DiGeorge Syndrome is a genetic condition that impacts the development of various body systems. It arises from issues during fetal growth, leading to a range of developmental abnormalities. Its presentation varies considerably among individuals. It is typically diagnosed in infancy or early childhood and is considered a lifelong condition.
The Primary Cellular Deficiency
Individuals with DiGeorge Syndrome often experience a deficiency in T cells, a specific type of white blood cell. T cells are a component of the adaptive immune system, identifying and eliminating foreign invaders like bacteria and viruses, as well as abnormal cells within the body. A reduced number or impaired function of these cells leads to immunodeficiency, increasing susceptibility to various infections.
The severity of this T cell deficiency can vary, defining two main forms of the syndrome. In “partial DiGeorge Syndrome,” individuals have some T cell function, and their immune response may improve as they age. Conversely, “complete DiGeorge Syndrome” involves a severe or total absence of T cells, making individuals highly vulnerable to severe infections and requiring specific interventions for survival.
The Thymus Gland’s Role
The underlying reason for the T cell deficiency in DiGeorge Syndrome relates to the thymus gland. This specialized gland, located in the chest above the heart, serves as a maturation site for T cells. Immature T cells migrate to the thymus, where they undergo a complex “education” process, learning to distinguish between the body’s own cells and foreign invaders.
In DiGeorge Syndrome, the thymus gland may be underdeveloped (hypoplasia) or entirely absent (aplasia). This abnormal development disrupts the normal maturation of T cells, leading to a reduced number of functional T cells released into the bloodstream. The degree of thymic abnormality directly correlates with the severity of the T cell deficiency observed in individuals with the syndrome.
Broader Health Implications
Beyond the immune system, DiGeorge Syndrome presents a wide array of health challenges, resulting from a genetic deletion, most commonly on chromosome 22q11.2. This deletion impacts the development of multiple body systems during fetal growth, leading to a combination of physical and developmental issues.
Common non-immune features include congenital heart defects, such as tetralogy of Fallot, interrupted aortic arch, or ventricular septal defects, which often require surgical correction shortly after birth. Dysfunction or absence of the parathyroid glands is common, leading to low calcium levels in the blood, which can cause muscle spasms. Distinctive facial features like low-set ears, a small chin, a shortened philtrum, and wide-set eyes are also common.
Additional manifestations include palate abnormalities, such as a cleft palate, which may affect speech. Developmental delays are also common, potentially affecting learning and requiring various therapeutic interventions. These diverse health issues underscore the systemic nature of DiGeorge Syndrome.
Diagnosis and Treatment Approaches
Diagnosing DiGeorge Syndrome involves a combination of clinical assessments and specific laboratory tests. A primary diagnostic method is a genetic test, such as a FISH test, to detect the 22q11.2 deletion on chromosome 22. Blood tests are also performed to evaluate T cell counts and function, as well as calcium levels to check for parathyroid gland dysfunction. Cardiac evaluations, including echocardiography, are conducted to identify any heart defects.
Treatment strategies for DiGeorge Syndrome are multifaceted, addressing the various symptoms. For the immune deficiency, management includes preventing infections and, in some cases, immunoglobulin therapy. For individuals with complete DiGeorge Syndrome and a severe T cell deficiency, transplantation of cultured thymus tissue or hematopoietic stem cell transplantation may be necessary to restore immune function. Other aspects of the syndrome are managed with specific interventions, such as calcium and vitamin D supplementation for hypocalcemia and surgical repair for heart defects or cleft palate.