RESUMEN
Molecular anomalies in MED13L, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without congenital heart defects. Phenotype of the patients was referred to "MED13L haploinsufficiency syndrome." Missense variants in MED13L were already previously described to cause the MED13L-related syndrome, but only in a limited number of patients. Here we report 36 patients with MED13L molecular anomaly, recruited through an international collaboration between centers of expertise for developmental anomalies. All patients presented with intellectual disability and severe language impairment. Hypotonia, ataxia, and recognizable facial gestalt were frequent findings, but not congenital heart defects. We identified seven de novo missense variations, in addition to protein-truncating variants and intragenic deletions. Missense variants clustered in two mutation hot-spots, i.e., exons 15-17 and 25-31. We found that patients carrying missense mutations had more frequently epilepsy and showed a more severe phenotype. This study ascertains missense variations in MED13L as a cause for MED13L-related intellectual disability and improves the clinical delineation of the condition.
Asunto(s)
Discapacidad Intelectual/genética , Complejo Mediador/genética , Niño , Preescolar , Femenino , Humanos , Discapacidad Intelectual/diagnóstico , Masculino , Mutación Missense , FenotipoRESUMEN
Growth retardation is a relatively consistent feature of Noonan syndrome but a standardized growth curve for height has never been calculated. Analysis of retrospective growth data on 112 patients with Noonan syndrome has permitted the establishment of preliminary reference growth standards for height for males and females. The results confirm the clinical impression that short stature among this group of patients occurs uniformly and is independent of chronological age. Various factors which may modify this are considered.