RESUMEN
â¢Several conditions may mimic Genetic Generalized Epilepsy GGE.â¢GGE is less frequently misdiagnosed compared to other subtypes of epilepsy.â¢KBG syndrome is a rare autosomal dominant condition.â¢KBG syndrome may mimic GGE.
RESUMEN
BACKGROUND: Haploinsufficiency of the gene encoding for transcription factor 4 (TCF4) was recently identified as the underlying cause of Pitt-Hopkins syndrome (PTHS), an underdiagnosed mental-retardation syndrome characterised by a distinct facial gestalt, breathing anomalies and severe mental retardation. METHODS: TCF4 mutational analysis was performed in 117 patients with PTHS-like features. RESULTS: In total, 16 novel mutations were identified. All of these proven patients were severely mentally retarded and showed a distinct facial gestalt. In addition, 56% had breathing anomalies, 56% had microcephaly, 38% had seizures and 44% had MRI anomalies. CONCLUSION: This study provides further evidence of the mutational and clinical spectrum of PTHS and confirms its important role in the differential diagnosis of severe mental retardation.
Asunto(s)
Apnea , Análisis Mutacional de ADN , Proteínas de Unión al ADN/genética , Cara/anomalías , Hiperventilación , Discapacidad Intelectual/genética , Factores de Transcripción/genética , Adolescente , Apnea/diagnóstico , Apnea/genética , Apnea/patología , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Niño , Preescolar , Cara/patología , Femenino , Genotipo , Humanos , Hiperventilación/diagnóstico , Hiperventilación/genética , Hiperventilación/patología , Lactante , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/patología , Masculino , Microcefalia , Fenotipo , Síndrome , Factor de Transcripción 4 , Adulto JovenRESUMEN
Shprintzen-Goldberg syndrome is one of a group of disorders characterized by craniosynostosis and marfanoid habitus. Eleven cases were reported previously. We present 4 new patients and review one of the patients of the original report of Shprintzen and Goldberg [1982: J Craniofac Genet Dev Biol 2:65-74], 15 years later. The clinical and radiologic findings on our patients are compared with those of the previously reported patients and also with those of Furlong et al. [1987: Am J Med Genet 26:599-604] and Lacombe and Battin [1993: Clin Dysmorphol 2: 220-224], who share many of the characteristics of Shprintzen-Goldberg syndrome. Some of the clinical data are helpful in determining if the patients of Furlong et al. [1987: Am J Med Genet 26:599-604] and Lacombe and Battin [1993: Clin Dysmorphol 2: 220-224] have a separate syndrome or represent a variant of Shprintzen-Goldberg syndrome. However, radiologic investigations appear to be more specific, since an abnormality of the first and second cervical vertebrae, hydrocephalus, dilatation of the lateral ventricles, and a Chiari-I malformation of the brain were found only in the patients with Shprintzen-Goldberg syndrome. The apparently diagnostic findings of the 15 patients with this syndrome may be helpful in differentiating between Shprintzen-Goldberg syndrome and other syndromes with craniosynostosis and marfanoid habitus.
Asunto(s)
Anomalías Múltiples/patología , Craneosinostosis/patología , Síndrome de Marfan/patología , Anomalías Múltiples/metabolismo , Adolescente , Adulto , Niño , Craneosinostosis/metabolismo , Femenino , Fibrilinas , Tórax en Embudo/patología , Pérdida Auditiva Sensorineural/patología , Humanos , Masculino , Síndrome de Marfan/metabolismo , Proteínas de Microfilamentos/metabolismo , SíndromeRESUMEN
Ehlers-Danlos syndrome (EDS) type VII results from defects in the conversion of type I procollagen to collagen as a consequence of mutations in the substrate that alter the protease cleavage site (EDS type VIIA and VIIB) or in the protease itself (EDS type VIIC). We identified seven additional families in which EDS type VII is either dominantly inherited (one family with EDS type VIIB) or due to new dominant mutations (one family with EDS type VIIA and five families with EDS type VIIB). In six families, the mutations alter the consensus splice junctions, and, in the seventh family, the exon is deleted entirely. The COL1A1 mutation produced the most severe phenotypic effects, whereas those in the COL1A2 gene, regardless of the location or effect, produced congenital hip dislocation and other joint instability that was sometimes very marked. Fractures are seen in some people with EDS type VII, consistent with alterations in mineral deposition on collagen fibrils in bony tissues. These new findings expand the array of mutations known to cause EDS type VII and provide insight into genotype/phenotype relationships in these genes.
Asunto(s)
Colágeno/genética , Síndrome de Ehlers-Danlos/genética , Adulto , Empalme Alternativo , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Preescolar , Colágeno/análisis , Colágeno/ultraestructura , Cartilla de ADN , Exones/genética , Femenino , Humanos , Recién Nacido , Masculino , Microscopía Electrónica , Datos de Secuencia Molecular , Mutación , Linaje , Reacción en Cadena de la Polimerasa , Procolágeno/análisis , ARN Mensajero/metabolismo , Análisis de Secuencia de ADNRESUMEN
Atelosteogenesis I (AT-I) and Boomerang dysplasia have been described as separate lethal bone dysplasias. The possibility of a common cause of both conditions was suggested by Hunter and Carpenter (Clin Genet 39(6): 471-480, 1991) in their report of a patient with apparent manifestations of both AT-I and Boomerang dysplasia. We report on a male fetus of 31 weeks gestation whose clinical, radiologic and histologic findings are compared to reported cases of AT-I, Boomerang dysplasia and the patient of Hunter and Carpenter (Clin Genet 39(6): 471-480, 1991). From the documentation of clinical and radiologic findings we demonstrate overlap of AT-I and Boomerang dysplasia in our patient, and, from histologic examination, suggest a defect of cartilage and bone formation as the basic abnormality in this lethal bone dysplasia.