Clinicopathological and pedigree investigation of a novel spinocerebellar neurological disease in juvenile Quarter Horses in North America
Andrew T. Willis, Anna R. Dahlgren, Kevin D. Woolard, Sharmila Ghosh, Callum G. Donnelly, Andres de la Concha‐Bermejillo, Ana Pacheco, Katherine D. Watson, Emily Berryhill, Monica Aleman, Fiona Wensley, Sarah Humphreys, Ashley E. Whitehead, Dayna Goldsmith, Berkley Chesen, John Ragsdale, James E. Tompkins, Ron Nash, Amanda H. Plunkett, Heath J. Qualls, Katarina Rodriguez, Damaris Hochanadel, Andrew D. Miller, Carrie J. FinnoAbstract
Background
In 2020, a novel neurologic disease was observed in juvenile Quarter Horses (QHs) in North America. It was unknown if this was an aberrant manifestation of another previously described neurological disorder in foals, such as equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM).
Hypothesis/Objectives
To describe the clinical findings, outcomes, and postmortem changes with Equine Juvenile Spinocerebellar Ataxia (EJSCA), differentiate the disease from other similar neurological disorders, and determine a mode of inheritance.
Animals
Twelve neurologically affected QH foals and the dams.
Methods
Genomic DNA was isolated and pedigrees were manually constructed.
Results
All foals (n = 12/12) had a history of acute onset of neurological deficits with no history of trauma. Neurological deficits were characterized by asymmetrical spinal ataxia, with pelvic limbs more severely affected than thoracic limbs. Clinicopathological abnormalities included high serum activity of gamma‐glutamyl transferase and hyperglycemia. All foals became recumbent (median, 3 days: [0–18 days]), which necessitated humane euthanasia (n = 11/12, 92%; the remaining case was found dead). Histological evaluation at postmortem revealed dilated myelin sheaths and digestion chambers within the spinal cord, most prominently in the dorsal spinocerebellar tracts. Pedigree analysis revealed a likely autosomal recessive mode of inheritance.
Conclusions and Clinical Importance
EJSCA is a uniformly fatal, rapidly progressive, likely autosomal recessive neurological disease of QHs <1 month of age in North America that is etiologically distinct from other clinically similar neurological disorders. Once the causative variant for EJSCA is validated, carriers can be identified through genetic testing to inform breeding decisions.