Beyond the Copy Number Differences: The Phenotypic Diversity of Children With 15q11.2 Microdeletions and Microduplications

Abstract

15q11.2 BP1-BP2 copy number variants involving NIPA1, NIPA2, CYFIP1, and TUBGCP5 genes may not warrant a clinical outcome because of the phenotypic variability and low penetrance. The study aims to provide a greater understanding of the phenotypic diversity associated with these copy number variants. We conducted a retrospective analysis of 37 pediatric patients with deletions or duplications in 15q11.2 BP1-BP2 region, and compared the results systemically with the previous literature. Of the 37 patients, 67.6% had microduplications and 32.4% had microdeletions. The mean copy number variant size was 482 ± 157 kb. Patients had a variety of phenotypes including neurodevelopmental delay, hypotonia, speech impairment, intellectual and learning disability, behavioral and psychiatric symptoms, epilepsy and seizures, neuroimaging abnormalities, and dysmorphism. These findings, in combination with previous reports, confirm that copy number variants in this region are linked to phenotypes ranging from normal to severe neurodevelopmental and neuropsychiatric features. Our data also confirm that microcephaly is a particularly prevalent phenotype in patients with microdeletions, rather than in those with microduplications.

Keywords: 15q112; copy number variant; microdeletion; microduplication; phenotypic diversity.