RESUMEN
BACKGROUND: Germline mutations in the CHRNG gene that encodes the γ subunit of the embryonal acetylcholine receptor may cause the non-lethal Escobar variant (EVMPS) or the lethal form (LMPS) of multiple pterygium syndrome (MPS). In addition CHRNG mutations and mutations in other components of the embryonal acetylcholine receptor may present with fetal akinesia deformation sequence (FADS) without pterygia. METHODS: In order to elucidate further the role of CHRNG mutations in MPS/FADS, this study evaluated the results of CHRNG mutation analysis in 100 families with a clinical diagnosis of MPS/FADS. RESULTS: CHRNG mutations were identified in 11/41 (27%) of families with EVMPS and 5/59 (8%) with LMPS/FADS. Most patients with a detectable CHRNG mutation (21 of 24 (87.5%)) had pterygia but no CHRNG mutations were detected in the presence of central nervous system anomalies. DISCUSSION: The mutation spectrum was similar in EVMPS and LMPS/FADS kindreds and EVMPS and LMPS phenotypes were observed in different families with the same CHRNG mutation. Despite this intrafamilial variability, it is estimated that there is a 95% chance that a subsequent sibling will have the same MPS phenotype (EVMPS or LMPS) as the proband (though concordance is less for more distant relatives). Based on these findings, a molecular genetic diagnostic pathway for the investigation of MPS/FADS is proposed.
Asunto(s)
Anomalías Múltiples/genética , Hipertermia Maligna/genética , Pterigion/genética , Receptores Nicotínicos/genética , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/mortalidad , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Retardo del Crecimiento Fetal/genética , Estudios de Asociación Genética , Genotipo , Humanos , Lactante , Recién Nacido , Hipertermia Maligna/diagnóstico por imagen , Hipertermia Maligna/mortalidad , Mutación , Embarazo , Pterigion/diagnóstico por imagen , Pterigion/mortalidad , Anomalías Cutáneas , Ultrasonografía PrenatalRESUMEN
The clinical features of the multiple pterygium syndrome are multiple congenital joint contractures, multiple skin webs, camptodactyly, vertebral anomalies, short stature, ptosis, and antimongoloid eye slant. We present 11 new cases to show the evolution of the full phenotype from birth and to confirm autosomal recessive inheritance. We emphasise morbidity secondary to respiratory impairment and that conductive deafness may be part of the syndrome.