DiGeorge Syndrome

Mr. Arvind Kumar

Introduction

  1. DiGeorge Syndrome (DGS) is a genetic disorder caused by a deletion on chromosome 22 (22q11.2 deletion).

  2. It affects the development of the thymus, parathyroid glands, and heart, leading to immune deficiency, low calcium levels, and congenital heart defects.

  3. The syndrome is part of a group of conditions known as 22q11.2 deletion syndromes, which also include Velocardiofacial syndrome and Conotruncal anomaly face syndrome.

  4. It was first described by Dr. Angelo DiGeorge in 1965.

  5. The condition varies in severity — some patients have mild symptoms, while others have life-threatening complications.

Genetic Basis (Cause)

 

Feature Details
Chromosomal abnormality Deletion in chromosome 22 at band q11.2
Type of mutation Microdeletion (small piece of DNA missing)
Inheritance pattern Autosomal dominant (but 90% are new mutations)
Genes involved TBX1 gene is the most critical for symptoms
Recurrence risk ~50% if one parent carries the deletion

  • The missing region on chromosome 22 contains genes needed for the normal development of the thymus, parathyroid glands, and parts of the heart.

  • The deletion leads to:

    • T-cell deficiency due to thymic hypoplasia.

    • Hypocalcemia (low calcium) due to parathyroid underdevelopment.

    • Congenital heart defects due to abnormal heart formation.

 

Epidemiology

 

Parameter Details
Incidence 1 in 4,000 live births
Gender Affects both equally
Inheritance Mostly sporadic (new mutations)
Risk factor Parental 22q11.2 deletion (inherited cases)

 

Clinical Features

DiGeorge Syndrome affects multiple organ systems — remember the triad:
Cardiac defects + Hypocalcemia + Immune deficiency

A. Classic Triad

System Defect Consequence
Thymus Hypoplasia / Aplasia ↓ T-cell production → Immunodeficiency
Parathyroid Hypoplasia ↓ PTH → Hypocalcemia → Tetany, seizures
Heart Conotruncal defects Cyanotic congenital heart disease

B. Detailed Clinical Features

Category Features
Facial features Small mouth, cleft palate, low-set ears, hypertelorism (wide eyes), micrognathia (small jaw)
Cardiac defects Tetralogy of Fallot, Interrupted aortic arch, Truncus arteriosus, VSD
Immune system Recurrent infections due to T-cell deficiency
Endocrine Hypocalcemia, tetany, seizures due to low parathyroid hormone
Growth & Development Delayed milestones, poor growth, learning disabilities
Psychiatric Anxiety, ADHD, depression, schizophrenia (in older patients)
Renal / Skeletal Kidney anomalies, scoliosis, skeletal malformations

 

Pathophysiology

 

Affected Organ Result of Deletion
Thymus Reduced T-lymphocyte production → immune deficiency
Parathyroid glands Decreased PTH → hypocalcemia, muscle cramps
Heart (conotruncal region) Defective cardiac septation → congenital heart disease
Face and palate Abnormal neural crest cell migration → facial deformities

 

Diagnosis

1. Clinical Evaluation

  • Characteristic facial appearance

  • Recurrent infections

  • Hypocalcemia symptoms (muscle spasms, seizures)

  • Congenital heart defects on echocardiography

2. Laboratory Tests

Test Findings
Serum calcium ↓ Decreased
Parathyroid hormone (PTH) ↓ Decreased
Lymphocyte count ↓ T-lymphocytes (CD3+)
Immunoglobulin levels May be normal or slightly low
Chest X-ray Small or absent thymic shadow

 

3. Genetic Tests

Test Purpose
FISH (Fluorescence in situ hybridization) Detects 22q11.2 deletion
Microarray / MLPA Confirms microdeletion
Prenatal diagnosis Possible through amniocentesis if family history present

 

Differential Diagnosis

 

Condition Difference from DGS
SCID (Severe Combined Immunodeficiency) Both T and B cell defects
Hypoparathyroidism (non-genetic) No thymic defect
Velocardiofacial syndrome Overlaps but with mild immune defects

 

Management

There is no cure, but early treatment can correct many problems.

1. Medical Management

Problem Treatment
Hypocalcemia Calcium and vitamin D supplements
Heart defects Surgical repair of cardiac malformations
Immunodeficiency Antibiotics, avoidance of live vaccines, thymus or bone marrow transplant in severe cases
Endocrine abnormalities Lifelong monitoring of calcium and thyroid function
Seizures Anti-epileptic drugs if needed

 

2. Supportive Care

  • Speech and occupational therapy for learning and speech delays

  • Psychological counseling for behavioral problems

  • Regular follow-up for cardiac, endocrine, and immune function

3. Genetic Counselling

Aspect Details
Recurrence risk 50% if one parent carries the deletion
Testing Chromosome analysis for parents
Prenatal testing FISH or microarray during pregnancy
Family advice Genetic counselling before the next pregnancy

 

Prognosis

 

Severity Outcome
Mild immune deficiency Near normal life expectancy with treatment
Severe thymic aplasia Life-threatening infections in infancy
Heart defects Correctable by surgery
Neurodevelopmental delay Improved by therapy and education

 

MCQs

  1. DiGeorge Syndrome is caused by a deletion in which chromosome?
    A. Chromosome 13
    B. Chromosome 18
    C. Chromosome 22
    D. Chromosome 21

  2. The exact chromosomal location of the deletion in DiGeorge Syndrome is:
    A. 22q11.2
    B. 21q22
    C. 13q14
    D. 15q11

  3. DiGeorge Syndrome is also known as:
    A. Turner Syndrome
    B. Velocardiofacial Syndrome
    C. Edwards Syndrome
    D. Cri-du-chat Syndrome

  4. The major organ systems affected in DiGeorge Syndrome include:
    A. Liver and spleen
    B. Thymus, heart, and parathyroid
    C. Brain and kidneys
    D. Skin and pancreas

  5. Which embryological structure is mainly affected in DiGeorge Syndrome?
    A. 1st pharyngeal pouch
    B. 2nd pharyngeal pouch
    C. 3rd and 4th pharyngeal pouches
    D. 5th pharyngeal pouch

  6. Defective development of the thymus in DiGeorge Syndrome leads to:
    A. T-cell deficiency
    B. B-cell deficiency
    C. Both T and B cell deficiency
    D. NK cell deficiency

  7. Hypocalcemia in DiGeorge Syndrome is due to:
    A. Vitamin D deficiency
    B. Hypoparathyroidism
    C. Renal failure
    D. Pancreatic insufficiency

  8. The most common cardiac defect in DiGeorge Syndrome is:
    A. Atrial septal defect
    B. Tetralogy of Fallot
    C. Mitral valve prolapse
    D. Patent ductus arteriosus

  9. Which gene is mainly responsible for DiGeorge Syndrome features?
    A. BRCA1
    B. TBX1
    C. TP53
    D. CFTR

  10. Which of the following best describes the inheritance pattern of DiGeorge Syndrome?
    A. Autosomal recessive
    B. Autosomal dominant
    C. X-linked
    D. Multifactorial

  11. Most cases of DiGeorge Syndrome occur due to:
    A. Viral infection
    B. New spontaneous mutation (de novo)
    C. Radiation exposure
    D. Drug toxicity

  12. The triad of DiGeorge Syndrome includes:
    A. Cardiac defects, hypocalcemia, and immune deficiency
    B. Renal failure, anemia, and edema
    C. Diabetes, obesity, and hypertension
    D. Skin rash, fever, and cough

  13. The thymus in DiGeorge Syndrome is usually:
    A. Enlarged
    B. Normal
    C. Hypoplastic or absent
    D. Inflamed

  14. The chest X-ray of a DiGeorge patient typically shows:
    A. Enlarged thymic shadow
    B. Absent thymic shadow
    C. Calcified thymus
    D. Normal findings

  15. Which immune cells are reduced in DiGeorge Syndrome?
    A. Neutrophils
    B. T-lymphocytes
    C. B-lymphocytes
    D. Platelets

  16. Hypocalcemia in DiGeorge Syndrome can lead to:
    A. Tetany and seizures
    B. Jaundice
    C. Anemia
    D. Muscle hypertrophy

  17. The facial appearance of a child with DiGeorge Syndrome may show:
    A. Cleft palate and low-set ears
    B. Large tongue and flat face
    C. Bulging eyes and high nasal bridge
    D. Thick lips and wide mouth

  18. Which diagnostic test confirms 22q11.2 deletion?
    A. ELISA
    B. FISH (Fluorescence In Situ Hybridization)
    C. Karyotyping only
    D. Coombs test

  19. What is the most common cause of death in untreated DiGeorge Syndrome?
    A. Cardiac defect and infection
    B. Anemia
    C. Dehydration
    D. Renal stones

  20. The main immunological defect in DiGeorge Syndrome is due to absence of:
    A. Bone marrow
    B. Thymus
    C. Spleen
    D. Lymph nodes

  21. Which endocrine gland is underdeveloped in DiGeorge Syndrome?
    A. Thyroid
    B. Parathyroid
    C. Adrenal
    D. Pituitary

  22. Parathyroid gland hypoplasia in DiGeorge Syndrome results in:
    A. Hypercalcemia
    B. Hypocalcemia
    C. Hyperkalemia
    D. Hypoglycemia

  23. Which of the following is a mnemonic for remembering DiGeorge Syndrome features?
    A. CATCH-22
    B. WAGR
    C. CAH
    D. TORCH

  24. In the mnemonic CATCH-22, “C” stands for:
    A. Cleft lip
    B. Cardiac defects
    C. Cataract
    D. Cystic fibrosis

  25. The “T” in CATCH-22 represents:
    A. Thymic hypoplasia
    B. Thyroid enlargement
    C. Tetanus
    D. Tumor formation

  26. The “H” in CATCH-22 stands for:
    A. Hypocalcemia
    B. Hypothyroidism
    C. Hypertension
    D. Hyperglycemia

  27. Which cardiac defect is commonly associated with DiGeorge Syndrome?
    A. Truncus arteriosus
    B. Mitral stenosis
    C. Aortic regurgitation
    D. Coarctation of aorta

  28. The most likely electrolyte imbalance in DiGeorge Syndrome is:
    A. High calcium
    B. Low calcium
    C. High sodium
    D. Low potassium

  29. In DiGeorge Syndrome, which type of infections are most frequent?
    A. Viral and fungal infections
    B. Bacterial only
    C. Parasitic
    D. Protozoal

  30. Which of the following laboratory findings supports the diagnosis?
    A. High calcium, low PTH
    B. Low calcium, low PTH
    C. Low calcium, high PTH
    D. Normal calcium, high PTH

  31. The FISH test detects deletion on chromosome 22 by using:
    A. Radiolabeled isotopes
    B. Fluorescent DNA probes
    C. Enzyme-linked antibodies
    D. Histological staining

  32. The recurrence risk if one parent carries 22q11.2 deletion is:
    A. 0%
    B. 10%
    C. 25%
    D. 50%

  33. Children with DiGeorge Syndrome should avoid:
    A. Inactivated vaccines
    B. Live attenuated vaccines
    C. Vitamin D supplements
    D. Calcium intake

  34. Which treatment is used to correct hypocalcemia in DiGeorge Syndrome?
    A. Iron supplements
    B. Calcium and Vitamin D therapy
    C. Insulin therapy
    D. Antihistamines

  35. Prognosis of DiGeorge Syndrome mainly depends on:
    A. Severity of heart defects and immune deficiency
    B. Hair color
    C. Eye color
    D. Height of patient

Answer Key

  1. C — Chromosome 22

  2. A — 22q11.2

  3. B — Velocardiofacial Syndrome

  4. B — Thymus, heart, and parathyroid

  5. C — 3rd and 4th pharyngeal pouches

  6. A — T-cell deficiency

  7. B — Hypoparathyroidism

  8. B — Tetralogy of Fallot

  9. B — TBX1

  10. B — Autosomal dominant

  11. B — New spontaneous mutation (de novo)

  12. A — Cardiac defects, hypocalcemia, and immune deficiency

  13. C — Hypoplastic or absent

  14. B — Absent thymic shadow

  15. B — T-lymphocytes

  16. A — Tetany and seizures

  17. A — Cleft palate and low-set ears

  18. B — FISH (Fluorescence In Situ Hybridization)

  19. A — Cardiac defect and infection

  20. B — Thymus

  21. B — Parathyroid

  22. B — Hypocalcemia

  23. A — CATCH-22

  24. B — Cardiac defects

  25. A — Thymic hypoplasia

  26. A — Hypocalcemia

  27. A — Truncus arteriosus

  28. B — Low calcium

  29. A — Viral and fungal infections

  30. B — Low calcium, low PTH

  31. B — Fluorescent DNA probes

  32. D — 50%

  33. B — Live attenuated vaccines

  34. B — Calcium and Vitamin D therapy

  35. A — Severity of heart defects and immune deficiency