Comprehensive phenotyping of 3q29 deletion syndrome: recommendations for clinical care

Purpose: To understand the consequences of the 3q29 deletion on medical, neurodevelopmental, psychiatric, and neurological sequalae by systematic evaluation of affected individuals. To develop evidence-based recommendations using these data for effective clinical care. Methods: 32 Individuals with the 3q29 deletion were evaluated using a defined phenotyping protocol and standardized data collection instruments. Results: Medical manifestations were varied and reported across nearly every bodily system, with congenital heart defects (25%) the most severe and heterogeneous gastrointestinal symptoms (81%) the most common. Physical exam revealed a high proportion of musculoskeletal findings (81%). Neurodevelopmental phenotypes represent a significant burden and include intellectual disability (34%), autism spectrum disorder (38%), executive function deficits (46%), and graphomotor weakness (78%). Psychiatric illness manifests across the lifespan with schizophrenia prodrome (15%), psychosis (20%), anxiety disorders (40%) and ADHD (63%) . On neurological exam study subjects displayed only mild or moderate motor difficulties. Conclusions: By direct evaluation of 3q29 deletion study subjects, we document common features of the syndrome, including a high burden of neurodevelopmental and neuropsychiatric phenotypes. Evidence-based recommendations for evaluation, referral, and management are provided to help guide clinicians in the care of 3q29 deletion patients.