Early-onset muscle weakness syndrome in Holstein cattle: molecular mechanisms, epidemiology, and control strategies

Abstract

Early-onset muscle weakness syndrome (MW) is a recessive genetic disorder in Holstein cattle associated with the missense mutation p.Gly1029Ser in the CACNA1S gene. The inclusion of this anomaly in the list of mandatory genetic defects for testing underscores its significance for modern dairy cattle breeding. The aim of this review is to systematize data on the molecular mechanisms, epidemiology, clinical diagnosis, and control strategies for MW. Publications from 2015 to 2025 indexed in PubMed, Google Scholar, eLibrary, and OMIA databases were analyzed. It was found that the carrier frequency of the mutation varies from 3% to 38%, depending on the region and assessment methodology, reaching maximum values in US populations and certain regions of the Russian Federation. The incomplete penetrance of the mutation complicates clinical diagnosis and necessitates the mandatory use of molecular genetic methods. The economic impact of MW spread is discussed, including direct losses from mortality of homozygous calves and indirect costs associated with restricted use of valuable carrier sires. The study substantiates the need to integrate genetic defect management into genomic selection systems, including mandatory genotyping of breeding stock, avoidance of carrier-to-carrier matings, and inbreeding control. The obtained data can serve as a basis for developing national programs for controlling hereditary anomalies in dairy cattle breeding.