Degeorge syndrome

What is DiGeorge Syndrome?

• DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a primary immunodeficiency disorder caused by a microdeletion on the long arm of chromosome 22 (at position q11.2).

• It affects the development of several body systems and leads to a wide range of clinical features.

• The syndrome is congenital (present at birth) and can vary widely in severity, with some individuals showing mild symptoms and others having life-threatening complications.

History

• First described in the 1960s by Dr. Angelo DiGeorge, who identified a pattern of thymic hypoplasia, hypoparathyroidism, and congenital heart defects.

• The genetic basis (22q11.2 deletion) was identified later with the advent of molecular genetic techniques such as FISH (Fluorescence In Situ Hybridization).

Causes

• Caused by a heterozygous deletion of about 3 million base pairs on chromosome 22 (22q11.2 region), which includes approximately 30–40 genes.

• Most cases (over 90%) occur de novo (new mutation), but it can also be inherited in an autosomal dominant manner.

Importance in Biology and Medicine

• Offers insights into gene dosage effects, developmental biology, and organogenesis.

• Studied extensively for its implications in neurodevelopmental disorders, cardiac morphogenesis, and immune system development.

Major Clinical Features

• Cardiac abnormalities (e.g., tetralogy of Fallot, interrupted aortic arch, ventricular septal defect)

• Thymic hypoplasia or aplasia, leading to T-cell immunodeficiency and increased susceptibility to infections

• Hypocalcemia due to parathyroid gland hypoplasia

• Craniofacial anomalies, including cleft palate, micrognathia, and low-set ears

• Developmental delays and learning difficulties

• Psychiatric disorders, such as schizophrenia, ADHD, and anxiety

• Palatal abnormalities, including velopharyngeal insufficiency and submucosal cleft

Diagnosis

• Confirmed by molecular genetic testing, especially FISH or microarray analysis to detect the 22q11.2 deletion

• Prenatal diagnosis is possible through amniocentesis or chorionic villus sampling if there is a known familial case

Management

• No cure, but symptom-specific treatment is provided

• Cardiac surgery for congenital heart defects

• Calcium and vitamin D supplementation for hypocalcemia

• Thymus transplant or immunoglobulin therapy for severe immunodeficiency

• Speech therapy, educational support, and behavioral therapy for developmental and psychiatric issues

• Regular multidisciplinary monitoring involving cardiology, immunology, endocrinology, and developmental pediatrics

Prognosis

• Prognosis depends on the severity of symptoms, especially heart defects and immune dysfunction

• With early diagnosis and supportive care, many individuals can lead relatively normal lives

Synonyms

• 22q11.2 deletion syndrome

• Velocardiofacial syndrome (VCFS)

• Conotruncal anomaly face syndrome

• Catch22 syndrome (mnemonic: Cardiac abnormality, Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia – 22q11 deletion)