DiGeorge syndrome

Overview

DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a disorder caused by a missing segment of chromosome 22. It affects multiple body systems and is one of the most common genetic deletion syndromes, occurring in approximately 1 in 4,000 live births. The condition is highly variable, with symptoms ranging from mild to severe, and may include heart defects, immune system dysfunction, cleft palate, developmental delays, and characteristic facial features. Because of its diverse manifestations, DiGeorge syndrome often requires multidisciplinary care.

Causes

DiGeorge syndrome is caused by a deletion of a small segment of chromosome 22, specifically at the q11.2 region. This deleted region contains genes critical for the development of several organ systems. The deletion usually occurs sporadically (de novo), meaning it happens as a random event during the formation of reproductive cells or in early fetal development. However, it can also be inherited in an autosomal dominant manner, meaning a parent with the deletion has a 50% chance of passing it on to their child.

Symptoms

Symptoms of DiGeorge syndrome vary widely among individuals and can affect multiple organs and systems. Common signs and symptoms include:

• Congenital heart defects: Such as interrupted aortic arch, ventricular septal defect (VSD), or tetralogy of Fallot.

• Immune system problems: Due to underdeveloped or absent thymus gland, leading to frequent infections.

• Hypocalcemia: Low calcium levels caused by underdeveloped parathyroid glands, which may lead to seizures or muscle cramps.

• Facial features: Including low-set ears, hooded eyelids, a long face, small chin (micrognathia), and a prominent nasal bridge.

• Cleft palate or other palate abnormalities: Causing feeding difficulties and speech problems.

• Learning disabilities and developmental delays: Ranging from mild to moderate cognitive impairment.

• Behavioral and psychiatric issues: Such as ADHD, autism spectrum disorder, anxiety, and increased risk of schizophrenia.

Diagnosis

Diagnosis of DiGeorge syndrome is based on clinical findings and confirmed through genetic testing. Steps in the diagnostic process include:

• Physical examination: To assess for characteristic features and congenital anomalies.

• Echocardiogram: To detect congenital heart defects.

• Blood tests: To measure calcium levels and evaluate immune function (T-cell counts).

• Genetic testing: Fluorescence in situ hybridization (FISH), chromosomal microarray, or MLPA to identify the 22q11.2 deletion.

Treatment

There is no cure for DiGeorge syndrome, but treatment focuses on managing specific symptoms and complications. A multidisciplinary approach is usually necessary. Common treatments include:

• Surgical repair: For congenital heart defects and cleft palate.

• Calcium and vitamin D supplementation: To manage hypocalcemia.

• Immunological support: Antibiotics, immunoglobulin therapy, or, in rare cases, thymus transplantation for severe immune deficiency.

• Speech and feeding therapy: For palate abnormalities and developmental delays.

• Educational support: Special education services and individualized learning plans for cognitive and developmental needs.

• Psychological and psychiatric care: Behavioral therapy and medications for mental health conditions such as ADHD, anxiety, or schizophrenia.

Prognosis

The prognosis for individuals with DiGeorge syndrome varies depending on the severity of organ involvement and associated complications. With early diagnosis and comprehensive medical care, many individuals lead fulfilling lives into adulthood. However, lifelong medical monitoring and support are often required, particularly for cardiac, immune, and neurodevelopmental issues. Regular follow-up with a coordinated care team helps manage symptoms and improve long-term outcomes.