SA15 - THE EMORY 3Q29 DELETION PROJECT: PROFILES OF NEURODEVELOPMENTAL AND NEUROPSYCHIATRIC PHENOTYPES

Abstract

Background 3q29 Deletion Syndrome (3q29DS) is a rare (~1:30000) genomic disorder characterized by a 1.6 Mb deletion on chromosome 3, and is associated with developmental delay, intellectual disability, and a significantly increased risk for neuropsychiatric disorders, including Autism Spectrum Disorders (ASD). The clinical presentation of these phenotypes is highly variable, which combined with the low frequency of the deletion has resulted in a poor understanding of 3q29DS. In a previous study, we found that 24% of 3q29DS registry participants self-reported a formal diagnosis of ASD, a 16-fold increase versus the general population. However, many more patients report “autism-like symptoms” without a formal diagnosis of ASD. In the current study, we use additional registry data to test the hypothesis that the true prevalence of ASD is underestimated in 3q29DS. Methods The 3q29DS registry (3q29deletion.org) is an IRB-approved, HIPPA-compliant patient ascertainment website. After informed consent, registrants fill out several questionnaires, primarily a custom medical and demographic questionnaire that includes prior diagnosis of ASD. In addition, several standardized surveys were adapted for the online platform: the Social Responsiveness Scale (SRS); the Social Communication Questionnaire (SCQ); the Autism Spectrum Screening Questionnaire (ASSQ); and the Child Behavior Checklist (CBCL). Data from 3q29DS patients was de-identified and securely downloaded for analysis. Responses to all questionnaires were hand-scored by three independent examiners and cross-checked to ensure identical scores. Statistical testing and data visualization was performed in R. Results Self-report data from 3q29DS registry participants shows a significantly increased prevalence of ASD diagnosis versus the general population (21.4% vs. 1.47%, p Discussion We have shown that the 3q29DS population is significantly enriched for ASD features measured via four ASD surveys. Self-report data confirms the increased prevalence of ASD in 3q29DS; however, several patients scored in the clinical range on all scales, despite reporting no diagnosis of ASD. These data support our hypothesis that the true prevalence of ASD in 3q29DS may be underestimated, and suggest that ASD testing should be the standard of care for 3q29DS patients. We have also identified differences in ASD presentation in 3q29DS patients versus the general population: male and female 3q29DS patients are equally impaired according to the scales employed in the present study, and males and females report similar proportions of formal ASD diagnoses. This implicates 3q29DS as a promising line of investigation into the underlying mechanisms of ASD, due to both the enrichment of ASD features and the reduction in gender bias.