The cognitive and behavioral phenotype of the 16p11.2 deletion in a clinically ascertained population

Biol Psychiatry. 2015 May 1;77(9):785-93. doi: 10.1016/j.biopsych.2014.04.021. Epub 2014 Jun 16.

Abstract

Background: Deletion of the recurrent ~600 kb BP4-BP5 chromosomal region 16p11.2 has been associated with a wide range of neurodevelopmental outcomes.

Methods: To clarify the phenotype of 16p11.2 deletion, we examined the psychiatric and developmental presentation of predominantly clinically referred individuals, with a particular emphasis on broader autism phenotype characteristics in individuals with recurrent ~600 kb chromosome 16p11.2 deletions. Using an extensive standardized assessment battery across three clinical sites, 85 individuals with the 16p11.2 deletion and 153 familial control subjects were evaluated for symptom presentation and clinical diagnosis.

Results: Individuals with the 16p11.2 deletion presented with a high frequency of psychiatric and developmental disorders (>90%). The most commonly diagnosed conditions were developmental coordination disorder, phonologic processing disorder, expressive and receptive language disorders (71% of individuals >3 years old with a speech and language-related disorder), and autism spectrum disorder. Individuals with the 16p11.2 deletion not meeting diagnostic criteria for autism spectrum disorder had a significantly higher prevalence of autism-related characteristics compared with the familial noncarrier control group. Individuals with the 16p11.2 deletion had a range of intellectual ability, but IQ scores were 26 points lower than noncarrier family members on average.

Conclusions: Clinically referred individuals with the 16p11.2 deletion have high rates of psychiatric and developmental disorders and provide a genetically well-defined group to study the emergence of developmental difficulties, particularly associated with the broader autism phenotype.

Keywords: 16p11.2 Deletion; Autism; Autism spectrum disorder; Developmental disability; Genetics; Psychiatric diagnosis.

Publication types

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

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 16*
  • Cognition*
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / physiopathology
  • Developmental Disabilities / psychology
  • Heterozygote
  • Humans
  • Intelligence / genetics
  • Mental Disorders / genetics*
  • Mental Disorders / physiopathology
  • Mental Disorders / psychology
  • Phenotype*
  • Young Adult