What is digeorge syndrome? |

Causes and Symptoms

Chromosomes possess two parts. The upper arms are called “p” arms and the lower arms are called “q” arms. Patients with DiGeorge syndrome are missing a tiny interstitial piece inside the long arm of chromosome 22. The specific region inside the long “q” arm is labeled 11.2. Thus, DiGeorge syndrome is also referred to as 22q11.2 deletion syndrome or chromosome 22 interstitial deletion.

Most microdeletions such as these cannot be observed under a microscope because they are so tiny. A molecular cytogenetic test known as fluorescence in situ hybridization (FISH) is used. It includes the use of deoxyribonucleic acid (DNA) probes made from the DiGeorge chromosomal region (DGCR). A green fluorescent probe is used to identify chromosome 22, while a red probe is specific to the DGCR. In DiGeorge syndrome, one of the chromosomes will lack the red fluorescence.

About 93 percent of patients have a spontaneous (de novo) deletion of a 22q11.2, and 7 percent have inherited the deletion from a parent. The very high de novo rate indicates that the deletion recurs with a high frequency as a result of new mutations occurring in the population. This deletion is inherited in an autosomal dominant manner. The offspring of persons with the deletion have a 50 percent chance of inheriting it. This interstitial deletion encompasses about three million base pairs of DNA in the majority of patients. About 90 percent of patients have the same three million base pair deletion, while 10 percent have a 1.5 million base pair deletion. Therefore, the deletion is large enough to contain nearly one hundred genes.

DiGeorge syndrome is initiated by defective embryonic development of the third and fourth pharyngeal pouches during the fifth week of development. These pouches normally become the thymus and the parathyroid glands. In the absence of a thymus, T lymphocyte maturation is stopped at the precell stage. DiGeorge syndrome is one of the most severe forms of deficient T cell immunity. Children with DiGeorge syndrome develop recurrent viral infections and have abnormal cellular immunity, as characterized by severely reduced or absent T lymphocytes. They also have defects in T cell–dependent antibody production. A spectrum of abnormal phenotypes may develop. These defects arise from the absence of key genes that are not available for normal development when a 22q microdeletion is present. Infants with this disease may suffer from congenital heart disease of various types, palatal abnormalities (such as cleft palate), and learning difficulties.

Treatment and Therapy

Children with a 22q11.2 deletion may exhibit a wide spectrum of problems and much variation in the severity of symptoms. A patient with DiGeorge syndrome may have several organs or systems affected. DiGeorge syndrome may result in problems in different body systems, such as the heart or palate, and in cognition, such as learning style. Consequently, a multidisciplinary approach is needed for management of a specific patient.

In the neonatal period, the following clinical and laboratory studies are pursued. The serum is tested for calcium; a low concentration points to the need for supplementation. The lymphocytes are measured; a low absolute count means referral to an immunologist, who will look at T and B cell subsets. A renal ultrasound examination should be performed because of the high incidence of structural renal abnormalities. A chest X-ray is needed to identify thoracic vertebral anomalies. A cardiac evaluation is recommended for all patients with DiGeorge syndrome because possible malformations may include tetralogy of Fallot, ventricular septal defect, interrupted aortic arch, or truncus arteriosus. Pediatric cardiologists are necessary for the treatment and therapy that is needed. An endocrinologist could follow up possible growth hormone deficiencies. Since there is a high incidence of speech and language delay, speech therapy and early educational intervention are highly recommended. All children with the 22q deletion should be seen by a cleft palate team to diagnose problems and schedule surgery if necessary.

Other medical needs of children are met through evaluation by a feeding specialist, especially in the newborn period; a neurologist, for possible seizure disorders or problems with balance; a urologist, for possible kidney problems; and an otorhinolaryngologist (ear, nose, and throat doctor) for problems in this region.

Perspective and Prospects

DiGeorge syndrome is relatively frequent, occurring with a frequency of one in four thousand live births. Therefore, this disorder is a significant health concern in the general population. Since the phenotype associated with it is broad and variable, many types of clinical and laboratory specialists are needed. The medical geneticist is the most likely person to have an overview of the diagnosis. A yearly genetics evaluation is beneficial in answering questions. Parents should be tested to determine their chromosomal status. Genetic counseling could provide individuals and families with information on the nature, inheritance, and implications of DiGeorge syndrome to help them make informed medical and personal decisions. Current and future research using model organisms may help to explain the problems of phenotypic variability in DiGeorge syndrome.

Bibliography:

American Academy of Allergy Asthma & Immunology. "DiGeorge Syndrome (DGS)." AAAAI, 2013.

Emanuel, Beverly S., et al. “The 22q11.2 Deletion Syndrome.” Advances in Pediatrics 48 (2001): 33–73.

King, Richard A., Jerome I. Rotter, and Arno G. Motulsky, eds. The Genetic Basis of Common Diseases. 2d ed. New York: Oxford UP, 2002.

Maroni, Gustavo. Molecular and Genetic Analysis of Human Traits. Malden, Mass.: Blackwell, 2001.

McCoy, Krisha. "DiGeorge Syndrome." Health Library, Dec. 11, 2012.

Rimoin, David L., et al., eds. Emery and Rimoin’s Principles and Practice of Medical Genetics. 5th ed. Philadelphia: Churchill, 2007.

Stocker, J. Thomas, and Louis P. Dehner, eds. Pediatric Pathology. 2d ed. Philadelphia: Lippincott, 2001.

Turnpenny, Peter, and Sian Ellard. Emery’s Elements of Medical Genetics. 13th ed. New York: Churchill, 2007.