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Key Points

  • Most common microdeletion syndrome reported in humans.

  • 22q11.2 deletion is associated with DiGeorge syndrome, velocardiofacial syndrome (VCFS), Opitz G/BBB syndrome, and Cayler cardiofacial syndrome (also known as asymmetric crying facies syndrome).

  • Incidence is 1 in 6000 livebirths.

  • Deletion is associated with specific types of congenital heart disease, including tetralogy of Fallot, truncus arteriosus, absent pulmonary valve, and aortic arch abnormalities.

  • Other associated sonographic findings include growth restriction, nuchal translucency, thymic hypoplasia, and renal anomalies. The presence of polyhydramnios is predictive of postnatal feeding difficulties.

  • Once the deletion is found, both parents should also undergo cytogenetic analysis.

  • Delivery should occur in a tertiary center.

  • Affected neonates are at risk for seizure disorders due to hypocalcemia.

  • Postnatal problems include speech defects due to palatal abnormalities, repeated infections due to immunodeficiency, developmental delay, feeding issues, and serious behavioral and psychiatric problems.

  • 22q11.2 deletion is inherited as an autosomal dominant trait.

  • The major causative gene is TBX1, a member of the T-box protein family of genes.


22q11.2 deletion is the most common microdeletion syndrome that has been reported in humans. It is also the most common syndrome associated with cleft palate and the most common syndrome associated with conotruncal anomalies (Shprintzen et al., 2005). Microdeletion syndromes are genetic disorders caused by the loss of a small chromosome segment contains multiple genes, but that is too small to be detected via the 400-band standard metaphase karyotype. 22q11.2 deletion is commonly thought of as being equivalent with DiGeorge syndrome.

DiGeorge syndrome was first described in 1965 by Dr. Angelo DiGeorge as a developmental field defect that affected structures derived from the 3rd and 4th pharyngeal arches. It is now known that 22q11.2 deletion is actually associated with a variety of different syndromes that appear to be phenotypic variants of the same disorder. 22q11.2 deletion encompasses DiGeorge syndrome, velocardiofacial syndrome (VCFS), conotruncal anomaly face syndrome, Opitz G/BBB syndrome, and Cayler cardiofacial syndrome, which is also known as asymmetric crying facies syndrome. Ninety percent of patients with DiGeorge syndrome who have an apparently normal karyotype actually have a microdeletion of chromosome 22q11.2 (Figure 139-1). This was not appreciated until the development of molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH).

Figure 139-1

Chromosome analysis demonstrating the presence of the 22q11.2 deletion by FISH. On the left is a normal control. On the right is an affected individual. The green probes, as indicated by green arrows, map to the end of chromosome 22. The red probes, as indicated by the red arrows, map to the 22q11.2 region. The image on the right shows the presence of only one red probe, which indicates a deletion of this region on one copy of 22. This finding is diagnostic of DiGeorge syndrome. (Photograph courtesy of Dr. Janet Cowan)

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