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Genetics Home Reference: your guide to understanding genetic conditions
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Liddle syndrome

Reviewed March 2013

What is Liddle syndrome?

Liddle syndrome is an inherited form of high blood pressure (hypertension). This condition is characterized by severe hypertension that begins unusually early in life, often in childhood, although some affected individuals are not diagnosed until adulthood. Some people with Liddle syndrome have no additional signs or symptoms, especially in childhood. Over time, however, untreated hypertension can lead to heart disease or stroke, which may be fatal.

In addition to hypertension, affected individuals can have low levels of potassium in the blood (hypokalemia). Signs and symptoms of hypokalemia include muscle weakness or pain, fatigue, constipation, or heart palpitations. The shortage of potassium can also raise the pH of the blood, a condition known as metabolic alkalosis.

How common is Liddle syndrome?

Liddle syndrome is a rare condition, although its prevalence is unknown. The condition has been found in populations worldwide.

What genes are related to Liddle syndrome?

Liddle syndrome is caused by mutations in the SCNN1B or SCNN1G gene. Each of these genes provides instructions for making a piece (subunit) of a protein complex called the epithelial sodium channel (ENaC). These channels are found at the surface of certain cells called epithelial cells in many tissues of the body, including the kidneys, where the channels transport sodium into cells.

In the kidney, ENaC channels open in response to signals that sodium levels in the blood are too low, which allows sodium to flow into cells. From the kidney cells, this sodium is returned to the bloodstream (a process called reabsorption) rather than being removed from the body in urine.

Mutations in the SCNN1B or SCNN1G gene change the structure of the respective ENaC subunit. The changes alter a region of the subunit that is involved in signaling for its breakdown (degradation) when it is no longer needed. As a result of the mutations, the subunit proteins are not degraded, and more ENaC channels remain at the cell surface. The increase in channels at the cell surface abnormally increases the reabsorption of sodium (followed by water), which leads to hypertension. Reabsorption of sodium into the blood is linked with removal of potassium from the blood, so excess sodium reabsorption leads to hypokalemia.

Related Gene(s)

Changes in these genes are associated with Liddle syndrome.

  • SCNN1B
  • SCNN1G

How do people inherit Liddle syndrome?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Where can I find information about diagnosis or management of Liddle syndrome?

These resources address the diagnosis or management of Liddle syndrome and may include treatment providers.

  • Genetic Testing Registry: Pseudoprimary hyperaldosteronism (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0221043)
  • Merck Manual for Health Care Professionals (http://www.merckmanuals.com/professional/genitourinary_disorders/renal_transport_abnormalities/liddle_syndrome.html)

You might also find information on the diagnosis or management of Liddle syndrome in Educational resources (http://ghr.nlm.nih.gov/condition/liddle-syndrome/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/liddle-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Liddle syndrome?

You may find the following resources about Liddle syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Liddle syndrome?

  • pseudoaldosteronism
  • pseudoprimary hyperaldosteronism

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Liddle syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding Liddle syndrome?

autosomal ; autosomal dominant ; breakdown ; cell ; channel ; constipation ; degradation ; epithelial ; gene ; hypertension ; hypokalemia ; inherited ; kidney ; palpitations ; pH ; potassium ; prevalence ; protein ; sodium ; sodium channel ; subunit ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Bogdanović R, Kuburović V, Stajić N, Mughal SS, Hilger A, Ninić S, Prijić S, Ludwig M. Liddle syndrome in a Serbian family and literature review of underlying mutations. Eur J Pediatr. 2012 Mar;171(3):471-8. doi: 10.1007/s00431-011-1581-8. Epub 2011 Sep 29. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21956615?dopt=Abstract)
  • Corvol P. Liddle's syndrome: heritable human hypertension caused by mutations in the Beta subunit of the epithelial sodium channel. J Endocrinol Invest. 1995 Jul-Aug;18(7):592-4. (http://www.ncbi.nlm.nih.gov/pubmed/9221280?dopt=Abstract)
  • Hansson JH, Nelson-Williams C, Suzuki H, Schild L, Shimkets R, Lu Y, Canessa C, Iwasaki T, Rossier B, Lifton RP. Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. Nat Genet. 1995 Sep;11(1):76-82. (http://www.ncbi.nlm.nih.gov/pubmed/7550319?dopt=Abstract)
  • Hansson JH, Schild L, Lu Y, Wilson TA, Gautschi I, Shimkets R, Nelson-Williams C, Rossier BC, Lifton RP. A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11495-9. (http://www.ncbi.nlm.nih.gov/pubmed/8524790?dopt=Abstract)
  • Lifton RP, Gharavi AG, Geller DS. Molecular mechanisms of human hypertension. Cell. 2001 Feb 23;104(4):545-56. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11239411?dopt=Abstract)
  • Rotin D. Role of the UPS in Liddle syndrome. BMC Biochem. 2008 Oct 21;9 Suppl 1:S5. doi: 10.1186/1471-2091-9-S1-S5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19007435?dopt=Abstract)
  • Schild L, Lu Y, Gautschi I, Schneeberger E, Lifton RP, Rossier BC. Identification of a PY motif in the epithelial Na channel subunits as a target sequence for mutations causing channel activation found in Liddle syndrome. EMBO J. 1996 May 15;15(10):2381-7. (http://www.ncbi.nlm.nih.gov/pubmed/8665845?dopt=Abstract)
  • Smith JH, Lindor NM, Rabinstein AA. Cerebrovascular consequences of pseudohyperaldosteronism. J Clin Hypertens (Greenwich). 2012 Aug;14(8):547-52. doi: 10.1111/j.1751-7176.2012.00639.x. Epub 2012 May 3. (http://www.ncbi.nlm.nih.gov/pubmed/22863163?dopt=Abstract)
  • Snyder PM, Price MP, McDonald FJ, Adams CM, Volk KA, Zeiher BG, Stokes JB, Welsh MJ. Mechanism by which Liddle's syndrome mutations increase activity of a human epithelial Na+ channel. Cell. 1995 Dec 15;83(6):969-78. (http://www.ncbi.nlm.nih.gov/pubmed/8521520?dopt=Abstract)
  • Staub O, Dho S, Henry P, Correa J, Ishikawa T, McGlade J, Rotin D. WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome. EMBO J. 1996 May 15;15(10):2371-80. (http://www.ncbi.nlm.nih.gov/pubmed/8665844?dopt=Abstract)
  • Warnock DG. Liddle syndrome: genetics and mechanisms of Na+ channel defects. Am J Med Sci. 2001 Dec;322(6):302-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11780687?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2013
Published: March 23, 2015