Therefore, dysfunction of TBX1 may be responsible for some of the symptoms in DiGeorge syndrome.Research in mouse models has shown that deletion of Tbx1 leads to several defects similar to those seen in humans, mainly affecting development of the great arteries and the thymus.The abnormalities seen in the great arteries of mice deficient of Tbx1 are a consequence of abnormal formation and remodelling of the aortic arches during early development. The role of Tbx1 for correct formation and remodelling of the aortic arches has been extensively studied in various mouse models suggesting the key role of Tbx1 for cardiovascular development and the phenotypes seen in DiGeorge syndrome. DGCR8
In mice, haploinsufficiency of the DGCR8 gene has been linked to improper regulation of the microRNA miR-338 and 22q11.2 deletion phenotypes. TANGO2
Transport and golgi organization 2 homolog (TANGO2) also known as chromosome 22 open reading frame 25 (C22orf25) is a protein that in humans is encoded by the TANGO2 gene.The gene coding for C22orf25 is located on chromosome 22 and the location q11.21, so it is often associated with 22q11.2 deletion syndrome. But with TANGO2 disorder being autosomal recessive, will not occur in all cases. Mutations in the TANGO2 gene may cause defects in mitochondrial β-oxidation and increased endoplasmic reticulum stress and a reduction in Golgi volume density. These mutations results in early onset hypoglycemia, hyperammonemia, rhabdomyolysis, cardiac arrhythmias, and encephalopathy that later develops into cognitive impairment. Parkinsons disease genes
22q11.2DS has been associated with a higher risk of early onset Parkinsons disease (PD).
It was also able to detect smaller atypical deletions that are easily missed using FISH. These factors, along with the lower expense and easier testing mean that this MLPA probe could replace FISH in clinical testing.Genetic testing using BACs-on-Beads has been successful in detecting deletions consistent with 22q11.2DS during prenatal testing. Array-comparative genomic hybridization (array-CGH) uses a large number of probes embossed in a chip to screen the entire genome for deletions or duplications. It can be used in post and pre-natal diagnosis of 22q11.2.Fewer than 5% of individuals with symptoms of DiGeorge syndrome have normal routine cytogenetic studies and negative FISH testing. In these cases, atypical deletions are the cause. Some cases of 22q11.2 deletion syndrome have defects in other chromosomes, notably a deletion in chromosome region 10p14. Treatment
No cure is known for DiGeorge syndrome. Certain individual features are treatable using standard treatments. The key is to identify each of the associated features and manage each using the best available treatments.For example, in children, it is important that the immune problems are identified early, as special precautions are required regarding blood transfusion and immunization with live vaccines. Thymus transplantation can be used to address absence of the thymus in the rare, so-called "complete" DiGeorge syndrome. Bacterial infections are treated with antibiotics. Cardiac surgery is often required for congenital heart abnormalities. Hypoparathyroidism causing hypocalcaemia often requires lifelong vitamin D and calcium supplements.