Syndromic Autism in Helsmoortel-Van der Aa Syndrome: From Clinical Suspicion to Genetic Diagnosis.

Syndromic autism refers to autism spectrum disorder (ASD) occurring as part of an identifiable genetic syndrome. Helsmoortel-Van der Aa syndrome (HVDAS/ADNP syndrome) is a rare autosomal dominant neurodevelopmental disorder caused by heterozygous pathogenic variants in the ADNP gene. We report a 10-year-old boy with ASD and intellectual disability who exhibited delayed motor and language development, characteristic facial dysmorphism, early tooth eruption, endocrine abnormalities, electroencephalography (EEG) abnormalities, and urogenital findings. Following unremarkable karyotyping and chromosomal microarray analysis (CMA), whole-exome sequencing identified a heterozygous pathogenic de novo frameshift variant, c.1239_1240del, p.(Gln414Valfs*25) in ADNP. This case emphasizes the importance of considering a syndromic etiology in children with ASD accompanied by developmental delay, dysmorphic features, neurological findings, or multisystem involvement, and supports comprehensive genetic evaluation when first-tier testing is unrevealing.