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To determine the genetic relationship between head circumference (HC) and Autism Spectrum Disorders (ASDs). Twin pairs with at least one twin with an ASD were assessed. HCs in affected and unaffected individuals were compared, as were HC correlations in monozygotic and dizygotic pairs. 404 subjects, ages 4-18, were included. 20 % of males and 27 % of females with an ASD had macrocephaly. Unaffected co-twins showed similar rates (16 % of males and 22 % of females). Statistical analysis revealed no significant difference in HCs between affected and unaffected twins. Twins with ASDs and unaffected co-twins have similar HCs and increased rates of macrocephaly. Correlations demonstrated partial inheritance of HCs. Thus, macrocephaly may represent an endophenotype in ASDs.

Lord (1992) published a brief report showing a trend for decreasing nonverbal IQ scores with increasing birth order in a sample of 16 autism multiplex families, and urged replication in a larger sample. In this report, analyses of nonverbal IQ scores for a sample of 144 autism multiplex families indicated that nonverbal IQ scores were significantly lower in secondborn compared with firstborn siblings with autism. This birth order effect was independent of gender as well as the age differences within sib pairs. No such birth order effects were found for social or communicative deficits as measured by the Autism Diagnostic Interview-Revised (ADI-R), but there was a modest tendency for increased scores for ritualistic behaviors for the firstborn sibs. Further, there were no gender differences on nonverbal IQ scores in this sample. Results are discussed in terms of implications for genetic studies of autism.

Several studies have suggested a role for the histocompatibility complex of loci (HLA) in the genetic susceptibility to autism. We have tested this hypothesis by linkage analysis using genetic marker loci in the HLA region on chromosome 6p in multiplex families with autism. We have examined sharing of alleles identical by descent in 97 affected sib pairs from 90 families. Results demonstrate no deviation from the null expectation of 50% sharing of alleles in this region; in fact, for most marker loci, the observed sharing was less than 50%. Thus, it is unlikely that loci in this region contribute to the genetic etiology of autism to any significant extent in our families.