CHINESE BEAGLE SYNDROME--Musladin-Lueke Syndrome

  This syndrome manifests itself by quite specific characteristics. It is often quite easy to identify a puppy/dog affected with this syndrome. Typically, MLS affected beagles have short outer toes and they walk upright on their front feet in what resembles a ballerina stance. Often all four feet are affected. Affected beagles often have tighter skin with limited “scruff”. Their bodies feel hard due to the tight skin, tendons and muscles. They often appear very well muscled. Their head shape is also notably different having a flat skull, higher ear set, ear folds and slanted eyes. Tails are often carried in a straight, stiff fashion and some beagles have noticeable kinks in the tail as well. The syndrome can be determined very early on at about 2 to 4 weeks if you know what to look for. (see picture of 4 week old puppies). The syndrome progressively gets worse until about 1 year of age when the dog then stabilizes. It is also important to note that there are varying degrees of “affectedness” with many beagles and breeders should look at any or all of the above indicators to assist in determining an MLS diagnosis or a potential MLS carrier. Ear folds, high toes or tight skin as a single trait does not automatically indicate carrier or affected status. There have been dogs with ear folds, high toes or tight skin that were not carriers. Dogs with total normal appearance have been determined to be carriers. The only way to determine normal or carrier status is to TEST. Unless there are associated congenital or genetic problems, these beagles will have a normal life span. A genetic marker test has been developed and this test is available through the Veterinary Genetics Laboratory (VGL) of the School of Veterinary Medicine at the University of California, Davis. The DNA test is being offered at the very reasonable cost of $50.

MLS is inherited as a recessive trait. Current evidence suggests that dogs that have two copies of the mutant gene are affected with MLS, though the severity of clinical signs can be variable. Dogs inheriting only one copy of the mutant gene can show subtle signs but do not appear to have health-related defects. To the best available knowledge, carriers cannot be identified based on their appearance.This test determines whether dogs are normal (clear of the mutation), carrier (have one mutant copy), and affected (have two mutant copies).

N/N: Normal. The dog does not have the MLS gene.
N/MLS: Carrier. The dog carries one copy of the MLS gene.
MLS/MLS: Affected. The dog has two copies of the MLS gene.

If a carrier dog (with a single mutant copy of the gene) is used in a mating, an offspring from the cross has a 50% chance of inheriting the mutation from this parent. If two carriers are mated, 25% of the offspring in the litter are expected to have MLS and another 50% of the puppies are expected to be carriers. Mating two clear dogs will only produce clear puppies, which need not be tested by DNA.

This Syndrome was first identified in the early 1990's. Below is an article describing this problem in the early 1990's. After reading this article, the links listed below will provide more information, pictures and comments from owners of beagles affected with CBS. This problem has been renamed to the Musladin-Lueke Syndrome, in recognition of the Drs. Tony and Judy Musladin and Ada Lueke. The dedicated beagle breeders that identified this problem and started investigating it in the beagle population. The genetic research was conducted by Dr.Mark Neff at University of California at Davis. DNA samples of affected beagles can be sent to Dr. Mark Neff. You can e-mail Dr.Mark Neff or his assistant KRRobertson for more information. Please send pedigrees to Darlene Stewart

Chinese Beagle Syndrome Revisited-An Article in the March 2005 Show Beagle Quarterly
A Case Study-Printed in the SBQ March 2005         Pictures of Case Study Beagle
Excerpts from Owners of beagles with CBS
Pictures of affected beagles. Use Back Button to return to this page.  PAGE ONE      PAGE TWO      PAGE THREE

Most owners and breeders that have MLS beagles have noted an abnormal ear cartilage. It may be felt as early as 3 weeks of age. Some beagles just have a odd "ribbon" type feel in the ear and others actual have extra folds from the cartilage. Abnormal ear carriage can be seen almost at birth.PICTURES OF ABNORMAL EAR CARTILAGE

The following are excerpts from the Supporting Membership Newsletter, National Beagle Club Summer 1992
Published here with permission from the author-Judy Musladin, April 2002.&

Though first reported to the NBC Health and Genetics Committee in 1990 as occurring in our current U.S. conformation population, reports from England and Australia date back to the late 1970s.  Imagine our surprise to find neuronal abiotrophy listed as an inherited disorder in the 1983 edition of Successful Dog Breeding by Bonnie Wilcox, DVM, and Chris Walkowicz.

To the best of our knowledge this particular manifestation of familial neuronal abiotrophy (inherited malformation of nerve cells) has not been reported in the veterinary literature (personal communication from H.W. Leipold, DVM, Professor of Pathology, College of Veterinary Medicine, Kansas State University, Manhattan, KS).  Only cerebellar abiotrophy (an inherited degenerative disease of the balance portion of the brain) has been described.

The purpose of this article is to describe the condition and to provide as much information as possible about its cause.  Since these affected beagles turn up periodically in relatively unrelated families, breeders need to be familiar with the signs and symptoms so that early diagnosis can be made.

CLINICAL DESCRIPTION

 
To date nineteen (19) affected beagles have been documented with undocumented reports of several more.  Typically these puppies are recognizable at birth by their broad skulls and wide-set slanted eyes.  As the puppy grows, short outer toes on all four feet (at least in the nineteen documented cases) become obvious.  With further growth, stiffening of the legs develops, resulting in restriction of flexion and extension at the joints.  These little beagles stand on their center two toes and run with a "bunny hop."  When they sit, the hindquarters are flexed at the hips and the legs are extended forward in contrast to the flexed stifle and hock joints  in the normal sit position.  Tight skin with little flexibility has been reported by some owners.  These little beagles feel stiff all over!

Of these nineteen, ten are living either in pet homes or with their breeders. two of these have concurrent heart defects, one with multiple defects, the other with pulmonary stenosis (narrowing of the pulmonary valve).  The former has also had grand mal seizures.

Eight are dead.  Four were euthanized once the problem was noted.  One was euthanized because of "pain" as a very young puppy.  Two of a litter of four affected puppies were put down after diagnostic studies at a school of veterinary medicine and sections of the brain, muscle, and spinal cord were examined for a pathologic diagnosis.  One died at age 15 years due to age-related problems after a long and healthy life.  The surviving ten range in age from six months to four years with no apparent progression of their disease.  One of the two with associated heart defects is now showing signs of increasing heart failure at the age of two years. The other is still without symptoms.  There is one puppy about which we do not have information other than it was one of two affected in the litter.

Similar beagles have been reported in Australia, Canada, and England.  Efforts to obtain information from Australia have so far proven fruitless.  Reference is made in Douglas Appleton's Beagles and Beagling to the "cat beagle" which fits the description of our "Chinese beagles" like a glove.  Mr. Appleton states that 2-3% of beagles in Great Britain suffer from this pattern of abnormalities.  He does not mention the short outer toe which is seen  in the American beagles.  A British breeder writes in a personal letter that these little beagles are thought to be  Downs syndrome" puppies, most likely because of the head shape, characteristic slanted eye, and perhaps because of a short outer toe, similar to the shortened fifth finger in Downs syndrome babies.

DIAGNOSTIC STUDIES

X-rays of the legs of some show only the shortened outer toe with otherwise normal bony and joint development, in contrast to the Xray findings in pups with chondrodystrophy.  Electromyography (testing of the electrical potential of muscles mediated through the nerves which supply these muscles) on two showed a generalized abnormality suggestive of spinal cord, spinal nerve root, and/or peripheral nerve disorder.

PATHOLOGICAL STUDIES

The 2 1/2-month old puppies studied and euthanized at a veterinary school of medicine had gross and histological studies of the brain, spinal cord, and skeletal muscle.  Findings include:
           1)  Some broadening and flattening of the joint between the skull and the highest cervical (neck) vertebra.
           2)  Skeletal muscles from various parts of the body showed great variation in muscle fiber size, some shrunken muscle bundles surrounded by mucinous material and multiple cell changes.
           3)  Spinal cord grey matter  (central cellular component)  showed an increased number of cells, though the cells themselves appeared normal.  Some areas demonstrated a marked increase in astrocytes (a particular type of nerve cell).
           4)  The chief portion of the brain showed many changes.   Many of the blood vessels were surrounded by cells not normally found (cuffing).  Areas of destruction of nerve tissue were scattered throughout.  The lining cells of blood vessels were swollen.  And there were scattered areas of individually destroyed nerve cells especially in the primitive areas of the brain.
      The pathologist's conclusion was that the muscle damage was most likely the result of defective nerve supply and the brain changes were most suspicious of a familial neuronal abiotrophy.

 WHAT IS NEURONAL ABIOTROPHY?

Put simply, the term is a general one which means an alteration of the nervous tissue resulting in a gradual impairment of muscular function.  The term "familial" is added when the degenerative process is inherited.  Not all abiotrophies are of primary central nervous system (brain and spinal cord) degenerative disease.  Some are the result of storage disease (failure of the body to supply essential enzymes critical to normal body function) which affects the nerve, cells.  Some of the abiotrophies have specific names based on the unique feature of the cellular degeneration.  Exposure to toxins can also lead to abiotrophy.

PROGNOSIS

The significant difference in the Chinese Beagle Syndrome from the abiotrophies in other breeds is that the disease appears to stabilize by about one year of age.  Characteristically in other breeds the course is progressive, resulting in increasing debility and disability and death.  Not so in our little affected beagles.  I would suspect there is also a range of affliction  with some puppies affected more seriously than others.

Unless there are additional genetic problems affecting the health of the beagle, it would the Chinese beagle's life span is the same as an unaffected beagle.  But our current reported group is young and also small in number.  We will have to wait and follow these beagles throughout their lives.

WHAT  TO  DO

For the present, the breeding which produces a Chinese beagle should not be repeated.  Those sires and dams when bred differently may not produce an affected puppy.  But if this is a simple, recessive mode of transmission, future generations are at risk.  As with so many of our inherited disorders, several generations may appear to be free from problems until the "time bomb" ultimately goes off.

As more information comes in, we will keep you informed.  Obviously if any of you have a Chinese beagle or have had one and have not reported it to either Ada or me, we would appreciate hearing from you.

                                                          ...Judy Musladin

PRELIMINARY COMMENTS ON THE GENETICS OF "CHINESE BEAGLES"

We have been getting more and more reports of the- syndrome that we call  "Chinese Beagle."  It is not clear whether it is actually on the increase or  whether breeders are just now recognizing those funny-looking little guys for  what they are.  We have several cases of breeders who are sure they have had it  in some of their litters, but haven't put the pedigrees together yet.  In any case,  we have nineteen reported cases, representing eleven pedigrees.

According to the experts, the mode of inheritance falls into that great maw of uncertainty called autosomal recessive.   Sometimes I think this term could also  be called "Darned if I know!"  But I digress.  It is clear that certain families  are having more affected puppies than other families, but we don't have enough  numbers to give a more precise analysis.  Remember that autosomal recessive means  it's not sex-linked and not dominantly inherited.  It can be a simple recessive or  multi-genetic.

I did inbreeding coefficients on all of the available pedigrees and they  range from less than 1%, to over 30% inbred.  This makes me want to jump to the con conclusion that this might even be a simple recessive problem (simple recessive meaning  that one gene is inherited from each parent to create the affected puppy).

Well, what does all this mean for the breeder?  I think that if the breeder treats this as a simple recessive it will help and might not do any harm.  This  means that any dog or bitch that has produced an affected puppy before is an automatic carrier of half the genes needed to produce it again.  Remember that if a carrier dog is bred to a carrier bitch 25%, of the puppies will be affected, 50%  will be carriers, and 25%, will be clear.  Test breedings to prove or disprove carrier status cannot be advised in this case.

As always, thanks for all your help and information and keep those pedigrees coming.
                                                                  ...Ada Lueke

MORE INFORMATION CAN BE FOUND IN "THE NEW BEAGLE"- 1998 EDITION-PUBLISHED BY  HOWELL BOOK HOUSE.