Historical CHD Information

severe-example-of-chondrodysplasia
An overview of chondrodysplasia in the Alaskan Malamute and of the Alaskan Malamute Club of America eradication program

Linda M. Dowdy Originally written May 1981 First update October 1999 Second update October 2004 Chondrodysplasia is a genetically-determined skeletal disorder that occurs primarily in the purebred Alaskan Malamute. The purpose of this article is to describe chondrodysplasia and to outline its relation to the veterinary practitioner.

Background

For a number of years Alaskan Malamute breeders in both Canada and the United States have been aware of occasional litters which contained deformed or “dwarfed” puppies. But it was not until the early 1970’s that these puppies were conclusively proven to be the manifestation of a genetic disorder. At first these affected dogs were known as “dwarfs” because of their diminutive size. This term however gave rise to considerable confusion with the dwarfism found in Hereford cattle. So another name, chondrodysplasia, was coined and brought into usage. This disorder, however, does involve far more than simply faulty cartilage maturation. Perhaps when it has been fully understood and defined, then a more comprehensive name will be in order.

Inheritability

Chondrodysplasia is transmitted as a simple autosomal recessive trait. Its mode of inheritance was determined by mating all combinations of unaffected, recessive carrier, and affected animals, until a total of one-hundred-fourteen (114) puppies had been produced. Identification of chondrodysplasia as a simple recessive has led to categorization of the Malamute into three distinct genotypes.

  1. Homozygous dominant – clear of the gene (symbol +/+)
  2. Heterozygous – recessive carrier of the gene (symbol +/dan)
  3. Homozygous recessive – chondrodysplastic (symbol dan/dan)

The term “dan” is taken from a concatenation of the words “dwarfism anemia”. d = dwarfism    an = anemia

Phenotype

The chondrodysplastic Malamute displays in varying degrees the following phenotypic characteristics.

  1. Excessively shortened front limbs with various degrees of bowing and deformity, especially the radius and ulna
  2. A topline that slopes from the pelvis down to the withers

Some chondrodysplastic Malamutes display a severe degree of deformity while others display almost no visible characteristics. It is important to note that the recessive carrier genotype displays no physical identifying characteristics, being completely normal in appearance.

Radiographic

Chondrodysplastic puppies, up to twelve weeks of age, are readily identifiable by radiographs of the carpal joint. Although all endochondral bones in the chondrodysplastic animal are affected, the condition is most apparent at the distal end of the ulna. In a normal puppy the distal metaphysis of the ulna appears V-shaped and evenly opaque, consistent with normal ossification and development. In the chondrodysplastic puppy, the distal metaphysis of the ulna is distinctly flattened and irregular, with a blunt widening of the distal diaphysis. There is variable evidence of normal ossification. The physis is increased in width with an irregular metaphyseal margin. After twelve weeks of age the joint begins to change. Some adult chondrodysplastics radiographically display relatively normal ossification. Therefore radiographs should not be assumed as a definitive diagnosis after twelve weeks of age. Radiographic evidence is most consistent between five and twelve weeks of age.

 
   

It is important to note that the sloping topline of many chondrodysplastic animals is a manifestation of alteration in conformation of the limbs and is not related to changes in the axial skeleton. The varying degree of topline slope is a direct result of the malformation which develops in the front limbs. The tubular bones at the distal radius and ulna are the most severely affected and growth retardation is excessive. The bones of the hind limbs are much less severely affected and achieve a more normal conformation. Some chondrodysplastic animals may display near normal conformation. Diagnosis of genotype in such cases must then be made by either test-mating the animal or by blood work.

Biochemical Aspects

The chondrodysplastic animal has an associated hemolytic anemia. There are several abnormalities in the red blood cell, including greater size, increased sodium content, and a smaller percentage of solids. The chondrodysplastic also has a trace mineral imbalance, and this eventually results in an excessive accumulation of copper in the liver. Some recessive carriers exhibit the same abnormalities of the red blood cell as the chondrodysplastic, but the overlap with those of clear dogs is excessive.

Blood Profile

As noted earlier, after twelve weeks of age, radiographs no longer provide a positive diagnosis of chondrodysplasia due to changes in the carpal joint. To diagnosis an older animal, it is necessary to utilize a blood profile. Dwarfism affects more than just the front limbs. There is an associated inherited hemolytic anemia that is characterized by morphologically abnormal red cells known as “stomatocytes”. In addition to the stomatocytes, the anemia is characterized by increased red cell size (MCV), decreased mean corpuscular hemoglobin concentration (MCHC), and a normal amount of red cell hemoglobin (MCH). The red cell sodium content is increased while the percent solids is decreased. The following table summarizes some of the work done by Dr. Sheilah Fletch. A second table shows the specific values for three dwarfs. The table of ranges was originally published in the Journal of the American Animal Hospital Association. The left side of the table shows the ranges of three blood parameters (MCHC, MCV, and MCH) for the three phenotypes of the Alaskan Malamute, namely clear, carrier, and chondrodysplastic. The second table shows the same three blood parameters for three known dwarfs (Cameo, Munchkin, and Duke).

  Clear Carrier Dwarf
MCHC 33.1 – 37.1 32.3 – 35.5 24.6 – 27.2
MCV  65.9 – 69.9  69.5 – 74.5  91.8 – 100.2
MCH 22.5 – 24.9  23.0 – 25.4  23.4 – 26.4
       Cameo     Munchkin       Duke
MCHC 25.0 27.1 26.7
MCV 93.2  97.0  93.8
MCH 23.3  22.5 25.0

Test-Breeding

The AMCA set up a screening and control program to address the problem of chondrodysplasia in the Alaskan Malamute. Initial screening was done by means of pedigree analysis. Using the dog’s pedigree, a statistical analysis was performed based upon the number of ancestors that were either known carriers or closely related to known carriers. The analysis yielded a number expressed as a percentage. This number represented the dog’s chances of being a recessive carrier of the gene, based upon the configuration of ancestors. If the number exceeded 6.25%, the dog was considered to be in the “suspect” or “potential” category. The value of 6.25% was selected because it represented one known carrier as a great-great-great-grandparent and also corresponds roughly to a 95% confidence level (04.37%). If the pedigree analysis indicated the animal fell into the “suspect” category, two recommendations were made to the owner.

  1. Withhold the animal from all breeding and preferably have it neutered
  2. Withhold the animal from all breeding until it could be test-mated with a chondrodysplastic or known recessive carrier.

Another method of testing, based on the blood profile of the animal, saw limited utilization. It was considered superior to pedigree analysis but not as good as test-breeding.

Genetics

Let the symbols for the various genotypes be as follows.

  • dan/dan = chondrodysplastic animal
  • +/dan = recessive carrier
  • +/+ = clear animal
  • +/? = unknown genotype animal

In test-mating with a chondrodysplastic animal, then: (+/?) X (dan/dan) => 1/2(+/dan) + 1/2(?/dan)

If all the test puppies in the litter are radiographically normal, then ? = +, and the genotype of the unknown is statistically identified as being clear. If however one or more chondrodysplastic puppies are detected, then ? = dan, and the suspect animal is conclusively proven to be a recessive carrier. Such an animal should be removed from all further breeding, unless it is the control dog in the test-mating of another suspect animal.

Radiographing Test Litters

Test litters are normally radiographed at four to six weeks of age. A high-detail A/P projection of the distal radius and ulna of one leg is needed of each puppy in the litter. Several puppies may be included on one sheet of film, thus reducing costs for the owner. Utilization of lead or leaded vinyl/rubber sheets as film blockers (or close collimation) will avoid radiation fogging on multiple exposures. The film should be clearly marked with the owner’s name, name of sire, name of dam, number of puppies in the litter, and date of birth of the puppies. Any dead puppies that have been preserved by freezing should be radiographed at this time. These are frequently inconclusive due to age, however, and it should be understood they may not be included in statistical evaluation unless chondrodysplasia is clearly evident. [reference 8] Radiographs must be evaluated by a professional who is familiar with chondrodysplasia, and the following information should be included.

  • Owner’s name and address
  • Sire’s name
  • Dam’s name
  • Status of control animal (chondrodysplastic or recessive carrier)
  • Number of puppies in litter and date of birth
  • Number of puppies x-rayed and date of x-rays

Disposition of Test-Litter Puppies

Test-litter puppies, even though normal in appearance, must not be allowed to slip back into open breeding. Where one parent is a chondrodysplastic, all normal puppies in the test litter are recessive carriers of the gene. The AMCA approved of the following methods for handling test puppies.

  1. Donation to institution working on problem of chondrodysplasia
  2. Euthanasia by humane means
  3. Early sterilization and subsequent placement in pet homes

Early sterilization encompasses tubal ligation on puppy bitches and vasectomy on puppy dogs. It is normally done between five and eight weeks of age. The AMCA produced a brochure on the early sterilization process. The only exceptions to the stated methods of disposition of test puppies would be the holding of chondrodysplastics, or possibly carriers, to be used as control animals in further test-breeding.

Blood-Testing

To a very limited extent, hematological testing was utilized as a third method of screening dogs. The process did not prove to be a valuable weapon in AMCA’s arsenal however. The necessity of baselining each laboratory’s instruments and procedures against a control group of known genotype dogs in order to establish normal values ultimately made the process infeasible. In blood testing, eleven different parameters were measured from a sample of blood. These parameters were then submitted to a statistical computer program that enhanced differences and weighted all values in order to determine the most likely genotype for that particular blood sample. Misclassification rate on the control group of fifty dogs was approximately 6% in either direction. Perhaps in the final analysis, the immensely valuable contribution of the blood test will be recognized as having conclusively demonstrated that the heterozygous animal has measurable differences from the clear animal.

Tubal Ligation and Vasectomy

This brochure, produced by the Alaskan Malamute Club of America, Inc., describes a method of rendering very young puppies incapable of reproduction. The procedures described were developed by AMCA member John Schmidt DVM and fellow veterinarian Dan F. Rice DVM. They were originally developed for the safe handling of puppies produced by test-breedings for chondrodysplasia, a genetic disorder that affects Alaskan Malamutes. For many years breeders have wanted a method of birth control that would render very young puppies incapable of breeding so that they could be sold as pets and not become a part of the breeding population. It is important to breeders to have these procedures completed before a pup is seven to eight weeks old as many prefer to make placements at that age. Such results may be obtained by salpingectomy (tubal ligation) in the bitch puppy when she is as young as three weeks old and by vasectomy in the male puppy when he is about 5 1/2 weeks old. These procedures are acceptable by the Chondrodysplasia Committee for handling puppies from test litters. Puppies should be examined carefully prior to surgery. They may be anesthetized and prepared for surgery by the standard methods used in any veterinary practice. In the female a small incision is made into the abdominal cavity caudal to the umbilicus and the ovary is elevated through the incision. The oviduct is easily seen in the mesovarium (see figure 1). It is grasped with forceps; a small section is removed and the cut ends are cauterized. The same procedure is repeated on the opposite side. Both ovaries are returned to the abdominal cavity and the abdominal incision is closed by standard methods. Please note that only a small portion of the oviduct is removed. The uterus and ovaries are left intact. Vasectomy in the male may be done as soon as the testicles are descended to the scrotum, usually when the puppy is about five weeks old. A single small midline incision is made cranial to the scrotum and a spermatic cord is elevated through the opening. A small incision is then made in the common vaginal tunic of the spermatic cord. The ductus deferens is located in a medial fold of the cord along with a small artery and vein (see figure 2 and 3). The ductus deferens is separated from the artery and vein; a small section is removed and the cut ends are cauterized. The common vaginal tunic is closed around the spermatic cord but usually no sutures are required to close this incision. The procedure is then repeated on the opposite cord. Fascia and skin are closed by standard methods. Again please note that only a small portion of the ductus deferns is removed. The testicles remain intact. Prospective owners of the pet puppies should be fully informed of the procedures that have been done. A bitch will still come into estrus and show all the signs of a normal heat. She will stand for a male but cannot conceive. It is suggested that bitches be confined when in heat and should be spayed at the usual time recommended by the veterinarian. This will prevent the undesirable manifestations of estrus and eliminate the possibility of later reproductive tract problems

Figure 1 and 2 are from: “Anatomy of the Dog”:Miller, Christiensen & Evans. W.B. Saunders Co., Philadelphia. Figure 3: “Guide to the Dissection of the Dog”: Miller. Lithographed by Edwards Bros. Inc., Ann Arbor, Mich. Cornell Univeristy, Ithaca, New York. 1952

References

1. Subden RE, Fletch SM, Smart ME, Brown RG “Genetics of the Alaskan Malamute Chondrodysplasia Syndrome” Journal of Heredity 63:149,1972 2. Sande RD, Alexander JE, Padgett GA “Dwarfism in the Alaskan Malamute: Its Radiographic Pathogenesis” Journal of the American Veterinary Radiology Society, 15, 1974    Sande RD, Pennock PW, Burt JK Personal correspondence, 1978 3. Sande RD Personal correspondence, 1978 4. Pinkerton PH, Fletch SM “Inherited Haemolytic Anaemia With Dwarfism in the Dog” Blood, 40:963,1972 Pinkerton PH, Fletch SM, Bruckner PJ,Miller DR “Hereditary Somtatocytosis With Hemolytic Anemia in the Dog”  Blood, 44:557,1974 5. Brown RG, Hoag GN, Subden RE, Smart ME  “Alaskan Malamute Chondrodysplasia I – V” Growth, Vol 41, 1977 6. Fletch SM, Pinkerton PH, Bruckner PJ “The Alaskan Malamute Chondrodysplasia (Dwarfism – Anemia) Syndrome in Review” Journal of theAmericanAnimalHospital Association, Vol 2 No. 3, 353-361,1975 7. Bourns TKR, Dodd HM, Dowdy LM, Lucus AJ, Pearson DS “The Master Plan for Control and Elimination of the Condition Known as Dwarfism” Alaskan Malamute Club ofAmerica Newsletter, November 1971 8. Sande RD, Pennock PW, Burt JK Personal correspondence, 1978 9. Schmidt JE “Tubal Ligation and Vasectomy” Brochure available from the Alaskan Malamute Club of America Online at Tubal Ligation and Vasectomy” Rice DF, Dewell CG “Sterilization of Nursing Puppies” Modern Veterinary Practice (Clinical Reports), Vol. 57, No. 10, Oct. 1976 10. Fletch, SM Personal correspondence, 1976-1977

Photo Credits

“Nori”, severely affected chondrodysplastic Photo by Bill Francis Radiographs – Radiographs of chondrodysplastic and phenotypic normal courtesy ofDept. of Radiology,OhioState University

Contributors and Advisors

My thanks goes to the following people who contributed their time and knowledge. Without their help and advise, this article would not have been possible.

  • Beckman, JM
  • Bourns, TKR
  • Burt, JK
  • Cox, MD
  • Fletch, SM
  • Pearson, DS
  • Pennock, PW
  • Sande, RD
  • Schmidt, JE
  • Smart, ME