Hormonal versus genetic factors in limb and heart anomalies

Three men, aged 18, 21 and 27 years, underwent surgery for atrial septal defect of the ostium secundum. All had bilateral absence of the forearm and thumb, with the rest of the hand directly attached to the upper arm. The patients had been exposed to synthetic progestogens during early intrauterine development. The oldest patient is described, together with a 6-year-old boy with limb reduction and Fallot's tetralogy who was exposed to the contraceptive pill during the first 2 months of gestation. During surgery he was found to have atrial septal defect of the ostium secundum. The most plausible diagnosis in such cases is the Holt-Oram syndrome, but the teratogenic effect of the synthetic hormones may be an important aetiological factor. Both hypotheses are discussed.