DiGeorge syndrome (DGS), also known as 22q11.2 deletion syndrome, is a congenital disorder affecting an estimated one in every 4,000 live births. This condition arises from an underlying genetic change and impacts the development of multiple body systems. The disorder results in a wide range of signs and symptoms that vary significantly among affected individuals, ranging from mild presentations to severe, life-threatening concerns.
The Genetic Origin of DiGeorge Syndrome
DiGeorge syndrome is caused by the loss of a small segment of genetic material on chromosome 22, designated 22q11.2. This region refers to segment 11 on the long arm (q). The deletion typically spans about three million base pairs, involving the loss of approximately 30 to 40 genes. This loss prevents the body from receiving the complete instructions necessary for proper fetal development.
This deletion is described as a contiguous gene deletion syndrome because it removes many genes located close together. The absence of these multiple genes causes the diverse, multi-system health issues. Most cases (about 90%) occur randomly as a new mutation during reproductive cell formation or early fetal development. Only about 10% of individuals inherit the deletion from an affected parent, who may have a milder, previously undiagnosed form.
Core Health Issues and Manifestations
Health problems are highly variable but consistently involve structures developing near the thymus and parathyroid glands. Many individuals present with congenital heart defects, often the most serious initial concern. These defects frequently involve the heart’s outflow tract (conotruncal malformations). Specific cardiac issues include Tetralogy of Fallot, interrupted aortic arch, and truncus arteriosus.
The immune system is commonly affected because the deletion results in an absent or underdeveloped thymus gland. The thymus is where T-cells, the white blood cells responsible for fighting infection, mature. Reduced T-cell production leads to immunodeficiency, causing frequent infections like recurrent ear and chest infections. Complete absence of the thymus, the rarest and most severe form, results in life-threatening severe immunodeficiency.
A frequent manifestation involves the endocrine system, specifically the parathyroid glands. These glands are often underdeveloped, leading to hypoparathyroidism. This causes low levels of parathyroid hormone, resulting in hypocalcemia (dangerously low calcium levels). Low calcium can cause seizures and may be one of the first signs noticed in newborns.
The syndrome also manifests structurally and developmentally. Palatal abnormalities, such as a cleft palate, are common. Even without a visible cleft, issues with palate function often result in speech difficulties and a nasal sound. Distinctive facial features can include small ears, hooded eyelids, and an underdeveloped chin.
Developmental delays (e.g., walking and talking) are often present. Learning difficulties are common and require specialized educational support. Older children and adults have an increased risk of developing psychiatric conditions, including schizophrenia and anxiety disorders. Other concerns include kidney abnormalities, hearing loss, and skeletal differences like scoliosis.
Identifying DiGeorge Syndrome Through Screening and Testing
Diagnosis is often suspected when common clinical features are observed. The presence of a conotruncal heart defect or unexplained seizures due to hypocalcemia are strong indicators that prompt genetic investigation. Although physical examination and clinical history raise suspicion, confirmation requires identifying the 22q11.2 deletion. Genetic testing can be performed prenatally if risk factors are present, or postnatally if symptoms appear.
The most common historical technique to confirm the deletion is Fluorescence In Situ Hybridization (FISH). This method uses fluorescent probes that attach specifically to the 22q11.2 region, showing a missing signal if the segment is deleted. While effective for detecting the typical deletion size, FISH may miss smaller, atypical deletions.
Chromosomal Microarray Analysis (CMA), also known as Array Comparative Genomic Hybridization (aCGH), is often the preferred initial test. CMA is a higher-resolution genome scanning procedure that detects the 22q11.2 deletion and other microscopic chromosomal changes. For rapid diagnosis, especially in newborns, techniques like Multiplex Ligation-dependent Probe Amplification (MLPA) can also be used. Precise diagnosis is necessary for coordinating multi-system care.
Managing Multi-System Health Needs
Since DiGeorge syndrome affects multiple body systems, management must be comprehensive and involve a team of specialists. Multi-disciplinary care is coordinated by a primary physician who oversees the patient’s overall health and developmental progress. Treatment focuses on managing specific symptoms and conditions.
Cardiovascular surgery is often necessary for heart defects, sometimes soon after birth, to repair structural anomalies and improve blood flow. Lifelong cardiac monitoring addresses subsequent heart issues. Metabolic issues from hypoparathyroidism are managed with calcium and Vitamin D supplementation to maintain stable blood calcium levels. Supplementation is adjusted throughout the lifespan, especially during periods of stress (puberty or surgery), when hypocalcemia risk increases.
Immune system dysfunction requires careful monitoring of T-cell counts and function by an immunologist. For individuals with a moderate deficiency, infections are treated normally, and many children follow standard immunization schedules. Severe immunodeficiency (complete absence of the thymus) requires specialized intervention, such as a thymus tissue transplant to restore T-cell production and immune function.
Developmental and behavioral challenges are addressed through various therapies. Speech therapy is recommended for difficulties related to palatal function or developmental delays. Occupational and physical therapy help children meet developmental milestones and build practical skills. Mental health support is integrated into care to manage the increased risk of anxiety, behavioral problems, and other psychiatric disorders.