{"id":17966,"date":"2020-04-28T17:14:14","date_gmt":"2020-04-28T17:14:14","guid":{"rendered":"http:\/\/labgenvet.ca\/?p=17966"},"modified":"2020-06-12T15:06:39","modified_gmt":"2020-06-12T15:06:39","slug":"hypp-hyperkalemic-periodic-paralysis","status":"publish","type":"post","link":"https:\/\/labgenvet.ca\/en\/hypp-hyperkalemic-periodic-paralysis\/","title":{"rendered":"HYPP, Hyperkalemic Periodic Paralysis"},"content":{"rendered":"

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HYPP, Hyperkalemic Periodic Paralysis<\/h1>\n

[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_column_text]\"\"<\/a>Written by Dr. Marine Rullier, MSc DMV (Translation DS)<\/p>\n

HYPP, Hyperkalemic Periodic Paralysis HYPP is a genetic muscular disease seen in horses, particularly in the Quarter Horse, the American Paint and the Appaloosa breeds.\u00a0 This condition is caused by a genetic mutation associated with the descendants of the stallion \u201cImpressive\u201d, an Appendix American Quarter Horse who was born in 1969 and died in 1995.\u00a0 Impressive was the recipient of the first World Champion Open Aged Halter title in 1974.\u00a0 In a notable example of the Popular Sire Effect<\/strong>, Impressive was bred to 2,250 mares during his lifetime and by 2006 had 355,000 descendants.\u00a0 Impressive was born with a mutation in the SCN4A<\/em> gene, giving him a well-developed musculature.\u00a0 Unfortunately, this gene mutation was also the origin of the HYPP disease.[\/vc_column_text][\/vc_column][\/vc_row][vc_row el_class=”bloc_info”][vc_column][vc_column_text]<\/p>\n

Clinical signs of HYPP<\/h3>\n

The SCN4A <\/em>gene codes for a protein that functions as a channel for sodium within the membranes of skeletal muscle cells.\u00a0 When this protein is mutated, as is the case in HYPP, the muscle cells become more easily excited which facilitates and prolongs the contraction time of muscles.\u00a0 This prolonged muscle contraction results in excessive movement of potassium from muscle cells into the blood resulting in a condition called hyperkalemia.\u00a0 Horses with HYPP can display multiple episodes of muscle spasms and paralysis during their lifetime.\u00a0 These episodes are characterized by continued muscle twitches (fasciculations) resulting in muscle fatigue and paralysis.\u00a0 The severity of these episodes can vary from one horse to another and from one episode to the next for the same horse. \u00a0Episodes are first seen by 2 to 3 years of age, are intermittent (periodic) in occurrence and typically last between 15 to 60 minutes.\u00a0 They often begin with twitching of muscles of the face followed by twitching of muscles in the neck, shoulders and flanks.\u00a0 A severe episode can affect muscles of the lungs resulting in respiratory distress and possibly the death of the animal.\u00a0 During episodes the horse remains conscious and alert.\u00a0 After an episode has passed, the horse regains a normal status without secondary effects.\u00a0 The environment can influence the precipitation of an episode, for example, an abrupt change in diet, a diet high in potassium, anesthetics, or stress due to hunger, transportation or foaling.\u00a0 A definitive diagnosis for HYPP is made by the occurrence of clinical signs and a positive DNA test for the presence of the mutation within the SCN4A<\/em> gene.[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_column_text]<\/p>\n

The Genetics of HYPP<\/h3>\n

\"\"<\/a>HYPP in the horse displays a simple (mendelian) pattern of genetic inheritance.\u00a0 The mutation responsible for HYPP is a single spelling error (substitution), where a single base (C) is replaced by another base (G) within the SCN4A<\/em> gene.\u00a0 \u00a0The consequence is that a defective sodium channel protein is expressed within muscle cells.\u00a0 Since every horse has two copies of the SCN4A<\/em> gene (one from each parent), an individual horse can be classified as clear (N\/N) with two normal copies, carrier (M\/N) with one normal copy and one mutated copy, or double mutant (M\/M) with two mutated copies of the SCN4A<\/em> gene. For more information about the nature of DNA and the basis of genetics, please refer to Horse Genetics 1.0: The Basics.[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_column_text]<\/p>\n

An Autosomal Dominant Disease<\/h3>\n

\"\"<\/a>The mutation responsible for HYPP is autosomal dominant because an individual (male or female) with one mutated copy of the SCN4A gene is at risk of showing clinical symptoms. In other words, a carrier animal (M\/N) is at risk of showing symptoms while a double mutant animal (M\/M) is at increased risk of HYPP. The mutation is said to have variable penetration since certain animals that are carriers (M\/N) do not show symptoms, while other animals with the same genetic status will show severe symptoms. There is a real possibility that additional genes in the genome can influence the severity of clinical signs; these \u201cmodifying\u201d genes remain to be defined. Additionally, environmental conditions can influence the onset and severity of clinical signs. For these reasons and depending on the severity of clinical signs, HYPP is variably described as a genetic condition or as a genetic disease. In spite of this, the known mutation within the SCN4A gene is a definite risk factor for HYPP, and the disease can be serious for the affected animal.[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_column_text]<\/p>\n

Mandatory Testing for Registering a Quarter Horse<\/h3>\n

Since 1998, DNA tests to identify the mutation associated with HYPP are mandatory in order to register a horse with the American Association of Quarter Horses (AQHA).\u00a0 Animals that are double mutant (M\/M) are not allowed to be registered, while carrier animals (M\/N) are allowed to be registered.[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_column_text]<\/p>\n

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Mating Strategies involving the HYPP Mutation<\/h3>\n

We can now look at the different possibilities that the mutation responsible for HYPP can be passed to a foal, depending on the mutation status of the parents:<\/p>\n