Difference between revisions of "Achondroplasia"

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The disease is multifactorial and results in dysregulation of growth of bones at the cartilage growth plates which may be severe or moderate (hypochondroplasia)<ref>Verheijen J & Bouw J (1982) Canine intervertebral disc disease: a review of etiologic and predisposing factors. ''Vet Q'' '''4(3)''':125-134</ref> or mild (pseudoachondroplasia)<ref>Breur GJ ''et al'' (1992) Cellular basis of decreased rate of longitudinal growth of bone in pseudoachondroplastic dogs. ''J Bone Joint Surg Am'' '''74(4)''':516-528</ref>.
 
The disease is multifactorial and results in dysregulation of growth of bones at the cartilage growth plates which may be severe or moderate (hypochondroplasia)<ref>Verheijen J & Bouw J (1982) Canine intervertebral disc disease: a review of etiologic and predisposing factors. ''Vet Q'' '''4(3)''':125-134</ref> or mild (pseudoachondroplasia)<ref>Breur GJ ''et al'' (1992) Cellular basis of decreased rate of longitudinal growth of bone in pseudoachondroplastic dogs. ''J Bone Joint Surg Am'' '''74(4)''':516-528</ref>.
  
Some dog breeds traditionally have been classified as achondroplastic based on their phenotypic appearance, such as the [[Dachshund]], [[Basset Hound]], [[Irish Setter]]<ref>Hanssen I ''et al'' (1998) Hypochondroplastic dwarfism in the Irish setter. ''J Small Anim Pract'' '''39(1)''':10-14</ref> and [[Bulldog]] breeds<ref>Martínez S ''et al'' (2000) Achondroplastic dog breeds have no mutations in the transmembrane domain of the FGFR-3 gene. ''Can J Vet Res'' '''64(4)''':243-245</ref>.
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Some dog breeds traditionally have been classified as achondroplastic based on their phenotypic appearance, such as the [[Dachshund]], [[Basset Hound]], [[Irish Setter]]<ref>Hanssen I ''et al'' (1998) Hypochondroplastic dwarfism in the Irish setter. ''J Small Anim Pract'' '''39(1)''':10-14</ref> and [[Bulldog]] breeds<ref>Martínez S ''et al'' (2000) Achondroplastic dog breeds have no mutations in the transmembrane domain of the FGFR-3 gene. ''Can J Vet Res'' '''64(4)''':243-245</ref>. Although the most frequent mutation in achondroplastic humans originates from a G/A transition in nucleotide 1138 of the transmembrane domain of gene FGFR3<ref>Shiang R ''et al'' (1994) Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. ''Cell'' '''78''':335–342</ref>, a similar mutation seems not to be involved in the bulldog, basset hound, and dachshund with the osteochondrodysplastic phenotype<ref>Martínez S ''et al'' (2000) Achondroplastic dog breeds have no mutations in the transmembrane domain of the FGFR-3 gene. ''Can J Vet Res'' '''64''':243–245</ref>.
  
 
The [[Cavalier King Charles Spaniel]] has achondroplastic phenotypic features characterized by [[Chiari malformations|chiari-like malformation]] due to [[syringomyelia]]<ref>Schmidt MJ ''et al'' (2012) Volume reduction of the jugular foramina in Cavalier King Charles Spaniels with syringomyelia. ''BMC Vet Res'' '''8(1)''':158</ref>.
 
The [[Cavalier King Charles Spaniel]] has achondroplastic phenotypic features characterized by [[Chiari malformations|chiari-like malformation]] due to [[syringomyelia]]<ref>Schmidt MJ ''et al'' (2012) Volume reduction of the jugular foramina in Cavalier King Charles Spaniels with syringomyelia. ''BMC Vet Res'' '''8(1)''':158</ref>.

Revision as of 20:43, 6 March 2017

Achondroplasia in a crossbred German Shepherd pup[1]

Achondroplasia (dwarfism; short limbs) is an autosomal-recessive genetic disease of dogs characterized by disproportionate dwarfism, macrocephaly, facial hypoplasia and vertebral malformations.

This disease, commonly reported in the German Shepherd, is associated with a failure of the oropharyngeal ectoderm of the cranial pharyngeal duct. Craniopharyngiomas also cause subnormal secretion of growth hormone, which results in dwarfism.

The disease is multifactorial and results in dysregulation of growth of bones at the cartilage growth plates which may be severe or moderate (hypochondroplasia)[2] or mild (pseudoachondroplasia)[3].

Some dog breeds traditionally have been classified as achondroplastic based on their phenotypic appearance, such as the Dachshund, Basset Hound, Irish Setter[4] and Bulldog breeds[5]. Although the most frequent mutation in achondroplastic humans originates from a G/A transition in nucleotide 1138 of the transmembrane domain of gene FGFR3[6], a similar mutation seems not to be involved in the bulldog, basset hound, and dachshund with the osteochondrodysplastic phenotype[7].

The Cavalier King Charles Spaniel has achondroplastic phenotypic features characterized by chiari-like malformation due to syringomyelia[8].

Achondroplasia has also been reported in association with oculoskeletal dysplasia in the Samoyed and Labrador Retriever. Osteochondrodysplasias have been reported mainly in dogs, including the Alaskan Malamute, Scottish deer hound, Norwegian elk hound, Maremmano–Abruzzese shepherd, Great Pyrenees, German shepherd, miniature poodle, Labrador retriever, beagle, and cocker spaniel. Most of the alterations in these dogs result from a de novo mutation, but in some cases they appear to be due to autosomal recessive inheritance[9][10].

In typical cases of achondroplasia, affected pups are born with severe anatomical deformities such as dorsoventral flattening of the thoracic cavity, malpositioning of the scapula and enlarged, disproportionate heads[11].

These variable phenotypic malformations invariably lead to osteoarthritis and poor quality of life in severely affected patients.

Less affected patients with arthritic changes can be treated with NSAID-based medication such as carprofen, fentanyl, tramadol, meloxicam[12], gabapentin or in severe cases, prednisolone.

References

  1. Pedigree Database
  2. Verheijen J & Bouw J (1982) Canine intervertebral disc disease: a review of etiologic and predisposing factors. Vet Q 4(3):125-134
  3. Breur GJ et al (1992) Cellular basis of decreased rate of longitudinal growth of bone in pseudoachondroplastic dogs. J Bone Joint Surg Am 74(4):516-528
  4. Hanssen I et al (1998) Hypochondroplastic dwarfism in the Irish setter. J Small Anim Pract 39(1):10-14
  5. Martínez S et al (2000) Achondroplastic dog breeds have no mutations in the transmembrane domain of the FGFR-3 gene. Can J Vet Res 64(4):243-245
  6. Shiang R et al (1994) Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell 78:335–342
  7. Martínez S et al (2000) Achondroplastic dog breeds have no mutations in the transmembrane domain of the FGFR-3 gene. Can J Vet Res 64:243–245
  8. Schmidt MJ et al (2012) Volume reduction of the jugular foramina in Cavalier King Charles Spaniels with syringomyelia. BMC Vet Res 8(1):158
  9. Minor RR & Farnum CE (1988) Animal models with chondrodysplasia/osteochondrodysplasia. Pathol Immunopathol Res 7:62–67
  10. Mazzullo G et al (2000) Achondroplasia in a Maremmano–Abruzzese shepherd dog puppy. Eur J Vet Pathol 6:65–69
  11. Louw GJ (1983) Osteochondrodysplasia in a litter of Bulldog puppies. J S Afr Vet Assoc 54(2):129-131
  12. Wernham BG et al (2011) Dose reduction of meloxicam in dogs with osteoarthritis-associated pain and impaired mobility. J Vet Intern Med 25(6):1298-1305