Expanding the pre- and postnatal phenotype of WASHC5 and CCDC22 -related Ritscher-Schinzel syndromes.
Eur J Med Genet
; 65(11): 104624, 2022 Nov.
Article
em En
| MEDLINE
| ID: mdl-36130690
ABSTRACT
Ritscher-Schinzel syndrome (RTSCS) is a rare genetic condition characterized by peculiar craniofacial features and cerebellar and cardiovascular malformations. To date, four genes are implicated in this condition. The first two genes described were the autosomal recessive inherited gene WASHC5 associated with Ritscher-Schinzel syndrome 1 (RTSCS1), and CCDC22, an X-linked recessive gene causing Ritscher-Schinzel syndrome 2 (RTSCS2). In recent years, two other genes have been identified VPS35L (RTSCS3) and DPYSL5 (RTSCS4). Only few patients with a molecular diagnosis of RTSCS have been reported, leaving the phenotypical spectrum and genotype-phenotype correlations ill-defined. We expand the number of genetically confirmed patients with RTSCS1 and 2; reporting three live born and three terminated pregnancies from two unrelated families. Four siblings carried compound heterozygous variants in WASHC5 while two siblings harboured a hemizygous CCDC22 variant. The most common findings in all patients were craniofacial dysmorphism, particularly macrocephaly, down slanted palpebral fissures and low set-ears. Developmental delay, intellectual disability and ataxic gait were present in all patients. One of the patients with the CCDC22 variant presented pubertas tarda. Elevation of nuchal translucency was observed in the first trimester ultrasound in three foetuses with compound heterozygous variants in WASHC5. None of the patients had epilepsy. The pre- and postnatal findings of this cohort expand the known phenotype of RTSCS1 and 2, with direct impact on postnatal outcome, management, and familial counseling.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anormalidades Craniofaciais
/
Síndrome de Dandy-Walker
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article