What are the features of 22q11.2 deletion syndrome?

Features of 22q11.2 Deletion Syndrome

22q11.2 deletion syndrome is a multisystem disorder characterized by congenital anomalies, developmental delay, and an array of early- and later-onset medical and psychiatric disorders affecting multiple organ systems, with variable expressivity even within families. 1, 2

Core Clinical Features

Cardiovascular Abnormalities

• Conotruncal cardiac anomalies (present in ~80% of cases diagnosed in infancy, ~54% in those diagnosed later) 1, 3
  • Tetralogy of Fallot
  • Ventricular septal defects
  • Truncus arteriosus
  • Aortic arch anomalies
• EKG abnormalities and arrhythmias may develop over time 2

Craniofacial and Palatal Features

• Velopharyngeal dysfunction
• Submucous cleft palate or overt cleft palate (25% of cases) 3
• Characteristic facial features:
  • Malar flatness
  • Hooded eyelids
  • Upslanting palpebral fissures
  • Bulbous nasal tip
  • Overfolded helices of ears 2
  • Micrognathia

Immunologic Abnormalities

• T-cell deficiency due to thymic hypoplasia (80% of infants) 1
• Recurrent infections, particularly upper and lower respiratory tract
• Autoimmune disorders (up to 20%)
• Allergies (up to 40%) 1, 2

Endocrine Disorders

• Hypocalcemia due to hypoparathyroidism (can cause seizures, tetany, cardiac arrhythmias)
• Thyroid dysfunction
• Growth hormone deficiency 2

Neuropsychiatric and Developmental Features

• Developmental delay/intellectual disability (median IQ ~76)
• Learning disabilities
• Speech and language delays
• Psychiatric disorders:
  • Attention deficit hyperactivity disorder
  • Anxiety disorders
  • Schizophrenia (20-25% of adults) 2

Gastrointestinal Features

• Feeding difficulties in infancy
• Gastroesophageal reflux disease
• Constipation
• Structural anomalies 2

Genitourinary Abnormalities

• Renal anomalies (~15-16% of patients) 1, 2:
  • Hydronephrosis
  • Unilateral renal agenesis
  • Multicystic dysplastic or hypoplastic kidney
  • Simple renal cysts
• Genital anomalies:
  • Males: cryptorchidism, hypospadias
  • Females: absent vagina and/or uterus 1

Skeletal Features

• Scoliosis (50%)
• Vertebral anomalies
• Limb differences (arachnodactyly, syndactyly) 2

Hematologic Features

• Mild to moderate thrombocytopenia (may progress with age)
• Increased platelet volume
• Risk for hematologic autoimmunity (immune thrombocytopenia, autoimmune hemolytic anemia) 1

Diagnostic Considerations

• Chromosomal microarray analysis (CMA) is the preferred diagnostic test
• FISH testing may miss smaller or atypical deletions (6% of cases) 2
• Features accumulate over time, with a median of 9 features per patient (range 3-22) 2
• Patients without cardiac defects often experience diagnostic delay 3

Clinical Patterns by Age at Diagnosis

• Infants typically present with:

  • Congenital heart defects (92% of those diagnosed before age 2) 3
  • Feeding difficulties
  • Hypocalcemia
  • Immunodeficiency

• Children diagnosed after age 2 typically present with:

  • Speech-language impairment
  • Developmental delay or learning difficulties
  • Recurrent infections
  • Characteristic mild dysmorphic features 3
  • Lower prevalence of cardiac defects (54%) 3

Atypical and Distal Deletions

• Central 22q11.2 deletions (LCR22-B to LCR22-D region) have:

  • Lower prevalence of congenital heart anomalies
  • Lower frequency of de novo deletions
  • Similar frequency of renal/urinary tract malformations, developmental delays, cognitive impairments and behavioral problems
  • Absence of cleft palate 4

• Distal 22q11.2 deletions are associated with:

  • Developmental delay or learning disability
  • Short stature
  • Microcephalus
  • Premature birth with low birth weight
  • Congenital heart malformations 5

Early diagnosis allows for better anticipatory care and improved outcomes, as many treatable conditions can be anticipated with appropriate surveillance 2.