Autism, Susceptibility To, 12

Description

Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006).

For a discussion of genetic heterogeneity of autism, see 209850.

Clinical Features

Molloy et al. (2005) reported 34 families in which 1 individual had autism, a relative had either autism or autism spectrum disorder, and both had a definite history of developmental regression. Developmental regression was defined as loss of language skills and/or loss of other socially communicative skills, such as eye contact or gestures, between the ages of 18 and 24 months. However, the authors noted that most children who experience regression do not have completely normal development prior to the regressive episode.

Mapping

By genomewide linkage analysis in 34 families segregating a phenotype of autism and developmental regression, Molloy et al. (2005) identified a candidate region on chromosome 21p13-q11 (nonparametric lod score of 3.0 near marker D21S1437; maximum multipoint lod score of 3.4 under a dominant mode of inheritance). The strongest evidence for linkage was a 2.7-Mb region between D21S1432 and D21S1899. Significant linkage for this phenotypic subgroup was also identified on chromosome 7q35-q36 (AUTS10; 611016).