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We thank Digilio et al for their interest in our paper, showing that 22q11.2 deletion syndrome (22q11.2DS) is underrecognised in adults with tetralogy of Fallot (TOF) and with pulmonary atresia (PA)/ventricular septal defect (VSD).1 Digilio et al disagree with our recommendation to consider genetic testing for the syndrome in all adults with TOF and PA/VSD. Rather they propose to reserve this for patients with associated ‘classic’ or ‘subtle’ extracardiac anomalies and to those with distinct anatomic cardiac subtypes.
We recognise that the issue of testing for 22q11DS is controversial. We surely agree with Digilio et al that specific additional cardiac anomalies are often present in patients with TOF and PA/VSD and 22q11DS, such as right/cervical aortic arch, hypoplasia or absence of the infundibular septum and major aortopulmonary collateral arteries. The presence of these abnormalities as well as extracardiac features including hypernasal speech, intellectual disability and specific facial features may indisputably help the clinician to suspect 22q11DS and should prompt genetic testing. However, because these additional features may only be present in a subtle manner, they may remain undetected or unrecognised as part of the syndrome. In an adult population with undetected 22q11.2DS, one can expect a bias towards those patients with more subtle features, as patients who exhibit clear features will probably have been diagnosed at an earlier stage. Although in retrospect the majority of patients show (subtle) facial features of the syndrome, physicians, including geneticists, do not always reliably recognise these facial features.2 Moreover, the facial features in adult patients are known to be often more subtle than in children.3 For these reasons, identifying adult patients who might carry the deletion may prove difficult. In clinical practice, given the high prevalence and the relevance of detecting the deletion in terms of clinical and reproductive issues, to our opinion genetic testing should not be reserved for TOF and PA/VSD patients with associated anomalies. Greater awareness of and more experience with the syndrome among physicians may eventually lead to a screening strategy as proposed by Digilio et al. Hopefully the current discussion will contribute to such greater awareness.
Competing interests None.
Provenance and peer review Commissioned; not externally peer reviewed.
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