Monozygotic twins with CATCH22 and discordant phenotype

CATCH22 (cardiac defect, anomaly faciès, thymic hypoplasia, cleft palate and hypocalcaemia) is due to deletion on chromosome 22q11. Goodship et al. recently described 22qll deletion in monozygotic twins having discordant phenotypes (J. Med. Genet. 1995; 32: 746-8). We report on male monozygotic twins with CATCH22 in whom phenotypic discordance was more conspicuous. They were delivered at 37 weeks' gestation with twin 1 weighing 1572g and twin 2 weighing 2376g. Twin-twin transfusion syndrome was diagnosed (hemoglobin, twin 1; 10.4 g/dl vs twin 2; 17.4 g/dl). FISH analysis showed microdeletion on chromosome 22qll in each and various blood types were identical (probability of monozygosity of 99.95%). Twin 1 had cardiac defect, characteristic facial appearance, swallowing dysfunction, anal atresia, and mental retardation. Twin 2 had characteristic facial appearance but no other stigmata of CATCH22. Our observation further suggests that phenotypic variability in CATCH22 may be in part due to early intrauterine environmental factors. The role of twin-twin transfusion syndrome appears to be subsidary, since it occurs late in intrauterine life.