Pituitary Dwarfism:  The Spectre of the Nineties? (Published October 1992)

Walker, J.R. (1992)  Pituitary Dwarfism:  the spectre of the nineties? - GSD National Magazine 6:10 pp300-303

This is one of the more complex bio-medical areas of research, in any species, and not one which is easy to write about so that the information can be understood by readers without relevant training.

I am writing this because I have recently suffered the misfortune to produce one dwarf bitch puppy - full details will appear later unless I am prevented from doing so.  My research into why I produced this defect from 55/60 German and 59/60 Stud Book breeding has frankly horrified me, to the extent that I am considering whether or not to quit the GSD breed.

Pituitary dwarfism in the GSD was probably first reported by Moch and Haase (1953) and since then the defect, or deficiency, has been largely ignored, at the risk of stating the obvious, for 40 years.

Continuing to call the problem 'pituitary dwarfism' is, in my opinion, a mistake because it tends to trivialise what I perceive to be a serious breed problem.  It also moves the focus of attention to the short term:  the problem is usually seen and depicted as being no more than the creation of a few defective puppies that have to be euthanased and the loss borne.

The true perspective shown by the genetic studies is that of a serious long-term problem which I would suggest is probably serious enough to endanger the viability, or even the survival, of what we regard as the quality, or top-end, of the breed.  The problem must show increasing frequency as time goes on.  I believe that the long-term viability of the breed and its current fitness for work have already suffered.

We long-since stopped calling this condition 'dwarfism' in man.  It is time we did the same for GSDs and started to give the condition the same serious consideration that we give to it in out own species.

More correctly the problem is not one of 'dwarfism' but apparently one of pituitary insufficiency or hypo-pituitarism.  The pituitary gland is arguably the most important gland in the body - sometimes called the master gland.  This controls the function of most other glands in the body and their associated metabolism, therefore a body existing in a hypo-pituitary state is, in effect, fundamentally unhealthy and weakened.  Remember - hypo is low, hyper is high, relative to the norm.

Amongst relatives of GSD dwarfs intermediate, that is predominantly lower, levels of a relevant hormone have been shown in a Danish study (Willeberg, Kastrup & Andresen - 1975) compared with unrelated 'control' animals.  This study concentrated on somatomedins which mediate the effects of growth hormone in man and dog.  A number of parallel conditions are known from human studies.

The pituitary gland produces six main hormones, with most of the releasing or effector hormones required being produced in the hypothalamus, a large gland at the base of the brain - very close by.  In the foetus part of the pituitary gland is formed from 'brain tissue' and part from tissue which forms the roof of the mouth.

There has been extensive study of the hypo-pituitary state in man and the physiological abnormalities show a fairly consistent pattern occurring in a series of overlapping 'stages' each linked to a particular hormone or group of hormones produced by the pituitary glands.

One of these stages is the human dwarf condition.  Most physiological and biochemical and hereditary mechanisms are remarkably similar between man and dog in most respects - this is how we seek to justify allowing Beagles to smoke cigarettes and so on.  It is therefore entirely reasonable to expect to see predominantly the same pattern of 'stages' appearing in GSDs.  The physiological, biochemical and hereditary evidence appears to support this hypothesis from the literature and from my own limited observations.

What we see in the 'dwarf' puppy is effectively a serious (usually terminal) case of hypo-thyroidism where the sufferer has also failed to grow - growth hormone and thyroid activity are largely controlled by the pituitary gland.  In physiological and pituitary biochemical terms, the growth hormone insufficiency can be regarded as 'stage 2'.  The hypo-thyroid condition can be regarded as 'stage 3'.

'Stage 1' is death.  The Danish, Australian, and my own observations all note still-born and short-lived puppies associated with the production of 'dwarfs' and, again, there is a very obvious link to the pituitary hormone (endocrine) system.

The Genetics and Possible Health Issues

The main genetic studies (Andresen and Willeberg 1976), (Andresen 1978), and (Nicholas 1978) show adequately that the genetic mode of inheritance is simple autosomal recessive, though the Danish population was highly inbred and polygenic threshold inheritance cannot be ruled out entirely.

Assuming that the autosomal recessive theory with a possible gene dosage effect is correct, then this means that the normal state is dominant and that two affected animals must be mated in order to produce a dwarf puppy.  It also means that heterozygotes (carriers of the defective gene) appear to be perfectly normal, fully grown animals.  Herein lies part of the problem.

It is therefore possible to mate a carrier dog or bitch to a normal partner ad infinitum without producing a dwarf puppy or seeing any other problem which one might associate immediately with 'dwarfism'.  Many breeders will be doing this unwittingly as I have done.  This in turn produces a further 50% of carriers and only 50% normal animals.  In this way a pool of defective genotypes with apparently normal phenotypes is being created unseen.

When two carriers are mated the situation gets worse.  In theory (remember these figures only apply to large populations and not necessarily to individual litters of puppies) then the ratio of carriers produced remains the same at 50% but the ratio of normal animals produced falls to only 25% with the other 25% being 'scrap' as dwarfs and dead puppies.  This is the normal Mendelian 1:2:1 ratio and the Danish, Australian, and my own ratios agree fairly well with the prediction.  In this case 2/3 (67%) of the survivors are defective genotypes;  but they all look normal.

The other side of the problem lies in the evidence that the apparently normal looking carriers may, in fact, have abnormal hormone balances.  They may not be normal fully functioning animals but animals which function under physiological/biochemical stress.  In consequence these animals be less viable than truly normal animals and will show tendencies arising from physiological stress;  typically a predisposition for infection, deficiency diseases, and reduced fertility and libido as well as possible character and temperament problems, which we can all do without.  In other words, they may well be costing more than average in veterinary services.

I have identified a number of possible deficiencies from the human condition and I have been able to correlate these (in theory at least) with some of the known health and management problems which have come to prominence in the breed over the last 10-20 years - problems which have not been explained to my satisfaction by other hypotheses.

It is my belief that efforts should now be made to identify those animals within the breeding population which carry the defective genetic material and that these animals should be graded out of the breeding population - voluntarily by preference and by compulsion if necessary.

In severity I have come to regard the problem as being slightly less serious than haemophilia-A and slightly more serious than Hip Dysplasia.  I fully support the U.K. Kennel Club in their stand against Haemophilia-A by requiring known affected bloodlines to be tested clear prior to registration.  I do not support the call for limitations on Hip Scores prior to registration or Breed Surveying.  This reflects the apparent accuracy and reliability of the tests currently available upon which to make the value judgement.

I am particularly keen to prevent the importation of more defective genotypes.

The problem with hypo-pituitarism is that there is no accurate canine test available at the moment.  However, a major immuno-diagnostic biochemical manufacturer with many years experience of the human condition is currently developing a canine version of one of the standard human tests at their veterinary research and development centre in Germany.  This test, or developments from it, may well be able to identify the carriers from the normal animals in the breeding population.

If a reliable cost-effective test can be produced then I certainly recommend that it should be used on animals from relevant bloodlines and that stud dogs and brood bitches should be advertised as being 'clear' of this problem.

The other method of identifying bloodlines at risk is by pedigree comparisons.  I have already started a database of affected bloodlines on a pedigree recording program which should assist in the identification of the heterozygotes (carriers) in the population.  I would be very please to hear from any breeder who has produced a 'dwarf' puppy of known descent - confidences will be honoured if requested.

Obviously, a combination of testing and pedigree recording would be better still.

The Danish work shows that the problem is one which must affect virtually every important German bloodline since WW2.  I am not interested in the pre-war genealogy.  I do not know whether the defect arose as a mutation around that time or whether it carried through.  I am only interested in the effect that this defect through the modern bloodlines is having on the breed now and for the future.

Many of the perceived carriers are VA (Excellent Select) animals which derive from the German inbreeding programme to rebuild the breed after the WW2 depletions.  The flow-chart (Fig 1.) shows a part of the production arising from two matings between Lex Preussenblut and Maja vom Osnabrücker Land.  Lex Preussenblut died young in suspicious circumstances but it has not been possible to determine whether either, or possibly both, were heterozygotes (carriers) or not.

Rolf (SZ693521) and Rosel vom Osnabrücker Land are effectively implicated as carriers (Andresen 1976 & 1978) though Ina (SZ693527) may have escaped.  Hein vom Richterbach (SZ700070) and Vello zu den Sieben-Faulen (SZ935874) are effectively implicated as carriers though Cäsar von der Malmannsheide (SZ862862) may have escaped.  In Fig. 1. an unshaded symbol means either a normal animal or 'status unknown'.  The Australian work (Nicholas 1978) implicates Vello as the ancestor of 7 out of 8 of the dwarfs in his study.

In modern pedigrees I would pick out Lasso di Val Sole (SZ1378829) twice Italian Sieger (1978 and 1979) and Uran vom Wildsteiger Land (SZ1526684) twice German Sieger (1984 and 1985) as being of particular importance (Willis 1991).  Both these important sires are included in the pedigree of my own recent 'dwarf' litter within four generations.

Although the physiological evidence has been around since the 1950s, the genetic evidence and some bio-chemical evidence has been around since the 1970s, the probable implications appear to have been overlooked, misunderstood, or deliberately covered up.  Is this the breed's best kept secret?  or is this the breed's second best kept secret after Haemophilia-A?

References:

Andresen, E. (1978)  Herkunkt und Verbreitung von hypophysärem Zwergwuchs beim Hund und Grundlage zur Ermittlung von Anlageträgern verschiedener genetisch bedingter Krankheiten unter Anwendung biochemischer Methoden - Kleintier Praxis 1978:23 pp65-74  Origin: Denmark  Language: German with English, French and  Italian Summaries

Andresen, E. & Willeberg, P. (1976)  Pituitary Dwarfism in German Shepherd Dogs: Additional Evidence of Simple, Autosomal Recessive Inheritance - Nordisk Vet. Med. 1976:28:481-486  Origin: Denmark   Language: English with German and Danish Summaries

Moch, R. & Haase, G. (1953)  Hypofunktion der Adenohypophyse eines Hundes - Tierärztlichen Umschen 1953:8 pp242-244  Origin: Germany Language: German

Nicholas, F. (1978) Pituitary dwarfism in German Shepherd Dogs: a genetic analysis of some Australian data - J. Small Anim. Pract. 1978:19 pp167-174   Origin: Australia   Language: English

Willeberg, P., Kastrup, K.W. et al (1975)  Pituitary Dwarfism in German Shepherd Dogs:  Studies on Somatomedin Activity - Nordsk Vet. Med. 1975:27 pp448-454  Origin:  Denmark    Language: English with German and Danish Summaries

Willis, M.B. (1991)  The German Shepherd Dog: a genetic history - H.F. & G. Witherby p.82 & p.84.  Origin:  U.K.  Language:  English