Hypokalemic periodic paralysis

What causes hypokalemic periodic paralysis?

HOKPP can be caused by mutations in any of at least 3 known genes: CACNA1S, SCN4A, or KCNJ18. All three of these genes give the body instructions to make parts of ion channels that are primarily expressed in skeletal muscle cells. Muscle contractions are triggered by the flow of ions into muscle cells. Mutations that cause HOKPP affect the usual structure or function of ion channels, impairing their ability to regulate the flow of ions into muscle cells. This, in turn, reduces the ability of skeletal muscles to contract, causing the weakness and paralysis associated with HOKPP.

Not all people with a clinical diagnosis of HOKPP are found to have a mutation in one of the genes mentioned above. This suggests that other, yet unidentified genes may also be responsible for the condition.

Last updated on 05-01-20

How is hypokalemic periodic paralysis diagnosed?

A clinical diagnosis of HOKPP is based on:

  • a history of episodes of paralysis
  • low levels of potassium during attacks, but not between attacks
  • the identification of typical "triggers" (i.e., rest after exercise, prolonged immobility)
  • a family history consistent with autosomal dominant inheritance. The diagnosis cannot be established by clinical findings alone in the absence of a known family history of the condition.

Various types of tests including blood tests, urine tests, and/or electromyograms may be used to differentiate between primary HOKPP and other possible causes of symptoms.

Of all individuals who meet diagnostic criteria and have genetic testing, approximately 60% have mutations in the CACNA1S gene, approximately 20% in the SCN4A gene, and approximately 3.5% in the KCNJ18 gene. No other genes have yet been found to cause HOKPP, suggesting that other, unidentified genes may be responsible for the condition.

Last updated on 05-01-20

How is hypokalemic periodic paralysis inherited?

Hypokalemic periodic paralysis (HOKPP) is inherited in an autosomal dominant manner. This means that having a change (mutation) in only one copy of one of the responsible genes in each cell is enough to cause symptoms of the condition.

In most cases, an affected person inherits the mutated gene from an affected parent. However, inheritance from a parent may sometimes be "masked" by a parent not having symptoms. This is because not all people with a mutation in a gene responsible for HOKPP develop symptoms of the condition - a phenomenon known as reduced penetrance. About 10% of males with a mutation do not develop symptoms, and a higher percentage of females do not develop symptoms. The penetrance of HOKPP appears to depend on the specific gene and mutation responsible for the condition, and the gender of the person with the mutation. For example, one reported mutation in the CACNA1S gene appears to be fully penetrant in males (100% develop symptoms) but non-penetrant in females (none develop symptoms). Identifying the responsible gene and mutation in an affected person may therefore help to assess risks to other family members.

It is also possible for a disease-causing mutation to occur for the first time in a person with no family history of HOKPP. This is called a de novo mutation. The proportion of cases caused by a de novo mutation is unknown.

Regardless of whether a mutation that causes an autosomal dominant condition is de novo or inherited, each child of a person with a mutation has a 50% chance to inherit that mutation.

Last updated on 05-01-20

What is the long-term outlook for people with hypokalemic periodic paralysis?

Treatment of HOKPP may lead to a significant decrease in the number of episodes and prevent muscle weakness in some people. However, a progressive proximal myopathy ultimately develops in most people with HOKPP, usually becoming apparent after the age of 50 years as attacks of paralysis lessen. The myopathy is generally worst in muscles of the pelvis as well as the proximal upper and lower extremities (the muscles of the arms and legs closest to the trunk). The severity of the myopathy varies, as some may be only mildly affected and others may be severely disabled. Several deaths in people with HOKPP have been reported, mostly related to aspiration pneumonia or inability to clear secretions.

Last updated on 05-01-20

Healthcare Resources

Periodic Paralysis Association

The Periodic Paralysis Association (PPA) has a "Find a Doctor" page where you can view a list of physicians who specialize in periodic paralysis. The list represents suggestions from PPA members or correspondents and does not represent an endorsement of the physicians or institutions appearing in the list by the PPA.

Last updated on 04-27-20

Name: Periodic Paralysis Association 155 West 68th Street Apartment 1732
New York, NY, 10023 , United States
Phone: 407-339-9499 Email: lfeld@cfl.rr.com Url: http://www.periodicparalysis.org
Name: Periodic Paralysis International 2235 B 36th St. SW
Calgary, Alberta, T3E 2Z3, Canada
Phone: +1-403-244-7213 Email: http://hkpp.org/contact Url: http://www.hkpp.org
Name: Muscular Dystrophy Association MDA 222 S Riverside Plaza Suite 1500
Chicago, IL, 60606, United States
Toll Free: 1-833-275-6321 (Helpline) Email: resourcecenter@mdausa.org Url: https://www.mda.org
Name: Muscular Dystrophy UK 61A Great Suffolk Street
London, SE1 0BU, United Kingdom
Phone: (+44) 0 020 7803 4800 Toll Free: 0800 652 6352 (Helpline) Email: info@musculardystrophyuk.org Url: https://www.musculardystrophyuk.org/

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The RareGuru disease database is regularly updated using data generously provided by GARD, the United States Genetic and Rare Disease Information Center.

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