Overview

DiGeorge Syndrome, also known as 22q11.2 deletion syndrome, is a rare genetic disorder caused by the deletion of a small segment of chromosome 22. It affects multiple body systems, leading to a wide range of clinical features including heart defects, immune system problems, cleft palate, developmental delays, and learning difficulties. DiGeorge Syndrome is one of the most common chromosomal microdeletion syndromes, occurring in approximately 1 in 4,000 live births. The severity and combination of symptoms vary widely among individuals, making early diagnosis and a multidisciplinary treatment approach essential for optimal care.

Causes

DiGeorge Syndrome is caused by a deletion of a segment on chromosome 22, specifically at the q11.2 region. This deleted region contains several genes that are important for normal development. The loss of these genes leads to the characteristic signs and symptoms of the syndrome.

Most cases (about 90%) occur due to a new (de novo) mutation, meaning it is not inherited from either parent. However, in approximately 10% of cases, the condition is inherited in an autosomal dominant manner, meaning an affected parent has a 50% chance of passing it to their child.

Symptoms

The clinical features of DiGeorge Syndrome vary greatly but commonly include:

• Congenital heart defects: Structural abnormalities of the heart such as tetralogy of Fallot, ventricular septal defects (VSD), or interrupted aortic arch.
• Facial features: Characteristic facial appearance including small ears, hooded eyelids, and a prominent nose with a rounded tip.
• Palatal abnormalities: Cleft palate or velopharyngeal insufficiency causing nasal-sounding speech and feeding difficulties.
• Immune system problems: Thymus gland abnormalities leading to immune deficiency and increased risk of infections.
• Hypocalcemia: Low calcium levels due to underdeveloped parathyroid glands, potentially causing seizures or muscle spasms.
• Developmental delays: Delayed milestones, particularly in speech and motor development.
• Learning difficulties: Mild to moderate learning disabilities, especially with problem-solving and mathematics.
• Behavioral and psychiatric issues: Increased risk of attention-deficit/hyperactivity disorder (ADHD), anxiety, autism spectrum disorder, and schizophrenia in adolescence or adulthood.
• Kidney abnormalities: Structural problems affecting kidney function.
• Hearing problems: Recurrent ear infections and hearing loss are common.

Diagnosis

Diagnosis of DiGeorge Syndrome involves a combination of clinical assessment and genetic testing:

• Clinical evaluation: Identification of characteristic signs such as heart defects, facial features, and developmental delays.
• Genetic testing:
  • Fluorescence in situ hybridization (FISH): Detects the 22q11.2 deletion in most cases.
  • Chromosomal microarray (CMA): A more sensitive test that identifies smaller deletions within chromosome 22.
• Echocardiogram: To diagnose congenital heart defects.
• Blood tests: To check calcium levels and immune function.
• Hearing and vision screening: To assess for common sensory impairments.

Treatment

There is no cure for DiGeorge Syndrome, but treatment focuses on managing individual symptoms and improving quality of life through a multidisciplinary approach:

• Heart defect correction: Surgery or medical management for congenital heart defects.
• Immune system support: Monitoring immune function, avoiding live vaccines if immunity is severely compromised, and treating infections promptly.
• Calcium supplementation: Medications and dietary changes to manage low calcium levels.
• Speech and feeding therapy: To address cleft palate and speech difficulties.
• Early intervention programs: Physical, occupational, and speech therapies to promote developmental progress.
• Educational support: Special education services and individualized education plans (IEPs) to address learning challenges.
• Mental health care: Counseling, behavioral therapy, and psychiatric support for emotional and psychological well-being.
• Regular follow-up: Lifelong monitoring of cardiac, immune, endocrine, and developmental health by a team of specialists.

Prognosis

The prognosis for individuals with DiGeorge Syndrome varies depending on the severity of symptoms and the presence of associated health issues. Many children with early intervention and proper medical care can lead active and meaningful lives. While some individuals may experience lifelong health and developmental challenges, others have only mild symptoms.

Advances in medical care have greatly improved outcomes, especially for heart and immune system problems. Lifelong monitoring and supportive therapies help manage health issues effectively, allowing most individuals with DiGeorge Syndrome to enjoy a good quality of life.