What is dwarfism
Testing of dogs: dwarfism
Pituitary dwarfism or nanism is a metabolic disorder that occurs in German Shepherds, Saarloos Wolfhounds, and Czechoslovakian Wolfhounds. This disease is characterized by degeneration of the pituitary gland and subsequent lack of pituitary hormones. Specifically, these are reduced levels of growth hormones, thyrotropin, prolactin and gonadotropins and, in contrast, the secretion of the adrenocorticotropic hormone is maintained.
Genetics of dwarfism
The dwarfism is caused by a mutation within the LHX3 gene on the CFA9 chromosome, which codes for the transcription factor that prevents the stem cells of the pituitary gland from spreading effectively after the differentiation of the corticotropic cells. The sequencing of the LHX3 gene discovered the deletion c.622-37-31del in one of six 7bp repetitions in intron 5 of the LHX3 gene, which causes the intron size to be reduced to 68 bp. In a German Shepherd, the heterozygosity for insertion of an ACA three-nucleotide sequence in exon 5 was demonstrated.
The Genomia Laboratory carries out tests to detect both of the above-described gene mutations that lead to dwarf growth.
Dwarfism is an autosomal recessive disease. This means that the disease will only develop in dogs who have inherited the mutated gene from both parents; these dogs are labeled as P / P (positive / positive). The carriers of this mutated gene (N / P, i.e. negative / positive) are clinically healthy, but transmit the disease to their offspring. If two heterozygous dogs (N / P) are mated, theoretically 25% of the offspring will be completely healthy (N / N), 50% will be carriers and 25% will inherit the mutated gene from both parents and will suffer from dwarfism (P / P) .
Clinical expression of dwarfism
The affected animals can be of normal size for the first few weeks of their lives. After that, they grow more slowly than their healthy siblings in the litter. This can also be seen in different increases in weight. The differences are noticeable between the 3rd and 4th month. The affected dogs are the smallest puppies in the litter with visibly slow growth that never reach normal size in adulthood. Another distinctive clinical manifestation of pituitary dwarfism is that the dwarfs keep their puppy fur. Over time, the fur goes out extensively and the animal shows alopecia, mostly on the body and neck. As a result of the increased hair loss in the affected animals, the skin can be irritated and hyperpigmented, making the skin appear darker. In addition, the dwarfs are significantly more susceptible to bacterial skin infections due to the reduced immunity of the skin.
Pituitary insufficiency is a serious disorder that affects other organs. For example, growth hormone insufficiency leads to underdevelopment of the kidneys, which leads to chronic kidney failure. The lack of TSH leads to an underactive thyroid, which makes the animal slow and cumbersome. In males, gonadotropin insufficiency leads to testicular cryptorchidism. The female dwarfs come into heat, but do not ovulate.
Treatment is based more on compensating for the accompanying health complications.
The most logical option would be to treat the affected dogs with canine growth hormone. Unfortunately it is not possible as this hormone is not available for therapeutic use. For this reason, the use of human growth hormone would suggest itself. Attempts to treat the pituitary gland in dogs with human growth hormone have been recorded in the past. Not only is this treatment very expensive, but its use is also prevented by the production of antibodies. The use of pig growth hormone appears to be a better treatment alternative. The administration of pig growth hormone will not result in the production of the adverse substances as the amino acid sequence of pig growth hormone is identical to canine growth hormone. But this treatment also has its disadvantages. This treatment can lead to the development of diabetes mellitus because of higher levels of growth hormone. It is therefore recommended to monitor the plasma concentration of growth hormone and glucose during treatment.
Alternatively, long-term treatment with medroxyprogesterone acetate or proligeston is possible. The progestin is able to induce the expression of the growth hormone in the mammary gland of the dogs. However, this treatment also brings further complications in the form of repetitive periods of itchy pyoderma and cystic hyperplasia of the endometrium in female dogs.
The recommended therapy for the treatment of secondary hypothyroidism is the administration of the synthetic levothyroxine. Since its absorption and metabolism are variable, the dose of levothyroxine must be adjusted in order to achieve a satisfactory clinical response.
Without proper treatment, the long-term prognosis is poor. By 3-5 years of age, the animal is usually almost naked, emaciated, and apathetic. Fortunately, if the puppies affected with dwarfism are treated correctly and in a timely manner with levothyroxine and either pig growth hormone or progestin, the prognosis improves significantly.
Annemarie M.W.Y. Voorbij; Hans S. Kooistra, DVM, PhD, Dipl ECVIM-CA; Pituitary Dwarfism in German Shepherd Dogs; JVCS, Vol. 2, No. January 1, 2009
Annemarie Voorbij and Hans Kooistra et al. ; Pituitary dwarfism in German shepherd dogs and Saarloos wolfhounds; Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University
Kate L. Tsai, Rooksana E. Noorai, et al. ; Genome-wide association studies for multiple diseases of the German Shepherd Dog; Mamm Genome (2012) 23: 203-211; DOI 10.1007 / s00335-011-9376-9
Annemarie, M.W.Y. Voorbij et al; A Contracted DNA Repeat in LHX3 Intron 5 Is Associated with Aberrant Splicing and Pituitary Dwarfism in German Shepherd Dogs; PLoS ONE 6 (11): e27940. doi: 10.1371 / journal.pone.0027940
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