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. ### Competing Interest Statement CAS recieves royalty payments from Pearson for her authorship of the Vineland. ### Clinical Trial NCT02447861 ### Funding Statement This study was supported by NIH grants R01 MH110701 and R01 MH118534. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Emory Institutional Board (IRB000088012) All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data from this manuscript are available in NDAR: https://nda.nih.gov/about.html