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 characteristics—cardiac defects
(C), abnormal facial features (A), thymus underdevelopment (T),
(C), and hypocalcemia due to hypoparathyroidism(H)—all resulting
from deletion of portions of chromosome 22. 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.
DiGeorge syndrome is also called congenital thymic hypoplasia, or third
and fourth pharyngeal pouch syndrome, because the congenital abnormalities
occur in areas known as the third and fourth pharyngeal pouches, which
later develop into the thymus and parathyroid glands.
The prevalence of DiGeorge syndrome, is debated; estimates have ranged
from one in 4,000 to one in 6,395. Because the symptoms caused by the
chromosomal abnormality vary somewhat from child to child, the syndrome
probably occurs much more often than was previously thought. In the United
States, autopsy studies for DiGeorge syndrome accounted for 0.7 percent of
3469 postmortem examinations in the Seattle, Washington, area over a
period of 25 years. Internationally, the incidence of DGS was estimated to
be one case per 20,000 persons in Germany and one case per 66,000 persons
in Australia. However, with the advent of fluorescence in situ
hybridization (FISH) techniques to detect monosomy 22 and the inclusion of
related syndromes, more recent estimates place the incidence of DiGeorge
syndrome in the range of one case per 3,000 persons.
No major difference is noted in the incidence of DiGeorge syndrome between
males and females. The syndrome also 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 children with
DiGeorge syndrome. According to a 1999 study, 6 percent of children with
DiGeorge syndrome inherited the deletion from a parent, while 94 percent
had a new deletion.
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 percent 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.
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
Because the immune system of a child with DiGeorge syndrome is defective,
a doctor should be consulted at any signs of illness or disease.
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
as early as the fourteenth week of pregnancy. It confirms about 95
percent 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. The child is also born with a defective immune system and an
abnormally low level of calcium in the blood. These defects usually become
apparent within 48 hours after 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. The doctor may make the diagnosis of
DiGeorge syndrome 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 a child with DiGeorge syndrome 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
Infants with life-threatening heart defects are treated surgically.
Children with DiGeorge syndrome should be kept away from crowds or other
sources of infection. They should not be immunized with vaccines made from
live viruses or given corticosteroids.
Children with DiGeorge syndrome should be kept on low-phosphorus diets.
The prognosis is variable; many infants with DiGeorge syndrome die from
overwhelming infection, seizures, or heart failure within the first year.
A one-month mortality rate of 55 percent and a six-month mortality rate of
86 percent has been reported due to
congenital heart disease
. 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, with mild to
moderate learning disabilities, and to have other developmental
difficulties, including short stature as well as psychiatric problems in
Genetic counseling and testing is recommended for a person with DiGeorge
syndrome who becomes pregnant, because the disorder can be detected prior
to birth. Although most children with DiGeorge syndrome do not inherit the
chromosome deletion from their parents, they have a 50 percent chance of
passing the deletion on to their own children. Parents should be screened,
however, to see if they are carriers, even though inheritance of DiGeorge
syndrome is rare.
Because of an association between DiGeorge syndrome and
fetal alcohol syndrome
, pregnant women should avoid drinking alcoholic beverages.
—A procedure performed at 16-18 weeks of pregnancy in which a
needle is inserted through a woman's abdomen into her uterus to
draw out a small sample of the amniotic fluid from around the baby for
analysis. Either the fluid itself or cells from the fluid can be used
for a variety of tests to obtain information about genetic disorders and
other medical conditions in the fetus.
—A microscopic thread-like structure found within each cell of
the human body and consisting of a complex of proteins and DNA. Humans
have 46 chromosomes arranged into 23 pairs. Chromosomes contain the
genetic information necessary to direct the development and functioning
of all cells and systems in the body. They pass on hereditary traits
from parents to child (like eye color) and determine whether the child
will be male or female.
—Present at birth.
—The absence of genetic material that is normally found in a
chromosome. Often, the genetic material is missing due to an error in
replication of an egg or sperm cell.
—A condition characterized by an abnormally low level of calcium
in the blood.
—An underdeveloped or incomplete tissue or organ usually due to a
decrease in the number of cells.
—A type of white blood cell that is produced in the bone marrow
and matured in the thymus gland. It helps to regulate the immune
system's response to infections or malignancy.
Moore, Keith L., et al.
Before We Are Born: Essentials of Embryology and Birth Defects.
Kent, UK: Elsevier—Health Sciences Division, 2002.
Schinke, M., and S. Izumo. "Deconstructing DiGeorge
27 (2001): 238–240.
Chromosome 22 Central.
237 Kent Avenue, Timmins, Ontario. Web site:
Immune Deficiency Foundation.
40 West Chesapeake Avenue, Towson, MD 21230. Web site:
Guduri, Sridhar, et al. "DiGeorge Syndrome."
, August 14, 2004. Available online at
http://www.emedicine.com/med/topic567.htm (accessed November 17,