Learning objectives

• Define DiGeorge syndrome
• Describe the signs, symptoms, and complications associated with DiGeorge syndrome
• Anesthetic management of a patient with DiGeorge syndrome

Definition and mechanisms

• DiGeorge syndrome, or 22q11.2 deletion syndrome, is a syndrome caused by a heterozygous microdeletion on the long arm of chromosome 22
• This deletion results in the poor development of several body systems
• 90% of cases occur due to a new mutation during early development, while 10% are inherited (autosomal dominant)
• Memory aid: CATCH-22
  • Cyanotic congenital heart defect
  • Abnormal facies
  • Thymic aplasia or hypoplasia
  • Cognitive impairment, cleft palate
  • Hypoparathyroidism, hypocalcemia
  • 22q11.2 deletion

Signs, symptoms, and complications

• Congenital heart disease (40%): Particularly conotruncal malformations (e.g., interrupted aortic arch, persistent truncus arteriosus, tetralogy of Fallot, and ventricular septal defect)
• Cyanosis
• Palatal abnormalities (50%): Velopharyngeal incompetence, submucosal cleft palate, and cleft palate with or without cleft lip
• Characteristic facial features (including hypertelorism): Underdeveloped chin (micrognathia and retrognathia), low-set ears, wide-set eyes, or a narrow groove in the upper lip
• Frequent infections due to thymic aplasia or hypoplasia
• Developmental delay 
• Learning difficulties (90%) including cognitive deficits, attention deficit disorders
• Hypocalcemia (50%) due to hypoparathyroidism
• Significant feeding problems (30%), gastroesophageal reflux disease (GERD), and failure to thrive
• Renal anomalies (37%)
• Hearing loss
• Laryngotracheoesophageal anomalies
• Growth hormone deficiency
• Autoimmune disorders (e.g., rheumatoid arthritis or Graves disease) 
• Immune disorders due to reduced T-cell numbers
• Seizures (with or without hypocalcemia)
• Skeletal abnormalities (e.g., scoliosis)
• Psychiatric disorders and behavioral problems (e.g., schizophrenia develops in 25-30% by adulthood, ADHD, autism spectrum disorder)

Pathophysiology

Treatment

There is no cure for DiGeorge syndrome, but certain individual features are treatable using standard treatments

• Hypoparathyroidism: Calcium and vitamin D supplements
• Congenital heart defects: Surgical repair soon after birth to repair the defect and improve the supply of oxygen-rich blood
• Limited thymus gland function: Infections (e.g., colds and ear infections) are generally treated as they would be in any child; normal schedule of vaccines
• Severe thymus gland function: Transplant of thymus tissue, specialized bone marrow, or specialized disease-fighting blood cells
• Cleft palate: Surgical repair
• Overall development: Speech therapy, occupational therapy, and developmental therapy 

Anesthesia considerations

• Airway
  • Difficult airway
    • Small mouth opening, retrognathia, micrognathia
    • Cleft palate, velopharyngeal insufficiency: Avoid nasal intubation
  • Aspiration risk 
    • Pharyngeal insufficiency, GERD
• Breathing
  • Nasal obstruction
  • Obstructive sleep apnea (OSA)
• Circulation
  • Conotruncal anomalies 
  • Long QT from hypocalcemia
• Disability
  • Developmental delay, behavioral issues
  • Tetany and seizures from hypocalcemia
• Genitourinary
  • Hypocalcemia from hypoparathyroidism (especially in newborns)
  • Renal anomalies
• Immunodeficiency
  • Thymic hypoplasia: Recurrent infections; aseptic technique needed
  • Thymic aplasia: Severe combined immunodeficiency (SCID)
• Musculoskeletal
  • Scoliosis

Management

Keep in mind

• Perform a recent cardiac evaluation in patients with residual congenital heart disease
• Anticipate a difficult intubation
• Use a careful aseptic technique
• Check calcium levels

Suggested reading

• Haché M. DIGEORGE SYNDROME. In: Houck PJ, Haché M, Sun LS. eds. Handbook of Pediatric Anesthesia. McGraw Hill; 2015. Accessed March 06, 2023. https://accessanesthesiology.mhmedical.com/content.aspx?bookid=1189&sectionid=70364073