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.
Keywords
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Article info
Publication history
Accepted:
May 29,
2002
Received:
April 23,
2002
Identification
Copyright
© 2002 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
