Clinical heterogeneity associated with deletions in the long arm of chromosome 15: Report of 3 new cases and their possible genetic significance

TLDR

Deletions, duplications, and rearrangements of chromosome 15q are commonly linked to Prader‑Willi syndrome, yet similar cytogenetic changes also underlie other clinical entities, indicating heterogeneity in this chromosomal region. The authors present three patients with 15q11–15q12 deletions lacking classic Prader‑Willi features and propose that distinct molecular lesions along chromosome 15q may explain the observed clinical diversity. The study examined three patients with 15q11–15q12 deletions, each presenting distinct syndromic features (Williams, Angelman, and hypotonia‑obesity‑developmental delay) rather than classic Prader‑Willi syndrome. These patients exhibit phenotypes of Williams syndrome, Angelman syndrome, and a hypotonia‑obesity‑developmental delay profile, respectively, demonstrating that 15q deletions can manifest outside classic Prader‑Willi syndrome.

Abstract

Abstract Deletions, duplications, and rearrangements of the long arm of chromosome 15 are frequently associated with the clinical diagnosis of the Prader‐Willi syndrome. However, a number of other clinical entities have also been associated with similar, if not identical, cytogenetic defects, arguing for clinical heterogeneity associated with abnormalities in this region of chromosome 15. We present 3 patients who all appear to have deletions in 15q11–15q12, such as described for many patients with Prader‐Willi syndrome; however, none of these patients has classical clinical features of the Prader‐Willi syndrome. The first patient is a child with Williams syndrome, the second, Angelman (Happy Puppet) syndrome, and the third is a child with hypotonia of infancy, obesity, and developmental delay, but who does not meet specific diagnostic criteria for the Prader‐Willi syndrome. It is proposed that different molecular abnormalities involving specific points or segments along the long arm of chromosome 15 might account for the clinical diversity seen among these and other patients.