Cerebella anomaly

This article is provided here for historical reference.

There is little to report regarding the Cerebella Anomaly. There are now twenty-five litters on the data base where pups have shown similar signs. In most cases the pups grew out of the symptoms and appeared quite normal by the time they were ten weeks or so. As yet we still do not have enough data to determine whether the defective gene/genes is inherited as a recessive or a dominant gene although I have been able to trace affected puppies back to the early nineteen eighties when pups showing similar symptoms (shaking, fitting, hypermetric movement) were observed.

With the lack of any genetic test for this Anomaly the only way to determine its mode of inheritance is by pedigree tracing allied to complete litter records. In the UK the KC publishes the details of every puppy bred, registered and transferred in the Breed Record Supplement published quarterly. Unfortunately not all National Kennel Clubs publish registrations so obtaining accurate details from overseas bred litters is very difficult. If any of our overseas Members know how the Club can obtain details of litters registered in Holland, Switzerland Germany & Finland please let us know.

So far four severely affected puppies have been autopsied. Two by Clare Rusbridge at Stone Lion Clinic in London, one at Helsinki University, Finland and one at Zurich University, Switzerland. All four showed symptoms in common but also variations so it is possible that we are dealing with two different conditions. About the only thing one can say with conviction is that the gene is very variable in expression and that genetic descent can be traced to common ancestors. So do Members have to worry about their dogs developing this anomaly? ABSOLUTELY NOT. It is only when breeding that the Anomaly may be produced. Furthermore if we followed (and by we I mean everyone in the world breeding Lagotto) the usual advice in eliminating an inherited disease – namely do not breed from a suspected carrier’s descendents, siblings or parents Lagotto would cease to exist as a breed. This anomaly is just one of many factors to be taken into consideration when planning a litter. What is important is that we “breed in knowledge.”

At the time of writing the LRCGB continue to raise funds for future research. Mrs Rusbridge has suggested that the next line of research should be to analyse urine samples from affected puppies. As we have not had any affected puppies born in the UK for almost three years, research is on hold until we do. Sadly reports still reach me regularly of breeders selling fitting puppies.

FROM THE SECRETARY: MRS GAEL STENTON
TO : ALL LAGOTTO ROMAGNOLO CLUBS/BREEDERS/OWNERS
21 April 2003

CEREBELLA ANOMALY IN LAGOTTO ROMAGNOLO

Following recent reports on Internet chat lines that a Cerebella anomaly has been found in Lagotto Romagnolo puppies the Lagotto Romagnolo Club of GB have decided to issue this statement.

A Data Base for the Anomaly was set up in order to determine whether the anomaly was genetically inherited. Through the tracing of pedigrees it has been able to establish that this Anomaly is inherited although the precise mode of transition is not yet known. Indications point to an autosomal recessive but governed by a variable penetration gene. In some litters the gene has been so barely expressed that affected puppies have appeared completely normal. This was the case with the first affected litter born in GB in November 1997. Of the eight puppies in the litter (plus one born dead) only one showed any sign of the anomaly. Between four and five weeks two puppy "shakes" were witnessed. These were not sufficiently severe enough to be described as seizures or fits and lasted only a few seconds. Another bitch was witnessed with a "hesitation" rather than a tremor. In all other respects the puppies were completely normal, healthy pups. Had the litter not been kept in the kitchen with an experienced breeder it is probable that the tremors would not have been noticed. In retrospect and on the presumption that the mode of transition is an autosomal recessive, this litter was the result of mating two dogs heterozygous for the defective gene together. i.e. both parents appeared quite normal (both were multi champions) but both inherited a defective gene from either their dam or sire and thus "carried" the gene to the next generation. The expected results of mating two carriers together fall within the following ratios: 25% Affected (i.e. the two bitches with the tremors) 50% Carrier and 25% Clear (homogyous for the normal gene) however results often fall outside this pattern.

Gael Stenton writes not only as Secretary of the LRCGB but also as the breeder of the first affected puppies born in Great Britain. This anomaly was first recognised in Great Britain in the late nineteen nineties and originally called Cortical Dysplasia by Mrs Claire Rusbridge BVMS DipECVN MRCVS who performed the first post-mortem at Stone Lion Veterinary Centre, 14 High Street, Wimbledon Village London SW19 5AU. Further research indicated that Cortical Dysplasia was probably something of a misnomer as it seems that the condition is more likely to be caused by a developmental anomaly (neuronal migration problems) rather than a degenerative anomaly.

Of the seventeen affected litters on the Anomaly Data Base all but two are probably either the result of mating two carriers together or possibly a carrier with an affected dog as indications are pointing to the 2 4 2 pattern.

The puppies in thirteen of the litters had more or less similar symptoms. Affected puppies have locomotor problems. In some the onset is as early as three weeks. Pups have difficulty in getting to their feet, may circle, tumble (fall over) and move in a sideways characteristic high stepping action in the back legs (hypermetric gait). In others the onset may not be until four or five weeks. Affected pups may also have seizures. These may be little more than a shake as in the first litter, or may be quite severe with the puppy fitting for several minutes and the sight affected. What is good news for breeders is that many of the less severely affected pups completely "grow out" of their problems within a few weeks and appear quite normal by ten weeks or so.

In one litter, details of only one puppy is available. This pup showed some of the symptoms (hypermetric gait & fitting)as described above but the onset was not until twelve weeks. The pup also developed marked swelling of the spinal tissue and was euthanised at six months.

In another litter a puppy displayed quite severe problems including being unable to stand and feed. This puppy was euthanised at twelve weeks and is being autopsied at Helsinki University.

Two litters do not fall into this pattern. In both of these litters (one in GB and one in Italy) all the pups (twelve) were grossly affected with very foreshortened muzzles (squashed in), protruding eyes, fitting and very badly affected movement (some could not stand at 5 weeks). A characteristic of these pups was that they were all severely undershot. (A similar condition exists in humans called "flatbrain") All but the three least affected were euthanised at a few weeks old. The remaining three largely grew out of their movement problems, their muzzles lengthened but all three remained quire badly undershot. It is possible that these two litters were the result of mating a sire homogyous for the gene (i.e. affected) with a dam also homogyous for the gene. This would result in 100% affected pups as occurred in these two litters.

Following the birth of the GB litter, clinical research into the anomaly was initiated by Gael Stenton and Ann Kemp when they referred the litter to Claire Rusbridge at Stone Lion.

What is noteworthy about these two litters is that dam of the GB litter was a bitch from the first affected litter but not one of the two bitches which showed transitory signs of the anomaly. On the presumption that the dam must have inherited the defective gene from both parents her dam (the pup’s grandam) must also have been either a carrier or affected. The grandam’s litter sister was the dam of the Italian litter. These two litters support the theory that the four parents were homogyous for the defective gene.

There are seventeen litters listed on the data base in which affected pups have been known to have occurred. Analysis of the pedigrees shows that all the litters are related. For example the bitch who is grandam/greatgrandam of the two grossly affected litters is also dam/grandam to other affected pups but by different sires.

Thus there is compelling evidence of a defective gene being passed from generation to generation. Affected puppies have been born in at least seven countries and from ALL the major Italian bloodlines. Whether two different anomalies exist or whether the different degrees of severity are due to the variable expression of the defective gene is not yet known.

Clinical research is beginning in two or three countries. The LRCGB are grateful to Mrs Rusbridge for agreeing to act as the co-ordinator. It is hoped that the results of post-mortems on suspect puppies will be made available to Mrs Rusbridge. It may be a very lengthy and expensive process before a genetic test for the gene is available, thus in the absence of a test the immediate way forward is through pedigree tracing. There are undoubtedly many other affected litters which have not been reported either because the breeder did not realise at the time that the anomaly was inherited or because the signs were so transitory (as in the first GB litter) that they were barely noticed.

At the end of this article there are the two forms for reporting the anomaly. One is for individual pups, one for the breeders of affected litters. The LRCGB hope that following this release of information breeders and owners will be feel able to add to the Data Base.

To answer some obvious questions.

How can I find out if the parents of my pup are carriers? why is a list of carriers not accompanying this article?
At the present moment it is not possible to publish a list because as yet many of the breeders/owners of listed carriers may be unaware that their dogs are affected. Often the indications that a dog must be a carrier comes from its affected descendants which may be in several different countries. It is a courtesy to notify the owners and breeder of these dogs before a list is placed in the public domain.

It might be thought by less experienced breeders that the dogs (and their descendants) listed should not be bred from. This cannot be the case in Lagotto as the gene pool is already very small. Some of the most illustrious, beautiful and successful Lagotto are probable carriers. There are many champions on the list of suspect dogs. To remove these dogs would decimate the breed. As a renowned geneticist once said about another cerebella anomaly "we mustn’t throw the baby out with the bathwater."

Other modes of inheritance must not be discounted and might result in different dogs listed.

Why do the Italians say that they don’t know about this problem when all the dogs come from Italy? Surely there must be lots of affected dogs in Italy?
Lagotto were rescued from extinction in the nineteen seventies mostly by people who bred one/two litters a year. Lagotto in Italy are still primarily working dogs. They are born and kept outside in kennels. Thus affected pups would never be noticed. Abnormalities of a non genetic nature often occur in dogs. Working owners would not have wasted their money with costly investigations. Working dogs have to earn their keep. Pups would have been put down and the parents mated to different dogs probably producing normal pups (but carriers). Thus a defective gene would have been spread through the population without anyone being aware. This anomaly has been traced through pedigrees but no written records were available to Italian breeders until the breed was recognised less than ten years ago.

If the first affected GB pups were born in 1997 why has it taken so long for the GB Club to share this knowledge?
It would have been highly irresponsible to publish suspicions until sufficient evidence had been amassed to prove a) that the anomaly exists and b) that it is inherited. Much of this evidence has come to light since November last when Mrs Stenton and Mrs Kemp visited Italy to report the findings. The Italian Breed Club were first notified of a possible anomaly three years ago.

If this is a developmental anomaly and most of the pups "grow out" of it and other affected pups appear perfectly normal do we need to be concerned?
As yet it is too soon to tell whether dogs which grow out of the anomaly will be affected in later life. Of more immediate concern is that unless steps are taken to limit the spread of the defective gene more and more breeders might have the unpleasant experience of unknowingly mating two affected/then normal Lagotto and breeding a litter of severely affected pups.

Where do we go from here?
The Committee of the LRCGB have discussed this anomaly at length. A planned breeding programme aimed at establishing the status of the most influential breeding stock has already started. By careful test mating it is hoped to identify which offspring of suspected carriers are clear of the defective gene thus enabling the gene pool to be kept as wide as possible. It is up to each Club to decide what steps if any they wish to take.

The GB Club are in the process of consulting a renowned geneticist. Other modes of inheritance must not yet be discounted. Findings will be published on the Club website.

The LRCGB realises that the above article will cause distress to many lovers of Lagotto. They wish to finish by mentioning a bitch entered at the Club 2002 Assessment. The Italian judge Ermanno Zavagli wrote of her "a very beautiful bitch, very good head, correct proportions, excellent coat moved very soundly." He felt that she was such an outstanding bitch that he gave her very good/excellent even though she is undershot. She also set one of the fastest times on the obstacle course. She is happy and healthy, everything a Lagotto should be. She lives with her lively litter brother and their beautiful Mum (Best in Assessment under Claudio de Guiliani). They are Mum and her remaining two pups from the severely affected GB litter.

(this article was originally written in 2001)

If you have had an affected puppy or have bred a litter that you think may have had affected puppies (even if the puppies now seem normal) please consider filling in an Owner's or Breeder's Report Form. If you have found have the above statement helpful, please remember it has only been possible to write such an informative statement because other owners & breeders have supplied data on their own affected puppies.

Download the Owner's/Breeder's Report Form here.

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