Intellectual disability (ID) and Autism Spectrum disorder (ASD) are the most common developmental disorders present in humans. Combined, they affect between 3-5% of the population. Additionally, they can be found together in the same individual thereby complicating treatment.

Introduction

Intellectual disability is a condition characterized by below average intellectual functioning (IQ<70) in conjunction with significant limitations in adaptive functioning. Intellectual disability may occur as an isolated phenomenon or accompanied with malformations, neurological signs, impairment of the special senses, seizures and behavioral disturbances. 

The genetic causes for ID and ASDs are quite varied and similar. Single gene mutations, as well as copy number variants (CNVs), either duplications or deletions, are associated with both conditions. Additionally, hypomorphic alterations in multiple genes suggesting an oliogenic mode of inheritance have recently been noted for both conditions. Recently, large-scale whole exome sequencing (WES) studies found that no single gene was significantly associated with ASD risk. Rather a likely contribution of rare risk variants scattered across hundreds of genes was speculated (Anney et al., 2012; Liu et al., 2013). The same mutation or CNV gives rise to either ID or ASDs and variations within a large number of these genes, for example, NRXN1, CNTNAP2, NLGN4, SHANK2 and SHANK1, have been found to be associated with ID as well as ASD (Berkel et al., 2010; Sato et al., 2012; Kim et al., 2008; Laumonnier et al., 2004; Zweier et al., 2009). These observations further substantiate the involvement of similar cellular and molecular processes and indicate the role of environment and genetic background plays in the expression of ID (Figure 1) and probably ASD.

Genes Linked to ID and ASD

Table 1