HYPEREKPLEXIA, HEREDITARY (STARTLE DISEASE)

Scientific Background

Hereditary hyperekplexia is a disease seen in newborns, or even at birth, that is associated with a seizure-like, massive generalized increase in muscle tone. A tap on the glabella is a sufficient to act as a trigger. Clinically, the condition resembles seizures, but the EEG is normal. The symptoms usually weaken during infancy. However, the pronounced startle response with loss of tone often remains, which carries the risk of injury from falls. The nose-tapping test is a diagnostic test, which in children with hyperekplexia leads to extreme hyperextension of the neck, while healthy newborns do not show any significant reaction. Therapy may include treatment with benzodiazepines.

The disease is caused by pathogenic variants in genes for glycine receptors, including GLRA1, GLRB and SLC6A5. The proteins encoded by these genes are involved in glycine-dependent neurotransmission. The GLRA1 and GLRB genes encode the alpha1 and beta subunits, respectively, of the postsynaptic glycine receptor, and the SLC6A5 gene encodes the presynaptic glycine transporter type 2. In addition, pathogenic nucleotide changes in the ARHGEF9 and ATAD1 genes have been detected in patients with hyperekplexia. Pathogenic variants in one of these genes can lead to the impairment of inhibitory neurotransmission pathways or the stimulation of excitatory signaling pathways in the nerve cells.

References

Lee et al. 2017, J Mov Disord 10:53 / Mine et al. 2015, Dev Med Child Neurol 57:372 / Dreissen et al. 2012, Epilepsia 53 Suppl 7:3