Patients with heart defects and immune deficiency, especially in combination with additional symptoms (as described above); close relatives of patients with microdeletion 22q11.2
DiGeorge Syndrome, VCFS, Microdeletion 22q11.2
DGS, Microdeletion 22q11.2
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.
Velocardiofacial Syndrome (VCFS or Shprintzen Syndrome) used to be differentiated from DiGeorge Syndrome; however, VCFS should be considered a symptom complex within DiGeorge syndrome.
DiGeorge Syndrome, as well as Velocardiofacial Syndrome (VCFS or Shprintzen Syndrome), is caused by a microdeletion in the long arm of chromosome 22 (22q11.2). Partial monosomy for 22q11.2 can be detected in 90 to 95 % of patients. As in other microdeletion syndromes, the mutations usually occur de novo. However, there are also families with more than one person affected, suggesting an autosomal dominant inheritance pattern with varying expression. 15 to 20 % of affected individuals have inherited the deletion from one healthy parent. Healthy deletion carriers frequently exhibit subtle facial dysmorphisms and show 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).
Partial monosomy 22q11.2: 1 : 5 000
DiGeorge syndrome: 1 : 20 000
2 - 4 ml of EDTA blood
approx. 2 - 3 week