Myotonia Congenita

 

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.

Mutations:

Australian Cattle Dog, Border Collie mutation: Insertion, CLCN1 gene; c.2647_2648 ins.A, p.(R883Q fs STOP 18)

Miniature Schnauzer mutation: Substitution, CLCN1 gene; c.803 C>T, p.(T268M)

Labrador Retriever mutation: Substitution, CLCN1 gene; c.2275 A>T, p.(R759 STOP)

American Bulldog mutation: Insertion, CLCN1 gene; c.436_437 ins.CTCT, p.(Y146S FS STOP 49)

Breeds: American Bulldog, Australian Cattle Dog, Border Collie, Labrador Retriever, Schnauzer - Miniature

Age of onset of symptoms: Around 6 weeks of age

Congenital Myotonia is a disease that affects the ion channels of skeletal muscles resulting in a delay in muscle relaxation following contraction. Affected animals exhibit skeletal muscle hypertrophy, stiff movements, difficulty getting up after rest and running with rabbit hops.  These animals can also have a longer upper jaw than the lower one, dental abnormalities, excessive panting and salivation, difficulty swallowing and an abnormal bark.  Despite clinical signs, life expectancy is normal.

 

References:

OMIA link: [0698-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Cerda-Gonzalez S, Packer RA, Garosi L, et al. (2021) International veterinary canine dyskinesia task force ECVN consensus statement: Terminology and classification. J Vet Intern Med 35:1218-1230 [pubmed/33769611]

Rodrigues DJ, Damasceno AD, Araújo CET, et al. (2020) Hereditary myotonia in American Bulldog associated with a novel frameshift mutation in the CLCN1 gene. Neuromuscul Disord 30:991-998. [pubmed/33246886]

Quitt PR, Hytönen MK, Matiasek K, et al. (2018) Myotonia congenita in a Labrador Retriever with truncated CLCN1. Neuromuscul Disord 28:597-605. [pubmed/22934119]

Finnigan DF, Brad Hanna WJ, Poma R, Bendall AJ (2007) A novel mutation of the CLCN1 gene associated with myotonia hereditaria in an Australian Cattle Dog. J Vet Intern Med 21:458-463. [pubmed/17552451]

Bhalerao DP, Rajpurohit Y, Vite CH, Giger U (2002) Detection of a genetic mutation for myotonia congenital among miniature schnauzers and identification of a common carrier ancestor. AJVR 63(10):1443-1447. [pubmed/12371774]

Rhodes TH, Vite CH, Giger U, et al. (1999) A missense mutation in canine ClC-1 causes recessive myotonia congenita in the dog.  FEBS Letters 456:54-58. [pubmed/10452529]

Vite CH, Melniczek J, Patterson D, Giger U. (1999) Congenital myotonic myopathy in the miniature schnauzer: an autosomal recessive trait. J Hered. 90(5):578-80. [pubmed/10544501]