RESUMEN
Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, and characterized by typical face, moderate-to-severe mental retardation, epilepsy, Hirschsprung disease, and multiple congenital anomalies, including genital anomalies (particularly hypospadias in males), congenital heart defects, agenesis of the corpus callosum, and eye defects. Since the first delineation by Mowat et al. [Mowat et al. (1998); J Med Genet 35:617-623], approximately 179 patients with ZEB2 mutations, deletions or cytogenetic abnormalities have been reported primarily from Europe, Australia and the United States. Genetic defects include chromosome 2q21-q23 microdeletions (or different chromosome rearrangements) in few patients, and ZEB2 mutations in most. We report on clinical and genetic data from 19 Italian patients, diagnosed within the last 5 years, including six previously published, and compare them with patients already reported. The main purpose of this review is to underline a highly consistent phenotype and to highlight the phenotypic evolution occurring with age, particularly of the facial characteristics. The prevalence of MWS is likely to be underestimated. Knowledge of the phenotypic spectrum of MWS and of its changing phenotype with age can improve the detection rate of this condition.
Asunto(s)
Anomalías Múltiples/genética , Envejecimiento/fisiología , Anomalías Craneofaciales/genética , Proteínas de Homeodominio/genética , Fenotipo , Proteínas Represoras/genética , Anomalías Múltiples/diagnóstico , Adolescente , Niño , Preescolar , Cromosomas Artificiales Bacterianos , Dextranos/metabolismo , Femenino , Colorantes Fluorescentes/metabolismo , Heterocigoto , Enfermedad de Hirschsprung/genética , Humanos , Hibridación Fluorescente in Situ , Indoles/metabolismo , Lactante , Discapacidad Intelectual/genética , Italia , Masculino , Mutación , Hibridación de Ácido Nucleico , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Síndrome , Adulto Joven , Caja Homeótica 2 de Unión a E-Box con Dedos de ZincRESUMEN
Holt-Oram syndrome (HOS) (OMIM 142900) is characterized by upper-extremity malformations involving the radial, thenar, or carpal bones and a personal and/or family history of congenital heart defects (CHDs). It is inherited in an autosomal dominant manner. The TBX5 gene located on chromosome 12 (12q24.1) is the only gene currently known to be associated with HOS and is associated with variable phenotypes. We report on the clinical and molecular characterization of a HOS family with three affected individuals and a novel mutation (Lys88ter). We discuss genotype-phenotype correlations, the presence of foot anomalies in one affected individual, and the role of atypical features in HOS differential diagnosis.