The complex behavioral phenotype of 15q13.3 microdeletion syndrome

Genet Med. 2016 Nov;18(11):1111-1118. doi: 10.1038/gim.2016.9. Epub 2016 Mar 10.

Abstract

Background: Chromosome 15q13.3 represents a hotspot for genomic rearrangements due to repetitive sequences mediating nonallelic homologous recombination. Deletions of 15q13.3 have been identified in the context of multiple neurological and psychiatric disorders, but a prospective clinical and behavioral assessment of affected individuals has not yet been reported.

Methods: Eighteen subjects with 15q13.3 microdeletion underwent a series of behavioral assessments, along with clinical history and physical examination, to comprehensively define their behavioral phenotypes.

Results: Cognitive deficits are the most prevalent feature in 15q13.3 deletion syndrome, with an average nonverbal IQ of 60 among the patients studied. Autism spectrum disorder was highly penetrant, with 31% of patients meeting clinical criteria and exceeding cutoff scores on both ADOS-2 and ADI-R. Affected individuals exhibited a complex pattern of behavioral abnormalities, most notably hyperactivity, attention problems, withdrawal, and externalizing symptoms, as well as impairments in functional communication, leadership, adaptive skills, and activities of daily living.

Conclusions: The 15q13.3 deletion syndrome encompasses a heterogeneous behavioral phenotype that poses a major challenge to parents, caregivers, and treating providers. Further work to more clearly delineate genotype-phenotype relationships in 15q13.3 deletions will be important for anticipatory guidance and development of targeted therapies.Genet Med 18 11, 1111-1118.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Activities of Daily Living
  • Adolescent
  • Adult
  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / physiopathology
  • Child
  • Chromosome Deletion
  • Chromosome Disorders / genetics*
  • Chromosome Disorders / physiopathology
  • Chromosomes, Human, Pair 15 / genetics
  • Cognitive Dysfunction / genetics*
  • Cognitive Dysfunction / physiopathology
  • Female
  • Genetic Association Studies
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Male
  • Pedigree
  • Seizures / genetics*
  • Seizures / physiopathology

Supplementary concepts

  • Chromosome 15q13.3 Microdeletion Syndrome