Congenital Heart Disease as a Warning Sign for the Diagnosis of the 22q11.2 Deletion

Background

To alert for the diagnosis of the 22q11.2 deletion syndrome (22q11.2DS) inpatients with congenital heart disease (CHD).

Objective

To describe the main CHDs, as well as phenotypic, metabolic and immunologicalfindings in a series of 60 patients diagnosed with 22q11.2DS.

Methods

The study included 60 patients with 22q11.2DS evaluated between 2007 and 2013(M:F=1.3, age range 14 days to 20 years and 3 months) at a pediatric referencecenter for primary immunodeficiencies. The diagnosis was established by detectionof the 22q11.2 microdeletion using FISH (n = 18) and/or MLPA (n = 42), inassociation with clinical and laboratory information. Associated CHDs, progressionof phenotypic facial features, hypocalcemia and immunological changes wereanalyzed.

Results

CHDs were detected in 77% of the patients and the most frequent type was tetralogyof Fallot (38.3%). Surgical correction of CHD was performed in 34 patients.Craniofacial dysmorphisms were detected in 41 patients: elongated face (60%)and/or elongated nose (53.3%), narrow palpebral fissure (50%), dysplastic,overfolded ears (48.3%), thin lips (41.6%), elongated fingers (38.3%) and shortstature (36.6%). Hypocalcemia was detected in 64.2% and decreased parathyroidhormone (PTH) level in 25.9%. Decrease in total lymphocytes, CD4 and CD8 countswere present in 40%, 53.3% and 33.3%, respectively. Hypogammaglobulinemia wasdetected in one patient and decreased concentrations of immunoglobulin M (IgM) intwo other patients.

Conclusion

Suspicion for 22q11.2DS should be raised in all patients with CHD associated withhypocalcemia and/or facial dysmorphisms, considering that many of these changesmay evolve with age. The 22q11.2 microdeletion should be confirmed by moleculartesting in all patients.