Anomalous inheritance in a kindred with split hand, split foot malformation

A South African family with autosomal dominant split hand, split foot (SHSF) malformation has been studied. The pedigree was unusual in that three unaffected siblings with normal parents had each produced affected offspring. New mutation, germinal mosaicism and autosomal recessive inheritance are unlikely. Possible explanations of this contentious situation may be an unstable premutation or non-penetrance due to an inhibiting factor associated with the gene responsible for SHSF. Pregnancy monitoring by ultrasound of unaffected close relatives of a person with SHSF is recommended.