DiGeorge syndrome

DiGeorge Syndrome (22q11.2 Deletion Syndrome)
Facial characteristics of a patient with 22q11.2 deletion syndrome
Synonyms	Velocardiofacial syndrome (VCFS), Conotruncal anomaly face syndrome (CTAF), Autosomal dominant Opitz G/BBB syndrome, Cayler cardiofacial syndrome
Pronounce	N/A
Specialty	N/A
Symptoms	Cleft palate, Congenital heart defects, Hypocalcemia, Immune system disorders, Developmental delay, Learning disabilities, Speech disorders
Complications	N/A
Onset	Prenatal development or early childhood
Duration	N/A
Types	N/A
Causes	22q11.2 deletion
Risks	N/A
Diagnosis	Clinical examination, Fluorescence in situ hybridization (FISH), Comparative genomic hybridization (CGH)
Differential diagnosis	N/A
Prevention	N/A
Treatment	Surgery, Speech therapy, Calcium supplementation, Early intervention therapy
Medication	N/A
Prognosis	N/A
Frequency	1 in 4,000 newborns
Deaths	N/A

Autosomal dominant inheritance

FISH analysis of DiGeorge syndrome

Brain CT of 22q11.2 syndrome

DiGeorge Syndrome, also known as 22q11.2 Deletion Syndrome or Velocardiofacial Syndrome (VCFS), is a genetic disorder caused by the deletion of a small portion of chromosome 22 at position 22q11.2. This syndrome affects multiple systems in the body and is associated with cleft palate, congenital heart defects, immune system dysfunction, hypocalcemia, developmental delays, and learning disabilities. It is one of the most common microdeletion syndromes, occurring in approximately 1 in 4,000 live births, though the actual number may be higher due to undiagnosed cases.

Signs and Symptoms

The symptoms of DiGeorge Syndrome vary widely, even among affected family members. Some individuals may have mild symptoms, while others experience severe complications.

Craniofacial Features

• Cleft palate or other palatal abnormalities
• Characteristic facial features, including:
• Elongated face
• Almond-shaped eyes
• Wide nose bridge
• Small ears
• Underdeveloped chin (micrognathia)

Cardiovascular Abnormalities

• Congenital heart defects, particularly affecting the conotruncal region of the heart:
• Tetralogy of Fallot
• Interrupted aortic arch
• Ventricular septal defect
• Truncus arteriosus

Immune System Dysfunction

• Thymic hypoplasia (underdeveloped or missing thymus gland) leading to:
• Frequent infections
• Increased susceptibility to bacterial and viral infections
• Immune system disorders similar to severe combined immunodeficiency (SCID)

Endocrine and Metabolic Issues

• Hypocalcemia (low calcium levels) due to hypoparathyroidism
• Can result in seizures, muscle spasms, and neuromuscular irritability
• Abnormal kidney structure or function

Developmental and Neurological Effects

• Learning disabilities (affects ~90% of individuals)
• Speech disorders (affects ~75%)
• Delayed motor and cognitive development
• Non-verbal learning disability
• Verbal IQ scores tend to be significantly higher than performance IQ scores
• Autism spectrum disorder-like social communication difficulties
• Increased risk of psychiatric disorders, including:
• Depression
• Anxiety
• Schizophrenia (affects ~25-30% of adults with 22q11.2 deletion)

Genetics and Pathophysiology

DiGeorge Syndrome is caused by a deletion on chromosome 22 at position 22q11.2, which results in the loss of approximately 30 genes. Two key genes associated with the syndrome are:

• TBX1 – A transcription factor essential for the development of the heart, thymus, and palate.
• COMT – Involved in dopamine metabolism and linked to cognitive function and psychiatric symptoms.

Most cases (93%) occur sporadically due to a de novo deletion, meaning neither parent carries the deletion. However, in 7-10% of cases, the syndrome is inherited in an autosomal dominant manner, meaning an affected parent has a 50% chance of passing the deletion to their offspring.

Diagnosis

Clinical Evaluation

DiGeorge Syndrome is suspected in individuals with a combination of cardiac, craniofacial, immunological, and endocrine abnormalities. A full medical history and clinical examination are performed to assess characteristic signs.

Genetic Testing

The deletion in chromosome 22q11.2 can be detected using:

• Fluorescence in situ hybridization (FISH) – Standard diagnostic test (~95% detection rate)
• Comparative genomic hybridization (CGH) – More sensitive for identifying smaller deletions
• Multiplex ligation-dependent probe amplification (MLPA) – Can detect smaller submicroscopic deletions

Treatment and Management

There is no cure for DiGeorge Syndrome, but treatment focuses on managing individual symptoms.

Cardiac Treatment

• Congenital heart defects are often surgically corrected in infancy.

Endocrine and Metabolic Treatment

• Hypocalcemia is treated with calcium supplementation and vitamin D to prevent seizures and muscle spasms.
• Thyroid function monitoring is necessary as thyroid abnormalities may be present.

Immune System Management

• Infants with severe immunodeficiency may require thymus transplantation or bone marrow transplantation.
• Antibiotic prophylaxis may be necessary for those with recurrent infections.
• Live vaccines are contraindicated in individuals with severe T-cell deficiency.

Speech and Developmental Therapy

• Speech therapy for palatal dysfunction and articulation difficulties.
• Early intervention programs for learning disabilities and developmental delays.

Psychiatric and Neurological Support

• Individuals at risk for psychiatric conditions may require counseling or medication.
• Cognitive behavioral therapy (CBT) for anxiety and depression.
• Special education programs tailored to support learning differences.

Inheritance and Genetic Counseling

DiGeorge Syndrome is caused by a spontaneous deletion in most cases, meaning the risk of recurrence in future siblings is low. However, if a parent carries the deletion, each child has a 50% chance of inheriting the syndrome.

Genetic counseling is recommended for:

• Parents of a child with the syndrome.
• Adults diagnosed with the syndrome who are planning a family.

Prognosis

The lifespan and quality of life of individuals with DiGeorge Syndrome depend on the severity of their symptoms. With early intervention, medical management, and supportive care, many individuals lead productive lives.

See Also

• Chromosome 22
• Cleft palate
• Congenital heart defects
• Immunodeficiency
• Genetic syndromes

External Links

• Genetics Home Reference - 22q11.2 Deletion Syndrome
• National Center for Biotechnology Information (NCBI) - DiGeorge Syndrome

NIH genetic and rare disease info

• NIH info on DiGeorge syndrome

DiGeorge syndrome is a rare disease.