Watson syndrome

Other Names

Alagille syndrome, Hepatic ductular hypoplasia; Watson Alagille syndrome; Alagille-Watson syndrome; Cholestasis with peripheral pulmonary stenosis; Arteriohepatic dysplasia; Paucity of interlobular bile ducts; Cardio-vertebral syndrome; Watson-Miller syndrome; Hepatofacioneurocardiovertebral syndrome

Clinical features

• Alagille syndrome is a genetic syndrome that can affect the liver and other parts of the body.
• Signs and symptoms of Alagille syndrome are generally noticed in infancy or early childhood.
• Type of symptoms and severity varies greatly, even among people in the same family, so that in some cases the symptoms are severe, and in others, very mild.
• The liver problems may be the first symptoms of the syndrome, and may include yellow color of the skin and whites of the eyes (jaundice); itchy skin; bumps on the skin caused by deposits of cholesterol and fats (xanthomas); pale, loose bowel movements; and poor growth.
• Alagille syndrome can also affect other parts of the body including the heart, brain, kidneys, blood vessels, eyes, face, and skeleton.
• People with Alagille syndrome may have distinctive facial features too, including a broad, prominent forehead, deep-set eyes, and a small, pointed chin.
• While there is no known cure for Alagille syndrome, there are treatments that can help control symptoms.
• Possible treatments may include medication that increases the flow of bile and careful management of diet to minimize nutrition and vitamin related problems.
• In severe cases, a liver transplant may be necessary.

Cause

The liver problems result from having fewer small bile ducts than normal in the liver. This leads to bile building-up inside the liver, which in turn causes liver scarring and damage. Alagille syndrome is caused by changes or mutations in the JAG1 and NOTCH2 genes.

Inheritance

Inheritance is autosomal dominant. However, in about half of cases the mutation occurs as a new change ("de novo") without being inherited from either parents.

Symptoms

Alagille syndrome is a complex multisystem disease involving the liver, brain, heart, eyes, face, and skeleton. Symptoms typically present in infancy or early childhood. The severity of the syndrome varies greatly, even within the same family. Symptoms range from so mild as to go unnoticed to severe enough to require heart and/or liver transplants.

80%-99% of people have these symptoms

• Cholestasis
• Corneal dystrophy
• Failure to thrive
• Hepatomegaly
• Reduced number of intrahepatic bile ducts

Autosomal Dominant Inheritance

Treatment

Many doctors may be necessary for the best management of Alagille syndrome, including specialists in medical genetics, gastroenterology (for digestive system and liver problems), nephrology (for kidney problems), nutrition, cardiology (for heart problems), ophthalmology (for eye problems), liver transplantation, and child development.

Treatment may include:

Medication that increases bile flow (ursodeoxycholic acid) and that reduces the itching, such as cholestyramine, rifampin, and naltrexone. Biliary diversion procedures (partial internal biliary diversion and ileal exclusion) that interrupt the normal bile circulation between the intestines and liver resulting in the bile being eliminated and therefore lowering the blood bile levels. These procedures relieve symptoms of liver disease, such as itching, and improve the quality of life, but do not prevent the progression of liver disease.

Vitamin and special nutrition supplementation to support proper growth and development.

Liver Transplantation to increase life span and improve liver function for those with end stage liver disease.

Watson syndrome is an autosomal dominant condition characterized by Lisch nodules of the ocular iris, axillary/inguinal freckling, pulmonary valvular stenosis, relative macrocephaly, short stature, and neurofibromas.

Watson syndrome is allelic to NF1, the same gene associated with neurofibromatosis type 1.

See also

• Westerhof syndrome
• List of cutaneous conditions

Latest research (Pubmed)

• Most recent articles
• Ongoing trials
• Alagille Syndrome.

Mitchell E, Gilbert M, Loomes KM. Clin Liver Dis. 2018 Nov;22(4):625-641. doi: 10.1016/j.cld.2018.06.001. Epub 2018 Aug 22. PMID: 30266153 Review. Alagille syndrome is a complex multisystem autosomal dominant disorder with a wide variability in penetrance of clinical features.

• Alagille Syndrome: An Overview.

Jesina D. Neonatal Netw. 2017 Nov 1;36(6):343-347. doi: 10.1891/0730-0832.36.6.343. PMID: 29185945 Review. Alagille syndrome (AGS) is a highly complex, multisystem, autosomal dominant disorder that is caused by a defect in the Notch signaling pathway.

• Alagille Syndrome

Wakim El-Khoury J, Venetz JP, Rutz T, Sciarra A, Unger S, Sempoux C, Moradpour D, Fraga M. Rev Med Suisse. 2019 Aug 28;15(660):1506-1510. PMID: 31496175 Review. French. Alagille syndrome is a rare disorder with low physician awareness. Inherited mutations affect the Notch pathway. Although the molecular basis of Alagille syndrome is well defined, no specific targeted therapy exists

• Alagille syndrome: pathogenesis, diagnosis and management.

Turnpenny PD, Ellard S. Eur J Hum Genet. 2012 Mar;20(3):251-7. doi: 10.1038/ejhg.2011.181. Epub 2011 Sep 21. PMID: 21934706 Free PMC article. Review. Alagille syndrome (ALGS), also known as arteriohepatic dysplasia, is a multisystem disorder due to defects in components of the Notch signalling pathway, most commonly due to mutation in JAG1 (ALGS type 1), but in a small proportion of cases mutation in NOTCH2.

Frequently asked questions

• What are the symptoms of Alagille syndrome?

See above - Jaundice, xanthomas, pale, loose bowel movements and poor growth etc.

• Is there a cure for Alagille syndrome?

No, there is no cure but there are many treatments as noted above including supportive care, vitamins, medications and or liver transplantation.

• What is Alagille syndrome life expectancy?

The life expectancy varies - about 75% of people diagnosed with the syndrome in childhood live to at least age 20.

• Is Alagille syndrome detectable prior to birth?
• Yes. Prenatal genetic testing can detect the Alagille syndrome as it is a genetic disorder.

The diagnosis of Alagille syndrome can be confirmed in many cases by molecular genetic testing, which reveals the presence of a JAG1 or NOTCH2 gene mutation.

• Is Alagille syndrome rare?

Yes. It is a rare genetic disorder. It affects about 1 in 70,000 newborns.

Answer these questions

• Can you live with Alagille syndrome?
• What does the 20th chromosome do?
• What do people with Alagille syndrome look like?
• Is Alagille syndrome a disability?
• Does Alagille syndrome affect development?
• What is ALGS?
• What is posterior Embryotoxon?

External links

• Wikipedia

Classification	ICD-10: Q87.1 MeSH: D009456 DiseasesDB: 32244
External resources	Orphanet: 3444