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Pamela A. Davol, 76 Mildred Avenue, Swansea, MA  02777-1620.
pdavol@labbies.com


SKELETAL MUSCLE MYOPATHY:

An Inherited Disorder of the Labrador Retriever


This page is dedicated to "Molly"

Diagnosed with HMLR in May 1997

Gone to Rainbow Bridge October 20th, 1997

Bob and Shirley....I know how much you tried. She was always in the most loving hands. Thank you.


WHAT IS SKELETAL MUSCLE MYOPATHY?

Skeletal muscle myopathy is a hereditary muscle disorder in which there is a deficiency of type II muscle fibers leading to a notable decrease in skeletal muscle mass. Although several breeds of dogs have been observed to demonstrate similar disorders, this condition is only seen in Labrador retrievers and was first reported and described in 1976. In 1981, the same researchers characterized the mode of inheritance in Labradors and since that time the condition has been referred to as "Hereditary Myopathy of Labrador Retrievers" (HMLR). Other names for HMLR include muscular dystrophy, myotonia, generalized muscle weakness, polyneuropathy, and hereditary myopathy.

WHAT ARE THE SYMPTOMS OF HMLR?

Muscle weakness, abnormal gait and posture, and a decrease in tolerance to exercise are the most common symptoms affecting Labradors with HMLR. On the average, onset of symptoms usually occur at 3-4 months of age, however, some dogs demonstrate symptoms as early as 6-8 weeks or as late as 6-7 months of age. Abnormalities in gait and posture include a short, stilted stride, "bunny-hopping," low head posture and an arched back. These symptoms become more obvious as the exercise continues and the dog tires or if the dog is exposed to cold weather. Eventually, if not allowed to rest or to keep warm, the dog may temporarily collapse. Rest improves symptoms but follow-up exercise quickly brings on a relapse. Other signs of HMLR include abnormalities of the joints including "splay-foot", "cow-hocking" and hip dysplasia. Additionally, as the disease progresses, atrophy of the muscles in the limbs and head becomes apparent.

HOW IS A DOG DIAGNOSED WITH HMLR?

Diagnosis can be difficult especially in mildly to moderately affected dogs since symptoms of HMLR can often be mistaken as produced by other disorders, particularly hip dysplasia. Often, other than intolerance to exercise, there is no outward evidence of other physiological or neurological abnormalities. Routine blood work is usually normal in affected dogs. Muscle biopsy, therefore, has produced the most reliable means for diagnosing HMLR. However, because other diseases affecting the heart and lungs, muscles and adrenal glands may produce symptoms of exercise-intolerance similar to HMLR, it is important that these disorders be ruled out as well.

WHAT IS THE TREATMENT FOR HMLR?

Currently, other than rest, there is no generally accepted medication which has been found to be effective for the treatment of HMLR. Some individuals have, however, responded to treatment with Diazepam or steroids. In many cases, the disease is non-progressive and stabilizes once the dog reaches between 1-2 years of age. Therefore, on the average, owners of affected dogs can expect an acceptable house pet with a normal life-span. However, affected dogs are not suitable to perform as working dogs since stress and exertion may bring on worsening of symptoms. Additionally, the potential for collapse during these periods of exercise may lead to losing the dog in the field or to drowning if the dog is working in water.

CAN HMLR BE PREVENTED?

In 1981, Kramer and colleagues reported that HLMR is inherited as an autosomal recessive trait; that is, a dog must receive one copy of the gene from each parent to have this disorder. Dogs which receive the gene from only one parent will be "carriers" of the disorder but will not have the disorder. Therefore, to even know that risk for HMLR exists in a particular bloodline, a "carrier" must be bred to another "carrier." In a litter produced by two carriers of the HMLR gene, 25% of the puppies will be at risk to having HMLR, 50% will be carriers like their parents but will not have HMLR, and 25% will not carry the HMLR gene. As with all recessive genes, breeding out HMLR from bloodlines can be difficult because there is no way of determining which of the offspring are "carriers" and which are genetically "clean."

new.gif (2232 bytes)Update: Advances in HMLR genetic screening and diagnosis.
Researchers at Alfort School of Veterinary Medicine in France have identified and mapped the gene mutation associated with HMLR, which they have renamed centronuclear myopathy in Labrador retrievers.  A genetic test to screen breeding stock that might be at risk for passing on the HMLR gene is now available and thus, provides a means for breeders to reduce incidence of this disorder within the breed while preserving the continuation of certain bloodlines.

For more information on genetic testing, please visit:  CNM online!

Medical Publications on HMLR:

Pele M, Tiret L, Kessler JL, Blot S, Panthier JJ. SINE exonic insertion in the PTPLA gene leads to multiple splicing defects and segregates with the autosomal recessive centronuclear myopathy in dogs.  Hum Mol Genet. 2005 Jul 1;14(13):1905-6.

Olby NJ, Sharp NJ, Anderson LV, Kunkel LM, Bonnemann CG. Evaluation of the dystrophin-glycoprotein complex, alpha-actinin, dysferlin and calpain 3 in an autosomal recessive muscular dystrophy in Labrador retrievers. Neuromuscul Disord 2001 Jan;11(1):41-49.

Mehta JR, Braund KG, Hegreberg GA, Thukral V. Lipid fluidity and composition of the erythrocyte membrane from healthy dogs and Labrador retrievers with hereditary muscular dystrophy. Neurochem Res 1991 Feb;16(2):129-35

Mehta JR, Braund KG, McKerrell RE, Toivio-Kinnuncan M. Intracellular electrolytes and water analysis in dystrophic canine muscles. Res Vet Sci 1989 Jul;47(1):17-22

Mehta JR, Braund KG, McKerrell RE, Toivio-Kinnucan M. Isoelectric focusing under dissociating conditions for analysis of muscle protein from clinically normal dogs and Labrador retrievers with hereditary myopathy. Am J Vet Res 1989 May;50(5):633-9

Amann JF, Laughlin MH, Korthuis RJ. Muscle hemodynamics in hereditary myopathy of Labrador retrievers. Am J Vet Res 1988 Jul;49(7):1127-30

McKerrell RE, Braund KG. Hereditary myopathy in Labrador retrievers: a morphologic study. Vet Pathol 1986 Jul;23(4):411-7

Treatments on the Horizon:

Skuk D, Tremblay JP. Progress in myoblast transplantation: a potential treatment of dystrophies. Microsc Res Tech 2000 Feb 1-15;48(3-4):213-22

Howell JM. Is there a future for gene therapy? Neuromuscul Disord 1999 Mar;9(2):102-7

 

For more information on HMLR:

Labrador Retriever Myopathy by Kyle G. Braund, B.V.Sc., M.V.Sc., R.R.C.V.S., Ph.D.

Information on Other Myopathies affecting Labrador Retrievers:

EXERCISE INDUCED COLLAPSE IN LABRADOR RETRIEVERS by Susan M. Taylor, DVM

Canine Stress Syndrome (CSS)-also known as Canine Malignant Hyperthermia (CMH)

REFERENCES:


Copyright © 1997, 2005. Pamela A. Davol. All rights reserved. Copyright & disclaimer.

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