Genetic causes of developmental disorders

Abstract

Purpose of review: Developmental disorders, including intellectual disability, autism and attention deficit hyperactivity disorder (ADHD), are neuropsychiatric disorders that manifest in early childhood as deviations from the normal development. At present, in the majority of cases a cause cannot be found. However, in the past 5 years major advances have been made in the identification of specific genetic causes of these disorders. Here, we review these findings and discuss possible implications for our current understanding of the cause of developmental disorders.

Recent findings: In addition to the disorders with known genetic cause that are associated with intellectual disability, autism and ADHD, an increasing number of novel recurrent structural variants are identified in association with these developmental disorders. These variants, as well as the genetic variants identified through sequencing approaches indicate the involvement of a large number of genes.

Summary: Similar to what is the case for intellectual disability, recent genetic studies indicate a large degree of genetic heterogeneity for autism and ADHD. Many of the disease risk variants display incomplete penetrance, indicating that additional genetic, and possibly nongenetic, factors are relevant. Despite the high number of causative or contributing genes, functional studies of these genes indicate a large degree of convergence into a smaller number of neurobiological pathways. Elucidating these shared biological mechanisms is a crucial step towards the rational development of novel therapeutic interventions.