HC PHPV OR THE EYE THING !
Those who have been in the breed for some years should be fully aware of those eye conditions that exist in Staffords and what is being done to counter them. However those who are newcomers, or only came into the breed a year or two ago, may not be fully aware of the problems or what is going on. It is for their benefit mainly that this article is included although all may benefit by being kept up-to-date
Two inherited eye conditions affect Staffords – Juvenile Hereditary Cataract (HC) and Persistent Hyperplastic Primary Vitreous (PHPV). These will be dealt with separately along with the on-going genetic research which might eventually lead to eradication, plus what breeders and owners should be doing themselves to ensure their dogs are not affected.
HC
HC was first described in Staffords over 30yrs ago although anecdotal evidence suggests that cases had been occurring for many years previously. The main ophthalmologist involved was Dr Keith Barnett, who published much of the early work, and it was clear that it was hereditary in its transmission and that a defective recessive gene was involved. A list of affected dogs and carriers was published at the time. This resulted in considerable acrimony, which may have led to matters being hushed up, and we ought to be aware that some of the dogs on the list might have been misdiagnosed as ophthalmic tests were not as good as those of today. Since then cases have occurred spasmodically but it gained greatest prominence a few years ago when a top quality red dog turned out to be a carrier along with other dogs and bitches which were closely related. Prior to that there was the well publicised case of two rather unrelated brindles being bred together producing three litters containing a number of affected offspring.
Clinically, cataracts develop in a puppy's eyes and, in time, progress so the sight is totally lost. It is important to note that both eyes are affected and that the condition is progressive. Initially it was thought that HC developed from about six to eighteen months of age with later onset being highly unlikely. This belief came about as it was between those ages that owners might become aware that their dogs' eyes were ‘not quite right' or that they were becoming increasingly opaque as the cataracts developed. Consequently it has sometimes been claimed that if it started under six months old it could not be HC – this is not true! . Using state of the art testing, the early changes may be detected very early, possibly around 9-10wks, maybe even at 8wks, old.
As stated above, it was soon clear that it was inherited via a recessive gene. This means that both the sire and dam of any affected puppies must be carriers of HC even although both do not suffer from it. Let us call the normal gene ‘X' and the bad recessive ‘x'. As a dog has two copies of the gene, one being inherited from each parent, it may therefore be: ‘XX' – normal sight and a non-carrier; ‘Xx' – normal sight but a carrier capable of passing the defective gene to offspring; ‘xx'- clinically affected and which will pass the gene on were it ever to be bred from. When two carriers are mated the offspring will, on average, be 25% affected, 50% normal but carriers, 25% normal and non-carrier. Looking at it another way, this means that any unaffected sibling of an affected dog has a two-thirds chance of being a carrier. It should also be noted that roughly a quarter of puppies from the brindle mating referred to above were affected, as could be expected. Some have forgotten about this brindle pairing and allowed discussion to concentrate on the problems encountered in reds. This is most unfortunate and it must be stressed that HC is not related to colour in any way whatsoever; it is just coincidence that the main problems recently have been in reds. In fact if you trace back the pedigrees of those red dogs for over seven generations you will encounter brindle carriers identified 30yrs ago.
(It is also of interest that Boston Terriers may also suffer from HC, which is virtually identical clinically to that in Staffords. If this is proven to be to the same genetically then it may be postulated that the defective gene was present, or originated, in the bull and terriers crosses of around 200yrs ago, from which both breeds were developed.)
The only treatment available for HC is surgical removal of the cataracts which is very expensive.
PHPV
This was first described in Staffords in the 1980's although there are earlier reports of it in Dobermanns in Holland . PHPV is the failure of the blood vessels supplying the developing eye of the puppy in the womb to wither and disappear completely by the time it is born. The amount of material remaining is variable. In mild cases there may just be some spots, or possibly a small encapsulated cataract, behind the lens while more severe cases will have greater quantities of residue from the foetal blood vessels.
In Staffords, mildly affected dogs are unlikely to have any further problems and will go through life as if nothing was amiss. However more severe cases have a high risk of problems, such as the development of secondary cataracts, which may lead to loss of vision. Both eyes are usually affected, as with HC, but unilateral cases with only one eye involved are not uncommon with PHPV, especially if mild.
There is little doubt that PHPV in an inherited condition. There have been several suggestions for its mode of transmission but none have been substantiated so for the moment we have to accept ‘We simply do not know'.
Eye Testing
Responsible breeders have for many years have been getting their dogs eyes tested by the ophthalmologists to ensure they are clear clinically of HC and PHPV. The earliest and one of the best times to test is when puppies are 6-7wks old and many breeders test whole litters at this age – the importance of this cannot be over-stressed! A definitive affected/unaffected diagnosis of PHPV can be made at this stage; consequently puppies may then be sold as being free of the condition or sold, if not seriously affected, as pets with endorsed papers to prevent their being bred from. However no decision can be made on HC at this early age so testing when older needs to be undertaken. Normally it is recommended that dogs are tested when 18mths old and certainly before being bred from. It should be realised that failure to test breeding stock might leave the breeder open to litigation should any of the conditions appear in the offspring.
The need for subsequent testing is debatable. If a dog passes its eye test for HC and PHPV at 18mths or older then it may be considered clear for life. However some breeders re-check at intervals when older or maybe before further litters. This may be regarded as unnecessary but they must be complimented for being so conscientious. Some vets too may suggest that all dogs, including Staffords, are re-tested yearly. This would seem to be to ensure that no other conditions, such as those that occur commonly in other breeds, have developed. Some may consider this wise but others might think it a ploy to fill the coffers. It is up to individuals to decide, especially as nothing more is likely to be found.
The testing of eyes is done mostly under the KC/BVA scheme with all reports being submitted and published in the Breed Record Supplement. Some testing may also be done under the European scheme but results of this are not made public. The KC/BVA scheme operates through a network of vets, with the necessary training in ophthalmology, covering the country. These vets will do the bulk of the testing and owners usually go to their local one for initial tests. If necessary the vet may suggest, and the owner may request, a second opinion arranged through the scheme co-ordinator or by reference to the Ophthalmology Dept. of one of the University Veterinary Schools. In fact it is recommended that the owner of any dog failing its eye test through HC or PHPV should seek a second opinion to confirm the diagnosis.
To the layman a diagnosis of affected or unaffected for HC and PHPV seems to be as clear as night and day. However this may not always be quite as simple as one might think as a case that occurred not so long ago exemplifies. A bitch was failed by one vet, so we were told, but then passed by one of possible greater experience. This led to some heated and forthright comments on the internet which could have produced a disastrous loss of confidence in the system, despite none knowing precisely what the initial vet had said to the owners. As people only take in part of what they are told and relaying the tale further leads to increasing distortion of the truth, it is easy to understand how matters can spiral out of control. The fact is that the vets can, and do, have problems. Eyes that are crystal-clear are no bother but often material, such as vitreous strands and debris, may be found within the eye. The question is one of deciding if this is significant of a pathological condition and, if so, is it inherited. It may be that no decision can be made in some instances, especially with young dogs, and re-testing a few months later may be necessary to see if there have been any changes or further developments. Any vet with a problem will frequently discuss the findings with the ‘top men' to ensure the diagnosis is as accurate as possible. Of course the odd vet may not be as good or as conscientious as we would like – it is to be hoped the system weeds them out but bear in mind the option of a second opinion.
Seeking a DNA Test
Over the last twenty years or so there have been massive advances in our understanding of genetics and, as a result, tests have been developed to identify certain hereditary conditions and carriers. Much of this has taken place in the human medical field but there have been advances also in conditions affecting dogs. Most will be aware of the ‘Human Genome Project' in which many researchers world-wide are collaborating to identify the entire chemical structure of human DNA and to identify all our genes, their functions and their locations on the individual chromosomes. Not so well publicised is the ‘Canine Genome Project' which is attempting to do the same with dogs. To simply think about pin-pointing the specific location of the thousands of genes possessed by dogs on their thirty-nine pairs of chromosomes highlights the enormity of the task. Nevertheless it is now possible to identify carriers of some recessive conditions affecting other breeds and with this in mind research was initiated to develop a test for the recessive gene causing HC in Staffords.
A sub-committee was set up by the Breed Council comprising the Northern Counties , Merseyside and the North West ; these three clubs had representatives either with specialist knowledge or were informed laymen with an individual interest in the topic. Since it was established, Ivor Keyes from Northern Cos. has acted as co-ordinator. Initially the sub-committee met with representatives of the Animal Health Trust and this enabled work to commence. There was of course the matter of funding as any research does not come free. A separate fund was started, controlled by the BC, to receive contributions from Clubs and individuals. The response was first-class and in time further support was received from the Kennel Club. Hopefully this will enable work to be completed.
The initial aim is to look for linked markers, which are pieces of DNA transmitted along with the gene that is being sought, a bit like ‘hangers-on' one might say. Such a test, if successful, would be over 95%, maybe 97-98%, accurate. (The ultimate would be a test detecting the gene itself – this would be 100% accurate). It must however be stressed that there is no guarantee of success for various good scientific reasons, although, based on the success of others, we can be optimistic in the long run.
The work required blood samples from cases of HC, their parents and siblings along with full pedigrees. These are essential from as many cases as possible but samples from others such as grandparents, off-spring, half-siblings etc. might also be useful. Most people involved were co-operative, although one or two had to be chased up, and sufficient samples were received eventually. More specimens would still be most welcome and currently preliminary discussions are being held with overseas contacts to see if bloods from cases from different lines abroad can be obtained. It should be noted that the AHT is happy to received bloods from cases of PHPV and their relatives as they can be stored for future investigations.
To ensure the diagnosis is correct, Dr Barnett is investigating all cases and trying to see as many as possible personally, at no further expense to owners. For this we are most grateful. To confirm the mode of transmission, a simulated analysis of pedigrees was carried out before the laboratory studies commenced.
There are several hundred possible linked markers to be investigated and the AHT has, to date, looked at over a third of them. Unfortunately luck has not been on their side and the markers one is looking for have not yet been found – to have been lucky enough to find them straight away might have been too much to ask! However a few have turned up that are worthy of further investigation and, with the ongoing work on the genome project, new avenues of investigation are continually appearing. Consequently there is still every chance of eventual success.
As for PHPV, nothing can be done at the moment but in time, if sufficient information is forthcoming, from pedigree analysis etc., to give some indication about a route of possible transmission, studies on any samples stored might be possible.
The Way Ahead
A linked marker test should enable HC to be controlled within a few years and eventually eradicated. Furthermore it will enable carriers (even affected cases theoretically) to be used in breeding programmes, assuming of course they have sufficient virtues to make them worthy of breeding from. The important thing is that two carriers must not be bred together. Breeding a carrier to a non-carrier will not produce any affected animals although half the off-spring will of course also be carriers but in time any breeder should be able to get stock of the desired quality which is free of HC. The fact that a linked marker test may not be 100% (maybe 97-98%) accurate does not matter. Breeding an animal falsely thought to be a carrier will be of no consequence as its partner will of course be a non-carrier, while the chances of mating a carrier dog and bitch, both of which have been missed by the test, will be remote and should not be a problem. The Kennel Club will almost certainly allow carriers to be bred from, if and when a test is available, but there may come a point, after several years have elapsed and after a test detecting the gene itself has been developed, that the KC will call a halt and refuse to register the off-spring of carriers. However if everyone co-operates, HC will probably be a thing of the past by then.
Until a test is available, what should those with a problem do? It is easy for others without a problem to say they should not breed any animals that are carriers or suspects, despite any virtues they may possess. Furthermore not all with potential problems are able, or willing, to recognise them. The only answer for such owners is to assess their stock very critically and, unless it is of exceptional quality, the best thing might be to start again. Another option might be to discuss the situation in depth with a trained geneticist who understands the problems fully but, whatever decision might be made eventually, anyone breeding from suspect stock must consider most seriously the risks of increasing the numbers of carriers in the gene pool. Sadly there is no easy way out.
Similar problems present themselves with PHPV. It is accepted that any dog with PHPV should not be bred from as even the mildest of cases might pass it on in a more severe form. But what about clear stock that have already produced affected off-spring? As the mode of transmission is unknown, the experts advise that such a mating should not be repeated but that the sire and dam in question may be bred again using different partners, preferably with a different background to the previous one.
It is very easy to get carried away when discussing eye problems in Staffords. Over the years they have tended to raise their ugly heads from time to time before disappearing underground again. But sadly we do not know how common they really are. Of course we can get some figures from the Breed Record Supplement giving the passes and fails under the KC/BVA testing scheme, but this does not include any tested under the European scheme. Furthermore it is unknown how many cases of cataracts, in dogs that have not been tested under the scheme, are operated on by the ophthalmologists. Some of those may have other causes but it is likely that many will be HC or secondary to more severe PHPV. Whenever cases of HC or PHPV crop up, emotions inevitably run high because of the serious effects they may have. In dealing with them, level heads are required and one might recall the pertinent reminder from Keith Barnett at the Breed Council symposium on the eye problems – ‘A dog is more than its vitreous (matter within the eye)!