Relation of genotype 22q11 deletion to phenotype of pulmonary vessels in tetralogy of Fallot and pulmonary atresia-ventricular septal defect

Abstract

Objective: To compare the morphology of the pulmonary vessels in tetralogy of Fallot or pulmonary atresia-ventricular septal defect (PA-VSD) with (del22q) and without 22Q11 deletion (non-del22q).

Patients: 94 consecutive infants (54 with tetralogy of Fallot, 40 with PA-VSD) were studied using ultrasound and catheterisation. MOLECULAR INVESTIGATIONS: Identification of the 22q deletion was performed either by fluorescent in situ hybridisation or polymerisation chain reaction genotyping.

Results: 25 patients were del22q (16/40 (40%) PA-VSD v 9/54 (17%) tetralogy of Fallot; p < 0.02). Major aortopulmonary collateral arteries was more common in patients with PA-VSD-del22q (p < 0.03). Such collaterals were identified in 13 patients: 10 del22q and three non-del22q (p < 0.001). The size of the right and left pulmonary arteries expressed as a standard deviation (SD) difference of the normal range was -4.2 (quartiles -5.3 and -2.9) for PA-VSD del22q, and -2.6 (-3.1 and -1.8) for PA-VSD non-del22q (p = 0.02). The mean (SD) difference between the measured and theoretical Nakata index was -373 (94) for PA-VSD del22q v -245 (93) in PA-VSD non-del22q (p = 0.0002). In tetralogy of Fallot patients with and without del22q, the size of the pulmonary arteries was similar (p = 0.6).

Conclusions: A "specific" phenotype could be defined in patients with deletion: PA-VSD, major aortopulmonary collateral arteries with complex loop morphology, and small central pulmonary arteries. Differences in the morphology of the pulmonary vessels may indicate a different timing of the faulty developmental pathway in patients with and without 22q11 deletion.

Figure 1

Distribution of tetralogy of Fallot (ToF) and pulmonary atresia-ventricular septal defect (PA-VSD) in the group del22q and in the group non-del22q.

Figure 2

Major aortopulmonary collateral arteries with complex loop morphology in a patient with pulmonary atresia-ventricular septal defect and del22q.

Figure 3

Variability of the phenotype of the pulmonary vessels in non-del22q patients. (A) Pulmonary atresia-ventricular septal defect (PA-VSD) with right aortic arch and a ductus arteriosus originating from the left common brachiocephalic artery; (B) right aortic arch with indirect major aortopulmonary collateral arteries (MAPCA) in a patient with PA-VSD; (C) tetralogy of Fallot with left aortic arch; (D) selective injection in a direct MAPCA.