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.