DiGeorge syndrome, now known as 22q11.2 deletion syndrome, is a genetic disorder caused by the absence of a small segment on chromosome 22. This deletion, located at position q11.2, can impact the development of various body systems. The condition presents with a wide range of features, with effects differing significantly from person to person.
Physical and Developmental Characteristics
Individuals with 22q11.2 deletion syndrome can present with a diverse array of physical and developmental features. Heart abnormalities are common, including complex defects such as tetralogy of Fallot, interrupted aortic arch, or ventricular septal defects.
Immune system challenges also frequently occur, primarily due to an underdeveloped or absent thymus gland, which produces T-cells. A reduced number of T-cells can leave individuals more susceptible to recurrent infections. The degree of immune impairment varies, with some individuals showing improved immune function as they age.
Differences in the palate are another common characteristic, including a cleft palate or a submucous cleft palate, where the roof of the mouth does not fully close. These structural differences can lead to feeding difficulties in infancy and nasal-sounding speech later in childhood. Surgical correction of a cleft palate is often performed, though other health concerns may delay the procedure.
Endocrine system issues are also observed, particularly hypoparathyroidism, which results in low blood calcium levels (hypocalcemia). This low calcium can manifest as muscle cramping, irritability, or seizures. Managing these calcium levels involves daily supplementation with calcium and vitamin D.
Developmental and learning challenges are frequently associated with the syndrome, including delays in acquiring skills like walking and talking. Many individuals experience learning disabilities, particularly with reading, math, and problem-solving. Behavioral and mental health conditions such as attention-deficit/hyperactivity disorder (ADHD), anxiety, and depression are also more common in affected children and adults.
Diagnosis and Genetic Testing
The identification of 22q11.2 deletion syndrome is often suspected based on specific physical characteristics observed at birth or early in life. For instance, congenital heart defects or abnormally low calcium levels can prompt medical professionals to consider the diagnosis. A comprehensive physical examination and medical history are the initial steps in this diagnostic process.
Confirmation of 22q11.2 deletion syndrome relies on specialized genetic testing, which definitively detects the missing genetic material on chromosome 22. The primary diagnostic test utilized today is chromosomal microarray analysis (CMA). This technique can identify the exact size of the deletion and also screen for other genetic changes across the entire genome.
While older methods like fluorescent in situ hybridization (FISH) were previously used, CMA offers higher resolution and can detect smaller or atypical deletions that FISH might miss. Diagnosis can sometimes occur before birth through prenatal tests such as amniocentesis or chorionic villus sampling (CVS), especially with a known family history or if prenatal ultrasounds reveal suspicious findings like heart abnormalities.
Multidisciplinary Treatment and Management
There is currently no cure for the underlying genetic deletion in 22q11.2 deletion syndrome, so treatment focuses on managing the specific symptoms and health issues that arise. Due to the wide range of affected body systems, a coordinated multidisciplinary team approach is considered the most effective way to provide comprehensive care.
Cardiologists manage and often surgically correct congenital heart defects. Immunologists monitor immune system function and guide strategies for managing recurrent infections. Endocrinologists oversee the management of hypoparathyroidism, prescribing calcium and vitamin D supplements.
Speech and feeding therapists address issues related to palate differences, helping with swallowing difficulties and improving speech clarity. Psychologists and psychiatrists provide support for developmental delays, learning disabilities, and behavioral or mental health conditions such as ADHD, anxiety, or depression. Other specialists, including otolaryngologists, nephrologists for kidney issues, and physical therapists for motor skill development, also contribute to ongoing care.
Inheritance Patterns and Family Planning
Understanding the inheritance patterns of 22q11.2 deletion syndrome is important for affected individuals and their families. In the majority of cases (approximately 90% to 95%), the 22q11.2 deletion occurs as a de novo event. This means the deletion is a new, random genetic change that happens during the formation of reproductive cells or very early in fetal development, and is not inherited from either parent.
In the remaining 5% to 10% of cases, the 22q11.2 deletion is inherited from a parent who also carries the deletion. A parent with the deletion may have a very mild form of the syndrome, sometimes so subtle that they have not been previously diagnosed. If a parent has the 22q11.2 deletion, there is a 50% chance they will pass it on to each of their children, following an autosomal dominant inheritance pattern.
Genetic counseling is recommended for families affected by 22q11.2 deletion syndrome. Genetic counselors can explain specific inheritance risks, discuss testing options for parents and other family members, and review reproductive choices for future family planning.