Muscular Dystrophy-Dystroglycanopathy

Muscular dystrophy-dystroglycanopathy is an inherited neuromuscular disease that mainly affects the Devon Rex and Sphynx breeds of cats. This condition is caused by a mutation in the COLQ gene, which plays a crucial role in neuromuscular transmission.

Symptoms

This disease causes generalized muscle weakness and severe locomotor difficulties, especially affecting the girdle and axial muscles. Affected cats also show fatigue, dorsal protrusion of the scapulae, passive ventroflexion of the head and neck, and head bobbing.

Disease Management

Although no specific therapy has yet been identified for this disease, management focuses on improving quality of life and reducing symptom progression. The study of this neuromuscular disorder has classified it as a congenital myasthenic syndrome, suggesting the possibility of evaluating the effectiveness of ephedrine, previously used successfully in patients with COLQ deficiency.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the cat, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected cat must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between cats carrying genetic variants that may cause disease is not recommended, even if they do not show symptoms.

Technical report

Neuromuscular disorders encompass a diversity of diseases that affect normal skeletal muscle function. Among them, congenital myasthenic syndromes (CMS) stand out as a heterogeneous group of inherited diseases. These disorders are characterized by abnormal signal transmission in the motor plate, which is crucial for communication between motor axonal nerve terminals and skeletal muscle fibers. In this context, the COLQ gene plays a crucial role by encoding an enzyme in the motor plate that degrades the neurotransmitter acetylcholine after its release, thus facilitating nerve signal termination and preparing the next neuromuscular transmission. A congenital myopathy has been identified in cats of the Devon Rex and Sphynx breeds, which is inherited in an autosomal recessive manner. This disease is caused by a mutation in the COLQ gene, specifically located in exon 15, which leads to the substitution of a cysteine for tyrosine in the C-terminal domain of COLQ. The breeds affected by this condition, Devon Rex and Sphynx, show a remarkable genetic similarity due to the frequent use of Devon Rex cats in Sphynx breeding programs.

Most affected breeds

Devon Rex
Sphynx

Bibliography

Abitbol M, Hitte C, Bossé P, et al. A COLQ Missense Mutation in Sphynx and Devon Rex Cats with Congenital Myasthenic Syndrome. PLoS One. 2015 Sep 1