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$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
     [phone]

     Immune Deficiency Foundation
     3565 Ellicott Mill Drive, Unit B2
     Ellicott City, MD  21043
     [phone]
     [phone]

     Frank Greenberg, M.D.
     Baylor College of Medicine
     Department of Molecular Genetics
     6621 Fannin Road
     Houston, TX  77030
     [phone]

     Craig B. Langman, M.D. and Samuel S. Gidding, M.D.
     Children's Memorial Hospital
     2300 Children's Plaza
     Chicago, IL  60614
     [phone]

     National Institute of Child Health and Human Development (NICHD)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]

For Genetic Information and Genetic Counseling Referrals:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Avenue
     White Plains, NY 10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

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.