Alagille syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Alagille syndrome is a multisystem genetic disorder that affects the liver, heart, eyes,face, skeleton, kidneys and vascular system. Problems associated with the disorder generally become evident in infancy or early childhood. The patients have a characteristic facial appearance. The disorder is inherited in an autosomal dominant pattern, and the estimated prevalence of Alagille syndrome is 1 in every 70,000 live births. The clinical features are highly variable even within the family.

Alagille syndrome can be associated with congenital heart disease, particularly Tetralogy of Fallot. The kidneys and central nervous system may also be affected. Cases of unilateral coronal craniosynostosis have also been described in association with this syndrome.

This condition is inherited in an autosomal dominant pattern.

The estimated prevalence of Alagille syndrome is 1 in every 70,000 live births.

Mortality is approximately 10%, with vascular accidents, cardiac disease, and liver disease accounting for most of the deaths. Vascular anomalies account for 34% of the mortality in this population ^[1].

The diagnosis is primarily clinical.

There is no known cure for Alagille’s Syndrome. Most of the treatments available are aimed at improving the functioning of the heart, and reducing the effects of impaired liver function.

Template:WH Template:WS

Please help WikiDoc by adding content here. It’s easy! Click here to learn about editing.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Alagille syndrome is a multisystem genetic disorder that affects the liver, heart, eyes,face, skeleton, kidneys and vascular system.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.

Approximately 30-50% of individuals have an inherited mutation and about 50-70% have a de novo mutation. The parents of a child with a de novo mutation have increased risk for recurrence because of the possibility of germline mosaicism. The offspring of an individual with Alagille syndrome have a 50% chance of having Alagille syndrome.

Mutations in the JAG1 gene cause Alagille syndrome.^[1] The JAG1 gene is involved in signaling between adjacent cells during embryonic development. This signaling influences how the cells are used to build body structures in the developing embryo. Mutations in JAG1 disrupt the signaling pathway, causing errors in development, especially of the heart, bile ducts in the liver, spinal column, and certain facial features.

NOTCH2 is also associated with Alagille syndrome.^[2]

Narrowed and malformed bile ducts in the liver produce many of the health problems associated with Alagille syndrome. Bile is produced in the liver and moves through the bile ducts into the small intestine, where it helps to digest fat. In Alagille syndrome, the bile builds up in the liver and causes scarring that prevents the liver from working properly to eliminate wastes from the bloodstream.

Children with Alagille syndrome may be at risk for pathologic fractures, which manifest at an early age and in a unique distribution favoring the lower extremity long bones ^[3].

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The disorder is inherited in an autosomal dominant pattern, and the estimated prevalence of Alagille syndrome is 1 in every 70,000 live births.

Template:WH Template:WS

Anyone who has a parent with the disease has a 50% chance of inheriting it.

Alagille syndrome is an autosomal dominant disorder, meaning it can be inherited from one parent who has the disorder. A child who has a parent with Alagille syndrome has a 50 percent chance of developing the disorder. Most people with Alagille syndrome have a mutation, or defect, in the Jagged1 (JAG1) gene. Mutations in the NOTCH2 gene are seen in less than 1 percent of people with Alagille syndrome.

Please help WikiDoc by adding content here. It’s easy! Click here to learn about editing.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The prognosis for Alagille syndrome patients varies largely on choice of treatment.

Children with Alagille syndrome may be at risk for pathologic fractures, which manifest at an early age and in a unique distribution favoring the lower extremity long bones ^[1]. In alagille syndrome, the bile may builds up in the liver and causes scarring that prevents the liver from working properly to eliminate wastes from the bloodstream.

The outlook for people with Alagille syndrome depends on several factors, including the severity of liver damage and heart problems and the early correction of malabsorption. Predicting who will experience improved bile flow and who will progress to end-stage liver failure is difficult. Fifteen percent of people with Alagille syndrome will eventually require a liver transplant.

Survival rates for people receiving liver transplants have improved over the past several years because of newer drugs that suppress the immune system and keep it from attacking and damaging the new liver.

Research studies report that 75 percent of children diagnosed with Alagille syndrome live to at least 20 years of age.^[2] Because of improvements in liver and heart therapies, this survival rate is increasing. Many adults with Alagille syndrome who improve with treatment lead normal, productive lives. Deaths in people with Alagille syndrome are most often caused by liver failure, heart problems, and blood vessel abnormalities.Mortality is approximately 10%, with vascular accidents, cardiac disease, and liver disease accounting for most of the deaths. Vascular anomalies account for 34% of the mortality in this population ^[3].

Template:WH Template:WS