Absence of 22q11 deletions in 211 patients with developmental delay analysed using PCR.

The 22q11 deletion syndrome has been described by the acronym “CATCH 22” (Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcaemia resulting from 22q11 deletions). Previous studies have indicated that other features such as growth retardation, developmental delay, renal abnormalities, psychiatric problems, and neurological abnormalities may also be associated with the deletion. There have been several estimates of the prevalence of the 22q11 deletion, ranging from 1 in 3000 to 1 in 10 000 live births. It is possible, however, that the frequency of the deletion has been underestimated because of the large phenotypic variability, or the failure to identify mildly affected subjects in the absence of more severely affected relatives. Ninety percent of patients have a common 3 Mb deletion and 7% have a nested 1.5 Mb deletion. Both require fluorescence in situ hybridisation (FISH) for reliable detection. FISH is not, however, routinely carried out in this laboratory unless there are two or more cardinal features of the syndrome or screening for a 22q11 microdeletion is specifically requested. If, therefore, a patient is referred with relatively mild expression of the 22q11 deletion spectrum, a deletion would not be detected using conventional cytogenetics and FISH analysis would not be undertaken. To determine whether it is worth testing patients with less obvious clinical features of a 22q11 deletion, we have used the fluorescent polymerase chain reaction (PCR) to screen a population of 291 subjects with just one of four cardinal features characteristic of this syndrome.