Portions of this article are written based on the article "Unmasking the Fatal
Flaw" by Jack Moore / Equus Magazine / March 1993.....along with information
published online from the UC Davis School of Veterniary Medicine.
More than 20 years have passed since the yearling Quarter Horse stud colt Impressive
was purchased for $20,000 at the Indiana State Fair. In three months time, his owners
doubled their investment, selling Impressive for $40,000 and feeling that they had
turned a tidy profit.
Little did anyone know at the time that they had in their possession the horse which
would prove to be one of the top-winning, top-producing Quarter Horse stallions
of all time. It soon became evident that Impressive would live up to his name, winning
31 blue ribbons out of 31 attempts in the halter ring. As a breeding stallion, he
proved himself equally deserving of his name, turning out champion after champion.
Many of Impressive's offspring bore the same dramatic physical stature as their
sire - they too went on to become outstanding and prolific stallions and broodmares.
Of the top 15 halter horses in 1992, 13 were descendants of Impressive. Even at the
age of 23, Impressive himself was fourth on the list. In 1993, it was estimated
that more than 55,000 Quarter Horses, Paints, and Appaloosas world-wide bore his
But what seemed like a winning streak to go down in history was soon to be overshadowed
by tragedy. Greatness, unfortunately, was not the only thing that Impressive passed
on. He has also been linked to a genetic mutation that only recently has been implicated
in the rare but burgeoning - and sometimes fatal - muscular disorder known as hyperkalemic
periodic paralysis. This particular defect is a dominant condition, meaning that
at least half of the affected horses' offspring will be affected as well. In the
words of one prominent Quarter Horse trainer, this discovery was "one of the
most devastating things that has ever hit the horse industry."
Within a few years of Impressive's ascendancy to the top of the sire's list, halter
horse owners began to notice a strange muscular twitching that often left their
horses temporarily unable to move. Usually mis-diagnosed as tying-up syndrom or
colic, these episodes varied widely in degree and duration....but all had one factor
in common, their pedigree. As a result, many people now know HYPP as its' more common
name: Impressive Syndrom.
Research funded by the AQHA and the University of California-Davis Equine Research
Laboratory subsequently linked the problem to elevated levels of potassium in the
blood serum. But even as researchers at leading veterinary schools began publishing
articles in professional journals and trade publications, the vast majority of Quarter
Horse owners remained unaware of the condition.
All the while, Impressive and his kin continued to make history.....breeding, showing,
winning ribbons, and making their owners fantastic sums of money. Most affected
horses can be controlled quite well with medication and a proper low-potassium diet,
therefore, many owners of affected horses considered HYPP a minor inconvenience
in light of the line's tremendous value. Given the fact that - at the time - there
was no proof that the disorder was exclusive to the Impressive line - not to mention
the fact that owners of stock descended from Impressive included some of the most
prominent and wealthy individuals in the industry - no one wanted to be the first
to publicly implicate the line. And, even later, when a breakthrough genetic test
removed all doubt, lessening the moral and ethical burdens associated with naming
Impressive as the carrier, neither the research community nor the AQHA was eager
to lift the lid of this Pandora's box: Each feared possible legal and financial
ramifications from a sector of the horse industry that would be shaken to its foundations.
In the past few years however, pressures both within and outside the Quarter Horse
industry finally shattered the secrecy surrounding HYPP. The genetic test, made
available in 1992, can identify affected horses with virtual certainty. As a result,
many owners of horses descended from Impressive have rushed to have their horses
tested, hoping that a negative result would protect their considerable investment
against the anticipated backlash. Breeders have purchased advertising in The Quarter
Horse Journal touting their HYPP-negative test results, and privately have urged
their peers to either test their Impressive bred horses, or remove them from breeding.
(for a complete copy of this article, please contact Equus magazine.)
From the Vet School at UC Davis, California
Blood Test Available for Hyperkalemic Periodic Paralysis in Quarter Horses By Sharon
J. Spier, D.V.M., Ph.D. University of California at Davis School of Veterinary Medicine,
Department of Medicine.
Hyperkalemic periodic paralysis (HYPP) is a muscle disease which has been reported
in certain lines of registered Quarter Horses, Appaloosas and Paints. Affected horses
often display well-developed muscles and are often very successful when shown in
halter classes. The condition may be seen in stallions, mares or geldings, can cross
breeds and, therefore, is not limited to stock-type horses. The disease also closely
resembles a heritable disease in man. Studies at the University of California at
Davis Equine Research Laboratory have produced much needed information about the
genetics, cause and control of HYPP in horses. An accurate blood test has been designed
for diagnostic purposes as well as to identify carriers of the disease.
Signs of the Disease
Hyperkalemic periodic paralysis is characterized by sporadic attacks of muscle tremors
(shaking or trembling), weakness and/or collapse. Attacks can also be accompanied
by loud breathing noises resulting from paralysis of the muscles of the upper airway.
Occasionally, sudden death can occur following a severe paralytic attack, presumably
from heart failure or respiratory muscle paralysis.
Attacks of HYPP can take various forms and commonly have been confused with other
conditions. Because of the muscle tremors and weakness, HYPP often resembles exertional
rhabdomyolysis ("tying-up" syndrome). "Tying-up" syndrome can
be caused by many different circumstances, including exercising a horse beyond the
capacity to which it has been trained, as well as nutritional deficiencies and metabolic
diseases. A distinguishing feature of this disease from "tying-up" syndrome
though, is that horses usually appear normal following an attack of HYPP. Horses
with "tying-up" syndrome, on the other hand, tend to have a stiff gait
and painful, firm muscles of the hind limbs, rump and/or back. "Tying-up"
syndrome is also generally associated with some type of exercise. HYPP, by contrast,
is not usually associated with exercise, but occurs when horses are at rest, at
feeding time, or following a stressful event such as transport, feed changes, or
Because a horse may be down and reluctant or unable to stand during an HYPP attack,
many owners have thought their horses were experiencing colic. HYPP has also been
confused with seizures due to the pronounced muscle trembling and collapse. Unlike
seizures and other conditions that cause fainting, however, horses with HYPP are
conscious and aware of their surroundings during an attack and do not appear to
be in pain. Respiratory conditions and choke have also been confused with HYPP because
some horses make loud breathing noises during an attack.
Causes of Attacks
Potassium is an important electrolyte and is vital for the normal function of muscles
and nerves. In fact, every cell in the body contains potassium, as it is vital for
maintaining the cell's volume and electrical activity. High concentrations of potassium
are present in the normal diet of horses and large amounts are found in forages
such as pasture grasses and hays.
Regulation of body potassium is very complicated and is strictly controlled by hormones
throughout the body produced by the kidneys, adrenal gland, thyroid and pancreas.
Because normal horses commonly consume an excess of potassium in their diets, the
kidneys must excrete excess potassium in urine. Initially, it could not be determined
whether this disease was caused by a disorder in potassium regulation or by a disorder
of muscle function. Studies of kidney, adrenal gland and thyroid function in horses
with HYPP were normal. Investigations of muscle function in these horses, however,
revealed a different story.
In early studies, abnormalities in the skeletal muscle by electromyography (EMG)
were observed. Electromyography measures the electrical activity present in selected
muscles. In affected horses, the muscles displayed a wide variety of abnormalities,
specifically spontaneous activity from muscles under no stimulation. These recordings
demonstrated that the affected horses' muscles were hyperexcitable (overly excitable).
Even when the horses appeared normal, in between attacks, the abnormalities were
reproducible. These abnormalities were also observed when the horses were under
general anesthesia and under the influence of nerve blocking agents. This proved
the theory that the muscle was abnormal.
Abnormal electrical activity within muscle fibers occurs in other muscle diseases
as well as HYPP, so the abnormal EMG findings are not enough to definitively diagnose
HYPP. Nonetheless, repeated episodes of muscle weakness or tremors in offspring
of an affected sire or dam coupled with abnormal EMG findings would be highly suggestive
Collaborative studies with human physiologists Drs. Joel Pickar and Richard Carlsen
of the University of California Davis School of Medicine and Dr. Jack Snyder of
the veterinary department of Surgery led to the development of a specialized muscle
biopsy procedure for horses which allowed researchers to isolate and study small
muscle strips in a laboratory setting rather than performing research on the whole
horse. Results from these studies confirmed that the isolated muscle was hyperexcitable
and that there were abnormalities in sodium and potassium levels.
In horses with HYPP, studies revealed a defect affecting a protein called the voltage-gaited
sodium channel, a tiny gateway in the membrane of muscle cells. This gateway controls
the movement of sodium particles in and out of the muscle cell. These sodium particles
carry a charge that changes the voltage current of a muscle cell, allowing it to
contract or relax. In horses with HYPP, the regulation of particles through the
sodium channel occasionally fails, disrupting the normal flow of ions in and out
of the muscle cell, causing uncontrollable muscle twitching or complete muscle failure.
Further studies using molecular genetics revealed a mutation at one important site
in the gene responsible for sodium and potassium regulation. This mutation allows
the production of an abnormal protein which alters the structure and function of
the sodium channel. As a result of these uncontrollable muscle contractions, potassium
leaks from inside the muscle cell into the bloodstream, thus, raising the blood
potassium concentration. The identification of this gene mutation is the basis for
the blood test used to diagnose HYPP.
An Inherited Trait in Horses: Breeding Trial Results
In humans, HYPP is inherited as a dominant trait which is not sex-linked or carried
on the X or Y chromosomes, and either sex may carry the trait. The proportion of
individuals carrying a genetic defect which actually demonstrate signs of the disease
is called penetrance. Sometimes, an individual can carry a genetic defect, but may
never show signs of disease. In humans, HYPP has a high penetrance, meaning that
the majority of individuals carrying the gene will demonstrate signs of disease
at some time during their lives.
The mode of inheritance of the disease in horses has been suggested to be similar,
although there had been no definitive studies to prove this theory. The purpose
of the breeding study was to document, in a laboratory setting, the mode of inheritance
of HYPP in horses through a controlled breeding study.
Four Quarter Horses (one stallion and three mares) with HYPP were bred to unaffected
horses to determine the genetic basis of the disease. The first trial consisted
of breeding the affected stallion to an affected mare. Three offspring (two colts
and one filly) were obtained using embryo transfer techniques and all three foals
were affected with HYPP. This initial study proved that the condition was heritable,
but could not distinguish if the trait was dominant or recessive.
The second trial consisted of breeding the affected stallion to 11 unaffected mares
of different breeds. The three affected mares were bred to an unaffected Quarter
Horse stallion. Seventeen foals were produced from these breedings. All foals were
tested for HYPP at two months of age. Of the 17 offspring, 10 were affected with
HYPP, proving that HYPP is a dominant trait.
Because HYPP is a dominant trait, the breeding of an affected mare or stallion to
a normal horse will result in approximately 50% of the offspring carrying the trait.
If two affected horses are bred, then at least 75% of the foals will be affected.
The breeding of a normal offspring from an affected horse to another normal horse
will result in normal offspring.
Prevention and Control of HYPP Attacks
During a severe attack of HYPP, emergency treatment from a veterinarian is necessary.
For long term therapy, many horses can be managed by exercise and diet control alone.
Regular exercise and access to a large paddock or pasture is preferred over stall
confinement. Maintain a regular feeding schedule, preferably equally spaced, two
to three times per day. Avoid rapid changes in feed, such as bringing a horse off
pasture grass and immediately switching to alfalfa hay. Most horses improve when
the potassium content in the diet is decreased.
An analysis of feed can be very helpful in problem situations. Oat hay contains
approximately 1.4% potassium, alfalfa hay - approximately 2.5%, timothy hay - approximately
2.0 - 2.5% potassium and molasses - approximately 6% potassium. The HYPP horses
at the Equine Research Laboratory do well on a diet of half alfalfa and half oat
hay. Feeding grain such as oats, corn and or barley (each contain only 0.5% potassium)
two to three times daily and access to a salt block can be helpful. If dietary management
is not sufficient to prevent attacks, then treatment with a diuretic (acetazolamide)
can be very helpful. Consult your local veterinarian for proper diagnosis and further
recommendations on treatment.
Eliminating this Disease from the Horse Industry
The major focus of this study has been to develop the use of a genetic marker associated
with HYPP to identify affected horses to assist veterinarians and breeders in controlling
the disease. In collaboration with Dr. Eric Hoffman, a molecular geneticist from
the University of Pittsburgh School of Medicine, a horse-specific HYPP gene probe
was created using DNA from the affected Quarter Horse stallion. This gene probe
offers breeders and veterinarians a tool which can be applied as a safer and more
reliable diagnostic test for this disease.
Affected horses which are carriers of this genetically determined disease have many
desirable traits. This is the reason that many of these horses are so successful
in the show ring. In a recent report by Dr. Jonathan Naylor of the University of
Saskatchewan, over 50,000 registered Quarter Horses are related to known carriers
of the disease. However, the disease is not widespread in the Quarter Horse breed
and only involves certain lines of halter type horses. At the present time, the
disease has not been recognized in racehorses or endurance horses.
The recently developed genetic marker test for this disease will allow breeders
to identify carriers of HYPP and thus, direct their breeding programs. To eliminate
this trait from certain lines, stallion and mare owners should have their horses
tested prior to breeding and select normal horses for their breeding stock...
Myths About HYPP
Some people have felt that the disease can be diluted out and not carried to distant
generations. This is false because an affected horse has just as much chance to
pass on the trait as the affected parent which passed the gene to him. Some people
also believe the horse will "grow out of it." This is not true. For unknown
reasons, attacks of HYPP tend to occur most often at the beginning of intense training
and fitting for shows (age three to seven years old). It is important to realize
that horses with HYPP are affected for life. It is possible that older horses do
not experience the same conditioning stresses as young horses or that owners have
discovered the best management strategies for the older horses with HYPP.
Some people also think that if a horse does not show any signs up to a certain age,
it does not carry the trait. Unfortunately, this is not the case. Once again, horses
with HYPP are affected for life. There was a stallion and a broodmare with HYPP
who did not show signs of the disease until age eight and 15, and both horses only
experienced one isolated attack.
owners and breeders of affected horses should inform prospective buyers of the management
constraints these horses have and the potential for future episodes of HYPP. To
have a horse tested for the specific DNA mutation causing HYPP, please send a whole
blood sample in an EDTA vacutainer tube (a purple-topped tube) labeled with the
horse's name, name of the owner or responsible agent, and a copy of the horse's
pedigree. Please include a check for $50 per sample made payable to "UC Regents."
For more information, call (916) 752-7416. Send sample to:
Veterinary Genetics Laboratory HYPP Testing
School of Veterinary Medicine
University of California
Davis, CA 95616-8744