Feline Myotonia Congenita (MC)
Acronym: | MC |
Gene: | CLCN1 |
Mutation: | c.1930+1G>T |
Inheritance: | Autosomal recessive |
Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Feline Myotonia Congenita (MC) is a hereditary neuromuscular disorder affecting skeletal muscles in domestic shorthair cats. Myotonia is defined as delayed relaxation of voluntarily or reflexively contracted muscle and the term derives from the Greek word ”Myo-” for muscle, and the Latin word ”Tonus” for tension. The condition is classified as channelopathy, a disease caused by the disturbed function of ion channel subunits of the proteins that regulate them. Myotonia congenita was first described in 1876 in a human patient, while reports about the feline form of the disorder did not appear until 1998. Except in humans and cats, myotonia congenita was identified in dogs, goats, horses, water buffalo, and mice, and in all those species MC is associated with a mutation in the same gene, the CLCN1 gene. Patterns of the disorders vary from dominant to recessive, as well as the degree of their severity.
Voltage-dependent chloride (Cl–) channels are transmembrane proteins. They are critical for the normal function of skeletal muscle cells and participate in many physiological processes, such as the maintenance of normal cellular excitability, the control of neurotransmitter release, and the transport of ions across epithelial cells. In case of a lack of sufficient functional chloride channels, the muscle fiber membrane becomes hyper-excitable and continues to be electrically active when stimulated for a longer period of time than a normal muscle fiber. In this case, muscle relaxation is delayed and contraction is prolonged.
General physical examination revels in affected cats restricted jaw opening, halitosis, varying degrees of gingivitis, pseudoptyalism (the dribbling of saliva caused by a difficulty in swallowing or paralysis of the lips), marked dental calculus accumulation with palpable loose teeth, and evidence of poor grooming habits. Severe muscle hypertrophy is present along the cervical spine. In one affected cat respiratory distress, such as stridor and open mouth breathing, has been reported. Mental activity in all affected cats appears normal. The gait shows as stiff, choppy, and short-stride in all limbs, especially in the pelvic limbs, followed by a decreased ability to adduct all limbs while walking. Affected cats show a protruding tongue with excessive drooling, prominent neck and proximal limb musculature, decreased range of jaw motion, oral disease, and a progressive decrease through successive attempts of visual placing in the thoracic limbs. No impact has been noticed on smooth or cardiac muscles, which is consistent with previous reports of myotonia congenita.
Feline Myotonia Congenita (MC) is caused by a mutation within the CLCN1 gene, which causes the expression of a truncated protein that is malfunctioning. MC in cats is inherited in an autosomal recessive mode of inheritance. Cat carrying one copy of the mutated gene is heterozygous and will not show the myotonia congenita symptoms. When mating two carriers (heterozygotes) at conception each kitten has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Gandolfi B, Daniel RJ, O’Brien DP, Guo LT, Youngs MD, et al. (2014) A Novel Mutation in CLCN1 associated with Feline Myotonia Congenita. PloS ONE 9(10): e109926. doi:10.1371/journal.pone.0109926.