Phenotypic Congruence in Multiplex Autism Families

Background: Clinical research investigating children with autism spectrum disorders (ASD) has yielded significant heterogeneity with regard to symptom severity and level of functioning. This complex clinical picture has contributed to difficulty in locating etiologically relevant genes. In order to better categorize this phenotypic variance and facilitate genetic research, much research has been devoted to studying multiplex cases of autism – families in which two or more individuals have been diagnosed with ASD. Research  focused on assessing sibling concordance (non-twin pairs) based on level of functioning have yielded mixed results. Some studies have found little to no evidence for familial aggregation of IQ, verbal ability, or specific behaviors (Spiker et al., 1994), while others have found familial aggregation of measures of social communication, IQ, and adaptive behaviors (Szatmari et al., 1996; MacLean et al., 1999; Goin-Kochel et al., 2008). Objectives: The current study investigated the familiality of symptom severity, IQ, and adaptive functioning within non-twin, multiplex families, in which the younger sibling was identified through a screening instrument.Methods: Thirty-eight pairs of multiplex siblings affected by an autism spectrum disorder (ASD) were evaluated as part of a larger study on the early detection of autism in toddlers. The younger siblings of children already diagnosed with an ASD were ascertained on the basis of screening positive on the Modified Checklist for Autism in Toddlers (M-CHAT). Their older siblings were evaluated to confirm their previous diagnoses. Evaluations for all pairs included a battery of diagnostic, cognitive, and adaptive tests. Diagnoses were assigned based on the DSM-IV symptom checklist, completed using information from testing and clinical judgment. All children in this sample received a diagnosis of Autistic Disorder, Pervasive Developmental Disorder – Not Otherwise Specified (PDD-NOS), or Asperger's Disorder. For the purposes of this study, sibling pairs were compared across the domains of the ADOS, DSM-IV, Mullen, and Vineland Adaptive Behavior Scales.Results: Consistent with findings from an investigation of repetitive behaviors in multiplex siblings from our group (Carr et al., presented), intraclass correlations (ICCs) conducted between older and younger siblings in a pair indicate that multiplex siblings were more similar to each other across all domains on the measures of symptom severity, IQ, and adaptive functioning than were unrelated children. Conclusions: Our findings support those of Goin-Kochel et al. (2008) who found that siblings with ASD were more similar on measures of IQ and adaptive functioning than affected non-siblings. These results further suggest the importance of stratifying families by symptom severity and level of functioning when conducting genetic studies of autism. The fact that the same parent often served as respondent might have inflated the similarity within sib pairs, but would not be expected to affect the direct testing and observation measures. Possible effects of birth order and diagnostic classification (Autistic Disorder versus ASD) will also be discussed.