Head circumference is an independent clinical finding associated with autism

Occipitofrontal circumference (OFC) is one of the few physical findings in autism that varies significantly from the norm and is distinct and measurab le. As part of a study of genetic heterogeneity of autism, we scrutinized d ata from a large sample of patients with idiopathic autism (N = 137), using OFC as the categorizing variable. The OFC standard deviation (OFCSD) value s of the autistic propositi (0.61 +/- 1.6) varied significantly from that o f the normal population (0.0 +/- 1.0), (P < 0.001), Comparison of the macro cephalic (OFCSD <greater than or equal to> 2.0, N = 32) with the normocepha lic individuals (-2 SD < OFCSD < +2 SD, N = 95) showed no significant diffe rences in sex ratio, morphological status, IQ, seizure prevalence, or recur rence risks. The macrocephalic individuals were slightly less apt than thos e with normocephaly to have a family history of Attention Deficit Hyperacti vity Disorder (ADHD) (P < 0.05), Each clinical subgroup of autism propositi , defined on the basis of phenotypic status, type of onset, seizure history , or IQ, had a higher than normal mean OFC indicating that macrocephaly is an independent clinical trait in autism. As in the non-autistic population, macrocephaly was highly familial with 45% of the macrocephalic and 37% of the normocephalic propositi having at least one macrocephalic parent. Micro cephaly, however, was an independent significant variable that predicted th e presence of other phenotypic or genetic traits and outcome. The microceph alic patients were more likely to have abnormal physical morphology, struct ural brain malformations, lower IQ, and seizures. Their sex ratio was close r to normal, and their relatives had a higher incidence of seizures. (C) 20 00 Wiley-Liss, Inc.