Behavioral phenotypic variation in autism multiplex families: Evidence for a continuous severity gradient

Abstract

Recent genetic investigations of autism have studied multiplex families, typically including families with multiple siblings who meet criteria for a diagnosis of autism. However, little is known about the specific behavioral characteristics of siblings with autism in these multiplex families. We investigated the behavioral phenotypic variability and similarity of 351 siblings with autism in 171 multiplex families using cluster analysis and correlations. The results of cluster analyses showed that the individuals with autism could be characterized on a severity gradient: a continuum based on severity of symptoms and impairment as measured by Autism Diagnostic Interview-Revised (ADI-R) scores, verbal-nonverbal status, and nonverbal IQ scores. Clusters based on scores from the ADI-R for the autism diagnostic criteria of the DSM-IV and nonverbal IQ scores still represented a severity gradient when the effects of verbal-nonverbal status were removed. The severity gradient was shown to be heritable, with a sib correlation of 30% or a heritability of 60%. In summary, in a sample of 171 autism multiplex families, there was no evidence of discrete behaviorally defined subgroups of affected individuals or families characterized by distinct patterns of behavioral symptoms. Rather, the clusters could be characterized along a single, heritable, continuous severity dimension.

Genetic correlation between autistic traits and IQ in a population-based sample of twins with autism spectrum disorders (ASDs)

“…In most studies of the parents of children with ASDs a cognitive impairment could not be established. [12][13][14][15][16] An understanding of the extent to which autistic traits and IQ share genetic and environmental factors is important for classifying ASDs as well as for locating and identifying genes that contribute to ASDs. Surprisingly, there is no other published study on twins that assesses the relationship between autistic traits and IQ.…”

Disparities in Diagnoses Received Prior to a Diagnosis of Autism Spectrum Disorder

“…Evidence for underlying behavioral phenotypes has been mixed. Some studies have identified distinct clustering of symptoms (Cuccaro et al, 2003;Tadevosyan-Leyfer et al, 2003), while others have found one, continuously distributed underlying factor (Constantino et al, 2003;Spiker, Lotspeich, Dimiceli, Myers, & Risch, 2002). Cuccaro et al (2005) report that African-American children with autism may have more impaired language development than white children, while oral communication with Lord (2005, oral communication) suggested no such differences.…”

A Family History Study of Asperger Syndrome

“…Sometimes referred to as the broader autistic phenotype (BAP) or the lesser variant, these deficits are not severe enough to justify the full diagnosis of autism. In order to investigate the familial aspects of AS and determine its degree of relatedness to autism, it is important to perform studies focusing on large series of probands with AS (Spiker, Lotspeich, Dimiceli, Myers, & Risch, et al, 2002). The purpose of this study is to address this issue.…”