Familial co-occurrence of autism spectrum disorder and 47 XYY syndrome: revisiting the role of Y chromosome dosage in neurodevelopment.

Abstract

We describe a rare familial occurrence involving two brothers: one diagnosed with autism spectrum disorder (ASD), and the other with a postnatally confirmed 47 XYY karyotype exhibiting autistic traits below the diagnostic threshold. The younger sibling met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Level 3 criteria, with prominent deficits in communication and behavior. The older sibling, though not fully meeting ASD criteria, showed borderline cognitive abilities, attentional difficulties, and limited social reciprocity. Both received individualized education and pharmacologic support. This case raises questions about Y chromosome dosage effects in neurodevelopment, particularly the role of Y-linked genes such as NLGN4Y. The co-occurrence of ASD and XYY-related traits within the same family highlights the possibility of a shared vulnerability and adds to the sparse literature on male-specific genetic influences. Early screening and multidisciplinary interventions may benefit at-risk siblings, even in the absence of full syndromic presentation.