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Genetic defect leading to a wide range of phenotypic presentations, mainly developmental defects in the outflow tract of the heart, hypoparathyroidism with hypocalcemia, and thymic hypoplasia/aplasia with immune defects.

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Pharyngeal Pouch Syndrome; Thymic Aplasia.

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Both sexes are equally affected. Deletion of 22q11 is estimated to occur in approximately 1:3000-5000 live births. It is more frequent in children with congenital cardiac defects (up to 25% of these patients) and with cleft lip/palate (up to 8% of children with a cleft reportedly have this deletion).

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Autosomal dominant; possibly a contiguous gene syndrome. Only 25% of 22q deletions are inherited, and most cases of DiGeorge Syndrome are isolated. In 90% of cases, DiGeorge syndrome is related to a monoallelic microdeletion of 22q11.2 (so-called DiGeorge syndrome critical region [DGCR]). This is the most frequent human gene deletion and, after trisomy 21, the second most common genetic cause of congenital heart defect. A few patients with DiGeorge syndrome have defects in other chromosomes (10p13, 18q21.33, 4q21.3-q25). In noninherited cases, maternal alcohol abuse, isotretinoin exposure, and uncontrolled diabetes mellitus during pregnancy have been considered risk factors.

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The chromosomal deletion leads to an abnormal migration of the cephalic and cardiac neural crest cells in the fourth week of embryogenesis, causing a developmental field defect that involves the third and fourth pharyngeal pouches. The developmental field defect theory is used to explain the narrow range of clinical expression of the different causes of DiGeorge syndrome. The principal basic defect leads to thymic aplasia or hypoplasia, heart defects, and hypoparathyroidism.

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The finding of thymic aplasia or hypoplasia radiologically, intraoperatively (for correction of congenital cardiac defect), or on autopsy, combined with the clinical features, confirms the diagnosis. However, immune function correlates poorly with thymus size. Measurement of the CD4+ subset of white cells, standard karyotype to exclude major rearrangements, and fluorescent in situ hybridization using probes from within the deletion segment (close to translocation breakpoint site preferably) finalize the diagnosis. Although CD3+, CD4+, and CD8+ T-lymphocyte counts are abnormally low, the number of natural killer cells and B lymphocytes is normal.

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Severe cases present with neonatal hypocalcemia (caused by hypoplasia of the parathyroid glands), which may result in tetany or seizures (presenting symptom in approximately 10% of patients) and susceptibility to infection as a consequence of a deficit of T cells (hypoplasia or aplasia of the thymus gland). Several cardiac malformations (tetralogy of Fallot, type B interrupted aortic arch [typical], persistent truncus arteriosus, double-outlet right ventricle, transposition of the great arteries, ventriculoseptal defect, pulmonary stenosis, right infundibular stenosis, right aortic arch, aberrant right subclavian artery) are common and the main cause of death during the first weeks of life. Recurrent infections start in the first 6 months of life. Cases with delayed diagnosis (late childhood) present usually with a milder spectrum of cardiac defects (mainly membranous ventricular septal defect), absence of, hypocalcemia and nearly normal immune function. Facial abnormalities ...

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