Cryptic subtelomeric translocations in the 22q13 deletion syndrome

Cryptic subtelomeric rearrangements are suspected to underlie a substantial portion of terminal chromosomal deletions. We have previously described tw o children, one with an unbalanced subtelomeric rearrangement resulting in deletion of 22q13-->qter and duplication of 1qter, and a second with an app arently simple 22q13-->qter deletion. We have examined two additional patie nts with deletions of 22q13-->qter. In one of the new patients presented he re, clinical findings were suggestive of the 22q13 deletion syndrome and FI SH far 22qter was requested. Chromosome studies suggested an abnormality in volving the telomere of one 22q (46,XX,?add(22)(q13.3)). FISH using Oncor D 22S39 and Vysis ARSA probes confirmed a terminal deletion. A multi-telomere FISH assay showed a signal from 19qter on the deleted chromosome 22. Resul ts were confirmed with 19qtel and 22qtel specific probes. The patient is th erefore trisomic for 19qter and monosomic for 22qter. The patient's mother was found to have a translocation (19;22) (q13.42;q13.31). We also reexamin ed chromosomes from two patients previously diagnosed with 22q deletions wh o were not known to have a rearrangement using the multi-telomere assay, On e of these patients was found to have a derivative chromosome 22 (der(22)t( 6;22)(p25;q13)). No evidence of rearrangement was detected in the other pat ient. Thus we have found the 22q13 deletion to be associated with a translo cation in three of four patients. This report illustrates the usefulness of examining patients with hypotonia, severe language delay, and mild facial dysmorphism for this syndrome and suggests that most of these deletions may be unbalanced subtelomeric rearrangements.