September 14, 2020, e-Pearl of the Week: Hereditary hyperekplexia (HH)

Hereditary hyperekplexia associated with GLRA 1 gene mutation

Hereditary hyperekplexia (HH) presents with exaggerated startle response to tactile or acoustic stimuli followed by brief generalized stiffness causing apnea, aspiration, or frequent falls, with preserved consciousness.1 HH is a rare neonatal disorder with marked improvement in hypertonicity by age 3, but startle response persists, requiring lifelong treatment. Non-habituation of startle to tapping of glabella and philtrum is the clinical hallmark.4 Pathophysiology is mutation in the alpha-subunit of glycine receptors located in the brainstem. HH has also been rarely associated with other genetic mutations including SLC6A5, GLRB, GPHN, ARHGEF9.3 EEG may show myogenic artifact correlating with tonic spasms.2 Differentials include startle epilepsy, paroxysmal kinesigenic dyskinesia, and secondary hyperekplexia (brainstem lesions, thalamic infarct, and cervicomedullary compression). Treatment options include clonazepam, phenobarbital, diazepam.1 Long term clinical sequelae include hypnagogic myoclonus, facial laceration, and skull or limb fractures due to frequent attacks. Untreated HH leads to frequent falls resulting in development of cautious gait and a wheelchair bound state.

References

  1. Zhou L, Chillag KL, Nigro MA. Hyperekplexia: a treatable neurogenetic disease. Brain Dev 2002; 24:669–674.
  2. Gastaut H, Villeneuve A. The startle disease or hyperekplexia. Pathological surprise reaction. J Neurol Sci 1967;5: 523–42
  3. Tijssen MAJ, Vergouwe MN, van Dijk JG, et al. Major and minor form of hereditary hyperekplexia. Mov Disord. 2002;17:826–30.
  4. Praveen V, Patole SK, Whitehall JS. Hyperekplexia in neonates. Postgrad Med J 2001;77:570–572

Tanay Satarkar, Medical Graduate, Bukovinian State Medical University (Chernivtsi, Ukraine) and Faisal Khan, MD, DABSM, DABPN, Consultant Neurologist, Sugar Land Neurology and Sleep (Sugar Land, Texas)

Tanay Satarkar and Dr. Khan report no disclosures.