To the Editor: We read with interest the paper by van Engelen et al.,1 analysing the prevalence of 22q11.2 deletion syndrome (22q11.2DS) in adults with tetralogy of Fallot (TOF) and with pulmonary atresia(PA)/ventricular septal defect (VSD). We agree with the experience that many adult patients with TOF have not been tested for 22q11.2DS in the past, so that awareness of the syndrome is needed among clinicians who care adults with congenital heart defects (CHDs). Nevertheless, we disagree to introduce as general practice the large-scale screening of all TOF patients irrespective of their clinical phenotype. Personal experience in paediatric patients with 22q11.2DS has evidenced that the deletion is virtually never found in non-syndromic patients with conotruncal defects.2 In addition, it has been evidenced that distinct subtypes of conotruncal heart defects are likely to be found in association with 22q11.2DS. In regard to TOF, patients with 22q11.2DS have often right/cervical aortic arch with/without aberrant left subclavian artery, hypoplasia or absence of the infundibular septum, absence of the pulmonary valve, and hypoplasia and discontinuity of the pulmonary arteries.2 Among children with TOF and PA, the 35% is carrying a 22q11.2DS, and distinctive recognizable patterns of CHDs include major aorto-pulmonary collateral arteries, sometimes with discontinuity of the pulmonary arteries.2 The review of the literature about clinical characteristics of adults with 22q11.2DS is showing that extracardiac anomalies can help clinician to suspect 22q11.2DS.3 Particularly, previous series reported that facial anomalies can be detected in 99-100% of the cases, ranging from subtle to characteristic. Additional evidenceable signs include hypernasal speech (90%), intellectual disability of any degree and/or learning difficulties (93-97%). The rare occurrence of extremely mild clinical expression of 22q11.2DS in a parent of an affected child can now be explained with the molecular mechanisms of genetic compensation (presence of a 22q11.2 deletion on one chromosome and 22q11.2 duplication on the other allele of chromosome 22).4 In conclusion, the search for 22q11.2DS is important in adult patients with TOF and with PA/VSD, since recognition of the syndrome has clinical and reproductive implications, but genetic testing, in our opinion, should be reserved to patients with associated "classic" or "subtle" extracardiac anomalies, and to those with distinct anatomic cardiac subtypes.

M.Cristina Digilio,1 Bruno Marino,2 Bruno Dallapiccola1 1 Medical Genetics, Bambino Gesu' Paediatric Hospital, IRCCS, Rome, Italy; 2 Department of Pediatrics, Pediatric Cardiology, La Sapienza University, Rome, Italy

Correspondence to Dr M.Cristina Digilio, Medical Genetics, Bambino Gesu' Paediatric Hospital, IRCCS, Piazza S.Onofrio 4, 00165 Rome, Italy; mcristina.digilio@opbg.net

REFERENCES 1. van Egelen K, Topf A, Keavney BD, et al. 22q11.2 deletion syndrome is under-recognized in adult patients with tetralogy of Fallot and pulmonary atresia. Heart 2010;96:621-4. 2. Marino B, Digilio MC, Toscano A, et al. Anatomic patterns of conotruncal defects associated with deletion 22q11. Genet Med 2001;3:45-8. 3. Fung WLA, Chow EWC, Webb GD, Gatzoulis MA, Bassett AS. Extracardiac features predicting 22q11.2 deletion syndrome in adult congenital heart disease. Int J Cardiol 2008;131:51-8. 4. Carelle-Calmels N, Saugier-Veber P, Girard-Lemaire F, et al. Genetic Compensation in a Human Genomic Disorder. N Engl J Med 2009;360:1211-6.

Conflict of Interest:

None declared