High risk for unbalanced segregation of some reciprocal translocations: A large pedigree containing distal 4q trisomy from t(4;7)(q28;p22)

We report on a familial t(4;7)(q28;p22) with 2:2 adjacent-1 unbalanced segr egation producing duplication of 4q28-->qter in multiple offspring. Within the large four-generation pedigree, a carrier had a reproductive outcome th at was approximately equal for 1) the balanced translocation, 2) normal chr omosomes, and 3) viable 4q trisomy or pregnancy loss. The three individuals with chromosomal confirmation of trisomy 4q28-->qter (comprising approxima tely 1.8% of the haploid autosomal length) had similar mental and developme ntal retardation, hypotonia, restricted speech, seizures, and facial anomal ies but no cardiac, renal, or skeletal anomalies. It is suggested that thes e latter severe malformations, associated with the classic 4q2 to 3 group o f anomalies, were from an imbalance outside 4q28-->qter and were not necess arily related to the relatively large size of the trisomic segment. Multipl e different chromosomes are reported to be rearranged with 4q in the produc tion of distal 4q trisomy. The incidence of 4q rearrangement remains unexpl ained, but once it is present in a family, viability of a large trisomy in 4q seems to explain the number of affected individuals reported. (C) 2001 W iley-Liss, Inc.