$Unique_ID{BRK03665} $Pretitle{} $Title{DiGeorge Syndrome} $Subject{DiGeorge Syndrome DGS Third and Fourth Pharyngeal Pouch Syndrome Thymic Hypoplasia Thymus, Congenital, Aplasia Thymic Aplasia Congenital Absence of the Thymus and Parathyroids Thymic Agenesis Pharyngeal Pouch Syndrome Harrington Syndrome Hypoparathyroidism Shprintzen Syndrome Agammaglobulinemias, Primary Nezelof Syndrome Severe Combined Immunodeficiency Wiskott-Aldrich Syndrome} $Volume{} $Log{} Copyright (C) 1986, 1988, 1992, 1993 National Organization for Rare Disorders, Inc. 74: DiGeorge Syndrome ** IMPORTANT ** It is possible that the main title of the article (DiGeorge Syndrome) is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms DGS Third and Fourth Pharyngeal Pouch Syndrome Thymic Hypoplasia Thymus, Congenital, Aplasia Thymic Aplasia Congenital Absence of the Thymus and Parathyroids Thymic Agenesis Pharyngeal Pouch Syndrome Harrington Syndrome Information on the following diseases can be found in the Related Disorders section of this report: Hypoparathyroidism Shprintzen Syndrome Agammaglobulinemias, Primary Nezelof Syndrome Severe Combined Immunodeficiency Wiskott-Aldrich Syndrome General Discussion ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. DiGeorge Syndrome is a very rare group of congenital abnormalities that are the result of defects during early fetal developmental. These defects occur in areas known as the 3rd and 4th pharyngeal pouches which later develop into the thymus and parathyroid glands. Developmental abnormalities may also occur in the 4th branchial arch. Normally the thymus gland is located below the thyroid gland in the neck and front of the chest and is the primary gland of the lymphatic system which is necessary for the normal functioning of the immune system. The parathyroid glands, located on the sides of the thyroid gland, are responsible for the maintenance of normal levels of calcium in the blood. The thymus and parathyroid glands are missing or underdeveloped in children with DiGeorge Syndrome. The symptoms of this disorder vary greatly depending on the extent of the missing thymus and parathyroid tissue. The primary problem caused by DiGeorge Syndrome is repeated infections due to a diminished immune system. Symptoms Abnormally low levels of hormone secretions from the parathyroid glands (hypoparathyroidism) are often the first symptom of DiGeorge Syndrome. This may result in seizures during the first few days of life. (For more information, choose "Hypoparathyroidism" as your search term in the Rare Disease Database.) Children with DiGeorge Syndrome who have a severely underdeveloped thymus gland, develop frequent infections from viruses, fungi, and certain bacteria including Pneumocystis carinii. Common symptoms of this disorder include chronic nasal infections, diarrhea, thrush (oral candidiasis), and pneumonia. The majority of children with DiGeorge Syndrome have some thymic tissue. When most of the thymus is present the deficiencies of the immune system may be minimal or absent. Children with DiGeorge Syndrome also have abnormal facial features such as wide set eyes (hypertelorism), a downward slant to the eyes, notched and/or low-set ears, and/or an abnormally small mouth (micrognathia). Structural abnormalities of the heart may also occur in children with DiGeorge Syndrome including malformations of a fetal artery that later develops into the aortic and pulmonary arteries (truncus arteriosus), interrupted aortic arch, and tetralogy of Fallot. (For more information on this disorder, choose "Tetralogy of Fallot" as your search term in the Rare Disease Database.) Some children affected with DiGeorge Syndrome also have abnormalities of the digestive system (gastrointestinal tract) and moderate mental retardation. Causes DiGeorge Syndrome is a very rare disorder that generally occurs spontaneously (for no apparent reason). In a few cases this disorder may be inherited as an autosomal dominant genetic trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In dominant disorders a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is fifty percent for each pregnancy regardless of the sex of the resulting child. In 5 to 10 percent of cases of DiGeorge Syndrome there is missing chromosomal material (deletion) on the long arm of chromosome 22. This disorder occurs in some infants of diabetic mothers or occasionally in infants who are born to mothers who regularly consumed alcohol during their pregnancy (Fetal Alcohol Syndrome). DiGeorge Syndrome also occurs along with a variety of other syndromes such as CHARGE Association. (For more information on these disorders, choose "Fetal Alcohol" and "CHARGE" as your search term in the Rare Disease Database.) DiGeorge Syndrome may also occur in infants with a defect in the metabolism of retinoic acid that occurred very early in fetal development (Retinoic Acid Embryopathy). Faulty development of the fetal tissue that gives rise to tissue of the brain and nerves (cephalic neural crest) is believed to be the common defect (pathogenetic mechanism) involved in all of these conditions. Affected Population DiGeorge Syndrome is a very rare disorder that affects males and females in equal numbers. Related Disorders Symptoms of the following disorders can be similar to those of DiGeorge Syndrome. Comparisons may be useful for a differential diagnosis: Hypoparathyroidism is a disorder that causes lower than normal levels of calcium in the blood due to insufficient levels of parathyroid hormones. This condition can be inherited or it can be associated with other disorders such as DiGeorge Syndrome. Symptoms of this disorder may include general weakness, muscle cramps, and tingling or burning of the hands and feet. Other symptoms may include excessive nervousness, loss of memory, headaches, and uncontrollable cramping muscle movements of the wrists and feet. (For more information on this disorder, choose "Hypoparathyroidism" as your search term in the Rare Disease Database.) Shprintzen Syndrome is a rare inherited disorder. The major characteristics include a cleft palate, heart abnormalities, learning disabilities, and distinct physical features including an abnormally small head, recessed jaw, tubular nose, flat cheeks, long upper jaw, and a long vertical groove in the middle of the upper lip. Children with this disorder may have no thymus gland, or it may be underdeveloped. This causes a deficiency of the immune system and the insufficient production of antibodies. (For more information on this disorder, choose "Shprintzen" as your search term in the Rare Disease Database.) Primary Agammaglobulinemias are a group of inherited antibody deficiency disorders characterized by abnormalities in the function of cells that are associated with the body's immunity (B and T lymphocytes). This causes a susceptibility to recurring bacterial infections. The bacteria, Giardia lamblia, is typically the cause of chronic inflammation of the intestines and diarrhea in patients with all forms of Primary Agammaglobulinemias. (For more information on this disorder, choose "Primary Agammaglobulinemias" as your search term in the Rare Disease Database.) Nezelof Syndrome is a rare immune deficiency disorder characterized by the impairment of cellular immunity against infections. Symptoms of this disorder may include frequent and severe infections from birth including oral candidiasis, diarrhea, skin infections, septicemia, urinary tract infections, measles, pulmonary infections, and vaccinia. A child with this disorder may be mentally retarded and have progressive loss of muscle tissue. (For more information on this disorder, choose "Nezelof" as your search term in the Rare Disease Database.) Severe Combined Immunodeficiency (SCID) is a group of rare, congenital disorders characterized by little or no immune response. A person with this disorder is susceptible to recurring infections with bacteria, viruses, fungi, and other infectious agents. If untreated, this disorder may result in frequent, severe infections, growth retardation, and can be life- threatening. Other symptoms of this disorder may include weight loss, weakness, infections of the middle ear, and skin infections. (For more information on this disorder, choose "Severe Combined Immunodeficiency" as your search term in the Rare Disease Database.) Wiskott-Aldrich Syndrome is a rare inherited disorder of childhood characterized by immunodeficiency that results in recurrent skin rashes (eczema) and abnormally low levels of circulating platelets in the blood (thrombocytopenia). Symptoms of this disorder may include excessive bleeding from circumcision or minor trauma. Bleeding, which can be severe, may also occur in the intestines or stomach. Red skin rashes (petechiae) are common in children with this disorder. (For more information on this disorder, choose "Wiskott-Aldrich" as your search term in the Rare Disease Database.) Therapies: Standard To control infantile seizures associated with DiGeorge Syndrome, blood calcium levels must be increased. Orally administered calcium and vitamin D may be sufficient to control seizure activity. In some cases of DiGeorge Syndrome the immune system tends to improve after the first few years of life unless the thymus gland is missing or severely underdeveloped. When infections occur in children with DiGeorge Syndrome, they must be treated vigorously with antifungal medications, antibiotic drugs, and/or supportive measures. Trimethoprim-sulfamethoxazole and the orphan drug, pentamidine isethionate, are used to treat infections by Pseudomonas carinii. Cytomegalovirus and generalized herpes simplex infections are usually treated with antiviral agents. Severe Candida and related fungi infections may respond to treatment with the drug amphotericin B. (For more information on these disorders, choose "Cytomegalovirus" and "Herpes Simplex" as your search term in the Rare Disease Database.) Patients with severe immunodeficiencies associated with DiGeorge Syndrome must be protected as much as possible from infections. They should not be immunized with live viral vaccines. The administration of corticosteroid drugs or any drug that suppresses the immune system (immunosuppressant) must be avoided. If blood transfusions are necessary due to accidents or surgery, the blood must be exposed to high levels of radiation (irradiated) or "washed" to remove all living white blood cells (lymphocytes) that might cause graft-versus-host disease (GVHD). (For more information on this disorder, choose "Graft Versus Host" as your search term in the Rare Disease Database.) Anatomical abnormalities associated with DiGeorge Syndrome may be corrected with surgery as necessary. Cardiac surgery is often necessary when heart defects are life threatening. Genetic counseling will be of benefit for patients and their families. Other treatment is symptomatic and supportive. Therapies: Investigational Transplantation of fetal thymus tissue, bone marrow transplantation, and administration of various thymic hormones have been used experimentally to treat severe cases of DiGeorge Syndrome. More research is needed to determine the safety and long-term effectiveness of these procedures for the treatment of DiGeorge Syndrome. This disease entry is based upon medical information available through June 1993. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on DiGeorge Syndrome, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Immune Deficiency Foundation 3565 Ellicott Mill Drive, Unit B2 Ellicott City, MD 21043 (800) 296-4433 (410) 461-3127 Frank Greenberg, M.D. Baylor College of Medicine Department of Molecular Genetics 6621 Fannin Road Houston, TX 77030 (713) 798-4951 Craig B. Langman, M.D. and Samuel S. Gidding, M.D. Children's Memorial Hospital 2300 Children's Plaza Chicago, IL 60614 (312) 880-4000 National Institute of Child Health and Human Development (NICHD) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5133 For Genetic Information and Genetic Counseling Referrals: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References MENDELIAN INHERITANCE IN MAN, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 1078-1080. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. P. 1450. THE MERCK MANUAL, 16th Ed.: Robert Berkow Ed.; Merck Research Laboratories, 1992. Pp. 305, 307, 314. BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 961-62. NELSON TEXTBOOK OF PEDIATRICS, 14th Ed.; Richard E. Behrman et al; W.B. Saunders Co., 1992. Pp. 553-554. IMMUNODEFICIENCY. R.H. Buckley; J Allergy Clin Immunol (Dec 1983;72(6)) Pp. 627-641. A GENETIC ETIOLOGY FOR DIGEORGE SYNDROME: CONSISTENT DELETIONS AND MICRODELETIONS OF 22q11. D.A. Driscoll; Am J Hum Genet (May 1992; 50(5)). Pp. 924-33. THE DIGEORGE ANOMALY. R. Hong; Immunodefic Rev (1991; 3(1)). Pp. 1-14.