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, also known as Lymphedema Cholestasis Syndrome, is a rare genetic disorder mainly affecting individuals of Norwegian descent. It involves both liver dysfunction due to cholestasis and lymphedema of the lower extremities. The disorder is inherited in an autosomal recessive manner.
• The primary risk factor is being of Norwegian ancestry, as the condition is found mainly in individuals of this background. It is also more likely to occur in those with a family history of the condition, given its genetic nature.
• Aagenaes Syndrome is caused by mutations in the LSC1 gene located on chromosome 15q. The genetic mutation disrupts bile flow in the liver and causes malformation of the lymphatic vessels, leading to the characteristic symptoms.
• The signs and symptoms typically begin in infancy and include jaundice, lymphedema (swelling) of the lower limbs, acholic stools, fatigue, hepatomegaly, and recurrent episodes of cholestasis. Additional symptoms like splenomegaly, skin pigmentation changes, and hyperlipidemia may also occur.
• The complications of Aagenaes Syndrome include malabsorption of nutrients, liver cirrhosis, recurrent infections, chronic lymphedema leading to tissue damage, and neurological damage from severe jaundice. In advanced cases, it can lead to liver failure, necessitating liver transplantation.
• The diagnosis involves clinical assessment, family history evaluation, and genetic testing for LSC1 mutations. Blood tests to assess liver function, imaging studies of the liver and lymphatic system, and biopsy may also be required.
• There is no cure for Aagenaes Syndrome. Treatment focuses on managing symptoms, such as physical therapy for lymphedema, surgical interventions for complications, and nutritional support. Liver transplantation may be necessary in cases of liver failure.
• The prognosis varies depending on the severity of liver disease and lymphedema. Early management of symptoms and complications can improve quality of life, but untreated liver issues can progress to severe liver disease or failure, potentially shortening life expectancy.

Who gets Aagenaes Syndrome? (Age and Sex Distribution)

• Aagenaes Syndrome primarily affects individuals of Norwegian descent, and it typically manifests in infancy.
• Both males and females are equally affected by this autosomal recessive genetic condition.
• The symptoms, including cholestasis and lymphedema, usually present early in life and can persist or worsen as the individual ages.
• The syndrome is rare, with only around 100 cases reported, predominantly in southern Norway.

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

• The primary risk factor for Aagenaes Syndrome is having both parents who carry a mutation in the LSC1 gene on chromosome 15q, as it is inherited in an autosomal recessive manner.
• Individuals of Norwegian descent, particularly from southern Norway, are at higher risk due to the higher prevalence of the condition in this population. Advanced maternal or paternal age has not been established as a risk factor.

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 is primarily caused by mutations in the LSC1 gene located on chromosome 15q.

• This genetic mutation disrupts the development and function of lymphatic vessels, leading to lymphedema and liver dysfunction.
• The syndrome is inherited in an autosomal recessive pattern, meaning both parents must carry the defective gene for the condition to manifest in their offspring.

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?

Individuals with Aagenaes Syndrome commonly exhibit lymphedema, particularly in the lower extremities, and recurring cholestasis (bile flow blockage) during infancy.

• Symptoms also include jaundice, hepatomegaly (enlarged liver), fatigue, and abnormal stools (often pale in color).
• Additional signs may involve nausea, vomiting, and skin abnormalities.
• In some cases, splenomegaly, bone pain, and cirrhosis may develop as the condition progresses.

How is Aagenaes Syndrome Diagnosed?

Aagenaes Syndrome is diagnosed based on clinical signs such as recurring cholestasis and lymphedema.

• Blood tests showing liver function abnormalities, including elevated bilirubin, transaminases, and alkaline phosphatase levels, help confirm the diagnosis.
• Imaging studies like liver ultrasounds and liver biopsies may be used to assess liver damage.
• Genetic testing for mutations in chromosome 15q can support the diagnosis, particularly in families with a known history of the disorder.

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, so treatment focuses on managing symptoms. This includes addressing cholestasis with medications that improve bile flow and prevent liver damage.

• Nutritional support, including fat-soluble vitamin supplements, is essential to combat malabsorption.
• Lymphedema is managed through compression therapy and physical therapy to reduce swelling.
• In severe cases, liver transplantation may be required due to progressive liver failure. Regular monitoring is vital to manage complications.

How can Aagenaes Syndrome be Prevented?

Since Aagenaes Syndrome is a genetic disorder inherited in an autosomal recessive manner, it cannot be prevented.

• However, genetic counseling for families with a history of the condition can help assess the risk for future offspring.
• Prenatal genetic testing may be available for at-risk families to identify the presence of the disorder during pregnancy.
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

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

The prognosis for Aagenaes Syndrome varies depending on the severity of the condition.

• Early episodes of cholestasis often improve during childhood, but recurrent liver issues and lymphedema can lead to complications such as cirrhosis and liver failure.
• Lifelong management of liver function and lymphedema can improve outcomes, and in severe cases, liver transplantation may be necessary.
• With appropriate treatment, many individuals can lead relatively stable lives, although recurrent infections and chronic swelling can impact quality of life.

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/