First European case of recessive early-onset muscle weakness syndrome in a Holstein calf

Early-onset muscle weakness (MW) syndrome is a genetic disorder in Holstein cattle, that was first described in the US in 2022 and is caused by a recessively inherited variant in the CACNA1S gene. This report documents the first confirmed case of MW in Holstein cattle in Europe. A 17-day-old female Swiss Holstein calf was presented for progressive, non-ambulatory weakness and inability to stand up without assistance. Clinical examination revealed generalized muscle atrophy and tremors, a wide-based stance, and inability to acquire the quadrupedal stance without assistance. Hematologic and biochemical analyses were unremarkable, except for mild monocytopenia and reduced plasma creatinine. Histopathological analysis of semitendinosus and semimembranosus muscles revealed pronounced fiber size variability, rounded hypertrophic fibers, small fibers with central nuclei, mild mononuclear infiltration, and increased connective tissue, findings consistent with chronic myopathic change. Pedigree analysis revealed that the affected calf was inbred and could be traced back to two known US MW carriers suggesting recessive inheritance. Genetic testing of the case confirmed homozygosity for CACNA1S, whereas both parents were heterozygous. The estimate of the frequency of this defect allele in the Swiss Holstein population is 0,56 %and 1,07 % in Swiss Fleckvieh. MW should be considered as a differential diagnosis in young calves of these two breeds presenting with signs of recumbency and weakness and should be tested accordingly using genetic diagnostics.