Hyperekplexia: A treatable neurogenetic disease

Lan Zhou, Kipp L. Chillag, Michael A. Nigro

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Hyperekplexia is primarily an autosomal dominant disease characterized by exaggerated startle reflex and neonatal hypertonia. It can be associated with, if untreated, sudden infant death from apnea or aspiration pneumonia and serious injuries and loss of ambulation from frequent falls. Different mutations in the α1 subunit of inhibitory glycine receptor (GLRA1) gene have been identified in many affected families. The most common mutation is Arg271 reported in at least 12 independent families. These mutations uncouple the ligand binding and chloride channel function of inhibitory glycine receptor and result in increased excitability in pontomedullary reticular neurons and abnormal spinal reciprocal inhibition. Three mouse models from spontaneous mutations in GLRA1 and β subunit of inhibitory glycine receptor (GLRB) genes and two transgenic mouse models are valuable for the study of the pathophysiology and the genotype-phenotype correlation of the disease. The disease caused by mutation in GLRB in mice supports the notion that human hyperekplexia with no detectable mutations in GLRA1 may harbor mutations in GLRB. Clonazepam, a gamma aminobutyric acid (GABA) receptor agonist, is highly effective and is the drug of choice. It enhances the GABA-gated chloride channel function and presumably compensates for the defective glycine-gated chloride channel in hyperekplexia. Recognition of the disease will lead to appropriate treatment and genetic counseling.

Original languageEnglish (US)
Pages (from-to)669-674
Number of pages6
JournalBrain and Development
Volume24
Issue number7
DOIs
StatePublished - Oct 1 2002

Fingerprint

Mutation
Glycine Receptors
Chloride Channels
Startle Reflex
Muscle Hypertonia
GABA Agonists
Clonazepam
Aspiration Pneumonia
GABA Receptors
Sudden Infant Death
Genetic Counseling
Genetic Association Studies
Apnea
Hyperekplexia
Glycine
gamma-Aminobutyric Acid
Transgenic Mice
Genes
Walking
Ligands

Keywords

  • Clonazepam
  • Gene mutation
  • Hyperekplexia
  • Inhibitory glycine receptor
  • Mouse model

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

Hyperekplexia : A treatable neurogenetic disease. / Zhou, Lan; Chillag, Kipp L.; Nigro, Michael A.

In: Brain and Development, Vol. 24, No. 7, 01.10.2002, p. 669-674.

Research output: Contribution to journalArticle

Zhou, Lan ; Chillag, Kipp L. ; Nigro, Michael A. / Hyperekplexia : A treatable neurogenetic disease. In: Brain and Development. 2002 ; Vol. 24, No. 7. pp. 669-674.
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