Genetic Diseases in Horses: HYPP, HERDA, GBED, SCID, OLWS

Genetic Disease Primer

            The birth of a foal is usually a joyous occasion, carrying with it the hopes, dreams and aspirations of the breeder and the future owner. Reputable breeders therefore put a great deal of effort into matching the right mare to the right stallion, in hopes of creating a foal that will have the qualities most desired in the breed. Unfortunately, that desire to perpetuate certain characteristics, coupled with the tendency to breed as many foals as possible out of horses that have those characteristics, has led to the proliferation of a number of heritable diseases that have very serious consequences. Although the science of genetics has helped us to understand why these diseases occur, and in some cases, provided us with tests to identify carriers, it is up to the horse owning public – especially those involved in breeding – to try to make these devastating diseases a thing of the past.  Here is a run-down of five genetic diseases you need to know about.

The Disease: Hyperkalemic Periodic Paralysis (HYPP)

HYPP is a muscular disease that is caused by a hereditary genetic defect that disrupts a protein called a sodium ion channel, which functions as a gateway in the membrane of muscle cells. The genetic defect disrupts the channel's normal opening and closing, allowing uncontrolled sodium influxes. According to Sharon Spier, DVM, PhD, Associate Professor of the Department of Medicine and Epidemiology at the University of California, Davis, “The sodium influxes change the voltage current of muscle cells, causing uncontrolled muscle twitching or profound muscle weakness. High levels of potassium in the blood usually are present when the disruptions in the ion channel occur.” HYPP is a dominant disease, meaning that a horse only needs to have one copy (from one parent) of a defective gene in order to have the disorder and exhibit symptoms.

Why You Need to Know About it:

HYPP can have profound implications for owners of affected horses, both in terms of care of the horse and breeding considerations. Symptoms of HYPP can range from virtually nothing to unpredictable attacks of paralysis which can lead to collapse and sudden death in severe cases. The cause of death usually is cardiac arrest and/or respiratory failure. Owners of horses with HYPP will most often notice intermittent episodes of muscle tremors that manifest as generalized or localized shaking, trembling, and weakness. “Occasionally,” adds Spier, “episodes are accompanied by respiratory noises resulting from paralysis of the muscles of the upper airway (larynx and pharynx). In cases of mild attacks, muscle tremors may be so subtle as to be detectable only by an experienced clinician performing EMG testing.”
Fortunately, keeping horses with HYPP on a strict dietary and exercise regimen can eliminate or lessen the severity of attacks in many cases. Many HYPP positive horses can lead relatively normal and productive lives if they receive the lifelong management they require.

 Research History and Breakthroughs:

Spier’s research, begun in 1989 and funded by the American Quarter Horse Association, led to the discovery that all horses with HYPP can trace their ancestry back to one stallion: Impressive. For this reason, the genetic defect that causes HYPP is sometimes referred to as “the Impressive gene”.
Dr. Spier and her team at UC Davis made history when they were able to identify HYPP with DNA testing in 1992. HYPP was the first genetic disease that could be identified by DNA testing, and testing soon became widespread for Quarter Horses and breeds that carry a heavy percentage of Quarter Horse blood, especially Paints and Appaloosas.
As for why HYPP became so widespread, this can be traced back to Impressive’s success as a halter horse. In fact, there still exists in the industry the idea that in order for a horse to win at halter, it has to carry the Impressive gene. However, the science does not support this.  Explains Dr. Spiers, “We were curious as to what effect the gene would have on muscle mass, which is just one of the qualities that are selected for in halter horses. We studied muscle cell (muscle fiber) diameter and muscle fiber type distribution (slow twitch and fast twitch fibers) in HYPP positive and negative horses. We found no relationship between large muscle diameter and the gene mutation.”

Where We Are Today:

Dr. Spiers emphasizes that decreasing the incidence of HYPP is important for the long-term health of the Quarter Horse breed. To facilitate this decrease, the AQHA has instituted policies specifically focusing on HYPP.  Says La Donna Wilkinson, Senior Director of Registration of the AQHA, “The HYPP rule was first enacted at the 1996 convention in response to concerns raised by the general membership and in the scientific community as to the adverse physical effects associated with HYPP. Effective January 1, 1998, HYPP was to be recognized as a genetic defect and notification was to be placed on the registration certificate of all foals descending from the stallion IMPRESSIVE. However, at that time testing was not mandatory. Effective with foals born on or after January 1, 2007, all descendants of the stallion IMPRESSIVE are required to be parentage verified and HYPP tested. Any foal testing H/H will not be eligible for registration with AQHA.”
According to the AQHA website, the AQHA will accept HYPP test results only if performed through a licensed laboratory. In Canada, these labs include Vita-Tech Canada Inc., Markham, Ontario; and Maxxam Laboratory at Guelph, Ontario.

What the Future Holds:

Dr. Cecilia Penedo, Associate Director of Service of the UC Davis Veterinary Genetics Laboratory, has noticed a trend in the number of horses being tested for HYPP. “Since the test was made available in the late 1990’s,” she says, “there has been somewhat of a decrease in the number of horses being tested, because a lot of the animals and breeding stock have already been tested.” Unfortunately, widespread testing has not resulted in a drop in the numbers of horses diagnosed with HYPP. States Tammy Canida, Director of Registration Operations at the AQHA, “As of our last statistical analysis, we have not noticed a reduction in the number of affected horses. People are testing them, and I think they know about the disease, but still, some of the traits that those horses have they like as far as what they produce in the show ring. I can’t predict what will happen in the future, but right now, it’s not going away.” One can only hope that further information and education of the public will prompt breeders to be more diligent in their attempts to rid the horse world of HYPP.

The Disease: Hereditary Equine Regional Dermal Asthenia (HERDA)

Hereditary equine regional dermal asthenia (HERDA) is a terrible disease that causes a collagen defect in affected areas of the skin, resulting in a lack of adhesion within the deep layer of skin called the dermis. Like HYPP, the disease affects Quarter Horses and breeds that have a strong component of Quarter Horse blood. The ancestry of most horses diagnosed with HERDA traces back to the prolific sire Poco Bueno on both sides of their pedigree. As such, As HERDA is a recessive trait, both the sire and the dam of a horse must be carriers of the genetic defect for a foal to be born with the condition. Carriers of the gene are not affected by HERDA themselves.

Why You Need to Know About it:

HERDA is a devastating disease that often causes the loss of a horse at the most exciting time for the owner – the beginning of training. The disease causes the outer layer of the skin in the affected areas to split, separate, or peel off completely, most often along the back but sometimes in other areas as well. Even relatively minor trauma to affected areas results in wounds that heal slowly and typically leave depressions (atrophic scars) in the skin. New damage appears frequently, even in the absence of apparent trauma. Traction on the skin may elicit a painful response. Areas of affected skin can range from small and well defined (with a depressed surface) to large regions involving most of the back.
Horses are often diagnosed with HERDA at the age of 2, when training begins and they are put under saddle for the first time. Pressure and movement from the saddle causes the skin to tear and separate, making these horses unsuitable for riding. Sunburn is also a problem for these horses. As there is no cure for the disease, affected horses are often euthanized due to quality of life issues and the fact that they cannot be ridden or bred.  Though some individuals have lived longer with careful management and medical care, the average lifespan for a horse with HERDA is 2-4 years.

Breakthroughs/Where We Are Now:

Recently, a genetic test was developed that can identify normal, carrier and affected horses. Says Dr. Penedo, “The mutation that causes HERDA was identified by Dr. Danika Bannasch, here at UC Davis, in 2007.  We now offer a genetic test for the disease, and there are a lot of horses being tested. Owners and breeders, certainly the ones that are in the section of the quarter horse population affected by it where the incidence is higher were certainly aware of it. However, it is obvious that the problem goes beyond the cutting horse segment of the population, so greater awareness is necessary.”

What the Future Holds:

Responsible breeders in all segments of the stock horse world are taking advantage of the test to eliminate HERDA from their breeding programs, and it is hoped that the incidence will soon begin to decrease. Because the disease is so destructive, it would be best if breeders would not continue to breed HERDA carriers. However, because breeding a carrier to a non-carrier prevents the production of affected horses, it is likely that some breeders will find this an acceptable practice, allowing the gene to remain in the breeding pool.

The Disease: Glycogen Branching Enzyme Deficiency (GBED)

GBED is a recessive genetic disorder that results in the lack of a particular enzyme involved in the storage of glycogen, a type of sugar. The foals lack the enzyme necessary to store glycogen in its branched form and therefore cannot store the sugar molecules necessary to support body or brain function. The genetic mutation traces back to Quarter Horse sire King or his sire, Zantanon. It is estimated that up to 8% of Quarter Horses and Paint horses carry the GBED defect. Unfortunately, pedigree analysis is not particularly helpful in identifying GBED carriers because both King and Zantanon are foundation stallions.

Why You Need to Know About it:

GBED affects Quarter Horse or Paint horse foals, causing abortion or high neonatal mortality. This disease is fatal as the heart muscle, brain and skeletal muscles are unable to function. Affected foals are often aborted in late term or are stillborn. If the foal is born alive, it will be weak, slow to stand and nurse, and it will have a low body temperature. It may also have mildly contracted tendons. Medical intervention may allow a GBED foal to survive for a while, and some may even show signs of improvement before deteriorating again. Others might initially experience respiratory distress, collapse from hypoglycemia, seizures, then sudden death. Even with the best care, most GBED foals will not survive longer than eight weeks.
James Mickelson, PhD, Professor of Biochemistry and Genetics, University of Minnesota College of Veterinary Medicine, notes, “The most common result of GBED is mid-late term abortion, and not the weak foals that people note and try to treat. Thus, a large percent of the GBED problem is going unrecognized and unreported.”

Breakthroughs/Where We Are Today:

It was Dr. Mickelson and Dr. Stephanie Valberg, also at the University of Minnesota, who first identified this deficiency and developed a test to detect the defective gene in 2004. However, it is now believed that GBED has been causing significant fetal and neonatal losses among stock horses for decades.  It is therefore recommended that foal owners try to identify a GBED foal as soon as possible to limit the financial and emotional investment involved in trying to save a foal that is terminally ill. Because it can be difficult to diagnose GBED clinically, suspicious foals (alive or stillborn) should be diagnosed through genetic testing, which is available through the Veterinary Genetics Lab at UC Davis using mane or tail hairs with intact roots, or samples of fetal liver tissue.

What the Future Holds:

 Identifying GBED foals will also help breeders make decisions about continuing to breed carriers of the disease. If a GBED foal has been produced and they choose to rebreed the same mare to the same stallion, they have a 1 in 4 chance of producing another doomed foal. A DNA test is also available to determine whether a horse is a carrier of the deadly disease or not.
Unfortunately, the horse community is not availing itself of testing for GBED as much as researchers hoped they would when they first began offering the test. Says Dr. Penedo, “There is less interest in testing horses for GBED than for HERDA,” she says, “and definitely less than for HYPP. It’s difficult to say why there hasn’t been as much interest generated, as there is no treatment and the disease is inevitably fatal, if the foal is even born alive.” If people don’t test their horses, foals will inevitably continue to be lost.

The Disease: Severe Combined Immunodeficiency (SCID)

SCID is a deadly genetic disease that affects primarily Arabian horses and part-bred Arabians. Like people with the “bubble boy” condition, SCID foals are born without a functioning immune system. The immune system has two major defense systems: the B-lymphocytes which produce antibodies, and the T-lymphocytes which are responsible for cell-mediated immunity. The SCID defect, or mutation, results in an inability to produce either kind of lymphocytes. Foals with this condition therefore have an enhanced susceptibility to infection and generally first show signs of disease between two days and eight weeks of age. Clinical diagnosis of the disease is generally difficult because the symptoms, such as raised temperature, respiratory complications and diarrhea, are typical of new-born foals with a range of infections. Currently, it is estimated that 28% of Arabian horses are carriers of SCID.

Why You Need to Know About it:

The sad reality is that SCID affected foals always die within the first six months of life, regardless of the level of veterinary care provided. Because the foal may not be identified as suffering from SCID, owners often make great emotional and financial investments in trying to save the foal. As this can go on for some time, it is particularly distressing.
Because the gene that causes SCID is recessive, adult horses may be carriers of the gene, but will not be affected by it themselves. Owners of Arabian and part-bred Arabian horses who are considering breeding their animals need to be aware of this disease and the implications of breeding a carrier animal.

Research History and Breakthroughs:

            The Arabian horse community first became aware of SCID in the 1970s, but at that time, it was extremely difficult to definitively identify carriers. Recalls chair of the Arabian Horse Association’s task force on genetic diseases, “When the Arabian horse community was faced with SCID back in the 1970s and 1980s, it responded with the formation of the Fight Off Arabian Lethals (FOAL) Commission to help educate owners and support genetic disease research. Since that time, a test for SCID has been developed, over 8,000 horses have been tested, and the AHA Code of Ethics has addressed SCID disclosure in the Code of Conduct. The lesson to be learned from this is that focused efforts can be very successful.”
            The genetic test for SCID was developed by a private biotechnology company in 1998. It is now licensed to VegGen, a genetics services and research laboratory that was formed in 1995 as a spin-off from the University of Michigan Department of Human Genetics and the Michigan State University College of Veterinary Medicine.

What the Future Holds:

It is hoped that the newly established genetic diseases task force announced earlier this year by the Arabian Horse Association will help reduce the incidence of not only SCID, but other heritable diseases that affect Arabians and other horses. Says AHA President, Lance Walters, “The purpose of the task force is to have a group of AHA members regularly focused on genetic diseases," said Walters. "The end result will be an Arabian horse community that is educated about genetic diseases and knowledgeable about testing and disclosure. The task force will guide the association in developing policies and educational programs to educate the Arabian horse community about genetic diseases associated with the Arabian breed.”
Currently, there are no regulations requiring testing of Arabian horses for SCID, and even those who do test their breeding stock do not always disclose the results for fear of their animals being ‘boycotted’. There is quite a bit of controversy over whether or not outstanding individuals who are also carriers should be allowed to breed, with heated opinions on both sides. Some feel it is necessary to breed them – albeit carefully – in order to preserve desirable characteristics. Others feel that the only way to rid the gene pool of this devastating disease is to avoid breeding carrier animals altogether. For now, it remains an individual decision.

The Disease: Overo Lethal White Syndrome (OLWS)

OLWS is an inevitably fatal recessive disease that affects Paint horses and other breeds that have Paint blood in them. Though the genetic defect is commonly associated with a certain type of overo coat pattern, the defect has in fact been found in overos, tobianos, toveros, solid-colored horses, crop-out Quarter Horses and pintos.  In terms of breeds, it has been found in Paints, Miniature Horses, half-Arabians, Thoroughbreds, and cropout Quarter Horses.
 OLWS foals are born completely white (or occasionally with small black areas) and suffer from an improperly developed intestinal tract caused by a failure of the embryonic cells that form parts of the gastrointestinal system. In most cases, the intestine does not reach the anal opening, making it impossible for food to pass completely through the foal's digestive system. Attempts to surgically bypass the problem have, to date, been unsuccessful.  

Research History and Breakthroughs:

            The genetic defect that causes OLWS was first identified in 1998 by a team led by Elizabeth M. Santschi, DVM, Dipl. ACVS, Clinical Associate Professor at the University of Wisconsin's School of Veterinary Medicine. In 1991, this same team more accurately determined the coat patterns associated with OLWS in newborn foals. Not all overo horses are phenotypically (how they look) or genotypically (what genes they carry) the same.  There are four distinct overo subtypes--frame, calico, sabino, and splashed white—and not all overos produce affected foals, which left questions about which subtypes are affected. The 1991 study found that in heterozygotes (horses with one normal and one defective allele in the responsible gene), the mutation is usually responsible for a frame overo pattern. However, since frame overos' characteristic pattern can be altered through breeding to horses with other patterns, accurate visual inspection of carriers of the defective gene can be difficult due to blending of the patterns.
It was also found that other genes control both overo and tobiano (the other main type of white patterning recognized by the American Paint Horse Association) patterning besides the one that causes OLWS. Therefore, researchers concluded that the DNA-based test is the only way to be certain whether a white-patterned horse can produce a foal affected with OLWS.

Why You Need to Know About it:

            Foals with OLWS die in an agony of colic if they are not euthanized. The foals initially appear normal except for their unusual white coloring and light eyes. The typically stand and nurse normally, but will fail to have a bowel movement after nursing or an enema. Signs of colic or intestinal cramping begin within twelve hours following birth, caused by the foal's inability to pass feces. In most cases, the foal will start to show signs of distress within three to five hours after birth by rolling up on their back repeatedly.  They can survive for up to several days if they are not released humanely from their suffering. This heartbreaking disease appears quite commonly in the yearly foal crop of Paint horses.

What the Future Holds:

            Although the APHA was financially involved in the research that led to the genetic discoveries related to OLWS, they do not currently regulate the breeding of OLWS carriers or require disclosure for registration purposes. Reducing the incidence of this disease or eliminating it altogether is the responsibility of individual breeders. Testing is highly recommended for anyone considering breeding their Paint or related horses, as the gene appears to have a relatively high prevalence.

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