MULTIFACTORIAL INHERITANCE OF NON-SYNDROMIC MACROCEPHALY

Objective: To reevaluate previous claims that non-syndromic macrocepha ly is usually inherited as an autosomal dominant trait. Design: Head s ize was measured in the parents and sibs of children with non-syndromi c macrocephaly. Outcome measures: If autosomal dominant inheritance is involved, the frequency distribution should be bimodal. Results: Head circumference of parents and sibs of the macrocephalic probands had a mean significantly greater than the population norm, and a unimodal d istribution. Probands with psychomotor impairment had bigger heads, an d more had a history of birth difficulty, than did unimpaired probands . Conclusions: The usual genetic basis for non-syndromic macrocephaly is multifactorial with a polygenic genetic basis, rather than autosoma l dominant. Risk of recurrence appears to be much lower than if it wou ld be on the assumption of autosomal dominant inheritance. Macrocephal y in a parent or sib of an unborn child may present a risk for birth i njury to that child, A larger series of patients will be necessary to resolve this question.