Background and objectives: 22q11.2 Deletion Syndrome (22q11.2DS) is an important genetic syndrome to cardiologists yet remains under-recognized in adults. There is no evidence-based guideline for genetic testing referrals. Feasibility issues in many jurisdictions preclude testing for 22q11.2 deletions in every congenital cardiac patient. We aimed to determine an optimal combination of extracardiac features that could be clinically helpful in identifying adults with tetralogy of Fallot (TOF) and related conotruncal anomalies at highest risk for 22q11.2DS.
Methods: Adults (n=103) at a congenital cardiac clinic (86 with TOF) had a brief clinical screening assessment and genetic testing for 22q11.2 deletions using standard fluorescence in-situ hybridization; 31 had a 22q11.2 deletion. Discriminant ability (DA), defined as (sensitivity+specificity)/2, was used to measure performance of 18 (17 clinical and one demographic) features in predicting 22q11.2DS (DA>80%=a good screening test).
Results: Combining two features was required for a good test: a global impression of 22q11.2DS dysmorphic facies, with either learning difficulties (DA=82.4%) or voice abnormalities such as hypernasality (DA=81.6%). A four-feature combination (suggestive dysmorphic facies, voice abnormalities, learning difficulties and age <30 years) yielded maximal sensitivity (100%) and DA>85% at a cut-off of three features. Neither rates of right aortic arch or cardiac surgery differed between patients with and without 22q11.2 deletions.
Conclusions: Clinicians who consider as few as two extracardiac features readily detectable in a brief clinical encounter could help identify those with 22q11.2DS among adults with congenital heart disease. Diagnosis of 22q11.2DS is important for optimizing management of these complex patients.