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

• Pseudoaldosteronism

What is Liddle Syndrome? (Definition/Background Information)

• Liddle syndrome is a rare, inherited condition that is primarily characterized by severe high blood pressure (hypertension) that often develops at an early age
• Although the condition may not be associated with signs and symptoms initially, untreated hypertension can eventually lead to heart disease or stroke
• Affected people may also have low levels of potassium in the blood (hypokalemia) and metabolic alkalosis
• Liddle syndrome is caused by mutations in either the SCNN1B or SCNN1G genes and is inherited in an autosomal dominant manner
• Treatment may include a low sodium diet and potassium-sparing diuretics to reduce blood pressure and normalize potassium levels. Conventional anti-hypertensive therapies are not effective

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

Who gets Liddle Syndrome? (Age and Sex Distribution)

• Liddle Syndrome is a rare disorder that typically affects young individuals, usually children
• It is observed in both males and females
• The condition may affect individuals of any race or ethnic group

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

• A positive family history may be an important risk factor, since Liddle Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for Liddle Syndrome

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 Liddle Syndrome? (Etiology)

Liddle Syndrome is caused by changes (mutations) in the SCNN1B or SCNN1G gene.

• Each of these genes provides instructions for making one piece of a protein complex called the epithelial sodium channel (ENaC). These channels are found on the surface of certain cells (epithelial cells) throughout the body, including the kidneys, lungs, and sweat glands. The ENaC channel transports sodium into cells
• Mutations in the SCNN1B and SCNN1G genes affect an important region of the protein involved in signaling for its breakdown (degradation). As a result of the mutations, the protein is not tagged for degradation when it is no longer needed, and more ENaC channels remain at the cell's surface
• The increase in channels at the cell surface abnormally increases the reabsorption of sodium, which leads to hypertension. Because removal of potassium from the blood is linked with reabsorption of sodium, excess sodium reabsorption leads to hypokalemia

Liddle Syndrome is inherited in an autosomal dominant manner.

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

Autosomal dominant mode of inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Liddle Syndrome?

Liddle Syndrome is primarily characterized by severe, early-onset hypertension (high blood pressure). Although the condition may not be associated with any signs and symptoms initially, untreated hypertension can eventually lead to heart disease and stroke.

Affected people may also have hypokalemia (low blood potassium) and metabolic alkalosis. Symptoms of hypokalemia can include weakness, fatigue, muscle pain (myalgia), constipation or heart palpitations. In most cases, the condition becomes apparent at a young age but some affected people are not diagnosed until well into adulthood.

The signs and symptoms of Liddle Syndrome may include:

• Decreased circulating aldosterone level
• Decreased circulating renin level
• Hypokalemic alkalosis

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

• Constipation
• Hypertension
• Hypokalemia

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

• Cerebral ischemia
• Fatigue
• Nephropathy
• Renal insufficiency

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

How is Liddle Syndrome Diagnosed?

A diagnosis of Liddle Syndrome is often suspected based the presence of early-onset hypertension (high blood pressure), especially in people with a family history of the condition. Additional testing can then be ordered to confirm the diagnosis. This may include:

• Blood tests which can detect low levels of potassium, renin and aldosterone
• Urine tests to identify low levels of sodium and aldosterone
• Genetic testing to look for a change (mutation) in the SCNN1B or SCNN1G gene

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

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 Liddle Syndrome?

The complications of Liddle Syndrome may include:

• Kidney problems
• Brain abnormalities
• Heart disease

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

How is Liddle Syndrome Treated?

• Treatment for Liddle Syndrome consists of following a low sodium diet and taking potassium-sparing diuretics, which reduce blood pressure and correct hypokalemia and metabolic alkalosis
• Conventional anti-hypertensive therapies are not effective for this condition

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

How can Liddle Syndrome be Prevented?

Currently, Liddle 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 Liddle Syndrome? (Outcomes/Resolutions)

• With treatment, the long-term outlook (prognosis) for people with Liddle Syndrome is good
• However, untreated hypertension may lead to stroke, heart disease and/or kidney problems which can be fatal 

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

Additional and Relevant Useful Information for Liddle Syndrome:

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

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