What is Alagille Syndrome?

 

Background

In 1975, a pediatric hepatologist in France, Dr. Daniel Alagille, first described a group of children with cholestatic liver disease that also exhibited other features including heart problems and characteristic facial features. This disorder has been referred to as Alagille-Watson syndrome, syndromic bile duct paucity and arteriohepatic dysplasia, but is most commonly known as Alagille syndrome (ALGS).

In 1997, the Children's Hospital of Philadelphia (CHOP) identified the gene that causes ALGS, which revolutionized the ability of physicians to provide accurate diagnoses and counseling for families. Recently researchers at CHOP identified a second gene that causes ALGS in a few cases, which has further informed treatment of this disease.

The ALGS Clinical Care Program at CHOP is a rich resource related to diagnosis and care of people with ALGS. The following is excerpted from ALGS Clinical Care Program website.  Those seeking more information are encouraged to follow the link at the bottom of this page to access additional resources at the ALGS Clinical Care Program at CHOP. More information about ALGS also is available at several of the resources listed on the Links tab under Resources on this ALGSA website.

What is Alagille Syndrome?

Alagille syndrome — also known as Alagille-Watson syndrome, syndromic bile duct paucity and arteriohepatic dysplasia — is an autosomal dominant inherited disorder associated with liver, heart, eye and skeletal abnormalities, as well as characteristic facial features. Individuals with ALGS may have:

Characteristic facial features:

  • Prominent forehead and pointed chin (giving the face a triangular appearance)
  • Deep-set eyes
  • Straight nose

Liver problems:

  • Cholestasis (stoppage of bile flow out of the liver)
  • Jaundice (yellow skin color) caused by the liver's failure to properly process bile
  • Too few bile ducts (intrahepatic bile duct paucity) seen on liver biopsy

Congenital cardiac (heart) abnormalities

  • Peripheral pulmonary stenosis (narrowing of the pulmonary artery)
  • Murmur only
  • Any cardiac anomaly, although the defects typically affect the right side of the heart (e.g. Tetralogy of Fallot)

Ocular (eye) abnormalities

  • Posterior embryotoxon
  • Axenfeld's anomaly

Renal (kidney) abnormalities

  • Renal tubular acidosis
  • Structural renal abnormality

Skeletal abnormalities

  • Butterfly-shaped vertebrae
  • Shortened interpedicular distance
  • Short stature

Causes

ALGS is predominately caused by changes in a gene called Jagged1 located on chromosome 20. In 3 to 5 percent of cases, the entire gene is deleted (missing) from one copy of chromosome 20. In the majority of cases of ALGS, there are changes or mutations in the DNA sequence that makes up the Jagged1 gene. In a very small number of cases, less than 1 percent, changes in another gene, Notch 2, result in ALGS.

About one-third of children with ALGS inherit the change in Jagged1 from a parent. In the remaining two-thirds of cases, the mutation in Jagged1 is a new one in that child. ALGS is an autosomal dominant disorder, which means someone who carries the Jagged1 gene mutation has a 50 percent chance of passing on that mutation to their child.

The effect of having a mutation in Jagged1 can vary widely. Some individuals who inherit a mutation have severe ALGS, involving heart and liver disease, while others experience only minor manifestations, such as posterior embryotoxon or characteristic facial features.

To read more about ALGS follow this link:  CHOP Alagille Syndrome page