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1.
Ital J Pediatr ; 45(1): 85, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31319890

RESUMO

BACKGROUND: Turner syndrome (45,X), accounts for 1-2% of conceptions which typically miscarry early in the first trimester. Cases detected prenatally often present with cystic hygroma, which is an ultrasound marker for aneuploidy generally, but Turner syndrome particularly. In this study, we report a second trimester intrauterine fetal demise (IUFD), complicated by a marked cystic hygroma and bilateral syndactyly of the fingers and toes. CASE PRESENTATION: A 25-year-old woman presented for her first prenatal visit at 22-week gestation with IUFD. Color Doppler ultrasound revealed a septated nuchal lymphatic hygroma and hydrops fetalis, characterized by edema of the whole body, substantial pleural effusion and abdominal fluid. Pregnancy was further complicated by oligohydramnios. Following labor induction, a stillborn female baby was delivered at 22 weeks gestation. Autopsy confirmed the presence of huge nuchal cystic hygroma (10 cm × 10 cm × 6 cm) and generalized edema. Bilateral, partial syndactyly involving digits 2-5 of the fingers and toes were also observed. Chromosomal analysis revealed a 45,X karyotype. CONCLUSIONS: We investigated an unusual case of severe septated nuchal cystic hygroma associated with bilateral syndactyly of the fingers and toes in a stillborn infant with Turner syndrome. Although cystic hygroma has been frequently reported in 45,X the severity is marked in this case. In addition, syndactyly is not a typical complication of Turner syndrome. This case emphasizes the importance of early ultrasound in pregnancy.


Assuntos
Hidropisia Fetal/diagnóstico por imagem , Linfangioma Cístico/diagnóstico por imagem , Sindactilia/diagnóstico por imagem , Síndrome de Turner/diagnóstico por imagem , Adulto , Feminino , Morte Fetal , Humanos , Oligo-Hidrâmnio/diagnóstico por imagem , Derrame Pleural/diagnóstico por imagem , Gravidez , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal
2.
Bone ; 116: 321-332, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30077757

RESUMO

Sclerosteosis (SOST) refers to two extremely rare yet similar skeletal dysplasias featuring a diffusely radiodense skeleton together with congenital syndactyly. SOST1 is transmitted as an autosomal recessive (AR) trait and to date caused by ten homozygous loss-of-function mutations within the gene SOST that encodes the inhibitor of Wnt-mediated bone formation, sclerostin. SOST2 is transmitted as an autosomal dominant (AD) or AR trait and to date caused by one heterozygous or two homozygous loss-of-function mutation(s), respectively, within the gene LRP4 that encodes the sclerostin interaction protein, low-density lipoprotein receptor-related protein 4 (LRP4). Herein, we investigated two teenagers and one middle-aged man with SOST in three families living in the state of Tamil Nadu in southern India. Next generation sequencing of their genomic DNA using our high bone density gene panel revealed SOST1 in the teenagers caused by a unique homozygous nonsense SOST mutation (c.129C > G, p.Tyr43X) and SOST2 in the man caused by homozygosity for one of the two known homozygous missense LRP4 mutations (c.3508C > T, p.Arg1170Trp). He becomes the fourth individual and the first non-European recognized with SOST2. His clinical course was milder than the life-threatening SOST1 demonstrated by the teenagers who suffered blindness, deafness, and raised intracranial pressure, yet his congenital syndactyly was more striking by featuring bony fusion of digits. All three patients were from consanguineous families and heterozygosity for the SOST mutation was documented in the mothers of both teenagers. Thus, on the endogamous genetic background of Indian Tamils, SOST1 from sclerostin deficiency compared to SOST2 from LRP4 deactivation is a more severe and life-threatening disorder featuring complications due to osteosclerosis of especially the skull. In contrast, the syndactyly of SOST2 is particularly striking by involving bony fusion of some digits. Both the SOST and LRP4 mutations in this ethnic population likely reflect genetic founders.


Assuntos
Hiperostose/patologia , Sindactilia/patologia , Adolescente , Sequência de Bases , Proteínas Morfogenéticas Ósseas/genética , Osso e Ossos/metabolismo , Análise Mutacional de DNA , Família , Feminino , Marcadores Genéticos/genética , Humanos , Hiperostose/diagnóstico por imagem , Hiperostose/genética , Índia , Proteínas Relacionadas a Receptor de LDL/genética , Masculino , Pessoa de Meia-Idade , Minerais/metabolismo , Linhagem , Sindactilia/diagnóstico por imagem , Sindactilia/genética
3.
JCI Insight ; 3(11)2018 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-29875318

RESUMO

The WNT pathway has become an attractive target for skeletal therapies. High-bone-mass phenotypes in patients with loss-of-function mutations in the LRP5/6 inhibitor Sost (sclerosteosis), or in its downstream enhancer region (van Buchem disease), highlight the utility of targeting Sost/sclerostin to improve bone properties. Sclerostin-neutralizing antibody is highly osteoanabolic in animal models and in human clinical trials, but antibody-based inhibition of another potent LRP5/6 antagonist, Dkk1, is largely inefficacious for building bone in the unperturbed adult skeleton. Here, we show that conditional deletion of Dkk1 from bone also has negligible effects on bone mass. Dkk1 inhibition increases Sost expression, suggesting a potential compensatory mechanism that might explain why Dkk1 suppression lacks anabolic action. To test this concept, we deleted Sost from osteocytes in, or administered sclerostin neutralizing antibody to, mice with a Dkk1-deficient skeleton. A robust anabolic response to Dkk1 deletion was manifest only when Sost/sclerostin was impaired. Whole-body DXA scans, µCT measurements of the femur and spine, histomorphometric measures of femoral bone formation rates, and biomechanical properties of whole bones confirmed the anabolic potential of Dkk1 inhibition in the absence of sclerostin. Further, combined administration of sclerostin and Dkk1 antibody in WT mice produced a synergistic effect on bone gain that greatly exceeded individual or additive effects of the therapies, confirming the therapeutic potential of inhibiting multiple WNT antagonists for skeletal health. In conclusion, the osteoanabolic effects of Dkk1 inhibition can be realized if sclerostin upregulation is prevented. Anabolic therapies for patients with low bone mass might benefit from a strategy that accounts for the compensatory milieu of WNT inhibitors in bone tissue.


Assuntos
Anabolizantes/administração & dosagem , Glicoproteínas/antagonistas & inibidores , Hiperostose/tratamento farmacológico , Osteogênese/efeitos dos fármacos , Sindactilia/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Anticorpos Neutralizantes/administração & dosagem , Proteínas Morfogenéticas Ósseas/genética , Modelos Animais de Doenças , Feminino , Fêmur/citologia , Fêmur/diagnóstico por imagem , Fêmur/patologia , Marcadores Genéticos/genética , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Hiperostose/diagnóstico por imagem , Hiperostose/genética , Hiperostose/patologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Mutação com Perda de Função , Masculino , Camundongos , Osteócitos , Coluna Vertebral/citologia , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/patologia , Sindactilia/diagnóstico por imagem , Sindactilia/genética , Sindactilia/patologia , Resultado do Tratamento , Regulação para Cima/efeitos dos fármacos , Microtomografia por Raio-X
4.
J Hum Genet ; 63(7): 851-855, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29703962

RESUMO

3-hydroxyisobutryl-CoA hydrolase (HIBCH) deficiency is a rare inborn error of valine metabolism characterized by neurodegenerative symptoms and caused by recessive mutations in the HIBCH gene. In this study, utilizing whole exome sequencing, we identified two novel splicing mutations of HIBCH (c.304+3A>G; c.1010_1011+3delTGGTA) in a Chinese patient with characterized neurodegenerative features of HIBCH deficiency and bilateral syndactyly which was not reported in previous studies. Functional tests showed that both of these two mutations destroyed the normal splicing and reduced the expression of HIBCH protein. Through a literature review, a potential phenotype-genotype correlation was found that patients carrying truncating mutations tended to have more severe phenotypes compared with those with missense mutations. Our findings would widen the mutation spectrum of HIBCH causing HIBCH deficiency and the phenotypic spectrum of the disease. The potential genotype-phenotype correlation would be profitable for the treatment and management of patients with HIBCH deficiency.


Assuntos
Anormalidades Múltiplas/genética , Erros Inatos do Metabolismo dos Aminoácidos/genética , Mutação , Sindactilia/genética , Tioléster Hidrolases/deficiência , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/enzimologia , Anormalidades Múltiplas/patologia , Adulto , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico por imagem , Erros Inatos do Metabolismo dos Aminoácidos/enzimologia , Erros Inatos do Metabolismo dos Aminoácidos/patologia , Sequência de Bases , Feminino , Expressão Gênica , Genes Recessivos , Estudos de Associação Genética , Humanos , Lactente , Masculino , Linhagem , Processamento de RNA , Sindactilia/diagnóstico por imagem , Sindactilia/enzimologia , Sindactilia/patologia , Tioléster Hidrolases/genética , Sequenciamento Completo do Exoma
6.
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
7.
BMJ Case Rep ; 20172017 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-29103005

RESUMO

The impact of in-utero isotretinoin exposure has been widely reported, with many affected pregnancies failing to reach term.1 2 Due to the low numbers of in-utero isotretinoin exposed pregnancies, the interactions between this drug and rare genetic defects such as microduplication 1q21.1 are unclear, particularly how they might manifest phenotypically. We present this case of in-utero isotretinoin exposure occurring in a child with microduplication 1q21.1. The child was born with congenital abnormalities which did not fit into a single syndrome. Regrettably in-utero exposure to isotretinoin continues to occur. We hope this case will trigger further discussion on the dangers of dispensing Isotretinoin without ensuring stringent pregnancy testing and its potential interaction with genetic abnormalities, in particular with microduplication 1q21.1.


Assuntos
Anormalidades Induzidas por Medicamentos/genética , Fenda Labial/diagnóstico , Fissura Palatina/diagnóstico , Isotretinoína/toxicidade , Sindactilia/diagnóstico , Teratogênios/toxicidade , Anormalidades Induzidas por Medicamentos/diagnóstico , Anormalidades Induzidas por Medicamentos/diagnóstico por imagem , Fenda Labial/induzido quimicamente , Fenda Labial/diagnóstico por imagem , Fissura Palatina/induzido quimicamente , Fissura Palatina/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Dedos/anormalidades , Humanos , Lactente , Imagem por Ressonância Magnética , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Sindactilia/induzido quimicamente , Sindactilia/diagnóstico por imagem , Dedos do Pé/anormalidades
8.
Skeletal Radiol ; 46(12): 1741-1743, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28748361

RESUMO

Syndactyly is a cutaneous and/or bony digital malformation with possible webbing of adjacent fingers or toes and uni- or bilateral occurrence. We report an 84-year old woman with a novel non-syndromic congenital malformation of her left hand. Clinical examination showed that she only had four digits. Radiograph of the hand revealed synostosis of the second and third proximal phalanx, resulting in a triangular shaped bone with relatively normal articulations at both ends. The phalangeal base of the fused finger tapers distally and is broader than the middle phalangeal bases of the ring and little finger. This malformation does not fit in any of the known types of syndromic or non-syndromic syndactylies. Our case report highlights that radiological imaging is crucial for identification of bony syndactyly and correct classification of a given syndactyly. Knowledge of the different types of syndactylies is important because certain malformations may occur as a defining part of a syndromic disease.


Assuntos
Sindactilia/diagnóstico por imagem , Idoso de 80 Anos ou mais , Feminino , Humanos
9.
Rom J Morphol Embryol ; 58(1): 277-280, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28523332

RESUMO

Apert syndrome - acrocephalosyndactyly - is a rare autosomal dominant disorder representing 1:65 000 cases of living newborns. Characteristic malformations of the Apert syndrome are early craniostenosis, microviscerocranium and II-V finger syndactyly of hand and toes with proximal phalanx of the bilateral thumb "in delta". It is difficult to determine prenatal diagnosis in the second quarter, when examining the morphology of fetal signs; the dysmorphism signs appeared in the third pregnancy quarter. We present here the case of a newborn with Apert syndrome that was born prematurely in our Clinic after a monitored pregnancy, where there was issued a suspicion of cranio-facial dysmorphism, malposition and malformation of the feet and hands in the third quarter of prenatal pregnancy. The diagnosis of Apert syndrome was placed on clinical signs, laboratory and genetic tests. The clinical outcome of the baby in the maternity was favorable, the therapeutic management being established by a multidisciplinary team. Immediate complications were due to the case of prematurity: respiratory distress syndrome and the characteristics of the syndrome: micrognathia and naso-facial dysmorphism, syndactyly, bilateral foot metatarsus adductus.


Assuntos
Acrocefalossindactilia/patologia , Acrocefalossindactilia/diagnóstico por imagem , Feminino , Humanos , Recém-Nascido , Gravidez , Reticulocitose , Sindactilia/diagnóstico por imagem , Sindactilia/patologia
11.
Bone ; 96: 51-62, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27742500

RESUMO

Sclerosteosis and van Buchem disease are two rare bone sclerosing dysplasias caused by genetic defects in the synthesis of sclerostin. In this article we review the demographic, clinical, biochemical, radiological, and histological characteristics of patients with sclerosteosis and van Buchem disease that led to a better understanding of the role of sclerostin in bone metabolism in humans and we discuss the relevance of these findings for the development of new therapeutics for the treatment of patients with osteoporosis.


Assuntos
Proteínas Morfogenéticas Ósseas/deficiência , Biomarcadores/metabolismo , Densidade Óssea , Osso e Ossos/patologia , Osso e Ossos/fisiopatologia , Marcadores Genéticos , Humanos , Hiperostose/diagnóstico por imagem , Hiperostose/patologia , Hiperostose/fisiopatologia , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/patologia , Osteocondrodisplasias/fisiopatologia , Sindactilia/diagnóstico por imagem , Sindactilia/patologia , Sindactilia/fisiopatologia
12.
J Hand Surg Am ; 41(12): e485-e489, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28029392

RESUMO

This case presents surgical treatment of a unique form of syndactyly: an isolated fenestrated, complex, crisscross syndactyly of the right middle and ring fingers. A 2-year-old boy presented with the ring finger lying dorsal and the middle finger lying volar, with the middle phalanges syndactylized. A surgical release was performed with a subsequent z-plasty, 2 years later, for scar elongation. At the age of 4, he has essentially full function of his hand with minimal limitations. This case demonstrates that 2 digits that were syndactylized in a coronal plane (ring finger dorsal and middle finger volar) can be successfully surgically separated.


Assuntos
Dedos/anormalidades , Sindactilia/cirurgia , Pré-Escolar , Dedos/diagnóstico por imagem , Dedos/cirurgia , Humanos , Masculino , Procedimentos Ortopédicos/métodos , Radiografia , Sindactilia/diagnóstico por imagem
13.
Prenat Diagn ; 36(13): 1270-1275, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27859469

RESUMO

OBJECTIVE: Fraser syndrome (FS) is a rare malformation recessive disorder. Major criteria are cryptophtalmos, syndactyly, respiratory, genital and urinary tract anomalies. Few prenatal presentations have been reported. METHOD: We analyzed the prenatal and postnatal fetal phenotype in 38 cases of FS, including 25 pregnancy termination cases, 8 intra-uterine death cases and 4 cases that died after birth. RESULTS: Including both prenatal and postnatal fetal phenotypic evaluation, all cases presented dysmorphic features with nose and ear dysplasia. Renal anomalies and syndactyly were present in 37/38 cases, cryptophtalmos in 36/38, airways anomalies in 30/37 and genital anomalies in 30/35 cases. Anomalies of the abdominal wall such as low set umbilicus and omphalocele were found in 31 cases. Among the 26 cases for which ultrasound data were available, detectable anomalies included oligohydramnios (22), ascites/hydrops (9), renal anomalies (20), evidence for high airways obstruction (11), ophthalmologic anomalies (4), ear dysplasia (2) and syndactyly (2). CONCLUSION: This study shows that the postnatal phenotype of FS is very specific, whereas oligohydramnios hampers the prenatal recognition of the cardinal FS diagnosis criteria. Association of oligohydramnios, kidney agenesis and CHAOS should lead to consider this diagnosis. © 2016 John Wiley & Sons, Ltd.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/embriologia , Síndrome de Fraser/diagnóstico , Síndrome de Fraser/embriologia , Diagnóstico Pré-Natal/métodos , Obstrução das Vias Respiratórias/diagnóstico por imagem , Obstrução das Vias Respiratórias/embriologia , Anormalidades Congênitas/diagnóstico por imagem , Anormalidades Congênitas/embriologia , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/embriologia , Orelha/anormalidades , Orelha/diagnóstico por imagem , Orelha/embriologia , Anormalidades do Olho/diagnóstico por imagem , Anormalidades do Olho/embriologia , Feminino , Síndrome de Fraser/diagnóstico por imagem , Idade Gestacional , Humanos , Hidropisia Fetal/diagnóstico por imagem , Recém-Nascido , Rim/anormalidades , Rim/diagnóstico por imagem , Rim/embriologia , Oligo-Hidrâmnio/diagnóstico por imagem , Fenótipo , Gravidez , Sindactilia/diagnóstico por imagem , Ultrassonografia Pré-Natal , Anormalidades Urogenitais/diagnóstico
14.
Am J Vet Res ; 77(9): 976-82, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27580109

RESUMO

OBJECTIVE To characterize a population of Brazilian minipigs with naturally occurring syndactyly by use of plain radiographs and CT images and to evaluate kinetic and temporospatial variables by use of a pressure-sensing walkway. ANIMALS 10 Brazilian minipigs from 6 to 8 months of age (group 1, 5 healthy pigs [body weight, 10.5 to 18.5 kg]; group 2, 5 pigs with syndactyly [body weight, 7.5 to 18.0 kg]). PROCEDURES Forelimbs and hind limbs of all pigs were assessed by use of radiography and CT. Gait was analyzed by use of a pressure-sensing walkway. RESULTS All limbs of all pigs of group 2 had syndactyly. Two forelimbs had complex-1 syndactyly, and 8 forelimbs had complex-2 syndactyly. Four hind limbs had simple syndactyly, 1 hind limb had complex-1 syndactyly, and 5 hind limbs had complex-2 syndactyly. Kinetic and temporospatial values and symmetry indices did not differ between groups. Plantar and palmar surfaces of healthy pigs had 2 areas of maximum pressure, whereas plantar and palmar surfaces of pigs with syndactyly had only 1 area of maximum pressure. CONCLUSIONS AND CLINICAL RELEVANCE In this population of pigs, the most common type of syndactyly was complex-2, and comparison with the healthy group revealed no alteration in kinetic and temporospatial variables. Therefore, results suggested that syndactyly in young minipigs did not cause locomotor disturbances.


Assuntos
Marcha , Doenças dos Suínos/diagnóstico por imagem , Porco Miniatura , Sindactilia/veterinária , Animais , Peso Corporal , Extremidades , , Cinética , Radiografia , Suínos , Doenças dos Suínos/fisiopatologia , Sindactilia/diagnóstico por imagem , Sindactilia/fisiopatologia , Tomografia Computadorizada por Raios X , Caminhada
15.
J Hand Surg Eur Vol ; 41(3): 301-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26269507

RESUMO

UNLABELLED: Synpolydactyly is an uncommon congenital anomaly characterized by polydactyly with syndactyly in the central hand. The purpose of this investigation was to develop and assess the reliability of a radiographic classification system for synpolydactyly. We identified 56 hands with central synpolydactyly and developed a radiographic classification system that categorizes by the location within the hand, the bony level of polydactyly, and the presence of a delta phalanx. Four paediatric hand surgeons independently reviewed each radiograph to establish reliability. There was exact agreement among raters in 40 cases (71%). The inter-rater reliability was 0.97 and intra-rater reliability was at least 0.87. Seven of 16 bilateral cases had symmetric deformity classification. The most common presentations were types 1A and 2A. We present a new, reliable radiographic classification system for synpolydactyly that will allow improved communication between clinicians and serve as a foundation for future investigations. LEVEL OF EVIDENCE: 2.


Assuntos
Radiografia , Sindactilia/classificação , Sindactilia/diagnóstico por imagem , Criança , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos
16.
Eur Spine J ; 25 Suppl 1: 167-74, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26525682

RESUMO

PURPOSE: This case series describes a novel condition characterized by familial pseudotail associated with scoliosis, and synpolydactyly that has not been previously reported in literature. METHODS: The authors present three siblings and one cousin from the same family living in the northern region of the Arabian Peninsula. All cases presented with pseudotail, scoliosis, and complex synpolydactyly. The authors demonstrated complete clinical and radiological descriptions in addition the detailed performed surgeries. RESULTS: The histopathological result of the resected pseudotail specimens revealed bony lesion covered with thick fibrous tissue and evidence of mature adipocytes within trabecular spaces. CONCLUSIONS: The described cases represent a novel condition that has not been previously reported in the literature. Familial pseudotail scoliosis synpolydactyly syndrome is a newly recognized form of familial pseudotail.


Assuntos
Cóccix/anormalidades , Família , Escoliose/genética , Irmãos , Sindactilia/genética , Criança , Pré-Escolar , Cóccix/diagnóstico por imagem , Feminino , Humanos , Masculino , Arábia Saudita , Escoliose/diagnóstico por imagem , Sindactilia/diagnóstico por imagem , Síndrome
17.
Clin Genet ; 89(2): 205-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26283468

RESUMO

Sclerosteosis, characterized by the hyperostosis of cranial and tubular bones, is a rare autosomal recessive hereditary disorder caused by mutation of SOST gene. Four nonsense mutations of SOST have been identified worldwide. Here, we report two affected siblings who carried a novel nonsense mutation of SOST in a consanguineous family from China. The proband manifested typical symptoms of sclerosteosis, whereas the symptoms were absent in another affected sibling. Two nucleotide substitutions in exon 2 of SOST were identified, c.444_445TC>AA, resulting in a premature stop codon, p.Cys148→Stop. This truncated mutation loses 66 amino acid residues which contain 3 cysteine residues of the cysteine-knot motif, leading to loss of function of SOST. The symptoms of sclerosteosis may be clinically heterogeneous in some patients, even with the same mutation. Our results support the notion that founder effects from the ancestors contribute to the disease onset.


Assuntos
Proteínas Morfogenéticas Ósseas/genética , Códon sem Sentido/genética , Consanguinidade , Marcadores Genéticos/genética , Hiperostose/genética , Mutação/genética , Sindactilia/genética , Adulto , Sequência de Bases , Família , Feminino , Homozigoto , Humanos , Hiperostose/diagnóstico por imagem , Recém-Nascido , Masculino , Dados de Sequência Molecular , Linhagem , Radiografia , Sindactilia/diagnóstico por imagem , Adulto Jovem
18.
Biomed Res Int ; 2015: 517815, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25984533

RESUMO

Sclerosteosis is a rare autosomal recessive condition characterized by increased bone density. Mutations in SOST gene coding for sclerostin are linked to sclerosteosis. Two Egyptian brothers with sclerosteosis and their apparently normal consanguineous parents were included in this study. Clinical evaluation and genomic sequencing of the SOST gene were performed followed by in silico analysis of the resulting variation. A novel homozygous frameshift mutation in the SOST gene, characterized as one nucleotide cytosine insertion that led to premature stop codon and loss of functional sclerostin, was identified in the two affected brothers. Their parents were heterozygous for the same mutation. To our knowledge this is the first Egyptian study of sclerosteosis and SOST gene causing mutation.


Assuntos
Proteínas Morfogenéticas Ósseas/genética , Marcadores Genéticos/genética , Hiperostose/genética , Mutação/genética , Sindactilia/genética , Adolescente , Adulto , Sequência de Aminoácidos , Sequência de Bases , Proteínas Morfogenéticas Ósseas/química , Criança , Análise Mutacional de DNA , Egito , Família , Feminino , Humanos , Hiperostose/diagnóstico por imagem , Masculino , Modelos Genéticos , Dados de Sequência Molecular , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Linhagem , Radiografia , Sindactilia/diagnóstico por imagem
19.
Pediatr Radiol ; 45(8): 1239-43, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25835322

RESUMO

We report a 4-year-old boy with sclerosteosis associated with severe digital dysostosis. The initial medical consultation was prompted by bilateral, asymmetrical syndactyly of the index and middle fingers. The left index finger had complicated phalangeal anomalies: hyperphalangy (supernumerary phalanx distal to the middle phalanx) and hypoplasia with bracket epiphyses of the proximal and middle phalanges. Development of facial nerve palsy, hearing impairment and generalized osteosclerosis had occurred between 3 years and 4 years of age, with the subsequent identification of a homozygous SOST mutation. Bilateral second and third fingers syndactyly associated with abnormal patterning of the same fingers should be considered prodromal signs of sclerosteosis.


Assuntos
Dedos/anormalidades , Dedos/diagnóstico por imagem , Deformidades Congênitas da Mão/diagnóstico por imagem , Hiperostose/diagnóstico por imagem , Sindactilia/diagnóstico por imagem , Pré-Escolar , Deformidades Congênitas da Mão/complicações , Humanos , Hiperostose/complicações , Masculino , Radiografia , Sindactilia/complicações
20.
Am J Med Genet A ; 167A(4): 683-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25708102

RESUMO

We report on a 5-month-old female with large and widely spaced anterior and posterior fontanelles, aplasia cutis congenita, Tessier 3 oblique facial cleft, polydactyly, and syndactyly of toes. The polydactyly is unusual as an accessory finger is attached to the left fifth finger with mirrored, end-to-end fusion. We are naming this anomaly "polydactyly inversus." The infant appears to have a previously unreported syndrome of unknown cause.


Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Fenda Labial/diagnóstico por imagem , Fissura Palatina/diagnóstico por imagem , Displasia Ectodérmica/diagnóstico por imagem , Polidactilia/diagnóstico por imagem , Sindactilia/diagnóstico por imagem , Fontanelas Cranianas/anormalidades , Feminino , Humanos , Lactente , Radiografia , Síndrome , Ultrassonografia Pré-Natal
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