Disease Category Type
Duchenne or dystrophin muscular dystrophy (DMD) is a severe X-linked disorder that causes muscle degeneration and formation of excess connective tissue. DMD is characterized by spinal curvature and a crouched posture. Due to the X-linked recessive mode of inheritance, mainly males are affected, although some female carriers were suggested to suffer from less severe muscle weakness. The disorder is caused by several different mutations in the dystrophin gene; this variant is associated with causing the condition in Cavalier King Charles Spaniels. Affected puppies are usually euthanized at a young age because of the severity of the disorder.
Duchenne muscular dystrophy results from sarcolemma (cell membrane of striated muscle fiber cells) dysfunction which causes degeneration and necrosis of muscle tissue. DMD is a progressive condition that eventually leads to muscle fibrosis (formation of excess fibrous connective tissue). First signs of disease, such as bunny-hopping gate, can be observed in eight to ten weeks old puppies. Affected puppies have a thick tongue base and are unable to open the mouth properly which causes eating difficulties and excess drooling. Duchenne muscular dystrophy is characterized by crouched posture caused by spinal curvature and bending of the back. Serum creatine kinase concentrations can be over 300 times higher than normal levels. Affected puppies are usually euthanized at a young age because of the severity of the disorder.
Mutation Found In:
Cavalier King Charles Spaniel, King Charles Spaniel, English Toy Spaniel
Gene Variant Tested
muscle fibrosis, high serum creatine kinase concentration, spinal curvature, crouched posture, thick tongue base, and excessive salivation
Mode of Inheritance
Signs Seen in Affected Carriers
less severe muscle weakness
References: Online Database
Online Mendelian Inheritance in Animals, OMIA (http://omia.angis.org.au/). Faculty of Veterinary Science, University of Sydney.
References: Scientific Articles
Kornegay, JN., Bogan, JR., Bogan, DJ., Childers, MK., Grange, RW. Golden retriever muscular dystrophy (GRMD): Developing and maintaining a colony and physiological functional measurements. Methods Mol Biol 709:105-23, 2011.
Cooper BJ, Winand NJ, Stedman H, Valentine BA, Hoffman EP, Kunkel LM, Scott MO, Fischbeck KH, Kornegay JN, Avery RJ, Williams JR, Schmickel RD, Sylvester JE. The homologue of the Duchenne locus is defective in X-linked muscular dystrophy of dogs. Nature 334:154-156, 1988.
Sharp NJH, Kornegay JN, Vancamp SD, Herbstreith MH, Secore SL, Kettle, S, Hung WY, Constantinou CD, Dykstra MJ, Roses AD, Bartlett RJ. An Error in Dystrophin Messenger RNA Processing in Golden Retriever Muscular Dystrophy, an Animal Homologue of Duchenne Muscular Dystrophy. Genomics 13:115-121, 1992.
Smith BF, Yue Y, Woods PR, Kornegay JN, Shin JH, Williams RR, Duan D. An intronic LINE-1 element insertion in the dystrophin gene aborts dystrophin expression and results in Duchenne-like muscular dystrophy in the corgi breed. Lab Invest 91:216-31, 2011.
Walmsley GL, Arechavala-Gomeza V, Fernandez-Fuente M, Burke MM, Nagel N, Holder A, Stanley R, Chandler K, Marks SL, Muntoni F, Shelton GD, Piercy RJ. A duchenne muscular dystrophy gene hot spot mutation in dystrophin-deficient cavalier king charles spaniels is amenable to exon 51 skipping. PLoS One 5:e8647, 2010.