Recurrent copy number variations as risk factors for neurodevelopmental disorders: critical overview and analysis of clinical implications

J Med Genet. 2016 Feb;53(2):73-90. doi: 10.1136/jmedgenet-2015-103366. Epub 2015 Oct 26.

Abstract

Neurodevelopmental disorders (NDs) encompass a spectrum of neuropsychiatric manifestations. Chromosomal regions 1q21.1, 3q29, 15q11.2, 15q13.3, 16p11.2, 16p13.1 and 22q11 harbour rare but recurrent CNVs that have been uncovered as being important risk factors for several of these disorders. These rearrangements may underlie a broad phenotypical spectrum, ranging from normal development, to learning problems, intellectual disability (ID), epilepsy and psychiatric diseases, such as autism spectrum disorders (ASDs) and schizophrenia (SZ). The highly increased risk of developing neurodevelopmental phenotypes associated with some of these CNVs makes them an unavoidable element in the clinical context in paediatrics, neurology and psychiatry. However, and although finding these risk loci has been the goal of neuropsychiatric genetics for many years, the translation of this recent knowledge into clinical practice has not been trivial. In this article, we will: (1) review the state of the art on recurrent CNVs associated with NDs, namely ASD, ID, epilepsy and SZ; (2) discuss the models used to dissect the underlying neurobiology of disease, (3) discuss how this knowledge can be used in clinical practice.

Keywords: Autism, Epilepsy; CNVs, Risk factors; Genetic counseling; Neurodevelopmental disorders; Schizophrenia, Mood disorders.

Publication types

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

MeSH terms

  • Animals
  • Autism Spectrum Disorder / genetics
  • DNA Copy Number Variations*
  • Disease Models, Animal
  • Epilepsy / genetics
  • Female
  • Genetic Counseling*
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Induced Pluripotent Stem Cells / physiology
  • Neurodevelopmental Disorders / diagnosis
  • Neurodevelopmental Disorders / genetics*
  • Pregnancy
  • Prenatal Diagnosis*
  • Risk Factors
  • Schizophrenia / genetics