Risk Factors (Genetics & Inherited Conditions)
Etiology and Genetics (Genetics & Inherited Conditions)
DiGeorge syndrome results from the deletion (loss) of a small part of the long arm of chromosome 22 at position 22q11.2. Most people with this deletion are missing about two million base pairs of deoxyribonucleic acid (DNA), which corresponds to about forty genes, although some patients have shorter deletions in the same region. The degree of phenotypic expression in different individuals seems to be related to the size of the deletion. There have been sporadic reports of patients with similar symptoms who have deletions on other chromosomes (at positions 10p13, 17p13, and 18q21).
Efforts to identify a single one or two genes in the 22q11.2 band that are most critical to the expression of the syndrome have largely been unsuccessful, and it appears likely that the diminished expression of several related genes affecting common developmental processes is responsible. Three genes, however, have been identified that may be particularly important. The TBX1 gene, which encodes the T-box transcription factor 1, is probably responsible for the heart defects characteristic of the syndrome. A gene called HIRA specifies another transcriptional regulator that acts early in the development of the nervous system, and the gene UFD1L codes for a protein involved in the degradation pathway of ubiquinated compounds.
The 22q11.2 deletion characteristic of DiGeorge syndrome can be inherited, but this is...
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Symptoms (Genetics & Inherited Conditions)
Features of DiGeorge syndrome are present at birth and do not worsen with age. Features may include immune deficiency leading to increased infections, cleft palate, heart defects, failure to thrive, small head, increased incidence of psychiatric disorders, and characteristic facial features, including elongated face, almond-shaped eyes, wide nose, and small ears. Other features of the disease may be learning difficulties; hypoparathyroidism, a disorder in which insufficient parathyroid hormone is secreted from the parathyroid glands, resulting in abnormally low levels of calcium in the blood; weak muscles; and short height. Occasional abnormalities include structural brain defects, scoliosis, umbilical or inguinal hernias, kidney abnormalities, anogenital abnormalities, eye abnormalities, thyroid problems, and tapered and hyperextensible fingers.
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Screening and Diagnosis (Genetics & Inherited Conditions)
The doctor will ask about a patient’s symptoms and medical history and will perform a physical exam. Other tests may include blood tests to rule out other conditions, detect parathyroid hormone levels, and discover immune problems; genetic tests to look for deletions in chromosome 22; and a chest X ray, a test that uses radiation to take pictures of structures inside the body, especially to determine if the thymus is present.
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Treatment and Therapy (Genetics & Inherited Conditions)
Patients should talk with their doctors about the best plans. In infants, thymic tissue transplantation or bone marrow transplantation may help restore immune function, but the risks and benefits of these procedures must be carefully considered.
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Prevention and Outcomes (Genetics & Inherited Conditions)
Further Reading (Genetics & Inherited Conditions)
Baker-Gomez, Sherry. Missing Genetic Pieces: Strategies for Living with VCFS, the Chromosome 22q11 Deletion. Phoenix, Ariz.: Desert Pearl, 2004.
Cutler-Landsman, Donna, ed. Educating Children with Velo-Cardio-Facial Syndrome. San Diego: Plural, 2007.
EBSCO Publishing. DynaMed: DiGeorge Syndrome. Ipswich, Mass.: Author, 2009. Available through http://www.ebscohost.com/dynamed.
_______. Health Library: DiGeorge Syndrome. Ipswich, Mass.: Author, 2009. Available through http://www.ebscohost.com.
Jones, Kenneth L. Smith’s Recognizable Patterns of Human Malformation. 6th ed. Philadelphia: Elsevier Saunders, 2006.
Kleigman, Robert M., et al., eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia: Saunders Elsevier; 2007.
Shprintzen, Robert J., and Karen J. Golding-Kushner. Velo-Cardio-Facial Syndrome. 2 vols. San Diego: Plural, 2008-2009.
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Web Sites of Interest (Genetics & Inherited Conditions)
Canadian Directory of Genetic Support Groups. http://www.lhsc.on.ca/programs/medgenet/c_sup.htm
“DiGeorge Syndrome.” Genes and Disease, National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/disease/DGS.html
“DiGeorge Syndrome.” MayoClinic.com. http://www.mayoclinic.com/health/digeorge-syndrome/DS00998
Genetics Home Reference. http://ghr.nlm.nih.gov
Health Canada. http://www.hc-sc.gc.ca/index-eng.php
Immune Deficiency Foundation. http://www.primaryimmune.org
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Causes and Symptoms (Magill’s Medical Guide, Sixth Edition)
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 3 million base pairs of DNA in the majority of patients. About 90 percent of patients have...
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Treatment and Therapy (Magill’s Medical Guide, Sixth Edition)
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...
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Perspective and Prospects (Magill’s Medical Guide, Sixth Edition)
DiGeorge syndrome is relatively frequent, occurring with a frequency of 1 in 4,000 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.
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For Further Information: (Magill’s Medical Guide, Sixth Edition)
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 University Press, 2002.
Maroni, Gustavo. Molecular and Genetic Analysis of Human Traits. Malden, Mass.: Blackwell Scientific, 2001.
Rimoin, David L., et al., eds. Emery and Rimoin’s Principles and Practice of Medical Genetics. 5th ed. Philadelphia: Churchill Livingstone/Elsevier, 2007.
Stocker, J. Thomas, and Louis P. Dehner, eds. Pediatric Pathology. 2d ed. Philadelphia: Lippincott Williams & Wilkins, 2001.
Turnpenny, Peter, and Sian Ellard. Emery’s Elements of Medical Genetics. 13th ed. New York: Churchill Livingstone/Elsevier, 2007.
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Digeorge Syndrome (Encyclopedia of Medicine)
DiGeorge syndrome (also called congenital thymic hypoplasia, or third and fourth pharyngeal pouch syndrome) is a birth defect that is caused by an abnormal chromosome and affects the baby's immune system. The syndrome is marked by absence or underdevelopment of the thymus and parathyroid glands. It is named for the pediatrician who first described it in 1965.
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 characteristicsardiac defects, abnormal facial features, thymus underdevelopment, cleft palate, and hypocalcemiaaused 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...
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DiGeorge Syndrome (Encyclopedia of Children's Health)
DiGeorge syndrome is a rare congenital disease that affects an infant's immune system and that is due to a large deletion from chromosome 22. The syndrome is marked by absence or underdevelopment of the thymus and parathyroid glands. It is named for the pediatrician who first described it in 1965.
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 normal functioning of the immune system. The parathyroid glands, located on the sides of the thyroid gland, are responsible for maintenance of normal levels of calcium in the blood. In children with DiGeorge syndrome, the thymus and parathyroid glands are missing or undeveloped. The symptoms of this disorder vary, depending on the extent of missing thymus and parathyroid tissue. The primary problem for children who survive with DiGeorge syndrome is repeated infections due to a defective immune system.
DiGeorge syndrome is sometimes described as a "CATCH 22" disorder, so named because of their characteristicsardiac defects (C), abnormal facial features (A), thymus underdevelopment (T), cleft palate(C), and hypocalcemia due to hypoparathyroidism(H)ll resulting from deletion of portions of chromosome 22. Specific facial features...
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