22q11.2 deletion syndrome

22q11.2 deletion syndrome, also known as the DiGeorge syndrome or velocardiofacial syndrome, is a syndrome where a small portion of the chromosome 22 is lost and results in a variable but a recognisable pattern of physical and behavioural features.

Epidemiology

The estimated incidence is at ~ 1 in 4000-6000 live pregnancies ^4,10.

Clinical presentation

CATCH 22 is the mnemonic to remember the chromosome and all the abnormalities.

• cleft lip +/- palate
• congenital heart disease (particularly conotruncal anomalies): often a major part of this syndrome
  • tetralogy of Fallot
  • interrupted aortic arch
  • truncus arteriosus
• characteristic facies
  • elongated face
  • short philtrum
  • facial asymmetry
  • prominent nose
• hypernasal speech
• learning disabilities
• decreased immunity
• malformation of third and fourth pharyngeal pouches that result in the defective development of the parathyroid and thymus which can, in turn, lead to
  • hypoparathyroidism
  • hypocalcemia

Pathology

Genetics

There is a near-universal association with a deletion within chromosome 22q11.2. The majority of cases have de novo mutations. 22q11 deletions are associated with some types of conotruncal cardiac defects as well as conotruncal anomaly face syndrome ⁵.

Associations

• Mondini malformation
• choanal atresia

Radiographic features

Temporal bone malformations are common: ⁷:

• lateral semicircular canal dysplasia with small or absent bony island, forming a wide or single cavity with the vestibule (42% and 26%, respectively)
• cochlear incomplete partition type II (32%)
• middle ear ossicles
  • dense stapes superstructure (39%)
  • malleus, incus, or other stapes abnormalities (7%)
• carotid canal dehiscence (10%)

Brain and cerebrovascular malformations are common ^6,8:

• persistent cavum septi pellucidi and/or cavum vergae (19-33%)
• aberrant cortical veins (25%)
• polymicrogyria or cortical dysplasia (17%)
• white matter hyperintensities (10%)
• hypoplastic internal carotid artery (8%)
• brain volume loss, most pronounced in the cerebellum (see hypoplastic cerebellum) ⁹

Cardovascular, particularly conotruncal, defects are usually the first imaging abnormality noted in these patients ¹⁰:

• cardiac anomalies
  • tetralogy of Fallot and variants (35%)
  • interrupted aortic arch (type B) (19%)
  • truncus arteriosus (9%)
  • ventricular septal defect (16%)
  • atrial septal defect (2%)
  • transposition of the great arteries (2%)
• vascular anomalies
  • right aortic arch (35%)
  • vascular ring (5%)
  • aberrant origin of subclavian artery (16%)
  • mirror image brachiocephalic vessel branching (12%)
  • left superior vena cava (9%)

History and etymology

First described in 1968 by Angelo DiGeorge (1921-2009), an American physician.