What are the other Names for this Condition? (Also known as/Synonyms)

• CHLS (Cholestasis Lymphedema Syndrome)
• Cholestasis Lymphedema Syndrome
• Lymphedema Cholestasis Syndrome (LCS)

What is Aagenaes Syndrome? (Definition/Background Information)

• Aagenaes Syndrome, or Lymphedema Cholestasis Syndrome (LSC1), is a form of idiopathic familial intrahepatic cholestasis associated with lymphedema of the lower extremities
• At least some cases of Aagenaes Syndrome have been attributed to mutations in the LSC1 gene on chromosome 15q
• This condition is inherited in an autosomal recessive manner and is found mainly in individuals of Norwegian descent

(Source: Aagenaes Syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Aagenaes Syndrome? (Age and Sex Distribution)

• Aagenaes Syndrome is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Aagenaes Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Aagenaes Syndrome can be inherited

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Aagenaes Syndrome? (Etiology)

• Aagenaes Syndrome may be caused by mutations in the LSC1 gene on chromosome 15q
• The disorder is inherited in an autosomal recessive manner

(Source: Aagenaes Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected)

What are the Signs and Symptoms of Aagenaes Syndrome?

The signs and symptoms of Aagenaes Syndrome may vary from one individual to another and may include:

Very frequently present symptoms in 80-99% of the cases:

• Abnormality of urine homeostasis
• Acholic stools
• Biliary tract abnormality
• Fatigue
• Hepatomegaly
• Hyperlipidemia
• Jaundice
• Lymphedema
• Nausea and vomiting
• Neonatal cholestatic liver disease

Frequently present symptoms in 30-79% of the cases:

• Abnormality of skin pigmentation
• Multiple lipomas
• Splenomegaly

Occasionally present symptoms in 5-29% of the cases:

• Bone pain
• Cirrhosis
• Gastrointestinal hemorrhage
• Portal hypertension
• Reduced bone mineral density

In addition to the above, the following additional signs and symptoms may be present:

• Conjugated hyperbilirubinemia
• Elevated alkaline phosphatase
• Elevated hepatic transaminases
• Erysipelas
• Malabsorption

(Source: Aagenaes Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Aagenaes Syndrome Diagnosed?

Aagenaes Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Aagenaes Syndrome?

The complications of Aagenaes Syndrome may include:

• Malabsorption
• Failure to thrive
• Cirrhosis of liver
• Neuropathy
• Serious brain damage due to severe jaundice (kernicterus)
• Pain due to lymphedema (swelling in arms/legs)
• Recurrent infections

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Aagenaes Syndrome Treated?

There is no cure for Aagenaes Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Aagenaes Syndrome be Prevented?

Currently, Aagenaes Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Aagenaes Syndrome? (Outcomes/Resolutions)

• The prognosis of Aagenaes Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Aagenaes Syndrome:

Aagenaes Syndrome is also known by the following additional synonyms: 

• LCS
• LCS1

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/