Tanner Marshall, MS, Rishi Desai, MD
The name DiGeorge syndrome isn’t the most descriptive name, which is why it’s often also referred to as 22q11.2 deletion syndrome, which is actually pretty descriptive, and describes a condition in which a small portion of chromosome 22 is deleted, which causes a bunch of developmental abnormalities and complications. Alright so our chromosomes are composed of genes, right? Which are essentially instructions for everything from development to day-to-day survival, and these genes are spread out across 23 pairs of chromosomes. 22q11.2 is like an address, so 22 stands for chromosome 22, with q designating the long arm of the chromosome, then it’s on region 1, band 1, and sub-band 2. This portion of dna, 22q11.2, spans about 30 genes and 1.5 to 3 million base pairs, which classifies it as a microdeletion since it’s less than 5 million base pairs. Even though this region is relatively small, it encodes for some really important genes, one of which is the TBX1 gene, which is thought to play a big role in the disease.
The TBX1 gene is involved in normal development of the pharyngeal pouches, specifically pouch 3 and 4, which are fetal structures that develop into parts of the head and neck. The third pharyngeal pouch goes on to develop into the thymus and the inferior parathyroid gland, the fourth pouch goes on to develop into the superior parathyroid gland. So with a 22q11.2 deletion and therefore no TBX1 gene, the thymus and parathyroid gland both end up underdeveloped, called hypoplasia.
T lymphocytes or T cells are immune cells that’re super important for the adaptive immune response, and are produced in the bone marrow but mature in the thymus. If someone has thymic hypoplasia and thymic dysfunction, the T cells don’t mature, and so these people often have a deficiency in mature T cells. It turns out, though, that most people with DiGeorge syndrome have mild to moderate thymic dysfunction, called partial DiGeorge syndrome, which means that the immunodeficiency isn’t life-threatening. Complete DiGeorge syndrome, though, where thymic dysfunction is severe, can be fatal within the first year of life, due to a severely compromised immune system. Now, let’s talk about the parathyroid glands - the other major organ that’s affected in DiGeorge syndrome. The parathyroid glands secrete parathyroid hormone, which helps increase the level of calcium ions in the blood. Parathyroid hypoplasia leads to low levels of parathyroid hormone, which causes low levels of calcium ions in the blood, called hypocalcemia.
In addition to affecting the thymus and parathyroid glands and causing hypoplasia, the 22q11.2 region encodes genes that can also affect other organs and tissues. Individuals with 22q11.2 deletion syndrome commonly have congenital heart defects, in particular truncus arteriosus and tetralogy of Fallot, as well as facial abnormalities such as cleft palate and a characteristic “facies” which means that they might have features that might be normal individually like a long face, small teeth, or broad nose, but taken together these and many other features become the characteristic facies of DiGeorge syndrome. Patients might have many other characteristic physical findings as well as higher rates of behavioral and mental health conditions like schizophrenia. Diagnosis can be difficult, but genetic testing can be done if DiGeorge syndrome is suspected, and certain blood tests looking at T cell numbers and function, calcium, and parathyroid hormone can also be helpful. Because the syndrome is due to a genetic deletion, there’s no known cure, though many of the symptoms can be treated or managed, for example infections due to the underlying immunodeficiency might be treated with antibiotics and hypocalcemia can be managed with vitamin D and calcium supplements. Surgery might be required for more severe cases though, like a thymus transplant for complete DiGeorge syndrome or heart surgery for children with congenital heart defects.
Alright as a quick recap, DiGeorge syndrome or 22q11.2 deletion syndrome, is a genetic condition where the q11.2 portion of DNA on chromosome 22 is deleted, which can cause developmental issues like thymic and parathyroid hypoplasia, congenital heart defects, facial abnormalities, mental health conditions, and others. Thanks for watching, you can help support us by donating on patreon, or subscribing to our channel, or telling your friends about us on social media.
Resources edit
https://en.wikipedia.org/wiki/DiGeorge_syndrome