Research Of Scottie Cramp And DMVD Expected To Benefit Affected Breeds

Efforts to learn more about two genetic conditions affecting terrier breeds may one day help breeders reduce the disease incidence of degenerative mitral valve disease (DMVD) in Norfolk Terriers and Scottie Cramp in Scottish Terriers. Here is an overview of the research studies.

While Scottie Cramp is not a new condition in Scottish Terriers, research at North Carolina State University College of Veterinary Medicine may reveal surprising new information. First reported in the Netherlands in 1942, Scottie Cramp causes episodes of stiff, spastic movements. As the name suggests, affected dogs appear to have cramping in their legs.

Lead investigator Natasha Olby, VetMB, Ph.D., DACVIM-Neurology, professor of neurology, studies Scottie Cramp and a neurodegenerative disorder in Scottish Terriers, cerebellar abiotrophy (CA). "In mildly affected animals, the two movement disorders can look similar, but they are different," she says.

Though the gene mutation for Scottie Cramp is not known, it is believed to be an autosomal recessive condition in which affected dogs inherit one copy of the mutation from each parent. "West Highland White Terriers and Cairn Terriers have a similar movement disorder and may share the mutation with Scotties," Olby says.

The investigation is supported by the AKC Canine Health Foundation, the Scottish Terrier Club of America (SCTA) and the STCA Health Trust Fund. Olby, who has studied Scottie Cramp for three years, has received DNA samples from affected and healthy Scottish and Cairn terriers. Owners have submitted videos showing their dogs having a cramping episode and completed questionnaires describing the condition. The research has shown a range in severity of cramping episodes. "The episodes reported by many owners are rather different than the classic Scottie Cramp event in which a dog's gait becomes stiff, and then his limbs become so spastic they are recumbent for a few minutes," Olby says. "We've had owners tell us their Scotties only had a single attack, while others report dogs having more severe episodes that last for hours and don't respond to treatment. Some owners have told us they've observed their dogs running around normally, and then suddenly their hind legs go stiff and they start bunny hopping and skipping for a few paces before a rapid return to normality.

"We've assumed that mild, classic and severe cases have been the same disease, but we don't know that for certain. That is why this research is so intriguing. We are trying to pinpoint what Scottie Cramp encompasses."

A Genomewide Association Study

The genomewide association study involves genotyping the DNA of affected dogs and attempting to identify associations between particular genotypes and the disease. Although previous studies indicated one mutation is responsible for Scottie Cramp, Olby feels there may be genetic modifiers involved that account for the range of severity.

"We've been unable to isolate a single region where the mutation is likely to exist," she explains. "If it were a single gene, we should have found the region by now. We have looked at candidate genes closely. For example, a similar disease seen in Cavalier King Charles Spaniels is caused by mutations in a gene called BCAN. We have checked for this mutation in affected Scottish Terriers, and they do not have it. We are now sequencing the entire genome of an affected dog to allow us to search for the mutation in more detail."

A definitive diagnosis of Scottie Cramp is based on recognizing signs of the disorder. Veterinarians first rule out seizure or orthopedic disorders. Most Scotties are under 1 year of age when they show signs. Scottie Cramp is believed to be related to dysfunction of signaling between neurons. Previous research indicated it was due to a deficiency of a neurotransmitter called serotonin.

Although Scottie Cramp is not a progressive disease and rarely worsens over time, treatment is limited. Veteri­narians may prescribe Valium or Prozac for dogs that experience severe, frequent episodes. Valium works within the nervous system to increase inhibitory signaling and to help reduce or prevent spasticity. Prozac increases concentrations of serotonin.

Avoiding situations that prompt an attack often works best. "Owners quickly figure out what triggers an episode and how to avoid it," Olby says. "Excitement or exercise — sometimes a combination of both — may bring on an attack. Dogs are conscious when it occurs. They learn to sit and wait for the episode to pass. With rest, a dog returns to normal, usually within minutes. In most cases, no treatment is necessary."

Deciphering the signs of Scottie Cramp and cerebellar abiotrophy can be challenging. Dogs with CA have a gait deficit that causes them to overstep and lose their balance. When running, they can lose control of their hind quarters and skip and bunny hop in a manner similar to Scottie Cramp. However, dogs with CA exhibit signs all the time, unlike Scottie Cramp in which dogs are normal between episodes. The difficulty comes when dogs are mildly affected with CA, showing obvious signs only when they are running.

CA occurs in many breeds, including several terrier breeds, such as the Airedale Terrier, Kerry Blue Terrier and Miniature Schnauzer. Signs and age of onset vary among breeds, but in the form seen in Scottish Terriers, signs of CA usually appear in a dog's first year similar to Scottie Cramp.

CA is a chronic and progressive condition caused by a loss of brain cells in the cerebellum. Though the gene mutation for CA in Scottish Terriers has not been discovered, CA is believed to have an autosomal recessive inheritance similar to Scottie Cramp. There also is no effective treatment for CA.

As Olby and her research team learn more about the genetics behind Scottie Cramp, they hope to identify the mutation causing the disease and to develop a genetic test that will allow breeders to eliminate it from the breed.

Understanding DMVD

At the University of Pennsylvania School of Veterinary Medicine, researchers aim to learn more about diagnosing and treating Norfolk Terriers that develop DMVD. The slow, progressive condition is believed to affect 30 percent of small-breed dogs over the age of 10.

"In the early stages of the disease, no clinical signs are apparent and a dog appears healthy," says lead investigator Mark Oyama, D.V.M., DACVIM-Cardiology, professor of clinical studies and chief of cardiology. "We are studying the dogs that have what we believe is a very early 'silent' form of the disease, when early degeneration of the mitral valve is present but the telltale sign of a heart murmur cannot yet be heard."

A previous University of Pennsylvania study of DMVD in Norfolk Terriers found that 12 of 48 dogs considered clinically normal actually showed evidence of the disease on an echocar­diogram test, despite not having a detectable heart murmur from an auscultation examination by a veterinary cardiologist. An echocardiogram is a cardiac ultrasound used to detect heart structure and function, whereas an auscultation involves a veterinarian using a stethoscope to listen to a dog's heart and lungs for abnormalities.

"This study raised the question whether an echocardiogram rather than auscultation should be used to identify dogs for DMVD," Oyama says. "It provided the foundation for our second study where we followed dogs with what we suspected was early disease over time to see if they eventually progressed to developing a heart murmur."

This study, supported by the AKC Canine Health Foundation and Friends of Norfolk Terriers, will be completed this year. Although it is too early to report on the findings, Oyama notes that so far some dogs have subtle, mild changes in the shape and function of the mitral valve — the early signs of DMVD — despite the absence of a heart murmur. "We plan to continue monitoring these dogs to determine whether they develop other classic signs of mitral valve disease," he says.

Among the findings reported in the first study, the research team discovered that dogs with severe DMVD had changes in six serum amino acids and a hormone called NT-proBNP that is produced by the heart when stressed or diseased. These indicators could be used to predict severity of disease.

An Inherited Disorder

DMVD is believed to be an inherited condition. Many small-breed dogs, including the Cavalier King Charles Spaniel, Toy Poodle and other terrier breeds, develop the condition. Cavaliers, which have the greatest risk, develop an early-onset form with rapid progression. A small percent of Norfolk Terriers develop the severe type that leads to heart failure.

"No one knows why these small breeds are prone to DMVD," says Oyama. "However, affected breeds have other diseases associated with connective tissue problems, such as luxating patella and collapsing trachea. The mitral valve has a lot of connective tissue, so it's possible these various conditions are somehow related."

The majority of Norfolk Terriers diagnosed with DMVD are recognized by their veterinarians during an auscultation examination. An audible heart murmur usually is followed by an echocardiogram that provides a visual tool to see early changes in the mitral valve and/or thoracic, or chest, radiographs.

Owners are not likely to notice signs of the disease unless it reaches the advanced stage. Excessive panting when exercising, shortness of breath, coughing, a distended abdomen, loss of appetite, and weight loss are the signs owners commonly report.

Degeneration of the mitral valve happens slowly. Located between the left atrium and left ventricle of the heart, the mitral valve helps regulate the flow of blood in and out of the heart and prevents a back flow from going into the atrium. The mitral valve is made of thin flaps of tissue, or valve leaflets, attached by long, tendon-like structures, the chordae tendineae, to the muscles of the left ventricle. These valve leaflets open and close to regulate the flow of blood, but as the disease progresses, they begin to thicken, contract and lose flexibility.

When the mitral valve functions correctly, blood in the left ventricle is pumped to the body as the heart contracts. As the mitral valve degrades, it cannot close properly and small amounts of blood leak back into the left atrium. Over time, the valve will continue to degrade until the heart can no longer compensate. Stress from the leak causes the heart to enlarge, eventually resulting in congestive heart failure. In severe cases, the chordae tendineae may rupture, damaging or causing complete collapse of the mitral valve.

A disease that is managed rather than cured, DMVD has limited treatment options for dogs with advanced disease and congestive heart failure. Although surgical repair currently is not available in the U.S., a research team in Japan at Nihon University in Tokyo has reported good results with valve repairs using an open heart surgical procedure.

"Many dogs will never develop the severe form of the disease that causes clinical signs requiring medications," Oyama says. "A relatively small percentage will have progressive heart enlargement and be at risk for heart failure."

Veterinarians prescribe medications on an individual basis. Dogs may be given:

  • diuretics, such as furosemide and spironolactone, to help remove excess fluid from the lungs
  • an ACE inhibitor to help prevent enlargement of the heart and congestive heart failure
  • pimobendan to dilate blood vessels and improve strength of the heart muscle


Breeder Recommendations

Due to concerns about DMVD in the breed, the Norfolk Terrier Club of America includes screening for heart disease among the tests required for a dog to receive a health clearance via Canine Health Information Center (CHIC) certification. Heart testing by a board-certified veterinary cardiologist using a color-flow doppler ultrasound involves looking for mitral valve abnormalities.

Breeders often debate whether they should breed a Norfolk Terrier diagnosed with DMVD since the disease is believed to be an inherited condition. On the other hand, not breeding dogs diagnosed with DMVD could potentially reduce genetic diversity and proliferate other diseases.

"I recommend that breeders monitor dogs showing mild changes in mitral valve structure from an echocardiogram test," Oyama says. "I don't think these dogs should automatically be removed from breeding programs. Doing so would further limit the already small gene pool, and until we know more about what echocardiographic changes constitute a definitive diagnosis of very early 'silent' mitral valve disease, auscultation for a heart murmur remains the recommended gold standard for screening for DMVD."

Owners May Contribute to Scottie Cramp Research

Owners of Scottish Terriers affected by Scottie Cramp may contribute to research under way at North Carolina State University College of Veterinary Medicine. Natasha Olby, VetMB, Ph.D., DACVIM-Neurology, professor of neurology, and her research team hope to better understand the gene mutation that causes the disorder.

Participants should submit DNA samples and videos showing their dogs' movement during an episode. They also should complete questionnaires describing the condition in their dogs. For more information, contact Olby at Natasha_Olby@ncsu.eduor 919-513-8286.