Lafora Disease in Miniature Wirehairs

ACHSHUND Update DA NESTLÉ PURINA PUBLICATION DEDICATED TO DACHSHUND ENTHUSIASTS VOLUME 18 | SPRING 2020

LAFORA DISEASE IN MINIATURE WIREHAIRS Caution & Awareness Advised SPRING 2020 AWARENESS OF LAFORA DISEASE IN MINIATURE WIREHAIRED DACHSHUNDS COULD AID PREVENTION Miniature Wirehaired Dachshund was first recognized in Mini breeder Dianne Graham of Wirehairs in the U.K. more than Pulaski, Virginia, learned about three decades ago. Graham Lafora disease five years ago quickly realized that few U.S. when she discovered an English breeders knew about Lafora. dog in her dog’s pedigree was A late-onset progressive myo- affected. Two of her bitches clonic epilepsy seen in dogs tested as carriers of the auto- around 7 years of age, Lafora dis- somal recessive condition that ease at its peak in 2013 affected

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GENOTYPE RESULTS FOR LAFORA DISEASE (AUTOSOMAL RECESSIVE INHERITANCE) P/P Affected dogs have two copies of the mutant gene that causes the Positive/Positive condition and will develop the disease.

P/N Carrier dogs have one copy of the normal gene and one copy of the Positive/Negative mutant gene. They will not develop the disease but will pass a mutant gene on to about half of their offspring.

N/N Clear dogs have no copies of the mutant gene responsible for the Negative/Negative condition and will neither develop the condition nor pass it on to their offspring. up to 10 percent of Miniature FAMILY OF MINI WIRE- Wirehaired Dachshunds in the HAIRS SHARES LAFORA U.K. and 42 percent were carriers. A different scenario took Gradually, after a genetic test place in Miniature Wirehaired became available in 2012 to Dachshunds in the U.K., where owners and breeders, disease for decades before the gene incidence began to decrease. mutation for Lafora disease was In 2017, only 3 percent of Mini discovered, breeders had pro- “As far as I know, there Wirehairs in the U.K. were affected duced litters in which some dogs and 26 percent were deemed later in life showed signs of haven’t been any recent carriers. epilepsy. They suspected it was affected dogs with Lafora Graham made it her mission a hereditary condition, though to educate North American the late onset of clinical signs disease in the U.S.” breeders about the incurable meant that most dogs had already condition that eventually claims been bred when it became Dianne Graham, Miniature Wirehaired the lives of all affected dogs. She apparent they were affected. Dachshund breeder, Pulaski, Virginia began a database to record the In the 1990s, veterinary testing results of North American neurologists Clare Rusbridge, Miniature Wirehaired Dachshunds BVMS, PhD, DipECVN, FRCVS, and investigated the history of of the University of Surrey in affected dogs in America. Guildford, England, and Sue “As far as I know, there haven’t Fitzmaurice, BVSc, MRCVS, been any recent affected dogs DACVIM (Neurology), of The with Lafora disease in the U.S.,” Ralph Veterinary Referral Centre Graham says. “The only dog I am in Marlow, Buckinghamshire, aware of was brought to Canada England, found an extended in the late ‘80s as a 5-year-old family of Miniature Wirehairs in Champion. He started showing which the disease was clearly signs when he was 7 years old inherited. They sent pedigree and was put down when he was information and DNA from those in his teens. His frozen semen dogs to Berge A. Minassian, MD, was later tested, and he was of The Hospital for Sick Children found to be affected.” at the University of Toronto in

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Canada, who was studying a their cells into large accumula- similar inherited, severe form of tions called Lafora bodies. The progressive myoclonic epilepsy gene mutation disables the gene in humans that occurs in late from controlling laforin and from childhood or adolescence. protecting tissue against carbo- Dr. Minassian identified the hydrate accumulation. As the Epm2b gene mutation for Lafora Lafora bodies gradually grow, disease in the Mini Wirehairs they have a neurotoxic effect in 2005 and matched it to the in the central nervous system. human Lafora disease mutations When Lafora bodies amass in the EPM2A gene and the within the nerve cells of the brain, EPM2B gene. Affected dogs, the cells start to malfunction as well as affected people, and degenerate causing neural inherit two copies of the gene problems such as twitching, mutation. The Epm2b gene jerking and sometimes seizures. mutation in dogs results in the As the disease progresses, the intracellular accumulation of dogs experience other neuro- abnormal glycogen phospha- logical problems, including tase laforin, a protein essential dementia and difficulty walking. for making normal structured Besides brain tissue, Lafora glycogen. bodies are found in muscles, Affected dogs are not able skin, liver, and heart. Although to convert starch into sugar, so Lafora disease appears as pro- insoluble glycogen builds up in gressive myoclonic epilepsy, it is actually a glycogen metabo- SIGNS OF LAFORA DISEASE lism disorder. Besides Miniature Wirehaired Among the initial signs of Lafora disease in Miniature Wirehaired Dachshunds, the disease is Dachshunds, owners participating in a breed health survey found in Basset Hounds and reported the following. The average age of onset for the dogs Beagles, with all three breeds in the survey was 6.94 years, with most dogs living a few years sharing the same single muta- after diagnosis. tion that leads to near-absent • Myoclonus, or sudden twitches or jerks, of the neck and limbs expression and loss of function was the most common sign, affecting 78 percent of dogs. of the gene. The canine mutation Myoclonus may be spontaneous or a reflex action triggered consists of a variable expansion by sudden noise, bright light, sudden movement, or flickering of a dodecamer repeat sequence visual stimuli. in the Epm2b gene. • Hypnic jerks, the type of sudden jerks people experience as Originally, gene sequencing they fall asleep, was the second most common sign, occurring options were limited, as the in 52 percent of dogs. traditional method of polymerase • Generalized tonic-clonic seizures were the third most common chain reaction (PCR)-based sign, affecting 41 percent of dogs. sequencing was unreliable for • Less common signs included focal seizures characterized by detecting carriers. At The Hospital “jaw smacking,” “fly catching” or panic attacks. for Sick Children, Dr. Minassian • Later signs include dementia, blindness, aggression to people and his team used a Southern and dogs, deafness, and fecal and urinary incontinence due blot test to identify the mutation to loss of housetraining. and to provide DNA screening of dogs using blood samples.

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U.K. DACHSHUND more than 40,000 pounds LOVERS JOIN FORCES ($52,000) toward the develop- “If we are concerned with The gene mutation discovery ment of a DNA test and for a for Lafora disease united mem- subsidy program to enable breed- breeding healthy dogs, we bers of the Wirehaired Dachs- ers to screen their dogs. After hund Club of the U.K. to work the test became available at The should be aware of Lafora together to educate breeders Hospital for Sick Children in 2012, and the opportunity to test about the estimation of breeding breeders could take advantage probability of the recessive condi- of the subsidized testing program our dogs to ensure the tion. The goal was to eradicate if they agreed not to breed the disease from the breed. carrier or affected dogs. disease does not affect Efforts to develop a commer- Further, the Wirehaired Dachs- dogs here.” cial test for the gene mutation hund Club asked The Kennel Club to require DNA testing for Lafora would not be easy since PCR Kenneth Levison, treasurer, disease for Miniature Wirehairs sequencing — the more common Dachshund Club of America and affordable type of genetic bred by the club’s Assured testing — was not possible to Breeders, a designation for identify carriers. The Southern breeders who adhere to good blot method required a blood breeding practices for their breed. sample, took months to process Results for every dog tested and cost around $300. would be published on The With help from the Dachshund Kennel Club’s health test website. Breed Council and The Kennel “The DNA test is now an official Club Charitable Trust, the Wire- requirement under The Kennel haired Dachshund Club raised Club’s Assured Breeder program,

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and no responsible breeder in ture Wirehairs in the U.K. were the U.K. would breed Miniature affected with Lafora, possibly Wirehairs without knowing the as many as 500 dogs, with 50 to Lafora status of the parents,” 100 affected dogs born a year, says Ian Seath, chair of the Seath says. “The proportion Dachshund Breed Council. of litters that could potentially To convince breeders who produce an affected puppy were not part of the Assured was estimated to be about Breeders program, Seath and 55 percent,” he says. other members of the Dachs- After the Wirehaired Dachs- hund Breed Council presented hund Club began holding Lafora data on the disease. “It was a screening sessions two times a much more powerful message year, with 50 to 60 dogs screened to state the number of Mini per session, the number began Wirehair puppies born over to decrease. Between 2012 and a particular time period and 2017, more than 700 Miniature the percent that we expect to Wirehairs were DNA tested for be affected by Lafora disease Lafora. With a goal of zero dogs because they were bred from affected, the Wirehaired Dachs- untested parents,” Seath says. hund Club of England continues In 2010, it was estimated that to monitor test results and from 5 to 10 percent of Minia- post them online quarterly.

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Caution about the risk of the disease spreading to other vari- eties is important, says Seath. “We have found no carriers of the mutation in Standard Wires in the U.K.,” he says. “But, we have reports that a Miniature Smooth Dachshund from the U.S. is a carrier. This dog was bred from two Miniature Wire- hair parents. The fact that U.S. and Fédération Cynologique Internationale breeders can cross the coats means Lafora could spread to other varieties.” Although Lafora originated in dogs in the U.K., the disease could become a problem in America, Seath cautions. “Some of the U.K. carrier dogs were used at concerned with breeding healthy stud, and it would be surprising dogs, we should be aware of if the mutation was not also in Lafora and the opportunity to test U.S. pedigrees with U.K. dogs our dogs to ensure the disease in the background,” he says. does not affect dogs here.” Graham, who had two bitches LOOKING TO REPRINT? EASIER DNA TESTING test as carriers, says, “I won’t AVAILABLE TODAY breed to an outside dog unless Dachshund Update articles may be reprinted provided the Fortunately, testing for Lafora I study the pedigree. It has been article is used in its entirety is easier today. The Hospital for a hard road to eliminate this from and in a positive manner. To Sick Children no longer offers my line. I finally have a male that request permission to reprint the test; however, two European tested clear. Every affected dog this article, please contact diagnostic testing laboratories is someone’s much-loved pet, the editor at: Barbara.Fawver perform the service. Laboklin and they may have to live with @purina.nestle.com. Reprints performs the Southern blot test the epileptic fits associated with should include the following previously used in Canada, and Lafora disease for six to 10 years. attribution: Used with per- Genomia uses PCR testing that That’s a hard price to pay when mission from the Dachshund can be done from a cheek swab. you consider how easy it is to Update, Nestlé Purina PetCare. Both labs provide testing results screen dogs prior to breeding.” n in two to three weeks. In the U.S., Kenneth Levison, Purina appreciates the sup- treasurer of the Dachshund Club port of the Dachshund Club of America (DCA), says, “At this of America and particularly point, the board of DCA is looking Dan Burke, DVM, chair of the for additional information and DCA Health Committee, in waiting on the availability of helping to identify topics for genetic testing in this country the Dachshund Update. before making genetic testing recommendations. If we are

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