A novel GLRA1 mutation associated with an atypical hyperekplexia phenotype

Mary L. Gregory, Greg F. Guzauskas, Terence S. Edgar, Kate B. Clarkson, Anand K. Srivastava, Kenton R. Holden

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Hyperekplexia (MIM #149400) is a rare neurological disorder characterized by an exaggerated startle response, infantile hypertonia and hyperreflexia without spasticity, a hesitant gait that usually improves by 3 years of age, and nocturnal myoclonus. Familial hyperekplexia is usually autosomal dominant resulting from mutations in the inhibitory glycine receptor subunit alpha 1 (GLRA1) gene on chromosome 5q. We identified a 3-generation family with progressively severe phenotypes of hyperekplexia. All affected family members were found to be heterozygous for a novel arginine271proline mutation in GLRA1. Long-term follow-up of the affected members of the third generation, now aged 6 and 7 years, reveals enhanced startle responses and persistent hypertonia of the extremities without clonus or a catch, tight heel cords and abnormal toe-walking gait, and plantar flexor reflexes. The 7-year-old child recently reponded well to a benzodiazepine. Future studies are warranted to examine whether this new missense mutation is solely responsible for this atypical phenotype.

Original languageEnglish (US)
Pages (from-to)1433-1438
Number of pages6
JournalJournal of Child Neurology
Issue number12
StatePublished - 2008


  • GLRA1
  • Gene mutation
  • Hyperekplexia
  • Neurodevelopment
  • Startle
  • Stiff-boy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

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