Deep phenotyping in 3q29 deletion syndrome: recommendations for clinical care

• Type of Material: Article
• Authors: Rossana Sanchez Russo, Emory University; Michael Gambello, Emory University; Melissa M. Murphy, Emory University; Katrina Aberizk, Emory University; Emily Black, Emory University; Teresa Burrell, Emory University; Grace Carlock, Emory University; Joseph Cubells, Emory University; Michael Epstein, Emory University; Roberto Espana, Emory University; Katrina Goines, Emory University; Ryan M. Guest, Emory University; Cheryl Klaiman, Emory University; Sookyong Koh, Emory University; Elizabeth Leslie, Emory University; Longchuan Li, Emory University; Derek M. Novacek, University of California Los Angeles; Celine Saulnier, Emory University; Esra Sefik, Emory University; Sarah Shultz, Emory University; Elaine Walker, Emory University; Stormi Pulver White, Emory University; Jennifer Mulle, Emory University
• Language: English
• Date: 2021-02-09
• Publisher: Springer Nature [academic journals on nature.com]
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41436-020-01053-1
• Title of Journal or Parent Work: GENETICS IN MEDICINE
• Volume: 23
• Issue: 5
• Start Page: 872
• End Page: 880
• Grant/Funding Information: Funding for this work was provided by National Institutes of Health (NIH) grants R01 MH110701 and R01 MH118534. REDCap is supported by grant UL1 TR000424.
• Research Categories: Biology, Genetics

Abstract

Purpose To understand the consequences of the 3q29 deletion on medical, neurodevelopmental, psychiatric, brain structural, and neurological sequalae by systematic evaluation of affected individuals. To develop evidence-based recommendations using these data for effective clinical care. Methods Thirty-two 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 organ system. The most severe manifestations were congenital heart defects (25%) and the most common were gastrointestinal symptoms (81%). Physical examination 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 psychosis prodrome (15%), psychosis (20%), anxiety disorders (40%), and attention deficit–hyperactivity disorder (ADHD) (63%). Neuroimaging revealed structural anomalies of the posterior fossa, but on neurological exam study subjects displayed only mild or moderate motor vulnerabilities. Conclusion 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.