Report of a Homozygous Nonsense Variant in the WDR91 Gene Associated With Severe Communicating Hydrocephalus, Dandy Walker Malformation, and Cerebellar Hypoplasia.
Rhea Shriyan, Tushar Kachhadiya, Rishi Sharma et al.
✦ AI-curated · Sources linked
Case in brief
A child presented with severe congenital communicating hydrocephalus, Dandy-Walker malformation, cerebellar hypoplasia, and facial dysmorphism. Trio exome sequencing identified a homozygous WDR91 nonsense variant, c.1245_1246delAG, predicted to cause p.(Arg415Serfs*64). Sanger sequencing confirmed the variant in the child; both asymptomatic parents were heterozygous, consistent with autosomal recessive inheritance. The report links this loss-of-function variant to the child’s brain malformations and, applying ClinGen gene-disease assertion guidelines, concludes that evidence for WDR91-related congenital hydrocephalus is strong.
What made this case unusual
The Dandy-Walker malformation was an unexpected feature: the authors state that it had not previously been described in association with WDR91.
Diagnostic / clinical pearl
In a child with congenital hydrocephalus and brain malformations, consider WDR91-related disease; trio sequencing can identify a homozygous loss-of-function variant and establish recessive inheritance through parental testing.
Why it matters
The report adds Dandy-Walker malformation to the described WDR91-associated phenotype and supports the authors’ assessment that the gene-disease evidence for congenital hydrocephalus is strong.