With an incidence of 1:4,000, the microdeletion 22q11.2 is the most frequent microdeletion and exhibits the highest variability of clinical signs and symptoms. The severe form is defined by the signs and symptoms of the DiGeorge syndrome, with a complex heart defect, thymus aplasia and a resulting immune defect, hypoparathyroidism resulting from aplasia of the parathyroid glands, developmental delay and short stature. Signs of the mild form are for instance discreet dysmorphia, possibly short stature and a hoarse voice. The individual syndromes may overlap; the levels of severity can also vary strongly within one family. The cause for this strong variability, even with the same deletion, has so far remained unknown.
The microdeletion 22q11.2 causes a developmental field defect of the 3rd and 4th pharyngeal pouches and the intervening 4th pharyngeal arch and their derived structures such as blood vessels near the heart, thymus, parathyroid glands. 75% of all patients suffer from cardiac defects, especially abnormalities of the aortic arch and conotruncal cardiac defects. Up to 70% of all patients have at least a temporary hypocalcemia. Dysmorphic features include wide-set eyes with a flat nasal bridge, hypoplastic nostrils, narrow mouth with bow-shaped upper lip overlapping the lower lip, a retrognathia. Up to 20% of all adult patients are thought to have psychiatric abnormalities. In the rare cases of psychosis in children, the microdeletion 22q11.2 is part of the differential diagnosis. In 5-10% of all cases, the microdeletion is already present in one parent, which results in a recurrence risk of 50% for future children. Therefore, the parents of the affected child should also be tested, especially if there is desire for further children.