22q11.2 deletion syndrome

Joseph R Siebert PhD (Dr. Siebert of the University of Washington has no relevant financial relationships to disclose.)
Harvey B Sarnat MD FRCPC MS, editor. (Dr. Sarnat of the University of Calgary has no relevant financial relationships to disclose.)
Originally released January 18, 1999; last updated July 24, 2016; expires July 24, 2019

This article includes discussion of 22q11.2 deletion syndrome, conotruncal-anomaly-face syndrome, conotruncal anomaly face syndrome, Shprintzen syndrome, DiGeorge syndrome, Sedlackova syndrome, Shprintzen syndrome, and velocardiofacial syndrome. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

DiGeorge and velocardiofacial syndrome (22q11.2 deletion syndrome) is the most common microdeletion disorder in humans and, hence, one of the most common multiple malformation syndromes, with an estimated prevalence of 1 in 2000 to 1 in 4000. It is characterized by craniofacial anomalies, conotruncal heart disease, thymic aplasia and hypoplasia, hypocalcemia, and psychiatric illness. In this article, the author reviews the history, clinical features, and genetic basis of this common disorder.

Key points

 

• DiGeorge and velocardiofacial syndrome (22q11.2 deletion syndrome) is the most common microdeletion disorder in humans and, hence, one of the most common multiple malformation syndromes, with an estimated prevalence of 1 in 2000 to 4000.

 

• It is characterized by craniofacial anomalies, conotruncal heart disease, thymic aplasia or hypoplasia, hypocalcemia, and psychiatric illness.

Historical note and terminology

In 1968, DiGeorge described congenital absence of the thymus and parathyroid glands in 4 infants with recurrent infections and hypocalcemia (DiGeorge 1968). In 1979, Conley and co-workers broadened the phenotype of DiGeorge syndrome to include conotruncal (outflow tract) defects of the heart as well as characteristic facial features including a bulbous nose, dysplastic ears, and micrognathia (Conley et al 1979).

Strong reported a familial syndrome of right-sided aortic arch, facial dysmorphism, and cognitive and psychiatric dysfunction in 1968 (Strong 1968). Ten years later, Shprintzen and colleagues profiled a series of 12 patients with a combination of cleft palate, congenital heart disease, unique facial features (long face with malar flattening, small palpebral fissures, long nose with bulbous tip, dysplastic ears, and micrognathia), learning disabilities, and short stature and called the condition velocardiofacial syndrome (Shprintzen et al 1978). Conotruncal anomaly face syndrome, originally described in the Japanese literature (Kinouchi et al 1976), comprises clinical features of both DiGeorge syndrome and velocardiofacial syndrome.

With the advent of molecular genetics, DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome were found to have a similar 22q11.2 microdeletion as the basis for their overlapping clinical features (Scambler et al 1991; Scambler et al 1992; Burn et al 1993). This 22q11.2 deletion syndrome is now recognized as one of the most common multiple malformation syndromes. The acronym “CATCH22” (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, and hypocalcemia) was conceived; however, because this term may be construed as insensitive, it is not universally accepted (Wilson et al 1993; Wulfsberg et al 1996). The compound term “DiGeorge and velocardiofacial syndrome” calls attention to the phenotypic spectrum using historically familiar names (Leana-Cox et al 1996) and is especially applicable when phenotypic features manifest in the absence of the chromosomal deletion (McDonald-McGinn and Sullivan 2011).

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