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An infant with cholestatic jaundice has a characteristic triangular face, butterfly vertebrae on X-ray, and posterior embryotoxon on eye exam. Echocardiogram reveals peripheral pulmonary stenosis.

AD; JAG1 (~95%) or NOTCH2

  • ~60% de novo
  • Variable expression: some family members have subtle features only

Major criteria:

  • Hepatic: Bile duct paucity, cholestasis
  • Cardiac: Peripheral pulmonary stenosis, TOF
  • Skeletal: Butterfly vertebrae
  • Ocular: Posterior embryotoxon
  • Facial: Triangular face, prominent forehead, deep-set eyes
  • Liver biopsy shows bile duct paucity; clinical diagnosis rests on cholestasis plus characteristic features (posterior embryotoxon, butterfly vertebrae, peripheral pulmonary stenosis, facial features)
  • JAG1 (~95%) or NOTCH2 molecular testing confirms the diagnosis and clarifies the variable familial phenotype
  • Echocardiography, ophthalmologic exam, and spine imaging characterize the multisystem involvement
  • Supportive: ursodeoxycholic acid and ileal bile acid transport inhibitors (such as maralixibat) for cholestatic pruritus
  • Aggressive nutritional support with fat-soluble vitamin (A, D, E, K) supplementation
  • Liver transplantation for end-stage liver disease or intractable pruritus; cardiology management of the pulmonary stenosis

Ala-gille = Wing-Fish: "Ala" is Spanish for "wing" (think butterfly wings for the butterfly vertebrae). "Gills" are fish lungs (think pulmonary artery stenosis). The remaining features: gille = gone are the bile ducts (bile duct paucity), triangular facies, and posterior embryotoxon.

Alagille syndrome mnemonic: "Ala" means wing in Spanish; think butterfly wings for the butterfly vertebrae
Alagille syndrome mnemonic: "Ala" means wing in Spanish; think butterfly wings for the butterfly vertebrae