Delineating lifetime multimorbidity associated with 16p13.11 duplication: A literature review, meta-analysis, and case study.

Abstract

The 16p13.11 duplication is a rare copy number variation (CNV) that appears to increase risk for multimorbidity across the life span. Initial reports implicated the duplication in autism spectrum disorder, intellectual disability, and various congenital anomalies; however, it was also observed in "phenotypically normal" individuals suggesting incomplete penetrance or non-pathogenicity. Recent studies suggest that duplication carriers often present with multimorbidity, but more data are needed to elucidate the full range of associated phenotypes. Lifetime multimorbidity remains unclear, and no reviews summarizing this literature currently exist. We report a systematic literature review and meta-analysis of published phenotypic characteristics. Speech delays, developmental delays, intellectual disability, learning disability, and autistic symptoms were reported in >30 % of cases. Musculoskeletal abnormalities and cardiovascular disorders were commonly reported. Included is a lifespan case report of a 71-year-old female with a history of behavioral disturbance and treatment-resistant schizophrenia, identified as being a 16p13.11 duplication carrier.