- Hypocalcemia (low calcium levels in the blood) due to hypoplasia (underdevelopment) of the parathyroid glands that are needed to control calcium;
- Immunodeficiency due to hypoplasia (underdevelopment) of the thymus (an organ behind the breastbone needed for the maturation of lymphocytes into T cells); and
- Congenital heart disease with defects of the outflow tracts (the pulmonary artery and aorta) from the heart. Next to Down syndrome, DiGeorge syndrome is the most common genetic cause of congenital heart disease.
DiGeorge syndrome is caused by a microdeletion in chromosome band 22q11.2. The key gene that is lost is Tbx-1, a master control gene that regulates other genes required for the connection of the heart with the blood circulation. Tbx-1 also controls genes involved in the development of the parathyroid and thymus glands and the shape of the face.
Babies with DiGeorge syndrome are highly susceptible to infections and, in the past, usually died by age 2. Transplantation of thymus tissue can restore normal immune function to infants with DiGeorge syndrome.
However, bone marrow cells babies with DiGeorge syndrome can spontaneously transform into rogue T cells that attack and reject the thymus transplant. An immunosuppressant drug called Thymoglobulin (antithymocyte globulin), which selectively targets T cells, given prior to the transplant has been found to quash the rogue T cells and permit a successful thymus transplant.
The syndrome is named for the American pediatric endocrinologist Angelo DiGeorge who worked at St. Christopher's Hospital in Philadelphia. Also known as hypoplasia of the thymus and parathyroids and as third and fourth pharyngeal pouch syndrome.