Hypertrophic Cardiomyopathy (MYBPC3 gene, Ragdoll)

Hypertrophic cardiomyopathy is a disorder characterized by thickening of the myocardium, specifically by increased volume of cardiac muscle tissue in the left ventricle and ventricular septum. It is the most common cardiac disease in domestic cats.

Symptoms

The manifestation of symptoms of hypertrophic cardiomyopathy usually occurs between two and three years of age, although the age of diagnosis may be later. Most affected cats do not experience symptoms immediately. The main clinical signs include congestive heart failure, arterial thromboembolism and a minority even experience sudden death. Congestive heart failure may involve shortness of breath, lethargy and exercise intolerance, and thromboembolism may involve the hind limbs causing pain and bilateral ischemia.

Disease Management

There is no preventive or curative treatment for this disease. Treatment focuses on controlling the symptoms by means of drugs such as antithrombotics to reduce the risk of clot formation.

Genetic basis

This disease follows an autosomal dominant mode of inheritance. Autosomal dominant inheritance means that cats only have to inherit one copy of the mutation or pathogenic variant to be at risk of developing the disease. Each kitten born to a parent carrying one copy of the mutation has a 50% chance of inheriting one copy of the mutation and being at risk for the disease. Breeding between cats carrying genetic variants that can cause disease is not recommended, even if they do not show symptoms.

Technical report

Hypertrophic cardiomyopathy is an autosomal dominant disorder characterized by thickening of the myocardium. Among the genes that have been extensively investigated in relation to this disease is the gene encoding cardiac myosin-binding protein C (MYBPC3), a protein with sarcomeric function, i.e., involved in the process of muscle contraction. Although the precise role of the protein produced by MYBPC3 is not fully understood, it is believed that it could interact with myosin or actin, or establish interactions with other sarcomeric proteins. The first variant identified in this gene (c.91G>C) was observed in the Maine Coon breed. Subsequently, in the Ragdoll breed, a new variant (c.2453C>T) was discovered that helped to explain hypertrophic cardiomyopathy in affected cats that did not have the c.91G>C variant. The c.2453C>T variant found in Ragdoll involves a base pair change at codon 820, affecting a conserved arginine. It is expected that this change may affect the function or structure of the protein. Guidelines established by the American College of Veterinary Internal Medicine do not recommend genetic testing for MYBPC3 c.2453C>T in non-Ragdoll cats.

Most affected breeds

Ragdoll

Bibliography

Akiyama N, Suzuki R, Saito T, et al. Presence of known feline ALMS1 and MYBPC3 variants in a diverse cohort of cats with hypertrophic cardiomyopathy in Japan. PLoS One. 2023 Apr 18