DiGeorge Syndrome
Also known as: 22q11.2 deletion syndrome, Velocardiofacial syndrome (VCFS), Congenital Thymic Aplasia, Immunodeficiency with Hypoparathyroidism and Cardiac Defects
DiGeorge syndrome is a genetic disorder caused by a deletion on chromosome 22, specifically at the 22q11.2 locus. This deletion leads to the maldevelopment of several body systems, including the heart, parathyroid glands, thymus gland, and facial features. The severity of symptoms varies widely among affected individuals.
Imagine your body is like a car, and sometimes a tiny piece of the instruction manual (chromosome 22) is missing. This can cause problems with the heart, immune system, and other parts, making it harder for the car to run smoothly. Doctors can help by giving medicine, doing surgery, and providing extra support to make the car work as best as it can.
Signs & Symptoms
- Congenital heart defects (e.g., tetralogy of Fallot, interrupted aortic arch)
- Hypoparathyroidism (leading to hypocalcemia)
- Thymic hypoplasia or aplasia (resulting in immunodeficiency)
- Facial dysmorphism (e.g., cleft palate, micrognathia, hypertelorism)
- Learning difficulties and developmental delay
- Speech and feeding difficulties
- Increased susceptibility to infections
- Kidney abnormalities
- Skeletal abnormalities
- Behavioral and psychiatric problems (e.g., ADHD, autism spectrum disorder, schizophrenia)
Treatment Options
Calcium and Vitamin D supplementation
HIGHLY EFFECTIVEThymus transplantation
HIGHLY EFFECTIVECorrective heart surgery
HIGHLY EFFECTIVEIntravenous immunoglobulin (IVIG)
MODERATELY EFFECTIVEPhysical therapy
SUPPORTIVESpeech therapy
SUPPORTIVEEarly intervention programs
SUPPORTIVEPsychiatric and behavioral therapy
SUPPORTIVEDiagnosis
- Fluorescence in situ hybridization (FISH) for 22q11.2 deletion
- Chromosomal microarray analysis (CMA)
- Echocardiogram to assess heart defects
- Blood tests to measure calcium and parathyroid hormone levels
- Immunological assessment to evaluate T-cell function
- Physical examination to identify characteristic facial features
History
DiGeorge syndrome was first described by Angelo DiGeorge in 1965, who noted the association between thymic aplasia and parathyroid abnormalities. The genetic basis of the syndrome, specifically the 22q11.2 deletion, was identified in the early 1990s.
Recent Breakthroughs
CRISPR-Cas9 Gene Editing for TBX1 Gene
Researchers are exploring CRISPR-Cas9 gene editing to correct TBX1 gene mutations in vitro, showing promise for future gene therapy approaches.
Improved Diagnostic Accuracy with Whole-Genome Sequencing
Whole-genome sequencing is being used to identify atypical deletions and duplications in the 22q11.2 region, improving diagnostic accuracy and understanding of genotype-phenotype correlations.