Familial Down syndrome: evidence supporting cytoplasmic inheritance

The frequently observed familial aggregation of Down syndrome (DS) 47, + 21 and other aneuploidies and the phenomenon of double aneuploidy involving DS cannot be accounted for by chance alone. To clarify possible aetiological factors, pedigrees from all 7 affected families with repeated marriages referred to two regional genetics centres were examined. In each case the recurrence of aneuploidy was on the mother's side (p < 0.01). Such a pattern suggests cytoplasmic inheritance of a risk factor. The hypothesis that mitochondrial DNA mutations have a role in the aetiology of DS is supported by other observations as well as by theoretical considerations.