[MIM 118 450, 610 205]

(arterio-hepatic dysplasia, Alagille-Watson syndrome, paucity of intrahepatic biliary tracts)

Estimated incidence: 1/30 000. Chronic cholestatic liver disease: dominant autosomal transmission with low penetrance of a mutation of the JAG1 (20p12) or NOTCH2 gene (1p12). Paucity of intrahepatic bile ducts or  arterio-hepatic dysplasia causing cholestatic jaundice with pruritus and xanthomas, associated with:

-         a typical facies (96 %): triangular face with a bulging forehead and pointed chin, retrognathia,  deep-set eyes, a hooked nose, hypertelorism, off-center pupils, down-slanted palpebral fissures 

-         a congenital heart disease (97 %): most often distal stenosis of the pulmonary arteries; ASD, VSD, tetralogy of Fallot

-         abnormal thoracic vertebrae: butterfly-like malformation (51 %)

-         a posterior embryotoxon (whitish lipid deposit) at fundus examination; sometimes a pigmentary retinopathy.

 

If all the above 4 items are present, the disease is qualified as a syndromic form; non-syndromic forms evolve more quickly towards a deterioration of liver function and biliary cirrhosis. 

There may also be:

-        renal anomalies (40 %): dysplasia or hypoplasia

-        osteopenia due to rickets

-        hypothyroidism

-        Moya-Moya like vascular cerebral abnormalities with a risk of intracerebral hemorrhage (25 %).  (see this term)

-        chronic arthritis similar to juvenile arthritis but resistant to classic treatments and apparently disappearing after  liver transplantation.

The pruritus (often very severe) of some patients responds well to oral maralixibat, an inhibitor of the ileal transport of the biliary salts that interrupts their enterohepatic cycle.

 Anesthetic implications: 

Liver failure. Risk of ADEK vitamins deficiency. Variable portal hypertension. Echocardiography. In case of neuraxial block: check the coagulation and avoid entering the spinal canal at the level of a malformed vertebra. Avoid nephrotoxic agents. Maintain adequate cerebral perfusion pressure and avoid hyperventilation. Check the mouth opening (temporomandibular arthritis ?)

References : 

-         Choudry DK, Rehman MA, Schwartz RE, Piccoli DA. 
The Alagille's syndrome and its anaesthetic considerations. 
Paediatr Anaesth 1998; 8: 79-82

-         Subramaniam K, Myers LB. 
Combined general and epidural anesthesia for a child with Alagille syndrome. 
Paediatr Anaesth 2004; 14: 787-91.

-         Rahmoune FC, Bruyère M, Tecsy M, Benhamou D. 
Alagille syndrome and pregnancy: anesthetic management for caesarean section. 
Int J Obstetr Anesth 2011; 20: 355-8. 

-        Ferrara G, Giani T, Lieberman SM, Kremer C, Hong S et al.
Alagille syndrome and chronic arthritis : an international case series.
J Pediatr 2020 ; 218 : 228-30.

Updated: January 2023