Clinical Spectrum of Chromosome 15q11–q13 Duplication Syndrome: A Scoping Review of Neurodevelopmental and Multisystem Manifestations

ABSTRACT Chromosome 15q11–q13 duplication syndrome (Dup15q) is a rare copy‐number disorder with marked phenotypic heterogeneity. This scoping review characterized its clinical spectrum and genotype–phenotype correlations. Following PRISMA‐ScR and Joanna Briggs Institute methodology, PubMed, Web of Science, and Google Scholar were searched through December 1, 2025. Ninety‐two studies comprising 395 molecularly confirmed patients were included. Cohen's kappa was 0.73, indicating substantial inter‐reviewer agreement. Neurodevelopmental manifestations predominated, particularly developmental delay, intellectual disability, autism spectrum disorder, epilepsy, hypotonia, motor and language impairment, and psychobehavioral abnormalities. Compared with interstitial duplications, supernumerary marker chromosomes were associated with higher odds of epilepsy (OR = 7.14, 95%, CI = 4.39–11.61; p < 0.001), intellectual disability (OR = 2.20, 95%, CI = 1.34–3.66; p = 0.002), and motor delay (OR = 1.70, 95%, CI = 1.02–2.84; p = 0.040), but lower odds of psychobehavioral manifestations (OR = 0.21, 95%, CI = 0.13–0.35, p < 0.001). Among 186 patients with reported parental origin, 155 (83%) were maternal and 31 (17%) paternal. Maternal duplications showed higher odds of seizures (OR = 4.26, 95%, CI = 1.42–12.79; p = 0.006) and motor delay (OR = 5.93, 95%, CI = 1.35–25.90; p = 0.006) than paternal duplications. Co‐occurrence analysis identified global developmental delay as the principal phenotypic hub. These findings refine the clinical spectrum of Dup15q and highlight associations with cytogenetic subtype and parental origin.