Neuropsychiatric Phenotypes and Novel Features of ASD in 3q29 Deletion Syndrome: Results from the 3q29 Registry

Background The 1.6 Mb 3q29 deletion is associated with neurodevelopmental and psychiatric phenotypes, including increased risk for autism spectrum disorder (ASD) and a 20-40-fold increased risk for schizophrenia. However, the phenotypic spectrum of the deletion, particularly with respect to ASD, remains poorly described. Methods We ascertained individuals with 3q29 deletion syndrome (3q29Del, “cases”, n=93, 58.1% male) through the 3q29 registry (https://3q29deletion.patientcrossroads.org); typically developing controls (n=64, 51.6% male) were ascertained for comparison. Self-report of neuropsychiatric illness was evaluated for 93 cases. Subsets of participants were evaluated with the Social Responsiveness Scale (SRS, n=48 cases, 56 controls), Social Communication Questionnaire (SCQ, n=33 cases, 46 controls), Autism Spectrum Screening Questionnaire (ASSQ, n=24 cases, 35 controls), and Achenbach Behavior Checklists (n=48 cases, 57 controls). Results 3q29Del cases report a higher prevalence of autism diagnoses versus the general population (30.1% vs. 1.47%, p Conclusions Our sample of 3q29Del is significantly enriched for ASD diagnosis, especially among females, and features of autism may be present even when an ASD diagnosis is not reported. Further, the presentation of ASD in this population is novel, with substantially less impaired social motivation compared to idiopathic ASD. Our study implies that ASD evaluation should be the standard of care for individuals with 3q29Del. From a research perspective, the novel ASD subtype present in 3q29Del is an ideal entry point for expanding understanding of ASD.