Head circumference is an independent clinical finding associated with autism
Version of Record online: 5 DEC 2000
Copyright © 2000 Wiley-Liss, Inc.
American Journal of Medical Genetics
Volume 95, Issue 4, pages 339–350, 11 December 2000
How to Cite
Miles, J.H., Hadden, L.L., Takahashi, T.N. and Hillman, R.E. (2000), Head circumference is an independent clinical finding associated with autism. Am. J. Med. Genet., 95: 339–350. doi: 10.1002/1096-8628(20001211)95:4<339::AID-AJMG9>3.0.CO;2-B
- Issue online: 6 DEC 2000
- Version of Record online: 5 DEC 2000
- Manuscript Accepted: 25 JUL 2000
- Manuscript Received: 5 JAN 2000
- the Missouri Department of Mental Health, Division of Mental Retardation and Developmental Disabilities
- the Leda J. Sears Trust
- head circumference;
- clinical morphology
Occipitofrontal circumference (OFC) is one of the few physical findings in autism that varies significantly from the norm and is distinct and measurable. As part of a study of genetic heterogeneity of autism, we scrutinized data from a large sample of patients with idiopathic autism (N = 137), using OFC as the categorizing variable. The OFC standard deviation (OFCSD) values of the autistic propositi (0.61 ± 1.6) varied significantly from that of the normal population (0.0 ± 1.0), (P < 0.001). Comparison of the macrocephalic (OFCSD ≥ 2.0, N = 32) with the normocephalic individuals (−2 SD < OFCSD < +2 SD, N = 95) showed no significant differences in sex ratio, morphological status, IQ, seizure prevalence, or recurrence risks. The macrocephalic individuals were slightly less apt than those with normocephaly to have a family history of Attention Deficit Hyperactivity 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. Microcephaly, however, was an independent significant variable that predicted the presence of other phenotypic or genetic traits and outcome. The microcephalic patients were more likely to have abnormal physical morphology, structural brain malformations, lower IQ, and seizures. Their sex ratio was closer to normal, and their relatives had a higher incidence of seizures. Am. J. Med. Genet. 95:339–350, 2000. © 2000 Wiley-Liss, Inc.