In other species: pig , rabbit

Categories: Cardiovascular system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 192600 (trait) , 160760 (gene) , 613426 (trait)

Mendelian trait/disorder: yes

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2019

Species-specific description: Hypertrophic cardiomyopathy (HCM) is a common heart disease in domestic cats. Other forms of inherited hypertrophic cardiomyopathy have been reported in cats - for examples see 'OMIA:000515-9685 Cardiomyopathy, hypertrophic (MYBPC3-related), 'OMIA:002316-9685 Cardiomyopathy, hypertrophic, ALMS1-related' and 'OMIA:002304-9685 Cardiomyopathy, hypertrophic, TNNT2-related'.

Molecular basis: Sequencing of comparative functional genes in an affected Domestic Shorthair cat enabled Schipper et al. (2019) to identify a likely causal variant, namely "MYH7 c.5647G>A (p.(Glu1883Lys))".

Clinical features: Due to variable expressivity, the clinical expression of HCM can be widely variable, ranging from asymptomatic, congestive heart failure (CHF), syncope, or sudden death with HCM identified post-mortem (Schipper et al., 2019; O'Donnell et al., 2021). Physical examination may reveal a murmur, gallop sound or arrhythmia (O'Donnell et al., 2021). Diagnosis is usually confirmed via echocardiography, with left ventricle hypertrophy being identified. Electrocardiogram may be normal or show increased R-wave voltage, left axis derivation, ventricular or supraventricular premature complexes or atrial fibrillation (O'Donnell et al., 2021). The single domestic shorthair cat with the MYH7 variant reported by Schipper et al. (2019) presented at approximately 6 years of age with “acute paraplegia, pain and severe dyspnoea with cyanosis. …Three weeks previously, he had developed a cough that did not respond to antibiotics. … Femoral pulses were absent and the hind legs were paralysed, cold and extremely painful when manipulated. Lung sounds were muffled ventrally and the dyspnoea made cardiac auscultation very difficult. The cat was hypothermic with a rectal temperature of 36 °C. Focused thoracic sonography showed multiple B-lines and focused cardiac sonography showed subjective thickening of the left ventricular free wall. The cat was diagnosed with thromboembolism of the distal aorta most likely due to HCM, with a suspicion of pulmonary oedema. … Because of the severity of the clinical signs and the poor prognosis, the cat was euthanized.” IT thanks DVM student Sheridan Gundry, who provided the basis of this contribution in May 2023.

Pathology: Pathologically the heart appears enlarged with increased weight due to concentric hypertrophy of the left ventricular walls (Schipper et al., 2019). Additionally, this increasing thickness results in narrowing of the ventricular lumen. Histopathological features are characterised by diffuse hypertrophy of the left myocardium, karyomegaly of cardiomyocytes, increased branching and myofiber disarray, and interstitial fibrosis (Schipper et al., 2019). Advanced stages of the disease may be associated with thromboembolism, congestion and oedema of the lungs or other signs consistent with CHF (Schipper et al., 2019; O'Donnell et al., 2021). IT thanks DVM student Sheridan Gundry, who provided the basis of this contribution in May 2023.

Prevalence: Schipper et al. (2019) reported that the c.5647G>A variant was absent from "125 [non-affected] Domestic Shorthairs and 25 cats each from the Ragdoll, Maine Coon and British Shorthair breeds". O'Donnell et al. (2021) evaluated "the presence of the known MYBPC3 and MYH7 variants in a population of cats with HCM. DNA was isolated from samples collected from non-Ragdoll and non-Maine Coon domestic cats diagnosed with HCM through the North Carolina State University College of Veterinary Medicine and genotyped for the three variants. One-hundred and three DNA samples from cats with HCM were evaluated from domestic shorthair, domestic longhair and purebred cats. All samples were wt for the MYBPC3 and MYH7 variants. Although this study was limited by its inclusion of cats from one tertiary hospital, the lack of these MYBPC3 and MYH7 variants in this feline HCM population indicates that the clinical utility of genetic testing for these variants may be isolated to the two cat breeds in which these variants have been identified."

Associated gene: