89  DiGeorge Syndrome

89.1 Introduction

DiGeorge Syndrome (DGS), or 22q11.2 deletion syndrome, is a rare genetic disorder with significant clinical variability. It affects multiple body systems, including the heart, immune system, endocrine organs, and facial structures. Due to its diverse presentations, this condition may go undiagnosed or misdiagnosed without appropriate genetic screening. Advances in medical research have improved the understanding and management of DiGeorge Syndrome, benefiting individuals and families impacted by this complex condition.

89.2 Definition

DiGeorge Syndrome is a chromosomal disorder caused by the deletion of a small segment of chromosome 22 at the q11.2 locus. It is characterized by congenital abnormalities affecting the heart, thymus, and parathyroid glands, leading to immune deficiency, hypocalcemia, and developmental delays. Also referred to as velocardiofacial syndrome (VCFS) or conotruncal anomaly face syndrome, DiGeorge Syndrome belongs to a spectrum of conditions grouped under 22q11.2 deletion syndromes.

89.3 Genetics

DiGeorge Syndrome occurs due to a microdeletion on the long arm (q) of chromosome 22 at position 11.2. This deletion results in the loss of approximately 30 to 40 genes. One of the most crucial genes affected is TBX1, which plays a vital role in embryonic development. The condition typically arises sporadically, although it can be inherited in an autosomal dominant manner. Inherited cases account for about 10% of all cases, meaning an affected individual has a 50% chance of passing the deletion to offspring. Most cases, however, result from de novo deletions during embryogenesis.

89.4 Clinical Features

The manifestations of DiGeorge Syndrome are highly variable, even among affected members of the same family. Clinical features can range from mild to severe and may affect multiple organ systems.

  1. Cardiac Abnormalities: Congenital heart defects are present in up to 75% of individuals. Common defects include:
  2. Immune Dysfunction: Hypoplasia or aplasia of the thymus results in impaired T-cell production, leading to varying degrees of immune deficiency. Severe cases may resemble complete DiGeorge Syndrome, which mimics severe combined immunodeficiency (SCID).
  3. Endocrine Abnormalities: These include
    • Hypoparathyroidism causing hypocalcemia
    • Thyroid dysfunction in some cases
  4. Craniofacial Features:
    • Cleft palate or submucosal cleft palate
    • Small or malformed ears
    • Long face with a prominent nasal bridge
  5. Neurodevelopmental and Psychiatric Disorders:
    • Developmental delays, learning disabilities
    • Speech and language difficulties
    • Increased risk of psychiatric conditions such as schizophrenia and anxiety disorders
  6. Gastrointestinal and Renal Anomalies:
    • Feeding difficulties in infancy
    • Structural abnormalities of the kidneys

89.5 Investigations

A thorough clinical assessment is essential for diagnosing DiGeorge Syndrome. The following investigations aid in confirming the diagnosis and assessing disease severity:

  1. Genetic Testing:

    • Fluorescence in situ hybridization (FISH) to detect the 22q11.2 deletion
    • Microarray analysis for more comprehensive chromosomal evaluation

  2. Immunological Studies:

    • Lymphocyte subset analysis to evaluate T-cell function
    • Immunoglobulin level measurement

  3. Cardiac Imaging:

    • Echocardiography to assess for congenital heart defects

  4. Calcium Levels:

    • Serum calcium and parathyroid hormone (PTH) measurements

  5. Endocrine Evaluation:

    • Thyroid function tests

  6. Radiological Imaging:

    • Renal ultrasound for structural anomalies

89.6 Treatment

Management of DiGeorge Syndrome requires a multidisciplinary approach tailored to each individual’s needs. Early diagnosis and intervention significantly improve outcomes.

  1. Cardiac Care:
    • Surgical correction of congenital heart defects when indicated
  2. Immune Management:
    • Prophylactic antibiotics and immunoglobulin replacement in cases of immune deficiency
    • Thymus transplantation in severe cases
  3. Calcium and Endocrine Management:
    • Calcium and vitamin D supplementation for hypocalcemia
    • Hormonal therapy for endocrine dysfunctions
  4. Speech and Developmental Support:
    • Speech therapy for communication difficulties
    • Educational interventions for cognitive delays
  5. Psychiatric Care:
    • Psychological counseling and psychiatric treatment for mental health conditions

89.7 Counseling

Genetic counseling plays a pivotal role in helping affected individuals and families understand the nature of the condition, its inheritance patterns, and reproductive risks. Key counseling points include:

  1. Risk of Recurrence: Parents of an affected child should be informed of the potential 50% inheritance risk if a parent carries the deletion.
  2. Prenatal Diagnosis: Options such as chorionic villus sampling (CVS) and amniocentesis can be offered to at-risk couples.
  3. Support Services: Families benefit from connections to support groups and advocacy organizations to navigate the challenges associated with the condition.

89.8 Conclusion

DiGeorge Syndrome is a complex genetic disorder with wide-ranging clinical manifestations. Advances in genetic testing have greatly improved diagnostic accuracy, enabling earlier interventions and better outcomes. Multidisciplinary care, including cardiac, immunological, developmental, and psychological support, is essential for managing the condition effectively. Through continued research and awareness, individuals living with DiGeorge Syndrome can achieved.