In other species: dog , horse , pig , taurine cattle , goat , sheep , water buffalo

Categories: Muscle phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 160800 (trait) , 255700 (trait) , 118425 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Probably autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2014

Cross-species summary: Myotonia congenita

Molecular basis: Using the candidate gene approach, Gandolphi et al. (2014) identified a likely causal mutation as a "c.1930+1G>T transversion [that] altered the 5′ splice site at the junction of exon 16 and intron 16" of CLCN1, These same authors also reported that "In silico translation of the altered transcript predicts the lack of 116 amino acids, from residues 557 to residue 643 of the protein . . . . The predicted premature CLCN1 protein truncation would cause the partial absence of the first highly conserved CBS1 (cystathionine β-synthase) domain and the third dimerization domain p.578Y". Woelfel et al. (2022) investigated a 10 month old affected domestic longhair cat: "A high impact 8‐base pair (bp) deletion across the end of exon 3 and the beginning of intron 3 of the gene CLCN1 was identified ... in the proband. Sanger sequencing was performed to verify the existence of this 8‐bp deletion ... and confirmed that the proband was homozygous for the deletion ... . All phenotypically normal cats in our database of whole genome sequences lacked this deletion. All 96 additional control cats tested by Sanger sequencing were also found to be negative for the deletion." Corrêa et al. (2023) identified "a missense variant (c.991G>C, p.Ala331Pro) in exon 9 of the CLCN1 gene" as likely causal variant for myotonia in "three mixed-breed cats from the same litter."

Clinical features: Clinically, myotonic cats usually have muscle hypertrophy with dimpling after percussion and may appear poorly groomed. Affected cats demonstrate blepharospasm upon testing the palpebral reflex and menace response but have normal mentation. They ambulate with an abnormally short stride and stiff, choppy gait, restricted limb adduction, and they may stiffen and fall in lateral recumbency when startled. Clinical presentation may also include a limited ability to open the jaws, dysphonia, dysphagia, facial spasms, a protruding hypertrophic tongue, and varying degrees of gingivitis and dental disease. (Toll et al., 1998; Gaschen et al., 2004; Gandolfi et al., 2014) Electromyography of these animals demonstrates classical myotonic discharges, seen as repetitive spontaneous “waxing and waning” discharges (Toll et al., 1998; Gaschen et al., 2004). Some cats have been reported to develop respiratory stridor and cyanosis when stressed by handling (Toll et al., 1998). IT thanks DVM student Alexandrea Costanza, who provided the basis of this contribution in May 2023.

Pathology: Muscle histopathology reveals hypertrophy of all muscle fibre types (Hickford et al., 1998; Gandolfi et al., 2014). IT thanks DVM student Alexandrea Costanza, who provided the basis of this contribution in May 2023.

Breeds: Domestic Longhair, Domestic Shorthair.
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: