Hyperekplexia in Miniature American Shepherds

Hyperekplexia, also now as Startle Disease, is a rare hereditary neurological disorder that affects the nervous system and the ability of muscles to relax properly. Clinical manifestations include exaggerated responses to stimuli that result in episodes of muscle stiffness and short-term inability to move. “Startle” episodes can be triggered by, for example, acoustic stimuli and are usually short-lived, but can be distressing and may lead to falls or injury. Dogs typically exhibit an unsteady gait after an episode.

The cause of the disease in miniature American shepherds is a mutation g.58338954_58338989del in the GLRA1 gene, which is important for the proper function of glycine receptors in the nervous system. These receptors help to inhibit nerve signals and allow muscles to relax.

The mutation is inherited in an autosomal recessive manner. This means that the disease only develops in individuals who inherit the mutated gene from both of their parents. Carriers of the mutated gene are of normal height, but they pass the mutation on to their offspring. In the case of mating two heterozygous individuals, theoretically 25% of the offspring will be so-called pure (without the mutation), 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

A genetic test can clearly reveal the genotype of the animal and is a suitable tool for breeders to prevent the unintentional breeding of affected puppies.

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References:

Heinonen, T., Flegel, T., Müller, H., Kehl, A., Hundi, S., Matiasek, K., Fischer, A., Donner, J., Forman, O.P., Lohi, H., Hytönen, M.K. : A loss-of-function variant in canine GLRA1 associates with a neurological disorder resembling human hyperekplexia. Hum Genet 142:1221-1230, 2023. Pubmed reference: 37222814