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A newborn with Tetralogy of Fallot is noted to have hypocalcemia and absent thymic shadow on chest X-ray. He has subtle facial features including hooded eyelids and a bulbous nasal tip. FISH confirms a 22q11.2 deletion.

  • Most common microdeletion syndrome (~1/4,000 live births)
  • Deletion: 22q11.2 (~3 Mb in 90%, ~1.5 Mb in 10%)
  • Includes TBX1 gene (cardiac/thymic/parathyroid development)
  • ~90% de novo; 10% inherited (AD with variable expression)
  • Cardiac: conotruncal defects (TOF, interrupted aortic arch, truncus arteriosus, VSD)
  • Hypocalcemia (hypoparathyroidism)
  • Immune deficiency (thymic hypoplasia)
  • Palatal abnormalities: VPI, cleft palate, hypernasal speech
  • Characteristic facies: hooded eyelids, bulbous nose, small ears
  • Learning disabilities, psychiatric illness (schizophrenia risk ~25%)
  • CMA or FISH for 22q11.2
  • Always test newborns with conotruncal heart defects (TOF, interrupted aortic arch, truncus arteriosus)
  • Parental testing indicated once a proband is identified (autosomal dominant; ~10% inherited from a mildly affected parent)
  • Multidisciplinary care: cardiology, immunology, endocrinology, ENT/speech, developmental support
  • Cardiac surgical repair of conotruncal defects; monitor calcium perioperatively
  • Monitor and treat hypocalcemia (calcium, vitamin D); endocrine follow-up
  • Immune evaluation before live vaccines; avoid in significant T-cell deficiency
  • Speech therapy and palate/VPI surgical evaluation; developmental and educational services
  • Psychiatric surveillance through adolescence and adulthood (anxiety, ADHD, psychosis risk)

CATCH 22: Cardiac defects, Abnormal facial features, Thymic hypoplasia, Cleft palate, Hypocalcemia, chromosome 22.