In horses, CA is a neurologic disease that develops almost exclusively in Arabians.1–4 Foals affected with the disease may appear clinically normal at birth; signs of disease generally develop between 6 weeks and 4 months of age but occasionally later. Clinical signs include ataxia, intention head tremor, exaggerated action of the forelimbs, a wide-based stance, and a lack of menace response.2–4 Affected horses often startle easily, fall, and may be unable to rise from a recumbent position.5
The pathological features of CA include postnatal degeneration of the Purkinje cells and associated neurons from the granular layer of the cerebellum, which results in disorganization of the molecular and granular layers.3,6 The remaining Purkinje cells are small and shrunken, with abnormal morphological characteristics.1,2 The death of Purkinje cells appears to be due to a failure of these cells to migrate correctly through the cerebellum during development. Recent research findings implicate an apoptosis mechanism in the loss of Purkinje cells.6
Although CA itself is not fatal, the general lack of balance equilibrium and hyperreactivity of affected horses poses a danger to the horses and handlers. Horses with CA are most often euthanized or, in some circumstances, maintained as pasture pets because they are never sufficiently coordinated to be ridden safely and do not generally make good breeding candidates. Diagnosis of the disease is almost always made following the recognition of clinical signs by an attending veterinarian. Definitive diagnosis can only be made after death via histologic examination of cerebellar tissue.
Cerebellar abiotrophy was first described in the veterinary medical literature in the late 1960s.1 Early publications were limited to case reports2–4 involving Arabians that had neurologic signs for which there was subsequent histologic confirmation of the disease. Examination of the affected foals' pedigrees, lack of environmental causes, and the fact that the disease was virtually restricted to the Arabian breed suggested a genetic basis for the condition.2–4 Although a recessive mode of inheritance has been suggested, the rarity of confirmed cases made it impossible to determine the mode of inheritance with any statistical support.3,4
Development of CA is a source of concern for breeders of Arabians. Currently, it appears that < 1% of Arabians are affected with the disease at birth but the incidence of affected foals seems to be increasing. For example, with regard to affected foals, we were informed of 5 born in 2008 but 14 born in 2009. Because of underreporting or misdiagnosis, available data may not reflect the actual incidence of the disease. The cost of a CA-affected foal in terms of lost revenue can be considerable, as many of these foals come from valuable breeding stock. Establishing the mode of inheritance of the disease will help breeders make informed decisions about the animals selected for mating to reduce the risk of producing a CA-affected foal. The purpose of the study reported here was to determine the mode of inheritance for CA among Arabians via complex segregation analysis of the phenotypic data (segregating for the disease) from familial horses.
Highest density region
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