Irish Wolfhound Startle Disease (SD) – Hyperekplexia
Irish Wolfhound Startle Disease (SD) is a hereditary neurological disorder, also known as hyperekplexia. The disorder is characterized by prominent startle responses triggered by noise or touch. Startle disease has been identified in humans and animals. Animal disorders similar to startle disease have been reported in cattle, horses and dogs, but in most, genetic cause remains unidentified. Until now, variety of causative genes has been identified, and depending on causative gene of the disorder, symptoms and mode of inheritance will vary. Recognized genes are GLRA1, GLRB, SLC6A5, GPHN and ARHGEF9. All of the named genes play an important role in glycine neurotransmission.
Glycine is an aminoacid and it is the smallest one of the 20 amino acids. Its principal function is as precursor to proteins and also as a building block to numerous natural products. It has an important role as an inhibitory neurotransmitter in the central nervous system, especially in the spinal cord, brainstem, and retina. Mutations in genes encoding glycine receptors or transporters cause malfunction of inhibitory glycinergic synapses in neuromotor pathways of the spinal cord and brainstem. This results in symptoms of startle disease or hyperekplexia, such as prominent startle reflex. Startle reflex is a brainstem reflectory reaction which acts in a way to protect vulnerable parts, as back of the neck (which causes whole-body startle) and the eyes (eye blink). Normally this reflex facilitates escape from sudden stimuli.
Irish Wolfhound Startle Disease (SD) is a disorder with a juvenile onset. Affected puppies start to exhibit clinical signs 5 to 7 days after birth in form of extensor rigidity and tremor. The symptoms cease when the animals are sleeping or are relaxed. The puppies are unable to stand and show rigid extended posture in all four limbs typical for this disorder. While sucking or during tube feeding, cyanosis (purple coloration of skin due to lack of oxygen in the tissue) occurs. Affected puppies are smaller and weight less than their unaffected littermates. Histopathological examination reveals consolidated and hemorrhagic lungs and dilated esophagus. The histopathological abnormalities appear as more severe in male puppies than in the female.
Irish Wolfhound Startle Disease (SD) is caused by a microdeletion in the gene SLC6A5 encoding the presynaptic glycine transporter GlyT2. The disorder is inherited as an autosomal recessive trait. Dog can be clear, carrier or affected. Healthy parents of an affected dog are obligate heterozygotes, and therefore carry one mutant allele. Heterozygotes have no symptoms. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Gill JL, Capper D, Vanbellinghen JF, Chung SK, Higgins RJ, Rees MI, Shelton GD, Harvey RJ. Startle disease in Irish wolfhounds associated with a microdeletion in the glycine transporter GlyT2 gene. Neurobiol Dis. 2011 Jul; 43(1):184-9.