Novel variant in WDFY3 in a girl with autism spectrum disorder, macrocephaly and no regression

Autism spectrum disorder (ASD) is a heterogeneous condition with complex genetic and environmental etiologies. Diagnostic yield can be low, but in certain cohorts the likelihood of a positive genetic diagnosis increases. We report a pediatric patient with global development delay with no regression, ASD, behavioral issues, and macrocephaly, carrying a novel de novo heterozygous loss-of-function variant in WDFY3. WDFY3 plays a key role in neurodevelopment and cerebral size regulation. This case adds to the emerging evidence implicating monoallelic WDFY3 variants in ASD and underscoring the diagnostic value of genetic testing in complex neurodevelopmental presentations.