Myotonia, congenital, CLCN1-related

Gene: CLCN1

Transmission: Autosomal, recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, CLCN1 gene; c.1775 A>C, p.(Asp592Ala), exon23, chromosome 4.

Breed: New Forest Pony

Medical system: Muscular

Age of onset of symptoms: By 6 weeks.

Myotonia is a muscle disorder characterized by prolonged muscle contraction due to a failure in normal muscle relaxation.  Congenital myotonia can be caused by molecular defects in ion channel genes.  Defects in the CLCN1 gene are known to be the cause of congenital myotonia in humans, goats and dogs.

The New Forest Pony is a pony breed originating from England.  A young New Forest Pony presented with clinical signs of myotonia, including muscle stiffness, a stiff gait, difficulty in rising from recumbency and a tendency for loss of balance.  Using a candidate gene approach, a homozygous mutation in the CLCN1 gene was identified.  When the DNA from 42 additional New Forest Ponies were analyzed, an overall carrier frequency of 21.4% was determined.  Both parents of the affected pony were asymptomatic carriers, and additional carriers were restricted to an individual pedigree pointing to a suspected founder stallion.  The true burden for the breed remains unknown.  The mutation was not seen in the DNA of 56 additional horses representing 13 other breeds.

Veterinarians and breeders of New Forest Ponies should be aware of this disease.  DNA testing should be performed as required to determine breed mutation frequencies, to identify possible carrier animals and to eliminate the mutation from the breed.

References:

OMIA link: [0698-9615]

Aleman M, Scalco R, Malvick J, et al. (2022) Prevalence of genetic mutations in horses with muscle disease from a neuromuscular disease laboratory. J Equine Vet Sci 118:104129.  [pm/36150530]

Valberg SJ. (2014) Myotonic Disorders in Horses.  MSD (Veterinary) Manual [https://www.msdvetmanual.com/musculoskeletal-system/myopathies-in-horses/myotonic-disorders-in-horses]

Wijnberg ID, Owczarek-Lipska M, Sacchetto R, et al. (2012) A missense mutation in the skeletal muscle chloride channel 1 (CLCN1) as candidate causal mutation for congenital myotonia in a New Forest pony. Neuromuscul Disord 22:361-7. [pm/22197188]

Contributed by: Élie Archambault and Karen Larose Labrecque, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)