Alagille syndrome Q44.7

• Chronic cholestasis with pruritus (100% of patients)
• Typical facies (85%)
• Hypoplasia or stenosis of the pulmonary artery (84%)
• Butterfly deformity of the vertebral arches (63%)
• Posterior embryotoxone (76%)
• Xanthome (28%).

Mutations in the NOTCH2 gene. NOTCH2 is a protein-coding gene. Diseases associated with NOTCH2 include Alagille syndrome 2 and Haydu-Cheney syndrome.

Integument: Pruritus, xanthomatosis ( xanthomas are observed on palms and fingers, elbows, groin region and popliteal fossa, and buttocks).

Extracutaneous manifestations: Cholestasis within the first 3 months of life (normal colored or acholic stools). Hepatomegaly is always present. Bilirubin levels are not excessive (70-120 µmol/l), but extremely high cholesterol and lipid levels are found. Typical facies with prominent forehead, sunken eyes and mild hypertelorism as well as a small prominent chin. The so-called "posterior embryotoxon" is a white line 1-2 mm above the limbus corneae, which is found in 10% of all healthy individuals and 10% of all patients with cholestasis.

Colestyramine (e.g. Colestyr from ct) 4-16 g/day p.o. In children weight-adapted dosage: adult dose x kg bw of child divided by 70.

Try non-sedating oral antihistamines such as levocetirizine (e.g. Xusal) 1 tbl. p.o. 1 time/day, Desloratadine (e.g. Aerius) 1 times/day 1 tbl. p.o. or sedating antihistamines such as clemastine (e.g. Tavegil) 2 times/day 1 tbl., dimetindene (e.g. Fenistil) 2 times/day 1 tbl. or hydroxyzine (e.g. Atarax) 1-3 tbl./day.

1. Alagille D et al (1975) Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur. J Pediatr 86: 63-71
2. Alagille D (1988) Paucity of Interlobular Bile Ducts. In: Waldschmidt J, Charissi G, Schier F (eds.) Cholestasis in Neonates. Zuckerschwerdt publishing house, Munich, S. 33-46
3. Dufour JF, Pratt DS (2001) Alagille syndrome with colonic polyposis. At J Gastroenterol 96: 2775-2777
4. Garcia MA et al (2005) Alagille syndrome: cutaneous manifestations in 38 children. Pediatric dermatol 22: 11-14
5. Krantz ID et al (2002) Alagille syndrome: chipping away at the tip of the iceberg. At J Med Genet 112: 160-162
6. Lykavieris P et al (2003) Bleeding tendency in children with Alagille syndrome. Pediatrics 111: 167-170
7. Odievre M et al (1981) Long-term prognosis for infants with intrahepatic cholestatis and patent extrahepatic biliary tract. Arch Dis Child 56: 373
8. Watson GH, Miller V (1973) Arteriohepatic dysplasia. Familial pulmonary artery stenosis with neonatal liver disease. Arch Dis Child 48: 459-466