DiGeorge Syndrome

  

Original Editor - Safiya Naz

Top Contributors - Safiya Naz and Vidya Acharya  

Introduction

DiGeorge syndrome

DiGeorge syndrome is a primary immunodeficiency disorder caused by the deletion of a small part of chromosome 22. This chromosomal deletion disrupts the development of multiple body systems, leading to a wide range of clinical symptoms. It is characterized by congenital heart defects, immunodeficiency, characteristic facial features, developmental delays, and metabolic abnormalities such as hypocalcemia.

Prevalence

• Occurs in about 1 in 4,000 live births, making it one of the most common chromosomal microdeletion syndromes.
• Equally affects males and females.
• The actual prevalence may be underestimated due to mild or unrecognized cases.

Diagnosis

Diagnosis is typically based on clinical symptoms and confirmed with genetic testing. The following methods are used:

• Genetic testing:
  • Fluorescence in situ hybridization (FISH) or microarray analysis can detect the deletion on chromosome 22 at location 22q11.2.
  • Comparative genomic hybridization (CGH) may also be used.
• Echocardiogram:
  • Used to evaluate heart defects, which are common in DiGeorge syndrome.
• Immunologic testing:
  • Testing T-cell function can help evaluate the degree of immune deficiency due to thymic hypoplasia or aplasia.
• Calcium levels:
  • Blood tests to check for hypocalcemia, especially in infants presenting with seizures.
• Physical examination:
  • Detailed examination for the characteristic facial features, cleft palate, and skeletal abnormalities like scoliosis.
• Hearing and vision tests:
  • Assess for hearing loss and eye issues.

Symptoms

The symptoms of DiGeorge syndrome vary significantly, depending on the size and location of the genetic deletion and which organs and systems are affected. Symptoms can be evident at birth or emerge in early childhood.

• Cardiac abnormalities:
  • Tetralogy of Fallot
  • Truncus arteriosus
  • Interrupted aortic arch
  • Ventricular septal defect (VSD)
  • Pulmonary atresia
  • Less common: transposition of the great arteries, coarctation of the aorta, atrial septal defect (ASD), pulmonary stenosis, patent ductus arteriosus (PDA)
• Immune system problems:
  • Thymic hypoplasia or aplasia, resulting in frequent infections due to impaired T-cell production.
• Facial features:
  • Underdeveloped chin (micrognathia)
  • Low-set or malformed ears
  • Wide-set eyes (hypertelorism)
  • Hooded eyelids
  • A prominent nasal bridge and bulbous nasal tip
  • Asymmetric crying facies due to underdeveloped facial muscles
• Cleft palate:
  • Cleft lip and/or cleft palate
  • Velopharyngeal insufficiency, leading to speech difficulties
• Feeding difficulties:
  • Poor sucking and feeding in infancy
  • Failure to thrive due to difficulty with weight gain and poor muscle tone
• Hypocalcemia:
  • Low calcium levels in the blood, often due to hypoparathyroidism, leading to muscle spasms or seizures
• Developmental delays:
  • Delayed motor development, poor muscle tone (hypotonia)
  • Speech and language delays
  • Cognitive impairments, often mild to moderate intellectual disability
• Other features:
  • Hearing loss
  • Vision problems such as strabismus
  • Kidney abnormalities, including structural defects
  • Scoliosis or other skeletal deformities
  • Behavioral and psychiatric disorders (e.g., ADHD, autism spectrum disorder, anxiety)

Management

1. Multidisciplinary Approach: Management of DiGeorge syndrome requires coordination among various subspecialties, as patient presentations and outcomes vary significantly. While there is limited research supporting specific management protocols, early diagnosis and a comprehensive approach are essential for improving patient outcomes.

2. Neonatal Management:

• Cardiac Anomalies: Approximately 75% of patients present with congenital heart defects, often diagnosed at birth. Early echocardiographic evaluation is critical, as not all cardiac anomalies are immediately obvious. These defects are a leading cause of mortality, making prompt surgical intervention crucial.
• Immune System: About 75-80% of infants show low T-cell counts due to thymic hypoplasia, necessitating careful management, especially before cardiac surgery. Severe immunodeficiencies may require specialized interventions.

3. Developmental Management:

• Speech and Communication: Communication delays are a significant concern for families. Phonation issues may arise from laryngeal webs, velopharyngeal insufficiency, or vocal cord paralysis. Although surgery can correct some of these anatomical issues, speech remains a common challenge. Early speech therapy is important to help improve communication.
• Motor and Cognitive Development: Developmental interventions like physical therapy, early childhood education programs, and special education services can aid motor skills and cognitive development, especially in children with learning disabilities.

4. Management of Immunodeficiency:

• Most patients have reduced T-cell numbers due to thymic hypoplasia, though fewer than 1% require thymus transplantation. For mild or moderate T-cell deficiencies, close monitoring and preventive care are typically sufficient. Immunoglobulin replacement therapy may be considered for patients with recurrent infections.

5. Comprehensive Management Plan:

• Cardiac Care: Surgical correction of congenital heart defects, often combined with medications to support heart function before surgery.
• Hypocalcemia Management: Calcium and vitamin D supplementation to prevent hypocalcemic complications, such as seizures.
• Immune Therapy: Thymus transplantation or immunoglobulin therapy for those with severe immune deficiencies.
• Developmental and Behavioral Support: Early intervention for motor and language skills, special education for learning disabilities, and psychiatric care for behavioral issues like ADHD or autism.
• Hearing and Vision Support: Regular evaluations and corrective devices like hearing aids and glasses.

Physical Therapy Management

Physical therapy plays a role in improving motor skills, muscle tone, and physical function in individuals with DiGeorge syndrome.

• Motor development:
  • Early physical therapy is essential for improving gross motor development, especially in children with hypotonia or developmental delays.
• Strengthening exercises:
  • Exercises to improve muscle strength, particularly in cases of poor muscle tone.
• Postural training:
  • Specific interventions to manage scoliosis or other postural abnormalities.
  • Postural control exercises can help reduce strain on the spine and improve overall alignment.