A family study of cases with unidentified multiple congenital abnormality

A family study was conducted in 1384 index patients affected by unidentified MCAs, which represented a 50.6% sample of the population-based material of the Hungarian Congenital Malformation Registry, 1973-1980. 39 cases due to misdiagnosis, and 32 cases due to a recently achieved nosological diagnosis were excluded. Furthermore, for 109 index patients no new home address was available and 166 families refused to cooperate or they were not able to give a complex dataset. Finally, affected first degree relatives of 1038 index patients were evaluated on the basis of medical documentation. 5.1% of fathers and 4.2% of mothers were affected and more than half of them were affected by one component congenital anomaly of index patients. The sib-occurrence of congenital anomalies and of multiple congenital abnormalities was 11.0% and 3.5%, respectively. The specific sib-occurrence (i.e. fully of half-concordant congenital anomalies in sibs) was 5.5%. Furthermore, there is an increased risk for fetal death in previous and subsequent pregnancies of index patients' mothers. By the help of the family study multiple congenital abnormality entities were identified in 78% of sib-occurrence of unidentified multiple congenital abnormalities. Some previously delineated congenital anomaly syndromes were recognized and six probably new syndromes or associations were delineated.