Biallelic loss-of-function variants in DSCAM cause a neurodevelopmental syndrome with nystagmus and retinal dysfunction

DSCAM (homozygous LOF variants, consanguineous)

Biallelic loss-of-function of DSCAM, a neuronal adhesion molecule from chromosome 21q22 (Down syndrome critical region); essential role in brain and retinal development

Identification of DSCAM as a new recessive NDD gene. DSCAM occupies a 1 Mb locus in the Down syndrome critical region (21q22) and encodes a neuronal adhesion molecule essential for brain and eye development. Two consanguineous individuals with intellectual disability, nystagmus and retinal dysfunction carry homozygous DSCAM LOF variants. This series consolidates and expands the two previous singleton reports (2017, 2021), documenting retinal dysfunction as a distinct phenotypic component for the first time.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

First AR NDD gene linking brain and visual system involvement in a coherent spectrum. The association of nystagmus + retinal dysfunction + ID should prompt DSCAM analysis in recessive NDD gene panels. The article broadens the pathological spectrum of the 21q22 locus beyond trisomy 21.

new gene +3; biallelic AR +2; characteristic phenotype (ID + nystagmus + retina) +1; HGG Advances Cell Press +1; consanguinity +1