National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Liddle syndrome


Other Names:
Pseudoaldosteronism; Liddle's syndrome
Categories:
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.[1][2]
Last updated: 11/15/2016
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.[2][1]
Last updated: 11/15/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat
[ more ] 		0011675
Constipation 0002019
Hypertension 0000822
Hypokalemia
Low blood potassium levels
0002900
30%-79% of people have these symptoms
Cerebral ischemia
Disruption of blood oxygen supply to brain
0002637
Fatigue
Tired
Tiredness
[ more ] 		0012378
Muscle weakness
Muscular weakness
0001324
Nephropathy 0000112
Renal insufficiency
Renal failure
Renal failure in adulthood
[ more ] 		0000083
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance 0000006
Decreased circulating aldosterone level
Low blood aldosterone level
0004319
Decreased circulating renin level 0003351
Hypokalemic alkalosis 0001949
Metabolic alkalosis 0200114
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Last updated: 7/1/2020
Liddle syndrome is caused by changes (mutations) in the SCNN1B or SCNN1G gene. Each of theses 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.[3][4]

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.[1]
Last updated: 11/15/2016
Liddle syndrome is inherited in an autosomal dominant manner.[1] This means that to be affected, a person only needs a change (mutation) in one copy of the responsible gene in each cell. In some cases, an affected person inherits the mutation from an affected parent. Other cases may result from new (de novo) mutations in the gene. These cases occur in people with no history of the disorder in their family. A person with Liddle syndrome has a 50% chance with each pregnancy of passing along the altered gene to his or her child.
Last updated: 11/15/2016
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:[5][2]
  • 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.
Last updated: 11/16/2016

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
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.[5][2]
Last updated: 11/16/2015

Management Guidelines

  • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.
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.[1][5]
Last updated: 11/16/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The clinical picture resembles that of primary hyperaldosteronism (see this term) but the hormonal profile resembles that of hyporeninism-hypoaldosteronism (see this term).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Liddle syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Liddle syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • I was told I may have Liddle's syndrome because of my low K and renin test. I need more information about this disease. This is the first time hearing of it and I need to know more. See answer


  1. Liddle syndrome. Genetics Home Reference. March 2013; https://ghr.nlm.nih.gov/condition/liddle-syndrome#.
  2. William F. Young, Jr. Genetic disorders of the collecting tubule sodium channel: Liddle's syndrome and pseudohypoaldosteronism type 1. UpToDate. Waltham, MA: UpToDate; 2016;
  3. SCNN1B. Genetics Home Reference. March 2013; http://ghr.nlm.nih.gov/gene/SCNN1B.
  4. SCNN1G. Genetics Home Reference. March 2013; http://ghr.nlm.nih.gov/gene/SCNN1G.
  5. Rosa Vargas-Poussou. Liddle syndrome. Orphanet. August 2011; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=526.