What are the symptoms and management of 22q11.2 deletion syndrome?

Symptoms and Management of 22q11.2 Deletion Syndrome

22q11.2 deletion syndrome presents with a complex constellation of multisystem manifestations requiring coordinated multidisciplinary care, with patients typically exhibiting 9 different clinical features (range 3-22) that accumulate over time. 1

Clinical Manifestations

Cardiovascular System

• Conotruncal cardiac anomalies (~80% in infancy-diagnosed cases, ~54% in later diagnoses) 1
  • Tetralogy of Fallot
  • Ventricular septal defects
  • Truncus arteriosus
  • Aortic arch anomalies

Immune System

• T-cell deficiency due to thymic hypoplasia (80% of infants) 1
• Recurrent and prolonged upper/lower respiratory tract infections 2
• Autoimmune disorders (up to 20%) 2
• Allergies (up to 40%) 2
• Progressive loss of antibody function 2

Endocrine System

• Hypocalcemia due to hypoparathyroidism causing seizures, tetany, and arrhythmias 1
• Thyroid dysfunction 1
• Growth hormone deficiency 1

Neurological/Developmental

• Developmental delay/intellectual disability (median IQ ~76) 1
• Speech and language delays/disorders 2
• Attention deficit hyperactivity disorder (up to ~40%, predominantly inattentive type) 2
• Autism spectrum disorder (up to ~30%) 2
• Anxiety disorders (~35% of children) 2
• Risk for psychotic disorders (~10% by late adolescence) 2
• Seizures (up to 15% unprovoked) 2

Musculoskeletal

• Scoliosis (50%) 1
• Cervical/occipital anomalies 2
• Limb differences (arachnodactyly, syndactyly) 1
• Clubfoot, patellar dislocation 2
• Nonspecific lower leg/foot pains 2

Genitourinary

• Renal anomalies (15-16%) 1
  • Hydronephrosis
  • Unilateral renal agenesis
  • Multicystic dysplastic or hypoplastic kidney
  • Simple renal cysts
• Genital anomalies 1
  • Males: cryptorchidism, hypospadias
  • Females: absent vagina and/or uterus

Hematological

• Mild to moderate thrombocytopenia 2
• Increased platelet volume 2
• Risk for hematologic autoimmunity 2
• Anemia and leukopenia 2

Gastrointestinal

• Feeding difficulties in infancy 1
• Gastroesophageal reflux disease 1
• Constipation 1

Management Approach

Diagnostic Testing

• Chromosomal microarray analysis (CMA) is preferred (94% detection rate) 1
• FISH testing may be used in some cases (85% detection rate) 1

Multidisciplinary Management

1. Cardiovascular

   • Regular cardiac evaluations 1
   • Cardiac surgical repair when indicated 1
   • Perioperative monitoring of calcium levels and complete blood count 2

2. Immunological

   • Early T-cell evaluation to determine need for thymus transplant 2
   • Assessment for live viral vaccine safety 2
   • Monitor for humoral deficiency 2
   • Immunoglobulin replacement therapy for select patients 2
   • Standard vaccinations including COVID-19 and influenza 2

3. Endocrine

   • Calcium and vitamin D supplementation for hypocalcemia 1
   • Regular monitoring of calcium, PTH, and thyroid function 1

4. Neurological/Developmental

   • Early intervention for developmental delays 1
   • Formal neuropsychological testing for all children 2
   • Reassessment at transition periods (primary to secondary school) 2
   • Standard management of treatable psychiatric conditions 2
   • Polysomnography for suspected sleep disorders 2

5. Musculoskeletal

   • Routine scoliosis screening 2
   • One-time screening for cervical spinal anomalies around age 4 2
   • Radiographs for suspected patellar dislocation 2

6. Hematological

   • Yearly complete blood counts 2
   • Careful perioperative monitoring 2

Special Considerations

Surgical Procedures

• Monitor calcium and complete blood count perioperatively 2
• Anticipate need for smaller intubation equipment 2
• Attention to anatomical variants 2

Transition to Adult Care

• Identify adult practitioners before age 18 2
• Consider legal guardianship before age 18 2
• Create portable health care summaries 2

Reproductive Health

• Preconception counseling 2
• Specialized care during pregnancy and delivery 2
• Contraceptive options discussion 2

Pitfalls and Caveats

1. Diagnostic Delays: Many patients are diagnosed late when presenting with non-cardiac symptoms 3

2. Accumulating Features: Clinical features accumulate over time, requiring ongoing surveillance 4

3. Ascertainment Bias: Clinical presentation varies based on how patients are identified (cardiac vs. psychiatric) 4

4. Mortality Risk: 5-15% mortality in children, primarily in first year of life due to complex CHD with comorbidities 2

5. Recessive Conditions: Variants on the non-deleted chromosome can unmask recessive conditions 5

6. Internet Safety: Patients are vulnerable to exploitation online due to social and cognitive challenges 2

7. Medication Considerations: Avoid medications that can worsen hypocalcemia or psychiatric symptoms 2