutiva/cirurgia , Cirurgia do Estribo/métodos , Estribo/anormalidades , Sinostose/cirurgia , Ossos do Tarso/anormalidades , Adolescente , Adulto , Idoso , Ossos do Carpo/cirurgia , Dinamarca , Feminino , Seguimentos , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/genética , Perda Auditiva Condutiva/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prótese Ossicular/efeitos adversos , Linhagem , Fenótipo , Estudos Retrospectivos , Cirurgia do Estribo/efeitos adversos , Sindactilia/genética , Sinostose/genética , Ossos do Tarso/cirurgia , Resultado do Tratamento
6.
Brain Dev ; 40(7): 576-581, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29625811

RESUMO

A 38-year-old female patient experienced recurrent episodes of neurological deterioration during febrile illness at the age of 7 and 8 months, and 2, 4, and 37 years. Acute symptoms comprised unconsciousness, headache, abnormal ocular movements, flaccid paralysis with areflexia, ataxia, dysphagia, and movement disorders. Each episode of neurological deterioration was followed by partial recovery with residual symptoms of progressive disturbance of visual acuity with optic atrophy and hearing loss, moderate intellectual disability, strabismus, ophthalmoplegia, as well as fluctuating degree of gait ataxia, chorea, tremor, and myoclonus. In addition, electrocardiography revealed incomplete right bundle branch block. The genetic testing revealed a de novo heterozygous mutation of c.2452G > A (p.Glu818Lys) in the ATP1A3 gene, which was compatible with the clinical phenotype of CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss)/CAOS syndrome. Here we discuss the significance of clinical features of a patient, overlapping with those of alternating hemiplegia of childhood, along with a literature review.


Assuntos
Ataxia Cerebelar/genética , Deformidades Congênitas do Pé/genética , Perda Auditiva Neurossensorial/genética , Mutação , Atrofia Óptica/genética , Reflexo Anormal/genética , ATPase Trocadora de Sódio-Potássio/genética , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Ataxia Cerebelar/diagnóstico por imagem , Ataxia Cerebelar/tratamento farmacológico , Ataxia Cerebelar/fisiopatologia , Progressão da Doença , Feminino , Deformidades Congênitas do Pé/diagnóstico por imagem , Deformidades Congênitas do Pé/tratamento farmacológico , Deformidades Congênitas do Pé/fisiopatologia , Perda Auditiva Neurossensorial/diagnóstico por imagem , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Atrofia Óptica/diagnóstico por imagem , Atrofia Óptica/tratamento farmacológico , Atrofia Óptica/fisiopatologia , Fenótipo
9.
Eur J Paediatr Neurol ; 22(2): 257-263, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29291920

RESUMO

Alternating Hemiplegia of Childhood (AHC), Rapid-onset Dystonia Parkinsonism (RDP) and CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) are three distinct, yet partially overlapping clinical syndromes that have long been thought to be allelic disorders. From 2004 to 2012, both autosomal dominant and de novo mutations in ATP1A3 have been detected in patients affected by these three conditions. Growing evidence suggests that AHC, RDP and CAPOS syndrome are part of a large and continuously expanding clinical spectrum and share some recurrent clinical features, such as abrupt-onset, asymmetric anatomical distribution and the presence of triggering factors, which are highly suggestive of ATP1A3 mutations. In this review, we will highlight the main clinical and genetic features of ATP1A3-related disorders focussing on shared and distinct features that can be helpful in clinical practice to individuate mutation carriers.


Assuntos
Ataxia Cerebelar/genética , Distúrbios Distônicos/genética , Deformidades Congênitas do Pé/genética , Perda Auditiva Neurossensorial/genética , Hemiplegia/genética , Atrofia Óptica/genética , Reflexo Anormal/genética , ATPase Trocadora de Sódio-Potássio/genética , Pré-Escolar , Feminino , Estudos de Associação Genética , Humanos , Mutação
10.
Indian J Ophthalmol ; 66(2): 334-336, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29380799

RESUMO

Here, we report a patient with oculodentodigital dysplasia (ODDD) caused by the c. 413G>A, p.Gly138Asp mutation in the gap junction protein alpha-1 gene. The patient suffered from characteristic dysmorphic features of ODDD. Ophthalmological investigation disclosed microcornea and a shallow anterior chamber, as expected. Surprisingly, the patient had a normal axial length and moderate myopia on both eyes. To the best of our knowledge, this is the first report on ODDD associated with relative anterior microphthalmos and myopia.


Assuntos
Anormalidades Múltiplas , Conexina 43/genética , Anormalidades Craniofaciais/diagnóstico , DNA/genética , Anormalidades do Olho/diagnóstico , Deformidades Congênitas do Pé/diagnóstico , Microftalmia/diagnóstico , Sindactilia/diagnóstico , Anormalidades Dentárias/diagnóstico , Adulto , Conexina 43/metabolismo , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/metabolismo , Análise Mutacional de DNA , Anormalidades do Olho/genética , Anormalidades do Olho/metabolismo , Deformidades Congênitas do Pé/genética , Deformidades Congênitas do Pé/metabolismo , Humanos , Masculino , Microftalmia/genética , Microftalmia/metabolismo , Sindactilia/genética , Sindactilia/metabolismo , Tomografia de Coerência Óptica , Anormalidades Dentárias/genética , Anormalidades Dentárias/metabolismo
11.
Am J Med Genet A ; 176(1): 219-224, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29159868

RESUMO

We report a family of Indian origin presenting with Tarsal-carpal coalition syndrome (TCC), which is a rare genetic disorder of skeletal abnormalities, inherited in autosomal dominant manner. In this family, three individuals (mother and two children) were found to be similarly affected with slight intrafamilial individual variability in the phenotype. Sanger sequencing revealed a novel heterozygous missense mutation in NOG gene (NM_005450.4:c.611G>A) in all the affected individuals of the family. Until now only six mutations have been reported in different families affected with TCC syndrome worldwide. This report further delineates the phenotypic spectrum of this rare disorder with the addition of a new variant to the mutation spectrum.


Assuntos
Ossos do Carpo/anormalidades , Proteínas de Transporte/genética , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/genética , Mutação de Sentido Incorreto , Fenótipo , Estribo/anormalidades , Sinostose/genética , Ossos do Tarso/anormalidades , Alelos , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Linhagem , Radiografia
12.
Am J Med Genet A ; 176(1): 235-240, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29090527

RESUMO

Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome (OMIM# 601338) is a rare autosomal dominant disorder characterized by episodic, fever-induced ataxic encephalopathy in childhood with residual symptoms. All identified patients have the same heterozygous missense variant c.2452G>A (p.Glu818Lys) in the ATP1A3 gene, encoding Na+ /K+ ATPase α3. We describe a large CAPOS pedigree with three generations of affected members, the first ascertained in the United States. Deafness, optic atrophy, and pes cavus were present in all three members of the family evaluated. In addition, one of the affected individuals experienced markedly worsening features during her three pregnancies and in the immediate postpartum period, a potential element of the natural history of CAPOS previously unreported. We conclude that the triggering factors and clinical spectrum of pathogenic ATP1A3 variants may be broader than previously described. Targeted sequencing of ATP1A3 should be considered in any patient presenting with cerebellar ataxia triggered by febrile illness, or pregnancy and delivery, especially in the presence of sensorineural hearing loss, optic atrophy, pes cavus, or early childhood history of acute encephalopathic ataxia. Prophylactic administration of acetazolamide or flunarizine may prevent acute episodes of ataxia or mitigate neurologic symptoms, although their efficacies have not been well studied.


Assuntos
Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/genética , Deformidades Congênitas do Pé/diagnóstico , Deformidades Congênitas do Pé/genética , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Atrofia Óptica/diagnóstico , Atrofia Óptica/genética , Fenótipo , Complicações na Gravidez , Reflexo Anormal/genética , Alelos , Pré-Escolar , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Lactente , Masculino , Linhagem , Gravidez , ATPase Trocadora de Sódio-Potássio/genética
13.
Acta Orthop ; 89(1): 113-118, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28946786

RESUMO

Background and purpose - Preaxial polydactyly of the foot is a rare malformation and clinicians are often unfamiliar with the associated malformations and syndromes. In order to give guidelines for diagnostics and referral to a clinical geneticist, we provide an overview of the presentation using a literature review and our own patient population. Patients and methods - The literature review was based on the Human Phenotype Ontology (HPO) project. From the HPO dataset, all phenotypes describing preaxial polydactyly were obtained and related diseases were identified and selected. An overview was generated in a heatmap, in which the phenotypic contribution of 12 anatomical groups to each disease is displayed. Clinical cases were obtained from our hospital database and were reviewed in terms of phenotype, genotype, heredity, and diagnosed syndromes. Results - From the HPO dataset, 21 diseases were related to preaxial polydactyly of the foot. The anatomical groups with the highest phenotypic contribution were lower limb, upper limb, and craniofacial. From our clinical database, we included 76 patients with 9 different diseases, of which 27 had a GLI3 mutation. Lower limb malformations (n = 55), upper limb malformations (n = 59), and craniofacial malformations (n = 32) were most frequently observed. Malformations in other anatomical groups were observed in 27 patients. Interpretation - Preaxial polydactyly of the foot often presents with other upper and lower limb malformations. In patients with isolated preaxial polydactyly of the foot, referral to a clinical geneticist is not mandatory. In patients with additional malformations, consultation with a clinical geneticist is recommended. When additional limb malformations are present, analysis of GLI3 is most feasible.


Assuntos
Deformidades Congênitas do Pé/patologia , Polidactilia/patologia , Feminino , , Deformidades Congênitas do Pé/genética , Deformidades Congênitas do Pé/cirurgia , Humanos , Masculino , Mutação/genética , Polidactilia/genética , Polidactilia/cirurgia
14.
Ann Clin Lab Sci ; 48(6): 776-781, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30610049

RESUMO

Oculodentodigital dysplasia (ODDD; MIM #164200), a rare genetic disorder characterized by abnormal craniofacial, dental, ocular, and digital features, is caused by mutations in the gap junction alpha-1 (GJA1) gene. We report a case of a 6-year-old male who presented with dysmorphic facial features (short palpebral fissure, thin nose with hypoplastic alae nasi, and flat face), bilateral syndactyly, abnormal dentition, and proportionate short stature with growth hormone deficiency. A novel de novo heterozygous missense mutation (c.221A>C, p.H74P) in GJA1 was identified by targeted gene panel sequencing. This is the first case report of a novel ODDD-causing mutation in GJA1 confirmed by genetic analysis in Korea.


Assuntos
Conexina 43/genética , Anormalidades Craniofaciais/genética , Anormalidades do Olho/genética , Deformidades Congênitas do Pé/genética , Mutação/genética , Sindactilia/genética , Anormalidades Dentárias/genética , Criança , Anormalidades Craniofaciais/diagnóstico por imagem , Análise Mutacional de DNA , Anormalidades do Olho/diagnóstico por imagem , Deformidades Congênitas do Pé/diagnóstico por imagem , Junções Comunicantes/patologia , Humanos , Masculino , Sindactilia/diagnóstico por imagem , Anormalidades Dentárias/diagnóstico por imagem
15.
Am J Med Genet A ; 173(11): 3104-3108, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28884947

RESUMO

We present a 4-year-old girl with delayed neuromotor development, short stature of prenatal onset, and specific behavioral and craniofacial features harboring an intragenic deletion in the ARID2 gene. The phenotype confirmed the major features of the recently described ARID2-related intellectual disability syndrome. However, our patient showed overlapping features with Nicolaides-Baraitser syndrome and Coffin-Siris syndrome, providing further arguments to reclassify these disorders as "SWI/SNF-related intellectual disability syndromes."


Assuntos
Proteínas Cromossômicas não Histona/genética , Deficiência Intelectual/genética , Transtornos Motores/genética , Fatores de Transcrição/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Pré-Escolar , Face/anormalidades , Face/patologia , Facies , Feminino , Deformidades Congênitas do Pé/diagnóstico , Deformidades Congênitas do Pé/genética , Deformidades Congênitas do Pé/patologia , Predisposição Genética para Doença , Deformidades Congênitas da Mão/diagnóstico , Deformidades Congênitas da Mão/genética , Deformidades Congênitas da Mão/patologia , Humanos , Hipotricose/diagnóstico , Hipotricose/genética , Hipotricose/patologia , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/patologia , Deficiência Intelectual/fisiopatologia , Micrognatismo/diagnóstico , Micrognatismo/genética , Micrognatismo/patologia , Transtornos Motores/fisiopatologia , Pescoço/anormalidades , Pescoço/patologia
16.
J Genet ; 96(4): 647-652, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28947713

RESUMO

Hand-foot-genital syndrome (HFGS) is a rare autosomal dominant inherited syndrome characterized by limb malformations and urogenital defects. HFGS is caused by mutations in the HOXA13 gene. The aim of this study was to identify causative mutations in individuals and to explore the molecular pathogenesis in a Chinese family with HFGS. We performed Sanger sequencing and identified a recurrent missense mutation in the homeodomain (c.1123G>T, p.V375F) of HOXA13, molecular modelling predicted the mutation would affect DNA binding, and a luciferase reporter assay indicated that it impaired the ability of HOXA13 to activate transcription of the human EPHA7 promoter. This is the first report of the molecular basis for HFGS caused by missense mutations of HOXA13.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Deformidades Congênitas do Pé/diagnóstico , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/diagnóstico , Deformidades Congênitas da Mão/genética , Proteínas de Homeodomínio/genética , Mutação de Sentido Incorreto , Anormalidades Urogenitais/diagnóstico , Anormalidades Urogenitais/genética , China , Análise Mutacional de DNA , Família , Feminino , Estudos de Associação Genética , Genótipo , Proteínas de Homeodomínio/química , Humanos , Masculino , Modelos Moleculares , Linhagem , Fenótipo , Regiões Promotoras Genéticas , Conformação Proteica
17.
Nat Genet ; 49(10): 1539-1545, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28846100

RESUMO

Copy number variations (CNVs) often include noncoding sequences and putative enhancers, but how these rearrangements induce disease is poorly understood. Here we investigate CNVs involving the regulatory landscape of IHH (encoding Indian hedgehog), which cause multiple, highly localized phenotypes including craniosynostosis and synpolydactyly. We show through transgenic reporter and genome-editing studies in mice that Ihh is regulated by a constellation of at least nine enhancers with individual tissue specificities in the digit anlagen, growth plates, skull sutures and fingertips. Consecutive deletions, resulting in growth defects of the skull and long bones, showed that these enhancers function in an additive manner. Duplications, in contrast, caused not only dose-dependent upregulation but also misexpression of Ihh, leading to abnormal phalanges, fusion of sutures and syndactyly. Thus, precise spatiotemporal control of developmental gene expression is achieved by complex multipartite enhancer ensembles. Alterations in the composition of such clusters can result in gene misexpression and disease.


Assuntos
Doenças do Desenvolvimento Ósseo/genética , Elementos Facilitadores Genéticos/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas Hedgehog/fisiologia , Osteogênese/genética , Animais , Sequência de Bases , Variações do Número de Cópias de DNA , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Deformidades Congênitas do Pé/genética , Deleção de Genes , Dosagem de Genes , Duplicação Gênica , Técnicas de Inativação de Genes , Genes Reporter , Proteínas Hedgehog/deficiência , Proteínas Hedgehog/genética , Camundongos , Camundongos Endogâmicos C57BL , Polidactilia/genética , Sequências Reguladoras de Ácido Nucleico , Análise de Sequência de DNA , Crânio/anormalidades , Transcrição Genética
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 34(4): 476-480, 2017 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-28777841

RESUMO

OBJECTIVE: To explore the genetic etiology of three families affected with split-hand/split-foot malformation (SHFM). METHODS: Peripheral venous blood samples from 21 members of pedigree 1, 2 members of pedigree 2, and 2 members of pedigree 3 were collected. PCR-Sanger sequencing, microarray chip, fluorescence in situ hybridization (FISH), real-time PCR, and next-generation sequencing were employed to screen the mutations in the 3 families. The effect of the identified mutations on the finger (toe) abnormality were also explored. RESULTS: Microarray and real-time PCR analysis has identified a duplication in all patients from pedigrees 1 and 3, which have spanned FKSG40, TLX1, LBX1, BTRC, POLL and FBXW4 (exons 6-9) and LBX1, BTRC, POLL and FBXW4 (exons 6-9) genes, respectively. A missense mutation of the TP63 gene, namely c.692A>G (p.Tyr231Cys), was found in two patients from pedigree 2. FISH analysis of chromosome 10 showed that the rearrangement could fita tandem duplication model. However, next-generation sequencing did not identify the breakpoint. CONCLUSION: The genetic etiology for three families affected with SHFM have been identified, which has provideda basis for genetic counseling and guidance for reproduction.


Assuntos
Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/genética , Deformidades Congênitas dos Membros/genética , Mutação/genética , Cromossomos Humanos Par 10/genética , Feminino , Testes Genéticos , Humanos , Masculino , Linhagem
19.
Pediatr Neurol ; 71: 60-64, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28483396

RESUMO

BACKGROUND: CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) is a rare disease that has been reported in 22 patients so far. In all cases, the mutation c.2452G>A (p.Glu818Lys) in the ATP1A3 gene was identified. Patients typically present at an early age with an acute-onset fever-induced episode of ataxia frequently associated with encephalopathy and weakness. They usually present one to three episodes. The acute symptoms improve within days, but most patients show slow progression afterward. METHODS: We describe three new patients, a woman and her two sons diagnosed with CAPOS syndrome. A systematic review of literature on previously reported patients was performed. RESULTS: The first son presented with acute-onset ataxia, encephalopathy, and sensorineural hearing loss, induced by febrile illness. The second one developed generalized areflexia and mild instability without an acute episode. The mother had been previously diagnosed with sensorineural hearing loss and optic nerve atrophy. The c.2452G>A mutation in ATP1A3 was found in all three patients. CONCLUSION: Only 25 Individuals with CAPOS syndrome have been reported, including our family. This is the first time a Spanish family has been described. The fact that both siblings were assessed before the first acute-onset episode contributes to the description of early symptoms and signs of the disease, which could aid early diagnosis and management before the onset of acute episodes.


Assuntos
Ataxia Cerebelar/diagnóstico , Deformidades Congênitas do Pé/diagnóstico , Perda Auditiva Neurossensorial/diagnóstico , Atrofia Óptica/diagnóstico , Adulto , Ataxia/diagnóstico , Ataxia/genética , Ataxia/fisiopatologia , Ataxia Cerebelar/genética , Ataxia Cerebelar/fisiopatologia , Criança , Diagnóstico Precoce , Família , Feminino , Deformidades Congênitas do Pé/genética , Deformidades Congênitas do Pé/fisiopatologia , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Masculino , Atrofia Óptica/genética , Atrofia Óptica/fisiopatologia , Reflexo Anormal/genética
20.
Rev Neurol ; 64(11): 481-488, 2017 Jun 01.
Artigo em Espanhol | MEDLINE | ID: mdl-28555453

RESUMO

INTRODUCTION: Ritscher-Schinzel syndrome (also known as cranio-cerebello-cardiac dysplasia or 3C syndrome) is a rare genetic syndrome that is mainly characterised by the association of cardiac and craniofacial anomalies together with others affecting the posterior fossa. PATIENTS AND METHODS: We report on 26 patients with Ritscher-Schinzel syndrome at a hospital in Medellin, in the Department of Antioquia, Colombia. RESULTS: Males account for 69% of this cohort. The mean age of the cohort was 30 months, and 42% were under the age of one year at the time of diagnosis. All of them presented ocular disorders, and megalocornea was the most frequent ocular manifestation (69%), whereas low-set ears (80.7%) and septal heart defects (68.7%) were the most common facial and cardiac malformations, respectively. The most frequent malformations of the posterior fossa were megacisterna magna (31.8%) and Dandy-Walker malformation (27%). 84% of the cases had delayed neurodevelopment or intellectual disability. Skeletal manifestations were frequent: the group consisting of camptodactyly, single palmar crease, overlapping fingers, vertical talus and nail hypoplasia were found in hands and feet in 96% of the cases. CONCLUSIONS: Ritscher-Schinzel syndrome is a heterogeneous syndrome from the genetic and clinical point of view. These results suggest that the skeletal and ocular abnormalities that were observed can facilitate the phenotypic diagnosis. However, it is necessary to conduct further studies that allow us to gain a deeper knowledge of its prevalence and help identify other genes involved in this syndrome.


Assuntos
Anormalidades Múltiplas/genética , Cerebelo/anormalidades , Fossa Craniana Posterior/anormalidades , Anormalidades Craniofaciais/genética , Síndrome de Dandy-Walker/genética , Deficiências do Desenvolvimento/genética , Anormalidades do Olho/genética , Comunicação Interatrial/genética , Deficiência Intelectual/genética , Anormalidades Múltiplas/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Colômbia , Córnea/anormalidades , Anormalidades Craniofaciais/patologia , Síndrome de Dandy-Walker/patologia , Feminino , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/genética , Comunicação Interatrial/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Estudos Retrospectivos , Síndrome
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