A Novel Homozygous Nonsense Variant in DCHS1 in a Brazilian Patient With Van Maldergem Syndrome Type 1: Clinical Report and Literature Review.

Abstract

Van Maldergem syndrome (VMLDS) is an ultra-rare autosomal recessive disorder characterized by craniofacial dysmorphism, intellectual disability, hypotonia, skeletal anomalies, and feeding difficulties. It is caused by biallelic variants in DCHS1 or FAT4 genes. Fewer than 20 molecularly confirmed cases of VMLDS have been reported, and only a small subset involves DCHS1. We report a Brazilian male patient presenting with clinical features consistent with VMLDS, including neonatal hypotonia, Pierre Robin sequence, craniofacial dysmorphisms, camptodactyly, interphalangeal webbing, joint laxity, and hydrocephalus. Whole-exome sequencing identified a novel homozygous nonsense variant NM_003737.4(DCHS1):c.9655A>T:p.(Lys3219Ter), located in the final coding exon, classified as likely pathogenic. This report contributes to the phenotypic and molecular characterization of this ultra-rare disorder.