IMPORTANCE OF MICRODELETIONS OF CHROMOSOMAL REGION 22Q11 AS A CAUSE OF SELECTED MALFORMATIONS OF THE VENTRICULAR OUTFLOW TRACTS AND AORTIC-ARCH - A 3-YEAR PROSPECTIVE-STUDY

Objectives: To assess the incidence of microdeletions of chromosomal r egion 22q11 in a population of infants coming to a regional pediatric cardiac center with selected abnormalities of the ventricular outflow tracts and aortic arch and, further, to provide phenotypic/genetic cor relations to determine whether patients with 22q11 deletions can be cl inically recognized in infancy. Background: DiGeorge syndrome and velo cardiofacial syndrome are frequently associated with malformations of the ventricular outflow tracts and aortic arch. Both are usually cause d by microdeletions of chromosomal region 22q11. The overall importanc e of such deletions as a cause of these cardiac malformations remains to be established. Study design: All infants with the candidate cardia c phenotypes during a 34-month period were studied, Dysmorphic feature s, type of cardiac defect, serum calcium concentration, and thymic sta tus were recorded, Cytogenetic studies, including high-resolution kary otyping and fluorescence in situ hybridization using cosmids (cEO or c H748) from the DiGeorge critical region, were performed after clinical assessment. Results: Fifty infants (including 36 with tetralogy of Fa llot with or without pulmonary atresia) were seen during the study per iod, Twenty-six infants (52%) were dysmorphic, including 19 who were c onsidered to have a phenotypic appearance consistent with 22q11 deleti on. Genetic analysis confirmed hemizygosity for 22q11 in 8 of these 19 cases, Results of fluorescence in situ hybridization studies were nor mal in 22 infants without dysmorphic features and in 5 infants with dy smorphic features not suggestive of a 22q11 deletion. Conclusions: Mic rodeletions of chromosomal region 22q11 are an important cause of sele cted malformations of the ventricular outflow tracts and aortic arch a nd account for about 15% to 20% of cases, These deletions may be clini cally recognized in early infancy and can be rapidly confirmed by fluo rescence in situ hybridization.