Multifactorial inheritance of non-syndromic macrocephaly.
OBJECTIVE
To reevaluate previous claims that non-syndromic macrocephaly is usually inherited as an autosomal dominant trait.


METHODS
Head size was measured in the parents and sibs of children with non-syndromic macrocephaly.


METHODS
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 distribution. Probands with psychomotor impairment had bigger heads, and 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 autosomal dominant. Risk of recurrence appears to be much lower than if it would be on the assumption of autosomal dominant inheritance. Macrocephaly in a parent or sib of an unborn child may present a risk for birth injury to that child. A larger series of patients will be necessary to resolve this question.
Arbour
L
L
Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
Watters
G V
GV
Hall
J G
JG
Fraser
F C
FC
D000328:Adult; D001720:Birth Injuries / Q000209:etiology* / Q000473:pathology; D002170:Canada / Q000453:epidemiology; D002508:Cephalometry; D036861:Delivery, Obstetric; D004198:Disease Susceptibility; D005260:Female; D005799:Genes, Dominant; D018740:Genetic Heterogeneity; D006257:Head / Q000002:abnormalities / Q000033:anatomy & histology*; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000209:etiology; D008297:Male; D010375:Pedigree; D011247:Pregnancy; D012306:Risk