Congenital cardiac malformations in fetuses with chromosome 22q11.2 microdeletion (CATCH 22)

Abstract

Objective: We report the spectrum of congenital cardiac malformations inautopsied abortions, stillborns and/or neonatal deaths. Prenatal and/or postnatal cytogenetic investigations were carried out in all of the cases. Three fetuses in whom a prenatal diagnosis of 22q11.2 deletion was made by fluorescence in situ hybridization (FISH) are described in detail. Design: During a five year period from 1996 to July, 2000, 132 fetuses with prenatally diagnosed cardiac disease were tested for 22q11.2 microdeletions. Autopsies were performed in 42 cases of abortions, stillborns and/ or neonatal deaths with congenital cardiac defects. Pathological findings, prenatal diagnosis, dysmorphic features and family history are described in detail in three fetuses with CATCH 22. Results: In all cases diagnosed prenatally, cardiac findings were confirmed by autopsy. We found 22q11.2 microdeletion in 5 out of 132 (3.8%) cases with prenatally diagnosed cardiac defects. Because of a severe cardiac defect, and aplasia of the thymus, the pregnancies were terminated in 3 out of these 5 cases diagnosed prenatally with CATCH 22. The cardiac defects in these three fetuses were: common arterial trunk (case 1); tetralogy of Fallot with “absent pulmonary valve syndrome” (case 2), and interruption of the aortic arch between the left common carotid and left subclavian arteries (“Type B”) with ventricular septal defect (case 3). Clinical and cytogenetic examinations of the families showed that, in two cases, the parents were not affected. In the other case, the mother had phenotypic features of the velo-cardio-facial syndrome (VCFS) and a microdeletion 22q11.2. Conclusions: Investigations for microdeletion 22q11.2 by FISH is indicated in addition to conventional karyotyping in fetuses with malformations of the outflow tracts and abnormalities of the arterial trunks. Because of marked phenotypic variability, a test for 22q11.2 microdeletion should be considered in both parents of any child with CATCH 22.