Syndrome, DiGeorge (DGS)

This congenital disorder is characterized by the convergence of the following three features: {{}}Low blood calcium levels: The low levels of calcium, also known as hypocalcemia, are due to underdevelopment (hypoplasia) of the parathyroid glands which are needed to control calcium; Thymus underdevelopment and immunodeficiency: The thymus is an organ behind the breastbone in which lymphocytes, cells that are needed by the immune system, normally mature and multiply. As a consequence of the thymus defect, children with DGS have immune deficiency. Heart defects: These heart defects involve the outflow tracts from the heart. DiGeorge syndrome is, next to Down syndrome, the most common genetic cause of congenital heart disease (that is, of heart defects present at birth). DGS is due to a very small deletion (microdeletion) of chromosome band 22q11.2. The key gene that is lost is called the Tbx-1 gene. Tbx-1 is 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. The disorder is named for the celebrated American pediatric endocrinologist Angelo DiGeorge who worked at St. Christopher's Hospital in Philadelphia. Other names for DGS include hypoplasia of the thymus and parathyroids and the third and fourth pharyngeal pouch syndrome. Transplantation of thymus tissue can restore normal immune function in infants with complete DiGeorge syndrome. Thymus tissue discarded from infants undergoing heart surgery (the thymus becomes disposable with time) was cultured in the laboratory and transplanted into 5 patients with profound immunodeficiency caused by DiGeorge syndrome. Four of the 5 patients then developed T-cell proliferative responses to mitogens (agents that trigger cell division). Early thymus transplantation may thus be a useful procedure for patients with DiGeorge syndrome who lack a T- cell system. The thymus transplant is best done early before the onset of infectious problems.