[Congenital cardiovascular malformations and chromosome microdeletions in 22q11.2]

Congenital cardiovascular (c-v) malformations are the leading signs of two syndromes of highly variable phenotypes, the DiGeorge syndrome (DGS) and the velo-cardio-facial syndrome (VCFS), both of which in the majority of cases are caused by microdeletion in the chromosome region 22q11.2. It was the aim of this study to ascertain the frequency of these chromosomal abnormalities in patients with unselected congenital cardiovascular malformation, and to assess the type of c-v malformation for which microdeletion analysis of the mentioned region would be indicated.

The cohort consisted of 90 patients with congenital c-v malformations (35 males, 55 females; mean age 3.6 years (19th week of pregnancy-36 years). Most of them were newborns. The c-v anomalies were: ventricular septal defect (n = 20), pulmonary atresia (10), Fallot's tetralogy (9), truncus arteriosus communis (6), aortic valve stenosis (6), atrioventricular canal (6), type B interrupted aortic arch (5), atrial septal defect (5), tricuspid atresia (4), hypoplastic left heart syndrome (4), persisting ductus arteriosus (3), pulmonary valve stenosis (3), complete (third degree) atrioventricular block (2), Ebstein's anomaly (1), tachycardia (1) and enlarged right atrium (1). Four of 14 fetuses included in this study had complex cardiac anomalies that could not be definitively classified. Cytogenetic karyotype analysis was unremarkable in all cases. Microdeletion detection was done by fluorescence-in-situ-hybridization (FISH).

14 of the 90 cases (about 16%) showed microdeletion in the examined chromosomal region 22q11.2. Among the group with microdeletion were aortic arch interruption (5/5), ventricular septal defect (2/20). Fallot's tetralogy (1/9) and atrial septal defect (1/5). All the deletion carriers had other signs of the DGS/VCFS complex. One parent each in two of the microdeletion patients had the same microdeletions.

In patients with congenital c-v and associated malformations of dysmorphism microdeletion diagnosis of 22q11.2 by FISH is indicated in addition to conventional cytogenetic testing. The incidence of this microdeletion seems to be especially high among patients with type B interrupted aortic arch.