PRRT2 mutations and paroxysmal disorders. Issue 6 (9th February 2013)

• Record Type: Journal Article
• Authors: Méneret, A.; Gaudebout, C.; Riant, F.; Vidailhet, M.; Depienne, C.; Roze, E.
• Is Part Of: European journal of neurology. Volume 20:Issue 6(2013:Jun.)
• Page Start: 872
• Page End: 878
• Publication Date: 2013-02-09
• Subjects: Neurology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/ene.12104
• Languages: English
• ISSNs: 1351-5101

Abstract

<abstract abstract-type="main" xml:lang="en" id="ene12104-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>In the past year, mutations in the <italic>PRRT2</italic> gene have been identified in patients with paroxysmal kinesigenic dyskinesia and other paroxysmal disorders. We conducted a review of the literature on <italic>PRRT2</italic> mutation‐associated disorders. Our objectives were to describe the wide clinical spectrum associated with <italic>PRRT2</italic> mutations, and to present the current hypotheses on the underlying pathophysiology. <italic>PRRT2</italic> mutations are associated with a wide range of clinical syndromes: the various paroxysmal dyskinesias, infantile seizures, paroxysmal torticollis, migraine, hemiplegic migraine, episodic ataxia and even intellectual disability in the homozygous state. The <italic>PRRT2</italic> protein, through its interaction with SNAP‐25, could play a role in synaptic regulation in the cortex and the basal ganglia. The pathogenesis may be caused by <italic>PRRT2</italic> loss of function, which may induce synaptic deregulation and neuronal hyperexcitability. However, this does not explain the phenotypic variability, which is likely modulated by environmental factors, modifier genes or age‐dependent expression. The clinical spectrum of <italic>PRRT2</italic> mutations has expanded among paroxysmal disorders and beyond. Unraveling the molecular pathways linking the genetic defect to its clinical expression will be crucial for the diagnosis and treatment of these disorders.</p> </abstract>