Genetics of autism: characteristics of affected and unaffected children from 37 multiplex families.

Evidence from twin and family studies strongly suggests that genetic factors play a prominent role in the etiology of some cases of infantile autism. Genetic factors would be expected to be especially strong in families with multiple autistic members (multiplex families). This report describes the identification and evaluation of 44 families with two or more autistic children collected as part of a genetic linkage study in autism. Families were referred with a presumptive classification of multiplex autism. Children referred as autistic, as well as their presumptively normal siblings, were assessed using the Autism Diagnostic Interview (ADI) and the Autism Diagnostic Observation Scale (ADOS). Thirty-seven of the 44 families (87%) had at least two children who met diagnostic criteria for autism on the ADI. Of the total group of 117 children evaluated in those families, 83 (71%) met all ADI criteria and could be unambiguously classified as autistic (affected), 26 (22%) met none of the ADI criteria and were classified as not autistic (unaffected), and 8 (7%) were classified as uncertain because they met one or more but not all of the ADI cutpoints. Autistic siblings were not significantly concordant for most autism characteristics, for IQ, or for verbal ability. Significant concordances were found, however, for behaviors related to rituals and repetitive play, and for social impairments in the expression and understanding of facial expressions of emotion. The results of this study suggests two major points: first, there does not appear to be a highly variable autistic phenotype expressed in multiplex families; in the vast majority of cases, children are either clearly affected or clearly unaffected, so that linkage analysis should not be complicated by a large number of ambiguous or uncertain cases. Second, multiplex families do not appear to associate into subgroups defined by clustering of specific autism behaviors. © 1994 Wiley-Liss, Inc.