RESUMO
Craniosynostosis caused by genetic factors includes a heterogeneous group of over 100 syndromes, most with autosomal dominant inheritance. Mutations in five genes (FGFR1-, -2, -3, TWIST, and MSX2) causing craniosynostosis as the main clinical feature were described. In most of these conditions, there are also limb malformations. We report a two-generation kindred segregating microcornea, optic nerve alterations and cataract since childhood, craniosynostosis, and distal limb alterations, with a great clinical intrafamilial variability. The ophthalmological problems here described seem to be unique to this genealogy while similar feet alterations were apparently only described in two other affected siblings with acro-cranial-facial dysostosis syndrome (ADS). However, ADS has an autosomal recessive inheritance instead of the dominant pattern of the present genealogy. The candidate exons of the five genes previously mentioned were tested through sequencing analysis presenting normal results in all cases. Therefore, clinical and laboratory analyses in our patients suggest that their phenotype represents a new syndrome very likely caused by mutation in a gene different from those studied.
Assuntos
Craniossinostoses/genética , Oftalmopatias/complicações , Predisposição Genética para Doença/genética , Deformidades Congênitas dos Membros/complicações , Proteínas Nucleares , Proteínas Tirosina Quinases , Adulto , Criança , Pré-Escolar , Craniossinostoses/complicações , Craniossinostoses/patologia , DNA/química , DNA/genética , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Éxons/genética , Saúde da Família , Proteínas de Homeodomínio , Humanos , Masculino , Mutação , Receptores Proteína Tirosina Quinases/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos , Receptores de Fatores de Crescimento de Fibroblastos/genética , Fatores de Transcrição/genética , Proteína 1 Relacionada a TwistRESUMO
Craniossinostose caracteriza-se pelo fechamento prematuro de uma ou mais suturas cranianas. As craniossinostoses formam um grupo bastante heterogeneo, com incidencia de um para 2000-3000 nascimentos...