DiGeorge syndrome
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DiGeorge syndrome is also called Microdeletion 22q11 syndrome (del 22q11.2) and Velocardiofacial syndrome (VCF). Individuals with a 22q11 deletion have a range of findings, including 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); and learning difficulties (70-90%). Seventy-seven percent of individuals have an immune deficiency regardless of their clinical presentation. Additional findings include: 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), and 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. 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. 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
The 22q11.2 deletion syndrome is inherited in an autosomal dominant manner. Almost all (about 93%0 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.
See Chromosome 22, microdeletion 22 q11es:Síndrome de Di Georgefr:Microdélétion 22q11