762-4 Importance of Microdeletions of Chromosomal Region 22q11 In the Etiology of Congenital Conotruncal Malformations: A 2 Year Prospective Study

Microdeletions of 22q11 are a well recognised cause of DiGeorge Syndrome, Velocardiofacial syndrome and familial conotruncal heart disease. We sought to clarify the importance of 22q11 microdeletions and other identifiable cytogenetic abnormalities in the etiology of conotruncal malformations and to establish clinical-genetic correlations. From 6/92-8/94 we prospectively studied 39 consecutive infants presenting to a regional pediatric cardiac centre with a conotruncal malformation. Diagnoses were: tetralogy (21), pulmonary atresia NSD (8), DORV (3). type B IAA (3), truncus (2). absent pulmonary valve syndrome (1) and isolated right aortic arch (1). 17 (44%) were considered dysmorphic by a clinical geneticist. In 5 cases the dysmorphic features were major. but no firm diagnosis was established on clinical grounds. One of these patients was shown to have an unbalanced translocation involving chromosomes 4 a 16. Twelve patients had subtler dysmorphic features. Nine of these cases were prospectively considered to have phenotypic appearances consistent with microdeletion of 22q11. In 7/9 the diagnosis was confirmed using fluorescence in situ hybridisation (FISH); 7 cases were confirmed using the cosmid EO and in one case with an equivocal result with cEO, hemizygosity of the 22q1 1 region was confirmed with use of a second cosmid for the TUPLE-1 gene region (cH487). FISH on samples from 19 infants considered free of phenotypic appearances of 22q1 1 microdeletions were all negative. Amongst the deleted patients. thymic aplasia was demonstrated at the time of cardiac surgery in 3. In the other 4 deleted patients no thymic shadow was evident on neonatal CXR. T cell studies were perfordeleted patients a were normal in 3 cases. Serious infection arose in only 1 patient with 22q11 deletion but with normal T cell studies. Transient symptomatic hypocalcemia developed in 2 patients. both deleted for 22q1 1. We conclude that 22q11 microdeletions are clinically recognisable in early infancy and constitute one of the commonest identifiable genetic causes of congenital head disease. Thymic aplasia is common in deleted patients, though serious infections are rare. These observations have important implications for transfusion management. long term follow-up and for genetic counselling.