Congenital diaphragmatic hernia in a family segregating a reciprocal translocation t(5;15)(p15.3;q24)

Congenital diaphragmatic hernia (CDH) is a relatively common malformation o f unknown cause with high mortality due to hypoplasia of the lungs and pulm onary hypertension. We studied a family in which two fetuses had CDH, and t wo pregnancies resulted in first trimester missed abortions. Both fetuses w ith CDH had an apparently normal karyotype. In a subsequent pregnancy, fluo rescent in situ hybridization analysis of amniocytes showed a balanced tran slocation 46,XY, t(5;15) (p15.3;q24) also present in the mother and in a no rmal child, suggesting that the diaphragmatic hernia in the first two fetus es was caused by a cryptic unbalanced translocation. This hypothesis is sup ported by a previous observation of CDH in a distal deletion of 15q as part of a multiple congenital anomalies syndrome. R is suggested that a gene di stal to 15q21 is important for the normal development of the diaphragm. Am. J. Med. Genet. 90:120-122, 2000 (C) 2000 Wiley-Liss, Inc.