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DiGeorge Syndrome, Microdeletion 22q11.2

DGS, Mikrodeletion 22q11.2

Clinical Features

The DiGeorge syndrome (DGS) is a malformation of the third and fourth pharyngeal pouch resulting in hypoplasia or aplasia of the thymus with T-cell deficiency and immune deficiency; hypoplasia of the parathyroid with hypocalcemia and tetany; heart defects (predominantly conotruncal defects) and characteristic facial dysmorphic features (hypertelorism, short palpebral axis, epicanthus, broad short nose with everted nasal plate, short philtrum, small pointed mouth, micro-retrognathia, low-set dysmorphic ears) and cleft palate. The DGS exhibits high phenotypic variability with both a severe form displaying immune deficiency and heart defects as well as milder forms exhibiting only partial or transient immune defects. Children with DiGeorge syndrome are frequently physically and mentally retarded.

The velocardiofacial syndrome (VCFS or Shprintzen syndrome) was used to be delineated from the DiGeorge syndrome; however, it has rather to be considered as a symptom complex within the DiGeorge syndrome.

Genetic Information

The DiGeorge syndrome, as well as the velocardiofacial syndrome (VCFS or Shprintzen syndrome) are caused by a microdeletion in the long arm of chromosome 22 (22q11.2). The partial monosomy for 22q11.2 can be detected in 90 to 95 % of patients. As in other microdeletion syndromes the mutations usually arise de novo. However, there are also families with more than one person affected suggesting an autosomal dominant inheritance pattern with variable expression. 15 to 20 % of the affected individuals have inherited the deletion from one healthy parent. The healthy deletion carriers frequently exhibit subtle facial dysmorphisms and represent the mild forms of a wide variation of phenotypes associated with monosomy for 22q11.2. Rarely seen is a microdeletion on the short arm of chromosome 10 (10p14; DGS2).

Prevalence

Partial monosomy 22q11.2: 1 : 5 000
DiGeorge syndrome: 1 : 20 000

Diagnostic