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Hyperkalemic periodic paralysis

Hyperkalemic periodic paralysis
Classification & external resources
ICD-10 G72.3
ICD-9 359.3
OMIM 170500
DiseasesDB 6252
MeSH D020513

Hyperkalemic periodic paralysis (HYPP), also known as Impressive Syndrome, is an inherited autosomal dominant disorder which affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood. It is most commonly associated with horses, but also occurs in humans, where it is also called Gamstorp episodic adynamy.


Disease in horses

Symptoms and presentation

This inherited disease is characterized by uncontrollable muscle twitching and substantial muscle weakness or paralysis among affected horses. HYPP is a dominant genetic disorder; therefore heterozygotes bred to genotypically normal horses have a statistic probability of producing clinically affected offspring 50% of the time.

Inheritance and prevalence

Horses affected with HYPP can be treated with some possibility of reducing symptoms, but the degree that medical treatment helps varies from horse to horse. Therefore, horses with HYPP should only be ridden by experienced riders, if anyone, because episodes of paralysis can come on very suddenly and a rider has to be extremely alert to recognize an impending episode which may cause the horse to lose control of its body.

The disease is most common in the bloodline of the famous Appendix American Quarter Horse stallion Impressive, who has over 55,000 living descendants as of 2003. Although the disease is primarily limited to the American Quarter Horse breed and closely related breeds such as American Paint Horses and Appaloosas at this time, cross-breeding has begun to extend it to grade horses and ponies. The spread of the disease is perpetuated by the favorable placings given to affected horses in halter competition at horse shows, because a secondary charactistic associated with N/H and H/H horses is heavy, bulky muscling that is favored by judges, a trend that began with Impressive and predates the modern understanding of the disease.


In 1994, researchers at the University of Pittsburgh, with a grant from various horse organizations, isolated the genetic mutation responsible for the problem and developed a blood test for it. Using this test, horses may be identified as:

  • H/H, meaning they have the mutation and it is homozygous. These horses always pass on the disease.
  • N/H, meaning they have the mutation and it is heterozygous. These horses are affected to a lesser degree, and pass on the disease 50% of the time.
  • N/N, meaning they do not have the mutation and cannot pass it on, even if they are descendants of Impressive.


Recently, horse organizations have begun instituting rules to attempt to eliminate this widespread disease. The American Quarter Horse Association (AQHA) now mandates testing for the "Impressive" mutation and will no longer register homozygous (H/H) foals as of 2007, with discussion of heterozygous (N/H) foals pending. The Appaloosa Horse Club (ApHC) will no longer accept homozygous foals as of 2008. It is believed that both primary palomino registries will exclude any foal carrying the "Impressive" mutation as of 2007. The main organization affected by HYPP that has not yet taken action is the American Paint Horse Association (APHA), although many other smaller organizations are also affected.

Disease in humans

Although much rarer, hyperkalemic periodic paralysis has also been observed in humans. In humans the disorder causes episodes of extreme muscle weakness, usually beginning in the second decade and depending on the type and severity of the HYPP will increase or stabilize until the fourth or fifth decade where attacks usually decline and can altogether stop. Factors that can trigger attacks include rest after exercise, potassium-rich foods, stress, fatigue, certain pollutants (eg: Cigarette smoke) and periods of fasting. Muscle strength improves between attacks, although many affected people may have increasing bouts of muscle weakness as time goes on (abortive attacks). Sometimes with HYPP those affected may experience degrees of muscle stiffness and spasms (myotonia) in the affected muscles. This can be caused by the same things that trigger the paralysis, dependant on the type of mytonia. (See also paramyotonia).

Some people with hyperkalemic periodic paralysis have increased levels of potassium in their blood (hyperkalemia) during attacks. In other cases, attacks are associated with normal blood potassium levels (normokalemia). Ingesting potassium can trigger attacks in affected individuals, even if blood potassium levels do not go up.

The most common underlying cause is one of several possible point mutations in the gene SCN4A. The SCN4A gene provides instructions for making a protein that plays an essential role in muscles used for movement (skeletal muscles). For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of certain positively charged atoms (ions), including sodium, into muscle cells. The SCN4A protein forms channels that control the flow of sodium ions into these cells. Mutations in the SCN4A gene alter the usual structure and function of sodium channels. The altered channels cannot properly regulate the flow of sodium ions 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 muscle weakness or paralysis.

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.


  • National Library of Medicine. Hyperkalemic periodic paralysis
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Hyperkalemic_periodic_paralysis". A list of authors is available in Wikipedia.
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