Genetics and characteristics
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, the genetic cause remains unidentified. Until now, a variety of causative genes has been identified, and depending on the 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 amino acid and it is the smallest one of the 20 amino acids. Its principal function is as a 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. The startle reflex is a brainstem reflective reaction that acts in a way to protect vulnerable parts, such as the 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 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 weigh less than their unaffected littermates. Histopathological examination reveals consolidated and hemorrhagic lungs and dilated esophagus. The histopathological abnormalities appear more severe in male puppies than in females. 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. A 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.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
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.