Two sibs with Wolf-Hirschhorn and DiGeorge deletions resulting from an unbalanced chromosome rearrangement, 45,XX/XY, der(4)t(4;22) (p16.3;q11.2) mat,-22.

A mother with apparently balanced translocation between chromosomes 4 and 22 gave birth to two children (sib 1 and twin A) with 45,XX,der(4)t(4;22) (p16.3;q11.2)mat,-22 and 45,XY,der(4)t(4; 22(p16.3;q11.2)mat,-22 karyotypes. The mother was a slow learner and required special education. The imbalance in the sibs arose through a 3:1 malsegregation in the mother. The net result was deletions 4p16.3pter and 22q11.2pter. Deletion 4p is associated with Wolf-Hirschhorn syndrome (WHS). The 22q11.2 microdeletion is associated with a wide range of overlapping phenotypes including DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), conotruncal facial abnormality, and sporadic or familial cardiac defect. Fluorescence in situ hybridisation (FISH) was performed. Cosmid probes D4S96, which maps to 4p16.3, and D22S75, which maps to 22q11.2, were used. In the mother, the translocation breakpoints were proximal to D4S96 on chromosome 4 and distal D22S75 on chromosome 22. The two sibs had deletions of a D4S96 and a D22S75 probe loci. Sib 1, a 2 1/2 year old girl, has multiple congenital abnormalities and profound developmental delay. The craniofacial features were generally of WHS. Hypoplasia of the thymus hypocalcaemia, and seizures in early infancy, which are clinical features of DGS, were also observed. Twin A was one of a pair of dizygotic twins. He had multiple congenital abnormalities and died soon after birth.