RESUMO
Taybi-Linder syndrome (TALS, OMIM 210710) is a rare autosomal recessive disorder belonging to the group of microcephalic osteodysplastic primordial dwarfisms (MOPD). This syndrome is characterized by short stature, skeletal anomalies, severe microcephaly with brain malformations and facial dysmorphism, and is caused by mutations in RNU4ATAC. RNU4ATAC is transcribed into a non-coding small nuclear RNA which is a critical component of the minor spliceosome. We report here four foetuses and four unrelated patients with RNU4ATAC mutations. We provide antenatal descriptions of this rare syndrome including unusual features found in two twin foetuses with compound heterozygosity for two rare mutations who presented with mild intrauterine growth retardation and atypical dysmorphic facial features. We also carried out a literature review of the patients described up to now with RNU4ATAC mutations, affected either with TALS or Roifman syndrome, a recently described allelic disorder.
Assuntos
Anormalidades Múltiplas/genética , Cardiomiopatias/genética , Nanismo/genética , Retardo do Crescimento Fetal/genética , Síndromes de Imunodeficiência/genética , Deficiência Intelectual Ligada ao Cromossomo X/genética , Microcefalia/genética , Osteocondrodisplasias/genética , RNA Nuclear Pequeno/genética , Doenças Retinianas/genética , Anormalidades Múltiplas/fisiopatologia , Alelos , Cardiomiopatias/fisiopatologia , Criança , Pré-Escolar , Nanismo/fisiopatologia , Feminino , Retardo do Crescimento Fetal/fisiopatologia , Feto , Humanos , Síndromes de Imunodeficiência/fisiopatologia , Lactente , Recém-Nascido , Masculino , Deficiência Intelectual Ligada ao Cromossomo X/fisiopatologia , Microcefalia/fisiopatologia , Mutação , Osteocondrodisplasias/fisiopatologia , Fenótipo , Doenças da Imunodeficiência Primária , Doenças Retinianas/fisiopatologia , Spliceossomos/genéticaRESUMO
We report a specific sonographic cerebral pattern of cobblestone lissencephaly (CL) that has not been described previously. This pattern was encountered in four index cases and allowed prenatal diagnosis of CL associated with Walker-Warburg syndrome. The pattern included both an outer echogenic band with reduced pericerebral space, corresponding to an infra- and supratentorial extracortical layer of neuroglial overmigration on pathological examination, and a 'Z'-shaped appearance of the brainstem. This pattern was found as early as 14 weeks' gestation in one of our cases.