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Alagille syndrome

What is Alagille syndrome?

Alagille syndrome is a rare disorder present from birth that can affect many different organs of the body. The major organs affected include the liver, heart, spine, and eye. 

Almost all people with Alagille syndrome have liver bile duct abnormalities. Normally, the liver makes bile that is carried through the bile ducts to the gallbladder and small intestine. Bile is important for digestion and absorption of important nutrients and to help remove waste products from the body. People with Alagille syndrome may have fewer bile ducts (bile duct paucity) or abnormal bile ducts, both of which can lead to a build-up of bile (cholestasis) that can damage the liver and may lead to liver failure in the long term. 

Most people with Alagille syndrome have a congenital heart defect, which are heart abnormalities present at birth. The most common heart defect seen in Alagille syndrome is a narrowing of the pulmonary valve in the heart (pulmonic stenosis) that leads to decreased blood flow from the heart to the lungs. The second most common is Tetralogy of Fallot, which is a more complex defect involving different parts of the heart that requires surgery to correct. 

The skeleton can also be affected in Alagille syndrome. The most common skeletal finding is a difference in how the spine looks, known as a “butterfly vertebrae”. This finding is often asymptomatic and is seen only on radiographs.  

Alagille syndrome is also associated with a white ring around the cornea of the eye called a posterior embryotoxon. This is usually found on an eye exam and is mostly asymptomatic. However, it can be helpful in diagnosing Alagille syndrome as it is considered specific to the condition. There are also other less common eye findings associated with Alagille syndrome.Overall, most people with Alagille syndrome do not have vision difficulties. 

Lastly, some individuals with Alagille syndrome may have characteristic facial features and may not look like other members of their family. Other findings in Alagille syndrome that are less common include kidney abnormalities, developmental delays, an enlarged spleen, and problems with the blood vessels.

 

Synonyms

  • Alagille syndrome
  • Alagille syndrome
  • Alagille syndrome
  • Alagille syndrome
  • Alagille syndrome
  • Alagille syndrome
  • Alagille syndrome
  • Alagille syndrome
  • Alagille syndrome

Alagille syndrome is a rare disorder present from birth that can affect many different organs of the body. The major organs affected include the liver, heart, spine, and eye. 

Almost all people with Alagille syndrome have liver bile duct abnormalities. Normally, the liver makes bile that is carried through the bile ducts to the gallbladder and small intestine. Bile is important for digestion and absorption of important nutrients and to help remove waste products from the body. People with Alagille syndrome may have fewer bile ducts (bile duct paucity) or abnormal bile ducts, both of which can lead to a build-up of bile (cholestasis) that can damage the liver and may lead to liver failure in the long term. 

Most people with Alagille syndrome have a congenital heart defect, which are heart abnormalities present at birth. The most common heart defect seen in Alagille syndrome is a narrowing of the pulmonary valve in the heart (pulmonic stenosis) that leads to decreased blood flow from the heart to the lungs. The second most common is Tetralogy of Fallot, which is a more complex defect involving different parts of the heart that requires surgery to correct. 

The skeleton can also be affected in Alagille syndrome. The most common skeletal finding is a difference in how the spine looks, known as a “butterfly vertebrae”. This finding is often asymptomatic and is seen only on radiographs.  

Alagille syndrome is also associated with a white ring around the cornea of the eye called a posterior embryotoxon. This is usually found on an eye exam and is mostly asymptomatic. However, it can be helpful in diagnosing Alagille syndrome as it is considered specific to the condition. There are also other less common eye findings associated with Alagille syndrome.Overall, most people with Alagille syndrome do not have vision difficulties. 

Lastly, some individuals with Alagille syndrome may have characteristic facial features and may not look like other members of their family. Other findings in Alagille syndrome that are less common include kidney abnormalities, developmental delays, an enlarged spleen, and problems with the blood vessels.

Acknowledgement of Alagille syndrome has not been added yet.

Alagille syndrome is estimated to affect 1:50,000 to 1:70,000 babies, although it may be underdiagnosed as some individuals only have mild or isolated symptoms.

Name Abbreviation
Alagille syndrome Alagille's syndrome
Alagille syndrome Alagille-Watson syndrome
Alagille syndrome Arteriohepatic dysplasia (AHD)
Alagille syndrome Cardiovertebral syndrome
Alagille syndrome Cholestasis with peripheral pulmonary stenosis
Alagille syndrome Hepatic ductular hypoplasia
Alagille syndrome Hepatofacioneurocardiovertebral syndrome
Alagille syndrome Paucity of interlobular bile ducts
Alagille syndrome Watson-Miller syndrome

Alagille syndrome is caused by a change (mutation) in either the JAG1 or NOTCH2 gene. Over 90% of cases are caused by mutations in the JAG1 gene. The JAG1 gene is involved in an important signaling pathway during embryo development.  Around 50-70% of the time, Alagille syndrome is not inherited but occurs de novo, meaning newly arising in an affected person. Of note, about 3% of people with Alagille syndrome do not have a genetic diagnosis. 

The signs and symptoms associated with Alagille syndrome usually appear in the first two years of life. Symptoms can be very mild or very severe, even amongst members of the same family. Some people may have isolated symptoms of the disease (e.g. only a mild congenital heart defect), while others may have life-threatening heart and/or liver failure. These include:

  • Congenital heart defects present at birth such as pulmonic stenosis and Tetralogy of Fallot

  • The spine may look different on an x-ray (butterfly vertebrae), but usually does not cause problems

  • Abnormal liver bile ducts that can lead to: 

    • Liver damage and liver failure

    • Difficulty absorbing nutrients that could lead to slower growth 

    • Buildup of a substance waste product called bilirubin that causes a yellow tinge to the eyes and/or skin (jaundice) and may cause itchy skin 

    • Hard skin bumps (xanthomas) caused by high cholesterol levels 

    • Pale, grey, or white stool 

  • A white ring around the eye (posterior embryotoxon) found on eye exam that usually does not affect the ability to see

  • Blood vessel abnormalities in different parts of the body such as in the head and neck which cause cause serious health problems such as a stroke 

  • Distinct facial features such as deep-set eyes, a prominent wide forehead, straight nose, and pointed chin, although these features may not be obvious until after infancy 

  • Smaller kidneys or kidneys with many cysts that may work less efficiently, but is usually asymptomatic 

A diagnosis of Alagille syndrome can be made by having enough features on an exam and tests to meet a set of criteria called the clinical diagnostic criteria. A diagnosis can also be made through genetic testing. 

Clinical diagnostic criteria 

  • Fewer bile ducts than normal confirmed by liver biopsy and at least three of the following: 

    • Liver abnormalities 

    • Bone/spine abnormalities (e.g. butterfly vertebrae) 

    • Congenital heart defect

    • Finding of a white ring around the cornea (e.g. posterior embryotoxon) 

    • Characteristic facial features 

Clinical diagnostic tests 

  • Liver biopsy

  • Heart and blood vessel tests

  • Eye exams

  • Spine X-ray

  • Abdominal ultrasound

  • Kidney function tests

  • Genetic testing

Genetic testing 

Found to have a mutation in one copy of the JAG1 or NOTCH2 gene.

An individual with Alagille syndrome should be managed by a multidisciplinary team. Treatment is based on what specific symptoms the person has. Examples of treatment include:  

  • Surgery to correct the heart defect 

  • Medications to increase bile flow out of the liver and/or surgery to redirect bile 

  • Liver transplant for individuals with liver failure 

  • Vitamin and high calorie food supplements, some may need assisted feeding such as through feeding tubes

  • Medications and moisturizers to reduce skin itching 

  • Avoiding contact sports and alcohol for those with liver disease and blood vessel abnormalities

Diagnosed individuals should also undergo regular monitoring by a cardiologist, gastroenterologist, and nutritionist.

Many people with Alagille syndrome with mild symptoms have a good prognosis and normal life expectancy. Those with more severe symptoms such as liver failure, serious heart defects, and blood vessel abnormalities can have reduced lifespan if not properly managed.

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We are the parent of Sophia which has been diagnosed with Alagille Syndrome in Montreal.
I'm a young girl with alagille syndrome. i was diagnoised at six months with the disorder. I have chronic kidney disease and chronic liver disease and two heart diseses.

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