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Hyperekplexia: Treatment of a Severe Phenotype and Review of the Literature

Published online by Cambridge University Press:  02 December 2014

Aleksandra Mineyko ,
Sharon Whiting  and
Gail E. Graham
Aleksandra Mineyko*
Affiliation:
Division of Neurology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
Sharon Whiting
Affiliation:
Division of Neurology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
Gail E. Graham
Affiliation:
Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
*
Division of Neurology, Department of Pediatrics, Alberta Children's Hospital, 2888 Shaganappi Trail NW, Calgary, Alberta, T3B 6A8, Canada
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Abstract

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Hyperekplexia is a rare disorder caused by autosomal dominant or recessive modes of inheritance and characterized by episodes of exaggerated startle. Five causative genes have been identified to date. The syndrome has been recognized for decades and due to its rarity, the literature contains mostly descriptive reports, many early studies lacking molecular genetic diagnoses. A spectrum of clinical severity exists. Severe cases can lead to neonatal cardiac arrest and death during an episode, an outcome prevented by early diagnosis and clinical vigilance. Large treatment studies are not feasible, so therapeutic measures continue to be empiric. A marked response to clonazepam is often reported but refractory cases exist. Herein we report the clinical course and treatment response of a severely affected infant homozygous for an SLC6A5 nonsense mutation and review the literature summarizing the history and genetic understanding of the disease as well as the described comorbidities and treatment options.

Résumé:

Résumé:

L’hyperekplexie est une maladie caracterises par des episodes de reaction exageree de sursaut et dont le mode d’heredite peut etre dominant ou recessif. A ce jour, cinq genes differents ont ete identifies. Le syndrome est connu depuis plusieurs dizaines d’annees et, a cause de sa rarete, la litterature fait etat surtout de descriptions de cas dont plusieurs, surtout les premieres, ne comportent pas de diagnostic moleculaire. La severite clinique est tres variable et, chez les cas severes, la maladie peut entrainer un arret cardiaque dans la periode neonatale et le deces, ce qui peut etre prevenu par un diagnostic precoce et une surveillance clinique. Son traitement demeure empirique parce qu’il n’est pas possible d’effectuer de grandes etudes sur ce sujet. Bien qu’une excellente reponse au clonazepam soit souvent rapportee, il existe des cas resistants a ce traitement. Nous rapportons ici l’evolution clinique et la reponse therapeutique chez un bebe severement atteint, homozygote pour une mutation non-sens de SLC6A5, et nous revoyons la litterature portant sur l’histoire et l’explication genetique de la maladie ainsi que sur les comorbidites decrites et les options therapeutiques.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 38 , Issue 3 , May 2011 , pp. 411 - 416
Copyright
Copyright © The Canadian Journal of Neurological 2011

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