Chromosome 10p13-14 and 22q11 deletion screening in 100 patients with isolated and syndromic conotruncal heart defects.

Heart defects are among the most common congenital anomalies, occurring in approximately 1% of newborn populations. Conotruncal heart defects (CTHD), which account for 50-60% of all congenital heart malformations, are known to have a strong genetic component. They occur either as an isolated malformation or in association with extracardiac anomalies. In particular, CTHD constitute a cardinal component of branchial arch syndromes, such as DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), and conotruncal anomaly-face syndrome (CTAFS). The wide phenotypic spectrum includes cardiac defects, abnormal facies, thymic hypoplasia or aplasia, cleft palate, and hypoparathyroidism. 3 The presence of a characteristic 3 Mb microdeletion on chromosome 22q11 in 70-90% of these patients indicates a common genetic aetiology. 5 Haploinsufficiency for the TbxI transcription factor in the critical region appears to be responsible for the aortic arch defects in these disorders. 22q deletions also occur in a high percentage (1040%) of syndromic cases (CTHD associated with at least one extracardiac anomaly) and in non-syndromic familial cases. Although 22q11 microdeletions in a few patients with isolated CTHD have been reported, 15 their exact prevalence remains unknown. In most studies, 8 10 11 16 no 22q11 deletions were found in isolated cases. One possible explanation may be that variant deletions occur in >10% of 22q11 deletion patients and the detection rate of different probes used for microdeletion screening may vary. On the other hand, 22q11 deletion patients who were originally diagnosed as isolated may have been classified retrospectively as syndromic, because of subtle (facial and other) dysmorphism upon re-examination. A second critical region for CTHD exists on chromosome 10p13-14. 19 However, the incidence of 10p13-14 deletions in DGS/VCFS patients is much lower than that of the classical 22q11 deletion. That the few patients with 10p13-14 deletions described so far were all severely affected may be an ascertainment bias, as the underlying deletions were relatively large. For these reasons, we decided to study prospectively the presence of 22q11 (DGS1) and 10q13-14 (DGS2) microdeletions in 100 patients with isolated and syndromic CTHD.