DIGEORGE SYNDROME
>DiGeorge syndrome (22q11.2 deletion syndrome), a disorder caused by a defect in
chromosome 22, results in the poor development of several body systems.
>Di George Syndrome is a congenital immune disorder characterized by lack of
embryonic development (stage in prenatal development between 2-8 weeks inclusive) or
underdevelopment of the third and fourth pharyngeal pouches. It is also called thymic
aplasia (failure of the thymus to develop naturally), thymic hypoplasia (defective
development of tissue), or third and fourth pharyngeal arch or pouch syndrome.
>include heart defects, poor immune system function, a cleft palate, poor function of the
parathyroid glands and behavioral disorders.
>Before the discovery of the chromosome 22 defect, the disorder was known by several
names — DiGeorge syndrome, velocardiofacial syndrome and others. Although the term
"22q11.2 deletion syndrome" is frequently used today — and is generally a more
accurate description — previous names for the disorder are still used.
22q11 DELETION
In humans, DNA, which encodes the master plan for our bodies, is organized as 23 pairs
of chromosomes. One pair, the sex chromosomes, consists of either two X
chromosomes (XX), resulting in a girl, or one X and one Y chromosome (XY), resulting
in a boy. The other 22 pairs of chromosomes, referred to as the autosomes, are
numbered 1 through 22. While some of the DNA code can vary between individuals, the
overall appearance of each chromosome is unique when viewed under a microscope
with staining. Each chromosome is organized into two or three parts: a short arm (not
present for some chromosomes), a central portion called the centromere, and a long
arm. The arms contain the DNA sequences that encode the genes. The long arm is
called by the number of the autosome and “q”. Therefore, the long arm of chromosome
22 is called 22q. Chromosomal arms also have sections that appear as light or dark
bands after special staining, which are numbered. Thus, 22q11 refers to the 11 band
(pronounced one-one) on the long arm of chromosome 22.
ALTERNATIVE NAMES
DGS
Hypoplasia of Thymus and Parathyroids
Third and Fourth Pharyngeal Pouch Syndrome
DiGeorge Syndrome Chromosome Region
Takao VCF Syndrome
DGCR
Catch 22
22q11.2 Deletion Syndrome
DiGeorge Anomaly
DGA
Microdeletion 22q11
Velocardiofacial Syndrome
SIGNS AND SYMPTOMS
Signs and symptoms may include some combination of the following:
Speech impairments
Immune deficiency
Learning disabilities
Hypocalcemia
Recurrent infections
Underdeveloped thymus gland
Hypoparathyroidism
Lack of T-cells
Congenital heart disease
Heart murmur
Heart failure
Underdeveloped parathyroid glands
Underdeveloped chin
Downward slanting eyes
Convulsions
FACIAL FEATURES OF CHILDREN WITH DIGEORGE SYNDROME may include the
following:
small ears with squared upper ear
hooded eyelids
cleft lip and/or palate
asymmetric crying facies
small mouth, chin, and side areas of the nose tip
CAUSES
DiGeorge syndrome is caused by the deletion of a portion of chromosome 22. Each person has
two copies of chromosome 22, one inherited from each parent. This chromosome contains an
estimated 500 to 800 genes.
If a person has DiGeorge syndrome, one copy of chromosome 22 is missing a segment that
includes an estimated 30 to 40 genes. Many of these genes haven't been clearly identified and
aren't well understood. The region of chromosome 22 that's deleted in DiGeorge syndrome is
known as 22q11.2. A small number of people with DiGeorge syndrome have a shorter deletion
in the same region of chromosome 22.
The deletion of genes from chromosome 22 usually occurs randomly in the father's sperm or in
the mother's egg, or it may occur very early during fetal development. Therefore, the deletion
occurs in all or nearly all of the cells in the body as the fetus develops.
DIAGNOSIS
Diagnosis is usually made on the basis of symptoms present at birth or within the first few
weeks of life.
Blood tests to evaluate the immune system
Blood tests for low calcium
Chest x-ray to look at the heart and thymus
Cardiac catheterization to examine the heart closely
Genetic studies to look for the Chromosome 22 problem
ASSOCIATION WITH AUTOIMMUNE AND OTHER DISEASES
As is true with other immunodeficiency syndromes, DiGeorge anomaly is associated
with autoimmune disorders. Association with Graves disease has been reported sporadically.
Other associated diseases include immune cytopenias,16 immune thrombocytopenic purpura,17
juvenile rheumatoid arthritis–like polyarthritis18 , autoimmune uveitis19 , and severe eczema.20
DiGeorge anomaly and VCFS were recently found to be significantly associated with eczema
and asthma but not with allergic rhinitis.21
TREATMENT
There is no cure for DiGeorge syndrome. Treatments can usually correct critical problems, such
as a heart defect or low calcium levels.
Hypoparathyroidism. Hypoparathyroidism can usually be managed with calcium
supplements, vitamin D supplements and a low-phosphorus diet. If enough of the
parathyroid tissue is intact, it's possible your child's parathyroid glands will eventually
regulate calcium and phosphorus levels without a specialized diet.
Limited thymus gland function. If your child has some thymic function, infections may
be frequent but not necessarily severe. These infections — usually frequent colds and
ear infections — are generally treated as they would be in any child. Most children with
limited thymic function follow the normal schedule of vaccines. For most children with
moderate thymus impairment, immune system function will improve as they grow older.
Severe thymus dysfunction. If the impairment of the thymus is severe or there's no
thymus, your child is vulnerable to a number of severe infections. Treatment requires a
transplant of thymus tissue, specialized cells from bone marrow, or specialized disease-
fighting blood cells.
Cleft palate. A cleft palate or other abnormalities of the palate can usually be surgically
repaired.
Heart defects. Most heart defects associated with DiGeorge syndrome require
surgeryto repair the heart and correct blood circulation.
Overall development. Your child will likely benefit from a range of therapies, including
speech therapy to improve verbal skills and articulation; occupational therapy to learn
everyday skills; and developmental therapy to learn age-appropriate behaviors, social
skills and interpersonal skills. In the United States, early intervention programs providing
these types of therapy are usually available through a state's health department.
Mental health care. Psychotherapy and psychiatric medications may be recommended
if your child is later diagnosed with attention-deficit/hyperactivity disorder, depression,
schizophrenia, or other mental health or behavioral disorders.
PATHOPHYSIOLOGY
The pathophysiology involves an embryologic defect in the 3rd and 4th pharyngeal pouch
development from which thymus and the parathyroid glands evolve. The embryologic defect
may affect not only 3rd and 4th pharyngeal pouch but also 4th, 5th and 6th branchial arches,
thereby resulting in a contiguous field defect such as esophageal atresia and distal tracheo-
esophageal fistula (12). Disruption of pharyngeal arch development in humans underlies many
of the craniofacial defects observed in the 22q11.2 deletion syndrome.
PROGNOSIS
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 later life
PREVENTION
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.
