NeurometPlus

Incidence

It is a 22q11.2 deletion syndrome, also known as DiGeorge anomaly, DiGeorge Syndrome, Velo-Cardio-Facial syndrome, Shprintzen syndrome, conotruncal anomaly face syndrome, Congenital Thymic Aplasia, Strong Syndrome, Thymic hypoplasia, and DiGeorge anomaly is a syndrome caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated q11.2 i.e., on the long arm of one of the pair of chromosomes 22. It has a prevalence estimated at 1:4000. Many cases are sporadic but a few are genetically inherited which are transmitted as autosomal recessive, autosomal dominant, and X-linked traits. Listed in OMIM in the autosomal dominant catalog.

Clinical Characteristics

DiGeorge syndrome (DGS) comprises hypocalcemia arising from parathyroid hypoplasia, thymic hypoplasia, and outflow tract defects of the heart. DiGeorge syndrome is characterized by neonatal hypocalcemia, which may present as tetany or seizures, due to hypoplasia of the parathyroid glands, and susceptibility to infection due to a deficit of T cells. It is a developmental defect of derivatives of the third and fourth pharyngeal pouches, almost always associated with agenesis or hypoplasia of the thymus and parathyroid gland, characteristic facies with downslanting palpebral fissures and ocular and nasal anomalies, hypocalcemia, cardiovascular anomalies, immunodeficiency, and other variable abnormalities. Patients who survive infancy are usually mentally retarded. The signs and symptoms of 22q11 deletion syndrome are so varied that different groupings of its features were once regarded as separate conditions. These original classifications included velo-cardio-facial syndrome, Shprintzen syndrome, DiGeorge syndrome, Sedlackova syndrome and conotruncal anomaly face syndrome. All are now understood to be presentations of a single syndrome. DiGeorge syndrome is considered by some researchers as a developmental field defect consisting of several casually distinct disorders, rather than a distinct syndromic entity. Conditions associated with the development of DiGeorge syndrome include diabetic embryopathy, fetal alcohol syndrome, and Zellweger syndrome. Major features of this syndrome have been designated by the Newcastle Upon Tyne Group CATCH 22 (Cardiac, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcemia), the number 22 indicating deletion of the long arm of chromosome 22 (22q11).

Precipitants

None

Provocation Tests

None

Diagnostic Procedures

The dysmorphic facial appearance in an individual with a major outflow tract defect of the heart or a history of recurrent infection should raise suspicion. In infancy, hypocalcemia is a characteristic feature although this may be intermittent and has a tendency to resolve during the first year. Immunological assessment relies on chest radiography to detect a thymic shadow, a notoriously unreliable investigation. The investigation of choice is now a standard karyotype to exclude major rearrangements and fluorescence in situ hybridization using probes from within the deletion segment.