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. DiGeorge Syndrome is considered a “not so rare disease.” It is characterized by hypocalcemia due to hypoparathyroidism, heart defects, and thymic hypoplasia or aplasia.
Although the literature makes a long list of potential synonyms (see below) based on the fact that these medical conditions present the same chromosomic deletion as DiGeorge Syndrome. One must be careful not to consider them all synonyms (see N.B. below). The list of names consists of: Pharyngeal Pouch Syndrome; Thymic Aplasia; Velocardiofacial Syndrome; VCFS; Shprintzen Syndrome; Conotruncal Anomaly Face Syndrome; CTAF Syndrome; Takao Syndrome; Sedlackova Syndrome; Cayler Cardiofacial Syndrome; CATCH22 Syndrome; 22q11.2 Deletion Syndrome.
N.B.: A great variety of names are used to describe this medical condition, such as Velocardiofacial, Shprintzen, DiGeorge, CATCH 22, Takao; Sedlackova, Cayler and conotruncal facial anomaly. Although, all disorders have the same chromosome 22q11.2 deletion, their phenotypes present several clinical differences and must be considered different clinical entities (see “Other conditions to be considered”).
The DiGeorge Syndrome was first described in 1968 by Angelo DiGeorge, an Italian American pediatric endocrinologist. It was reported as a primary immunodeficiency resulting from the abnormal development of the third and fourth pharyngeal pouches during embryonic life.
The exact incidence remains unknown but deletion of 22q11 has been established around 1:3000 to 5000 live births worldwide. Despite its high frequency, little is known about its natural history and progression. Both sexes are equally affected. 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). More recent observations obtained from testing for 22q11.2 in over 9500 pregnancies revealed a prevalence rate of 1/992. The incidence for this medical condition may need to be reevaluated at one in 2000 live births. Of course, this does not suggest that it is solely for DiGeorge Syndrome but rather all phenotypic diseases affected by the same chromosomal deletion.
It is an autosomal dominant disease. DiGeorge Syndrome is typically due to the deletion of 30 to 40 genes in the middle of chromosome 22 at a location known as 22q11.2. It is 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 ...