Congenital cardiovascular malformations and chromosomal microdeletions in 22q11.2

Background and objective: Congenital cardiovascular (c-v) malformations are the leading signs of two syndromes of highly variable phenotypes, the DiGe orge syndrome (DGS) and the velo-cardio-facial syndrome (VCFS), both of whi ch in the majority of cases are caused by microdeletion in the chromosome r egion 22q11.2. It was the aim of this study to ascertain the frequency of t hese chromosomal abnormalities in patients with unselected congenital cardi ovascular malformation, and to assess the type of c-v malformation for whic h microdeletion analysis of the mentioned region would be indicated. Patients and methods: The cohort consisted of 90 patients with congenital c -v malformations (35 males, 55 females; mean age 3.6 years (1 9th week of p regnancy - 36 years). Most of them were newborns. The c-v anomalies were: v entricular septal defect (n = 20), pulmonary atresia (10), Fallot's tetralo gy (9), truncus arteriosus communis (6), aortic valve stenosis (6), atriove ntricular canal (6), type B interrupted aortic arch (5), atrial septal defe ct (5), tricuspid atresia (4), hypoplastic left heart syndrome (4), persist ing ductus arteriosus (3), pulmonary valve stenosis (3), complete (third de gree) atrioventricular block (2), Ebstein's anomaly (1), tachycardia (1) an d enlarged right atrium (1). Four of 14 fetuses included in this study had complex cardiac anomalies that could not be definitively classified. Cytoge netic karyotype analysis was unremarkable in all cases. Microdeletion detec tion was done by fluorescence-in-situ-hybridization (FISH). Results: 14 of the 90 cases (about 1 6%) showed microdeletion in the examin ed chromosomal region 22q11.2. Among the group with microdeletion were aort ic arch interruption (5/5), ventricular septal defect (2/20). Fallot's tetr alogy (1/9) and atrial septal defect (1/5). All the deletion carriers had o ther signs of the DGS/VCFS complex. One parent each in two of the microdele tion patients had the same microdeletions. Conclusion: In patients with congenital c-v and associated malformations of dysmorphism microdeletion diagnosis of 22q11.2 by FISH is indicated in add ition to conventional cytogenetic testing. The incidence of this microdelet ion seems to be especially high among patients with type B interrupted aort ic arch.