RESUMO
The detection of carriers of the X-linked disorder hypohidrotic ectodermal dysplasia is problematic because of random X-inactivation; the diagnosis was previously based on the observation of subtle defects in ectodermal structures in at-risk females. Linkage studies have recently mapped hypohidrotic ectodermal dysplasia to the region Xq11-q21.1. We assessed the improvement in carrier detection by the method of linkage analysis, in which restriction fragment length polymorphisms were used as markers, in 72 at-risk female members of 29 families. Carriers analyses were based on pedigree information, dental examination of at-risk females (phenotype), and DNA analyses at seven linked marker loci. Linkage analysis based on restriction fragment length polymorphisms significantly improved risk estimates over those based on phenotype and pedigree alone. When all available information was combined, 85% (61/72) of the at-risk females had final risks of less than 5% or greater than 95%, and 68% (49/72) had risks less than 1% or greater than 99%. A diagnosis of hypohidrotic ectodermal dysplasia was also excluded (97.5% probability) by DNA and linkage analyses from a sample of cord blood from an at-risk male; a similar approach can be taken for prenatal diagnosis of the disorder.
Assuntos
Displasia Ectodérmica/genética , Triagem de Portadores Genéticos , Ligação Genética , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Cromossomo X , Teorema de Bayes , Mapeamento Cromossômico , DNA/análise , Feminino , Humanos , Hipo-Hidrose , Masculino , Linhagem , Fenótipo , Fatores de RiscoRESUMO
We report 21 patients with choanal atresia or ocular coloboma or both who have certain other associated anomalies, including congenital heart disease, postnatal growth deficiency, mental retardation and/or CNS anomalies, microphallus and cryptorchidism, and ear anomalies and/or deafness. Facial palsy, micrognathia, cleft palate, and swallowing difficulties were also common. It has not been possible to define a single etiology or a syndrome in these patients. We propose the mnemonic CHARGE (C-coloboma, H-heart disease, A-atresia choanae, R-retarded growth and retarded development and/or CNS anomalies, G-genital hypoplasia, and E-ear anomalies and/or deafness) to describe the features of this association.
Assuntos
Anormalidades Múltiplas , Coloboma/complicações , Cardiopatias Congênitas/complicações , Nasofaringe/anormalidades , Nariz/anormalidades , Adulto , Sistema Nervoso Central/anormalidades , Surdez/complicações , Deficiências do Desenvolvimento/complicações , Orelha/anormalidades , Anormalidades do Olho , Feminino , Transtornos do Crescimento/complicações , Humanos , Masculino , Disfunções Sexuais Fisiológicas/complicaçõesRESUMO
The Grebe syndrome is a nonlethal form of severe short-limbed dwarfism which was previously called "achondrogenesis-Brazilian or Grebe type". We have studied three patients with severe short-limbed dwarfism originally considered to have this syndrome. On re-evaluation of their clinical and radiographic features, only one of them had the typical features of the Grebe chondrodysplasia, whereas the other two appear to have clearly distinct, previously unreported skeletal dysplasias. These patients illustrate the heterogeneity that exists among the nonlethal forms of severe short-limbed dwarfism.
Assuntos
Nanismo , Adulto , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Criança , Pré-Escolar , Diagnóstico Diferencial , Nanismo/diagnóstico por imagem , Nanismo/genética , Feminino , Humanos , Masculino , Osteocondrodisplasias/diagnóstico por imagem , Radiografia , SíndromeRESUMO
Cerebral gigantism is a syndrome consisting of characteristic dysmorphic features, accelerated growth in early childhood, and variable degrees of mental retardation. Its etiology and pathogenesis have not been defined. Three families are presented with multiple affected members. The vertical transmission of the trait and equal expression in both sexes in these families indicates a genetic etiology with a dominant pattern of inheritance, probably autosomal. As in previously reported cases, extensive endocrine evaluation failed to define the pathogenesis of the accelerated growth present in this disorder.