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22q11.2 deletion syndrome is a disorder caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated q11.2. It has a birth incidence estimated at 1:4000.
The features of this syndrome vary widely, even among members of the same family, and affect many parts of the body. Characteristic signs and symptoms include heart defects that are often present from birth, an opening in the roof of the mouth (a cleft palate or other defect in the palate), learning disabilities, recurrent infections caused by problems with the immune system, and mild differences in facial features. Affected individuals may also have kidney abnormalities, low levels of calcium in the blood (which can result in seizures), significant feeding difficulties, autoimmune disorders such as rheumatoid arthritis, and an increased risk of developing mental illnesses such as schizophrenia and bipolar disorder.
Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. Doctors named these conditions DiGeorge syndrome (see below DiGeorge Confusion), velocardiofacial syndrome (also called Shprintzen syndrome), and conotruncal anomaly face syndrome. In addition, some children with the 22q11.2 deletion were diagnosed with Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.
Symptoms
Individuals with a 22q11 deletion have a range symptoms. 22q11's symptoms range from mild problems to major illnesses that range up to 200+ symptoms. These symptoms are included:
- Congenital heart disease (74% of individuals), particularly conotruncal malformations (tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and truncus arteriosus)
- palatal abnormalities (69%), particularly velopharyngeal incompetence (VPI), submucosal cleft palate, and cleft palate; characteristic facial features (present in the majority of Caucasian individuals)
- learning difficulties (70-90%)
- an immune deficiency regardless of their clinical presentation (77%)
- hypocalcemia (50%)
- significant feeding problems (30%)
- renal anomalies (37%)
- hearing loss (both conductive and sensorineural)
- laryngotracheoesophageal anomalies
- growth hormone deficiency
- autoimmune disorders
- seizures (without hypocalcemia)
- skeletal abnormalities
Thymus, parathyroid glands and heart derive from the same primitive embryonic structure and that is why these three organs are dysfunctioned together in this disease. Affected patients (usually children) are prone to yeast infections.
Cause
The disease is related with genetic deletions (loss of a small part of the genetic material) found on the long arm of the 22nd chromosome. Some patients with similar clinical features may have deletions on the short arm of chromosome 10.
Treatment
Although genetic transplantation methods are currently being developed by researchers, there is no genetic treatment of this disease, as yet. Therefore, the treatment is symptomatic, that is calcium is administered, infections are treated with antibiotics, and these patients may occasionally undergo cardiac surgery for their heart abnormalities.
Diagnosis/testing
The 22q11.2 deletion syndrome is diagnosed in individuals with a submicroscopic deletion of chromosome 22 detected by fluorescence in situ hybridization (FISH) using DNA probes from the DiGeorge chromosomal region (DGCR). Such genetic testing is widely available for the clinical and prenatal testing of the 22q11.2 deletion syndrome. Fewer than 5% of individuals with clinical symptoms of the 22q11.2 deletion syndrome have normal routine cytogenetic studies and negative FISH testing. They may have variant deletions of DiGeorge syndrome that may be detectable on a research basis only.
Genetics
Most people with 22q11.2 deletion syndrome are missing about 3 million base pairs (the building blocks of DNA) on one copy of chromosome 22 in each cell. This region contains about 30 genes, but many of these genes have not been well characterized. A small percentage of affected individuals have shorter deletions in the same region. This condition is often described as a contiguous gene deletion syndrome because a deletion in chromosome 22 leads to the loss of many genes.
Researchers have not yet identified all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of one particular gene on chromosome 22, TBX1, is probably responsible for many of the syndrome's characteristic signs (such as heart defects, a cleft palate, distinctive facial features, and low calcium levels). A loss of this gene does not appear to cause learning disabilities, however. Additional genes in the deleted region are likely to contribute to the signs and symptoms of 22q11.2 deletion syndrome.
The 22q11.2 deletion syndrome is inherited in an autosomal dominant manner. Almost all (about 93%) of cases have a de novo (new to the family) deletion of 22q11.2 but about 7% inherit the 22q11.2 deletion from a parent. Children of individuals with del 22q11.2 have a 50% chance of inheriting the 22q11.2 deletion. Prenatal testing, such as amniocentesis, is available for pregnancies determined to be at risk. Also pregnancies who have findings of congenital heart disease and/or cleft palate detected by ultrasound examination may be offered prenatal testing. Genetic counseling may be helpful for families who may have DiGeorge syndrome.
Epidemiology
22q11.2 deletion syndrome affects an estimated 1 in 1800 live births. The condition may be more common, however, because some people with the deletion have few signs and symptoms and may not have been diagnosed.
DiGeorge Confusion
In the medical world 22q11 is often called DiGeorge Syndrome. However, DiGeorge is only one of the many symptoms of 22q11. This means that a person can have 22q11 and not DiGeorge. DiGeorge is a symptom rather then the disgonosis.
References
- PMID 15096950
- PMID 12175881
- PMID 11925570 Full text
- PMID 12436034
- PMID 14585638
- PMID 13129704
External links
Síndrome de DiGeorge | Microdélétion 22q11 | Syndroom van DiGeorge | Zespół Di George'a
"22q11.2 deletion syndrome"