Hyperekplexia or Startle Disease (SLC6A5 gene)

Hyperecplexia or startle disease is a rare disorder in which non-epileptic seizures, triggered by sudden stimuli, produce muscle stiffness. This condition is usually caused by a genetic mutation in the SLC6A5 gene.

Symptoms

Hyperecplexia is a disease that manifests early in dogs, with symptoms commonly presenting as early as the first postnatal week. Common clinical signs include involuntary muscle contractions, stiffness and tremors, which can hinder the animal's normal mobility. Cyanosis and respiratory problems, such as apnea, have also been documented.

Disease Management

The use of anxiolytics such as clonazepam (benzodiazepine) can help control muscle spasms and increase the survival rate of the disease. Additionally, behavioral therapy is recommended, which aims to teach the dog to control its exaggerated response to sudden stimuli.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Hyperecplexia or startle disease is a rare disorder characterized by an exaggerated response to sudden stimuli such as noise or touch. The disease has been linked to a deletion in the SLC6A5 gene, responsible for encoding the presynaptic glycine transporter GlyT2. This transporter is crucial for maintaining a presynaptic reserve of glycine, necessary for inhibitory neurotransmission. Lack of synaptic glycine correlates with clinical symptoms of the disease.

Most affected breeds

Irish Wolfhound
Spanish greyhound

Bibliography

Gill JL, Capper D, Vanbellinghen JF,et al. Startle disease in Irish wolfhounds associated with a microdeletion in the glycine transporter GlyT2 gene. Neurobiol Dis. 2011 Jul;43(1):184-9.

Murphy SC, Recio A, de la Fuente C,et al. A glycine transporter SLC6A5 frameshift mutation causes startle disease in Spanish greyhounds. Hum Genet. 2019 May;138(5):509-513.