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DiGeorge Syndrome
Tuesday, 12 July 2005
Monday, 04 December 2006
Velo-Cardio-Facial Syndrome, 22q11.2 Deletion Syndrome, Conotruncal Anomaly Face Syndrome

What

DiGeorge Syndrome is a genetic disorder with symptoms that generally include increased susceptibility to infection due to immune deficiency, defects of the heart, and low blood calcium levels. DiGeorge Syndrome affects each person differently, so there is a great variability of presentation from person to person. There are a variety of characteristic facial features associated with this disorder. Often the thymus and parathyroid glands are underdeveloped (potentially dysfunctional). DiGeorge syndrome is actually one of the most common genetic disorders and is known by a variety of names, including Velo-Cardio-Facial Syndrome (VCFS), 22q11.2 Deletion Syndrome, or Conotruncal Anomaly Face Syndrome (CTAFS). Genetic tests have shown that the same genetic defect is involved.

Who

DiGeorge Syndrome affects males and females with equal frequency. It occurs in approximately 1 in 4000 live births and is often diagnosed shortly after birth due to the obvious facial features and the heart problems associated with this disorder. The infant will likely be diagnosed with DiGeorge Syndrome if the triad of immune deficiency, heart defect, and low blood calcium levels are present. If only one or two of those symptoms are present, then the infant may be diagnosed with Velo-Cardial-Facial Syndrome (VCFS) or Conotruncal Anomaly Face Syndrome (CTAFS). CTAFS, while having the same genetic defect as DiGeorge Syndrome and Velo-Cardio-Facial Syndrome (VCFS), is characterized by heart defects and facial features that are similar but not exactly the same as DiGeorge Syndrome and VCFS. CTAFS is predominantly described among the Japanese. Generally, children with VCFS or CTAFS do not have severe immune deficiency like children with DiGeorge Syndrome.

Signs and Symptoms

As mentioned previously, children with DiGeorge Syndrome may present with a spectrum of physical findings. Cardiac defects are among the major physical manifestations of DiGeorge Syndrome and are often found early in life. These defects may include obstruction of the blood vessels leaving the heart (the aorta and pulmonary arteries), ventricular septal defects (a hole in the wall between the lower chambers of the heart), or thickening of the wall of one of the lower chambers of the heart. Common facial features include a small chin, low-set and prominent ears, a sloping forehead, a bulbous tip of the nose, cleft palate, and downward slanting eyes. Normally, the parathyroid glands help maintain normal calcium levels in the body; therefore low calcium levels are common in DiGeorge patients due to underdeveloped parathyroid glands. The thymus gland, which normally helps the immune system by providing T cells to fight infection, may also be underdeveloped or missing, thus increasing the child’s risk of suffering from serious fungal or viral infections. Often the child will have feeding difficulties, skeletal problems, kidney problems, and developmental delay. Speech delay is especially common. There is an increased incidence of autoimmune diseases like Graves disease (hyperthyroidism) and juvenile rheumatoid arthritis associated with DiGeorge Syndrome.

Possible Causes

DiGeorge Syndrome is a genetic problem most commonly caused by a microdeletion (the absence of a segment) from the long arm of chromosome 22. Humans have 23 pairs of chromosomes (46 total) in each cell (the building blocks of the human body). These chromosomes are numbered 1 to 22 with the last pair being sex chromosomes that determine gender. Each chromosome pair is made up of one chromosome from the mother’s egg and one from the father’s sperm. In DiGeorge Syndrome, the segment that is missing from chromosome 22 has several genes that help the fetus develop normally and the body to function correctly. Without these genes, a variety of abnormalities occur when the fetus is developing, including effects on the thymus and parathyroid glands, causing the symptoms described above. About 10% of DiGeorge patients actually have microdeletions in other chromosomes, including chromosomes 10, 17, or 18. The majority of deletions causing DiGeorge Syndrome are sporadic, but the deletion in a very small minority of people is due to one parent who already has the deletion and passes it on to the child (autosomal dominant inheritance). The parent with the deletion may or may not have symptoms.

Diagnosis

While the observance of any one or more of the major signs and symptoms associated with DiGeorge Syndrome should raise suspicion, the criteria for a definitive diagnosis includes reduced numbers of specific T cells (immune deficiency) and at least two of the following three features: a specific heart defect, low calcium levels, or the deletion involving the long arm of chromosome 22. Low calcium levels are a characteristic feature, but this may occur only periodically and may resolve around age one. Blood tests are done to analyze the function of the immune and endocrine systems. Imaging studies may reveal cardiac defects and other developmental anomalies, such as the absence or underdevelopment of the thymus. A standard karyotype, which produces a picture of all the chromosomes, does not usually detect the disease because the defect is a microdeletion. Therefore, a special genetic test called a FISH study can be done to detect the deletion.

Treatment

Along with the general pediatrician, specialist physicians like endocrinologists, cardiologists, and immunologists will be consulted concerning the child’s care. Management of DiGeorge Syndrome includes correction of the low calcium levels with the administration of calcium supplements and vitamin D. Surgery is often performed to correct the cardiac problems. Antibiotics may be given to boost the deficient immune system and help fight infections. Transplantation of the thymus and/or bone marrow may also be done to treat the immunodeficiency. Extreme caution should be taken with live viral vaccines like measles and chicken pox, due to the body not being able to respond correctly and develop an immune response against the small amount of the virus in the vaccine. Children with DiGeorge Syndrome should undergo a variety of evaluations for the heart, kidneys, other affected organ systems as well as assessments of hearing and development.

Prognosis

The prognosis for children with DiGeorge Syndrome varies significantly according to the degree of involvement of the cardiac and immune systems. Heart problems are the major cause of serious complication in this disorder, with most deaths occurring early in childhood. Opportunistic infections (infections that occur due to the severe immune deficiency) are the second most fatal complication. However, the manifestation of DiGeorge Syndrome can be different in each individual, and many children who are born with some thymic tissue may eventually develop a mature immune system in time.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

E-Medicine
This site is strictly informative and is comprehensive and detailed. It is appropriate for both parents and physicians.

The VFC Syndrome Educational Foundation, Inc.
This site offers information and support, and includes information about annual conferences and an optional email newsletter.

22q and You Newsletter
This site is an online version of the 22q and You Newsletter for patients and their families published quarterly by the Children’s Hospital of Philadelphia. It includes links to the editions of 1996 and 1999.

Family Village
This site lists multiple links for information and chat groups.

Google Search for DiGeorge Syndrome

References and Sources

UpToDate: Syndromic Immunodeficiencies www.utdol.com/application/topic.asp?file=immunnon/5974&type=P&selectedTitle=1~14 Sullivan, K.E. The clinical, immunological, and molecular spectrum of chromosome 22q11.2 deletion syndrome and DiGeorge syndrome. Current Opinion in Allergy and Clinical Immunology 4: 505-512, 2004. gateway.ut.ovid.com.ezp.slu.edu/gw1/ovidweb.cgi?T=JS&PAGE=fulltext&D=ovft&AN=00130832-200412000-00006&NEWS=N&CSC=Y&CHANNEL=PubMed Patrick, C.C. Clinical Management of Infections in Immunocompromised Infants and Children. Pennsylvania: Lippincott Williams & Wilkins, 2001. Ochs, H.D., Edvard Smith, C. I., Puck, J. M. Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. New York: Oxford University Press Inc., 1999. www.geneclinics.org/profiles/22q11deletion/ www.emedicine.com/med/topic567.htm www.familyvillage.wisc.edu/lib_dig.htm www.cbil.upenn.edu/VCFS/22qandyou/index.html vcfsef.org