Genetics of canine subvalvular aortic stenosis (SAS)

Abstract

Subvalvular aortic stenosis (SAS) is one of the most common congenital heart defects of dogs. The disease is characterized by obstruction of the left ventricular outflow tract, resulting in pressure overload on the left ventricle. The etiology of obstruction is a fibromuscular nodule, ridge, or ring of tissue that increases aortic outflow tract velocity. This review is focused on the prevalence, inheritance pattern, and current genetic insights of canine SAS. The prevalence of this disease was reported at 4.7 % in a large veterinary referral hospital. The mode of inheritance for this disease has also been described in breeds with a high disease prevalence such as the Bullmastiff, Bouvier des Flandres, Dogue de Bordeaux, Golden Retriever, Newfoundland, and Rottweiler. Genetic investigations seeking to identify causative mutations for SAS are lacking with only a single published variant associated with SAS in Newfoundlands.

Infective endocarditis in dogs in theUK: 77 cases (2009‐2019)

“…Six dogs had underlying congenital heart disease (SAS) which has been previously suggested to predispose dogs to IE due to creating turbulent blood flow and damage to the aortic cusps (MacDonald 2010 ). In addition, SAS is one of the most common congenital heart conditions in large breed dogs which may account for their predisposition to IE (Ontiveros & Stern 2021 ). Male dogs have also been shown to be predisposed to SAS which may also partly explain their higher prevalence (Schrope 2015 ).…”

Anästhesie bei Hunden und Katzen mit Herzerkrankungen

“…Die Aortenstenose ist die häufigste angeborene Herzpathologie bei großen Hunden und kommt selten bei der Katze vor 10 , 51 . Die Verengung der Aorta führt zu einer verminderten Ausflussfähigkeit des linken Ventrikels.…”

Subvalvular Aortic Stenosis: Learning From Human and Canine Clinical Research

“…Therefore, the current most commonly employed treatment for SAS in dogs is pharmacological. A beta-adrenergic blocker serves to lower a patient’s heart rate and increase myocardial perfusion; atenolol, which is cardio-selective, tends to be the beta-blocker of choice [ 42 , 62 - 64 ]. Treatment is generally selected for dogs with moderate to severe forms of SAS, as mild cases do not often exhibit symptom development or significant lifespan alterations.…”

“…Their studies implicate a polygenic mode of inheritance or an autosomal dominant mode of inheritance (possibly with modifiers). These continue to be the leading hypothesized modes of inheritance; additional information is required to more definitively support or refute these contradicting hypotheses [ 5 , 6 , 64 ]. Furthermore, their results suggested that the trait may not have complete specificity, for some crosses between affected individuals yielded offspring with valvular and subvalvular pulmonic stenosis in addition to SAS [ 5 ].…”

“…A three-nucleotide insertion in exon 16 of PICALM (phosphatidylinositol-binding clathrin assembly protein), located on chromosome 11, was discovered in Newfoundlands in 2014 and is the sole variant associated of SAS to date, yet this variant was not replicated in a European breed sample [ 99 , 100 ]. More recently, a genome-wide association study (GWAS) with the five aforementioned breeds yielded a region of association on chromosome 13 in Golden Retrievers, Newfoundlands, and Rottweilers (both within and across breeds) [ 64 ]; chromosome 21 in Bullmastiffs; and chromosome 20 in Bouviers. However, a subsequent whole-genome sequencing (WGS) analysis did not reveal any coding variants within candidate genes to be associated with SAS, as they neither segregated perfectly, nor did their known functions align with the pathophysiological changes established to occur over the course of the disease.…”