Delineating the 15q13.3 microdeletion phenotype: a case series and comprehensive review of the literature

Genet Med. 2015 Feb;17(2):149-57. doi: 10.1038/gim.2014.83. Epub 2014 Jul 31.


Purpose: Recurrent 15q13.3 deletions are enriched in multiple neurodevelopmental conditions including intellectual disability, autism, epilepsy, and schizophrenia. However, the 15q13.3 microdeletion syndrome remains ill-defined.

Methods: We systematically compiled all cases of 15q13.3 deletion published before 2014. We also examined three locally available cohorts to identify new adults with 15q13.3 deletions.

Results: We identified a total of 246 cases (133 children, 113 adults) with deletions overlapping or within the 15q13.3 (breakpoint (BP)4-BP5) region, including seven novel adult cases from local cohorts. No BP4-BP5 deletions were identified in 23,838 adult controls. Where known, 15q13.3 deletions were typically inherited (85.4%) and disproportionately of maternal origin (P < 0.0001). Overall, 198 cases (121 children, 77 adults; 80.5%) had at least one neuropsychiatric diagnosis. Accounting for ascertainment, developmental disability/intellectual disability was present in 57.7%, epilepsy/seizures in 28.0%, speech problems in 15.9%, autism spectrum disorder in 10.9%, schizophrenia in 10.2%, mood disorder in 10.2%, and attention deficit hyperactivity disorder in 6.5%. By contrast, major congenital malformations, including congenital heart disease (2.4%), were uncommon. Placenta previa occurred in the pregnancies of four cases.

Conclusion: The 15q13.3 microdeletion syndrome is predominantly characterized by neuropsychiatric expression. There are implications for pre- and postnatal detection, genetic counseling, and anticipatory care.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Aged
  • Chromosome Breakpoints
  • Chromosome Deletion
  • Chromosome Disorders / diagnosis*
  • Chromosome Disorders / epidemiology
  • Chromosome Disorders / etiology*
  • Chromosomes, Human, Pair 15
  • Cohort Studies
  • Female
  • Genetic Association Studies
  • Homozygote
  • Humans
  • Inheritance Patterns
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / epidemiology
  • Intellectual Disability / etiology*
  • Male
  • Middle Aged
  • Pedigree
  • Phenotype*
  • Placenta Previa
  • Pregnancy
  • Prevalence
  • Seizures / diagnosis*
  • Seizures / epidemiology
  • Seizures / etiology*

Supplementary concepts

  • Chromosome 15q13.3 Microdeletion Syndrome