Encyclopedia
Hypokalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness typically beginning in childhood or adolescence.
- genetic conditions
1. Introduction
Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Attacks cause severe weakness or paralysis that usually lasts from hours to days. Some people may have episodes almost every day, while others experience them weekly, monthly, or only rarely. Attacks can occur without warning or can be triggered by factors such as rest after exercise, a viral illness, or certain medications. Often, a large, carbohydrate-rich meal or vigorous exercise in the evening can trigger an attack upon waking the following morning. Although affected individuals usually regain their muscle strength between attacks, some develop persistent muscle weakness later in life.
People with hypokalemic periodic paralysis typically have reduced levels of potassium in their blood (hypokalemia) during episodes of muscle weakness. Researchers are investigating how low potassium levels may be related to the muscle abnormalities in this condition.
2. Frequency
Although its exact prevalence is unknown, hypokalemic periodic paralysis is estimated to affect 1 in 100,000 people. Men tend to experience symptoms of this condition more often than women.
3. Causes
Mutations in the CACNA1S or SCN4A gene can cause hypokalemic periodic paralysis. These genes provide instructions for making proteins that play essential roles in muscles used for movement (skeletal muscles). For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of certain positively charged atoms (ions) into muscle cells. The CACNA1S and SCN4A proteins form channels that control the flow of these ions. The channel formed by the CACNA1S protein transports calcium ions into cells, while the channel formed by the SCN4A protein transports sodium ions.
Mutations in the CACNA1S or SCN4A gene alter the usual structure and function of calcium or sodium channels. The altered channels are "leaky," allowing ions to flow slowly but continually into muscle cells, which reduces the ability of skeletal muscles to contract. Because muscle contraction is needed for movement, a disruption in normal ion transport leads to episodes of severe muscle weakness or paralysis.
A small percentage of people with the characteristic features of hypokalemic periodic paralysis do not have identified mutations in the CACNA1S or SCN4A gene. In these cases, the cause of the condition is unknown.
4. Inheritance
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.
5. Other Names for This Condition
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Familial Hypokalemic Periodic Paralysis
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HOKPP
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HypoKPP
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HypoPP
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Primary Hypokalemic Periodic Paralysis
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Westphall disease
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/hypokalemic-periodic-paralysis
References
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- Cannon SC. Channelopathies of skeletal muscle excitability. Compr Physiol.2015 Apr;5(2):761-90. doi: 10.1002/cphy.c140062. Review.
- Fouad G, Dalakas M, Servidei S, Mendell JR, Van den Bergh P, Angelini C,Alderson K, Griggs RC, Tawil R, Gregg R, Hogan K, Powers PA, Weinberg N, Malonee W, Ptácek LJ. Genotype-phenotype correlations of DHP receptor alpha 1-subunitgene mutations causing hypokalemic periodic paralysis. Neuromuscul Disord. 1997Jan;7(1):33-8.
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- Sansone V, Meola G, Links TP, Panzeri M, Rose MR. Treatment for periodicparalysis. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD005045. doi:10.1002/14651858.CD005045.pub2. Review.
- Statland JM, Fontaine B, Hanna MG, Johnson NE, Kissel JT, Sansone VA, ShiehPB, Tawil RN, Trivedi J, Cannon SC, Griggs RC. Review of the Diagnosis andTreatment of Periodic Paralysis. Muscle Nerve. 2018 Apr;57(4):522-530. doi:10.1002/mus.26009.
- Venance SL, Cannon SC, Fialho D, Fontaine B, Hanna MG, Ptacek LJ,Tristani-Firouzi M, Tawil R, Griggs RC; CINCH investigators. The primary periodicparalyses: diagnosis, pathogenesis and treatment. Brain. 2006 Jan;129(Pt 1):8-17.
- Weber F, Lehmann-Horn F. Hypokalemic Periodic Paralysis. 2002 Apr 30 [updated 2018 Jul 26]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University ofWashington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK1338/
