Hyperekplexia: abnormal startle response due to glycine receptor mutations.
BACKGROUND
Hyperekplexia is a rare but well-delineated clinical syndrome of pathological startle response and neonatal hypertonia. Many cases result from mutations in the alpha 1 subunit of the glycine receptor (GLRA 1).


METHODS
The clinical features, management and recent genetic studies of hyperekplexia are reviewed.


RESULTS
Diagnosis of the disorder should not be difficult, if one is aware of the syndrome. The treatment of first choice is with the benzodiazepine drug clonazepam, which often causes a dramatic although incomplete diminution of startle. Both recessive and dominant mutations in GLRA 1 have been found in affected individuals. The study of mouse mutants with startle phenotypes suggests that the remainder of cases may well be due to mutations in the beta subunit of the glycine receptor.


CONCLUSIONS
Hyperekplexia is the first human disease shown to result from mutations within a neurotransmitter gene. The demonstration of both dominant and recessive inheritance resulting from different mutations in the same gene is of considerable interest, as other neuropsychiatric disorders may result from mutations in ligand-gated ion channels. Mutation analysis of GLRA 1 is also likely to be useful as an aid to genetic counselling and in diagnostic evaluation of neonatal hypertonia.
Andrew
M
M
Department of Psychological Medicine, University of Wales College of Medicine, Cardiff.
Owen
M J
MJ
D003937:Diagnosis, Differential; D006801:Humans; D007231:Infant, Newborn; D009122:Muscle Hypertonia / Q000151:congenital* / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D018009:Receptors, Glycine / Q000235:genetics*; D013216:Reflex, Startle; D013577:Syndrome
D018009:Receptors, Glycine