rare paroxysmal movement disorder hyperekplexia true true MPheno.ontology MP:0005604 Hyperekplexia is characterised by an exaggeration of the normal startle response and has several genetic associations (GLRA1, GPHN, GLRB, ARHGEF9 and SLC6A5) all linked to dysfunction of the inhibitory glycinergic pathway in the nervous system. Symptoms are evident from the neonatal period or early infancy. Infants are commonly hypertonic, with rigidity, rather than spasticity, which is relieved by sleep. In response to normal touch, noise or any unexpected stimulus they can startle excessively with flexion of the limbs and retraction of the head. A gentle tap using the tip of the examiner's finger on the tip of the individual's nose should trigger an excessive startle that does not habituate with repeated nose taps. The startle may be a rapid jerk or series of jerks, which can mimic a myoclonic, tonic or tonic-clonic seizure. If an EEG is performed during an episode of stiffening, rhythmic muscle action potentials may be misdiagnosed as spikes. A severe startle response may be associated with apnoea and cyanosis. Severe attacks are particularly linked to SLC6A5 mutations and may be linked to sudden infant death in this syndrome. Severe attacks can be aborted by flexing the trunk and neck of the child - the Vigevano manouvre. Clonazepam may be effective in reducing the startle and increased tone. The symptoms tend to resolve after infancy, but adults may have increased startle-induced falls and/or experience nocturnal muscle jerks. There are rarer subtypes of hyperekplexia associated with mutations in the gephyrin and collybistin genes in which epilepsy can co-exist. The onset of excessive startle in later childhood or adult life may be associated with development of autoantibodies to the glycine receptor. https://www.ncbi.nlm.nih.gov/books/NBK2609/ disorder characterized by pathologic startle responses, protective reactions to unanticipated, potentially threatening, stimuli of any type, particularly auditory https://rarediseases.org/rare-diseases/hyperekplexia/