β Scribed by Miles, Judith H.; Hillman, Richard E.
No coin nor oath required. For personal study only.
In an effort to delineate more homogeneous autism subgroups for genetic study, we evaluated 133 consecutive individuals referred to the University of Missouri Autism Center. Each index case underwent a diagnostic evaluation, including a clinical morphology examination, laboratory studies, brain MRI, EEG, and collection of historical, medical, and family data. The 71% (94/133) who fulfilled DSM-IV and CARS autism diagnostic criteria were included in this study. Six of 94 were diagnosed with a known genetic disorder. Of the remaining 88 with apparently "idiopathic autism," 58% (51/88) were phenotypically normal, 22% (19/88) were clearly abnormal, and for 20% (18/88) the clinical morphology examination was equivocal. The percentage of phenotypically abnormal individuals is higher than generally thought and disagrees with the perception that children with autism are usually normally formed. The phenotypically abnormal individuals were 10 times more likely to be diagnosed with a known genetic syndrome (21% vs. 2%) and were more than twice as likely (29% vs. 14%) to have structurally abnormal brain MRIs than the phenotypically normal propositi. Moreover, the male to female ratio correlated with the presence of physical anomalies. The total study group had a male to female ratio of 4.2:1; the morphologically normal subgroup, defined on the basis of a normal physical examination, had a sex ratio of 7.5:1 and the normal subgroup, defined on the basis of both a normal physical examination and a structurally normal brain by MRI had a 23:1 sex ratio. For the phenotypically abnormal subgroup, the sex ratio was 1.7:1. Since differences in sex ratio are presumably a reflection of differences in genetic constitution, we postulate that the phenotypically normal subgroup of individuals with "idiopathic autism" is genetically different from the phenotypically abnormal individuals and that differences in the sex ratio in different autism populations is one indicator of a population's genetic heterogeneity.
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