DiGeorge syndrome represents a part of the highly variable clinical spectrum of the microdeletion 22q11.2. It is caused by a developmental defect of the third and fourth pharyngeal pouches or derived structures such as the thymus and parathyroid glands and the fourth gill arch. In the complete clinical picture, thymic hypoplasia or aplasia is found, resulting in a cellular immunity defect. In about 10% a severe immunodeficiency is present. In about 60% there is hypoplasia of the parathyroid glands, which may cause hypocalcemia and is sometimes accompanied by seizures. Hypocalcemia usually develops in the neonatal period, but may occur later. Calcium levels can normalize spontaneously at any time, but long-term calcium substitution is often required. Heart defects are another leading symptom, and aortic arch anomalies, conotruncal heart defects such as tetralogy of Fallot or truncus arteriosus, but also ventricular septal defects or patent ductus arteriosus have been observed. Cleft palate also occurs. Signs of velopharyngeal insufficiency include a hoarse voice or nasal speech later on.
Almost all patients have a mild developmental delay, and about 30 to 40% have short stature. External features include hypertelorism, epicanthus, a small mouth with a curved upper lip, microretrognathia, and round, wide ears.
In about 5 to 10% of cases, microdeletion 22q11.2 is inherited from one parent. Therefore, an examination of the parents of an affected child is recommended, especially for future family planning.
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