DiGeorge syndrome(redirected from conotruncal anomaly-face syndrome)
DiGeorge syndrome (also called 22q11 deletion syndrome, congenital thymic hypoplasia, or third and fourth pharyngeal pouch syndrome) is a birth defect that is caused by an abnormality in chromosome 22 and affects the baby's immune system. The disorder is marked by absence or underdevelopment of the thymus and parathyroid glands. It is named for Angelo DiGeorge, the pediatrician who first described it in 1965. Some researchers prefer to call it DiGeorge anomaly, or DGA, rather than DiGeorge syndrome, on the grounds that the defects associated with the disorder represent the failure of a part of the human embryo to develop normally rather than a collection of symptoms caused by a single disease.
The prevalence of DiGeorge syndrome is debated; the estimates range from 1:4000 to 1:6395. Because the symptoms caused by the chromosomal abnormality vary somewhat from patient to patient, the syndrome probably occurs much more often than was previously thought. DiGeorge syndrome is sometimes described as one of the "CATCH 22" disorders, so named because of their characteristics—cardiac defects, abnormal facial features, thymus underdevelopment, cleft palate, and hypocalcemia—caused by a deletion of several genes in chromosome 22. The specific facial features associated with DiGeorge syndrome include low-set ears, wide-set eyes, a small jaw, and a short groove in the upper lip. The male/female ratio is 1:1. The syndrome appears to be equally common in all racial and ethnic groups.
Causes and symptoms
DiGeorge syndrome is caused either by inheritance of a defective chromosome 22 or by a new defect in chromosome 22 in the fetus. The type of defect that is involved is called deletion. A deletion occurs when the genetic material in the chromosomes does not recombine properly during the formation of sperm or egg cells. The deletion means that several genes from chromosome 22 are missing in DiGeorge syndrome patients. Although efforts have been made in the early 2000s to identify individual candidate genes for DGA, it appears that a combination of several genes in the deleted area is responsible for the disorder. Detailed genetic mapping of chromosome 22 has, however, identified a so-called DiGeorge critical region (DGCR), which has been completely sequenced.
According to a 1999 study, 6% of children with DiGeorge syndrome inherited the deletion from a parent, while 94% had a new deletion. Other conditions that are associated with DiGeorge syndrome are diabetes (a condition where the pancreas no longer produces enough insulin) in the mother and fetal alcohol syndrome (a pattern of birth defects, and learning and behavioral problems affecting individuals whose mothers consumed alcohol during pregnancy). Other chromosomal abnormalities that have been found in patients diagnosed with DGA include deletions on chromosomes 10p13, 17p13, and 18q21.
The loss of the genes in the deleted material means that the baby's third and fourth pharyngeal pouches fail to develop normally during the twelfth week of pregnancy. This developmental failure results in a completely or partially absent thymus gland and parathyroid glands. In addition, 74% of fetuses with DiGeorge syndrome have severe heart defects. The child is born with a defective immune system and an abnormally low level of calcium in the blood. Some children with DGA are also born with malformations of the genitals or urinary tract.
These defects usually become apparent within 48 hours of birth. The infant's heart defects may lead to heart failure, or there may be seizures and other evidence of a low level of calcium in the blood (hypocalcemia).
DiGeorge syndrome is also associated with an increased risk of autoimmune disorders. Cases have been reported of DGA in association with Graves' disease, immune thrombocytopenic purpura, juvenile rheumatoid arthritis, and severe eczema.
Diagnosis of DiGeorge syndrome can be made by ultrasound examination around the eighteenth week of pregnancy, when abnormalities in the development of the heart or the palate can be detected. Another technique that is used to diagnose the syndrome before birth is called fluorescence in situ hybridization, or FISH. This technique uses DNA probes from the DiGeorge region on chromosome 22. FISH can be performed on cell samples obtained by amniocentesis as early as the fourteenth week of pregnancy. It confirms about 95% of cases of DiGeorge syndrome.
If the mother has not had prenatal testing, the diagnosis of DiGeorge syndrome is sometimes suggested by the child's facial features at birth. In other cases, the doctor makes the diagnosis during heart surgery when he or she notices the absence or abnormal location of the thymus gland. The diagnosis can be confirmed by blood tests for calcium, phosphorus, and parathyroid hormone levels, and by the sheep cell test for immune function.
Hypocalcemia in DiGeorge patients is unusually difficult to treat. Infants are usually given calcium and vitamin D by mouth. Severe cases have been treated by transplantation of fetal thymus tissue or bone marrow.
Infants with life-threatening heart defects are treated surgically.
Defective immune function
Children with DiGeorge syndrome should be kept on low-phosphorus diets and kept away from crowds or other sources of infection. They should not be immunized with vaccines made from live viruses or given corticosteroids.
The prognosis is variable; many infants with DiGeorge syndrome die from overwhelming infection, seizures, or heart failure within the first year. One study of a series of 558 patients reported 8% mortality within six months of birth, with heart defects accounting for all but one of the deaths. Infections resulting from severe immune deficiency are the second most common cause of death in patients with DGA. Advances in heart surgery indicate that the prognosis is most closely linked to the severity of the heart defects and the partial presence of the thymus gland. In most children who survive, the number of T cells, a type of white blood cell, in the blood rises spontaneously as they mature. Survivors are likely to be mentally retarded, however, and to have other developmental difficulties, including seizures or other psychiatric and neurological problems in later life.
Genetic counseling is recommended for parents of children with DiGeorge syndrome because the disorder can be detected prior to birth. Although most children with DiGeorge syndrome did not inherit the chromosome deletion from their parents, they have a 50% chance of passing the deletion on to their own children.
Deletion — A genetic abnormality in which a segment of a chromosome is lost. DiGeorge syndrome is caused by a deletion on human chromosome 22.
Fetal alcohol syndrome — A cluster of birth defects that includes abnormal facial features and mental retardation, caused by the mother's consumption of alcoholic beverages during pregnancy.
Fluorescence in situ hybridization (FISH) — A technique for diagnosing DiGeorge syndrome before birth by analyzing cells obtained by amniocentesis with DNA probes. FISH is about 95% accurate.
Hypocalcemia — An abnormally low level of calcium in the blood.
Hypoplasia — A deficiency or underdevelopment of a tissue or body structure.
T cells — A type of white blood cell produced in the thymus gland. T cells are an important part of the immune system. Infants born with an underdeveloped or absent thymus do not have a normal level of T cells in their blood.
Because of the association between DiGeorge syndrome and fetal alcohol syndrome, pregnant women should avoid drinking alcoholic beverages.
Beers, Mark H., MD, and Robert Berkow, MD, editors. "Immunodeficiency Diseases." Section 12, Chapter 147 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.
McDonald-McGinn, Donna M., et al. 22q11 Deletion Syndrome. Philadelphia: The Children's Hospital of Philadelphia, 1999.
Guduri, Sridhar, MD, and Iftikhar Hussain, MD. "DiGeorge Syndrome." eMedicine May 28, 2002. http://www.emedicine.com/med/topic567.htm.
Verri, A., P. Maraschio, K. Devriendt, et al. "Chromosome 10p Deletion in a Patient with Hypoparathyroidism, Severe Mental Retardation, Autism and Basal Ganglia Calcifications." Annales de génétique 47 (July-September 2004): 281-287.
Yatsenko, S. A., A. N. Yatsenko, K. Szigeti, et al. "Interstitial Deletion of 10p and Atrial Septal Defect in DiGeorge 2 Syndrome." Clinical Genetics 66 (August 2004): 128-136.
Canadian 22q Group. 320 Cote Street Antoine, West Montreal, Quebec H3Y 2J4.
Chromosome Deletion Outreach, Inc. P.O. Box 724, Boca Raton, FL 33429-0724. (888) 236-6680.
International DiGeorge/VCF Support Network, c/o Family Voices of New York. 46 1/2 Clinton Avenue, Cortland, NY 13045. (607) 753-1250.
National Organization for Rare Disorders (NORD). 55 Kenosia Avenue, P. O. Box 1968, Danbury, CT 06813-1968. (203) 744-0100. Fax: (203) 798-2291. http://www.rarediseases.org.
Di·Geor·ge syndrome(di-jōrj'), [MIM*188400]
a condition arising from developmental failure of the third and fourth pharyngeal pouches, resulting in the absence or underdevelopment of the thymus and parathyroid gland, associated with abnormalities of the outflow tract of the heart, distinctive facies, hypoparathyroidism, hypocalcemia with tetany, and deficiency in T-cell immunity; this is a contiguous gene deletion s. involving chromosome 22q11 with the loss of TBX1 gene; autosomal dominant inheritance.
DiGeorge syndromeHypoplasia of thymus & parathyroids, 3rd & 4th pharyngeal pouch syndrome A disorder characterized by
1. low blood calcium levels–hypocalcemia due to underdevelopment–hypoplasia of the parathyroid glands needed to control calcium;.
2. underdevelopment–hypoplasia of the thymus, an organ behind the sternum in which lymphocytes mature and multiply; and.
3. defects involving the outflow tracts from the heart; most cases of DGS are due to a very small deletion–microdeletion in chromosome band 22q11.2; a small number of cases have defects in other chromosomes, notably 10p13; named for the US pediatric endocrinologist Angelo DiGeorge.
Di·George syn·drome(di-jōrj' sin'drōm)
Congenital absence of the thymus gland. This results in a complete absence of functional T cells. Normal B-cell function is present.
DiGeorge,Angelo Mario, U.S. pediatrician.
DiGeorge syndrome - a condition arising from developmental failure of the third and fourth pharyngeal pouches, associated with facial deformity, hypoparathyroidism, and deficiency in cellular (T-lymphocyte) immunity. Synonym(s): congenital aplasia of thymus; immunodeficiency with hypoparathyroidism; pharyngeal pouch syndrome; third and fourth pharyngeal pouch syndrome