1002-90 Deletions in Chromosome 22: A Common Cause of Conotruncal and Aortic Arch Defects

Abstract

The acronym CATCH 22 (Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcemia from deletions in chromosome 22) has been coined to describe the occurrence of microdeletions at the 22q11 locus in 75–90% of patients with DiGeorge and Shprintzen syndromes. Because little data are available regarding the frequency of deletions in non-syndromic patients with congenital heart defects, we screened 61 patients with conotruncal cardiac defects and aortic arch abnormalities. Testing included FISH (fluorescent in situ hybridization) studies with the N25 (D22S75) digoxigenin-labeled DNA probe (Oncor, Gaithersburg, MD) and high resolution cytogenetic analysis. FISH revealed deletions in 8 of 20 patients with tetralogy of Fallot, 5 of 6 with absent pulmonary valve, 4 of 9 with pulmonary atresia/malalignment ventricular septal defect, 3 of 11 with truncus arteriosus, 4 of 8 with interrupted aortic arch, 1 of 2 with anomalous origin of the right pulmonary artery (hemitruncus), and 0 of 5 patients with double outlet right ventricle. Only 7 of the 25 patients with a deletion had a clinical diagnosis of DiGeorge or Shprintzen syndromes. FISH testing in 8 sets of parents demonstrated 3 individuals with deletions. These data show a high (41%) prevalence of CATCH 22 deletions in patients with congenital conotruncal or aortic arch defects. Early detection of patients with deletions facilitates genetic counseling and the identification of medical problems associated with CATCH 22 deletions.