Recurrence of holoprosencephaly in families with a positive history

A holoprosencephalic child was born into a family with 6 other affected members in 3 generations. A chromosome study of the proband was normal. The recurrence risk of holoprosencephaly was 22% in first degree relatives of affected individuals in this family. The recurrence risk was 22.9% for holoprosencephaly and 34.3% for holoprosencephaly and facial and neural defects when families with affected members in the medical literature in two generations were added. Dominant inheritance with reduced penetrance in family members best explains the inheritance pattern of familial holoprosencephaly.