The paroxysmal dyskinesias
Department of Neurology and Clinical Neurophysiology, Academic Medical Centre, University of Amsterdam, The Netherlands. Practical Neurology
05/2009; 9(2):102-9. DOI: 10.1136/jnnp.2009.172213
The paroxysmal dyskinesias are a challenging group of movement disorders characterised by painless dystonic and/or choreiform movements. Lack of familiarity with their features and a normal neurological examination between attacks frequently cause diagnostic delays, or even the diagnosis of a non-organic disorder. They are classified by their mode of triggering, and also by the duration and frequency of attacks, effectiveness of medication, and any associated syndromes. Four subtypes are recognised: paroxysmal kinesigenic dyskinesia induced by sudden movement; paroxysmal non-kinesigenic dyskinesia precipitated by for instance alcohol or caffeine; paroxysmal exercise-induced dyskinesia triggered by longer lasting activity; and paroxysmal hypnogenic dyskinesia occurring during sleep. Here we will summarise the characteristics of the subtypes, discuss the differential diagnosis, genetic aspects and pathophysiology, and give practical advice on the diagnostic work-up and treatment.
Available from: Roberto Erro
- "They last longer than attacks of PKD, often from 10 min to 1 h, but can last as long as 12 h. However, they are much more infrequent and occur only a few times a year (Mount and Reback, 1940; Bhatia, 1999; Lombroso and Fischman, 1999; Vercueil, 2000; Lee et al., 2004; Engelen and Tijssen, 2005; Friedman et al., 2009; Ghezzi et al., 2009; van Rootselaar et al., 2009; Benz et al., 2012; Pons et al., 2012). The gene responsible for PNKD was identified as the MR-1 gene in 2004, but it is now referred to as PNKD (Raskind et al., 1998; Lee et al., 2004; Rainier et al., 2004). "
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ABSTRACT: Paroxysmal dyskinesia can be subdivided into three clinical syndromes: paroxysmal kinesigenic dyskinesia or choreoathetosis, paroxysmal exercise-induced dyskinesia, and paroxysmal non-kinesigenic dyskinesia. Each subtype is associated with the known causative genes PRRT2, SLC2A1 and PNKD, respectively. Although separate screening studies have been carried out on each of the paroxysmal dyskinesia genes, to date there has been no large study across all genes in these disorders and little is known about the pathogenic mechanisms. We analysed all three genes (the whole coding regions of SLC2A1 and PRRT2 and exons one and two of PNKD) in a series of 145 families with paroxysmal dyskinesias as well as in a series of 53 patients with familial episodic ataxia and hemiplegic migraine to investigate the mutation frequency and type and the genetic and phenotypic spectrum. We examined the mRNA expression in brain regions to investigate how selective vulnerability could help explain the phenotypes and analysed the effect of mutations on patient-derived mRNA. Mutations in the PRRT2, SLC2A1 and PNKD genes were identified in 72 families in the entire study. In patients with paroxysmal movement disorders 68 families had mutations (47%) out of 145 patients. PRRT2 mutations were identified in 35% of patients, SLC2A1 mutations in 10%, PNKD in 2%. Two PRRT2 mutations were in familial hemiplegic migraine or episodic ataxia, one SLC2A1 family had episodic ataxia and one PNKD family had familial hemiplegic migraine alone. Several previously unreported mutations were identified. The phenotypes associated with PRRT2 mutations included a high frequency of migraine and hemiplegic migraine. SLC2A1 mutations were associated with variable phenotypes including paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, episodic ataxia and myotonia and we identified a novel PNKD gene deletion in familial hemiplegic migraine. We found that some PRRT2 loss-of-function mutations cause nonsense mediated decay, except when in the last exon, whereas missense mutations do not affect mRNA. In the PNKD family with a novel deletion, mRNA was truncated losing the C-terminus of PNKD-L and still likely loss-of-function, leading to a reduction of the inhibition of exocytosis, and similar to PRRT2, an increase in vesicle release. This study highlights the frequency, novel mutations and clinical and molecular spectrum of PRRT2, SLC2A1 and PNKD mutations as well as the phenotype–genotype overlap among these paroxysmal movement disorders. The investigation of paroxysmal movement disorders should always include the analysis of all three genes, but around half of our paroxysmal series remain genetically undefined implying that additional genes are yet to be identified.
Brain 12/2015; 138(12):3567-3580. DOI:10.1093/brain/awv310 · 9.20 Impact Factor
Available from: Marina A J Tijssen
- "Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterized by recurrent attacks of involuntary dystonia and/or chorea triggered by sudden movement. Most of the reported cases of PKD are familial and inherited in an autosomal dominant trait  . In a number of PKD pedigrees, patients and/or family members report infantile convulsions that fit the description of benign familial infantile seizures (BFIS) . "
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ABSTRACT: Paroxysmal kinesigenic dyskinesia (PKD) is characterized by involuntary dystonia and/or chorea triggered by a sudden movement. Cases are usually familial with an autosomal dominant inheritance. Hypotheses regarding the pathogenesis of PKD focus on the controversy whether PKD has a cortical or non-cortical origin. A combined familial trait of PKD and benign familial infantile seizures has been reported as the infantile convulsions and paroxysmal choreoathetosis (ICCA) syndrome. Here, we report a family diagnosed with ICCA syndrome with an Arg217STOP mutation. The index patient showed interictal EEG focal changes compatible with paroxysmal dystonic movements of his contralateral leg. This might support cortical involvement in PKD.
Parkinsonism & Related Disorders 03/2012; 18(5):645-8. DOI:10.1016/j.parkreldis.2012.03.006 · 3.97 Impact Factor
Available from: Koh-Ichiro Yoshiura
- "Most (40–70%) were familial cases in which PKC was transmitted in an autosomal dominant mode of inheritance with incomplete penetrance (Tomita et al. 1999; Valente et al. 2000). Males are affected more often than females, with an estimated ratio of 3–4:1 (Bhatia 1999). "
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ABSTRACT: Paroxysmal kinesigenic choreoathetosis (PKC) is a paroxysmal movement disorder of unknown cause. Although the PKC-critical region (PKCCR) has been assigned to the pericentromeric region of chromosome 16 by several studies of families from various ethnic backgrounds, the causative gene has not yet been identified. In the present study, we performed linkage and haplotype analysis in four new families with PKC, as well as an intensive polymerase chain reaction (PCR) based mutation analysis in seven families for a total of 1,563 exons from 157 genes mapped around the PKCCR. Consequently, the linkage/haplotype analysis revealed that PKC was assigned to a 24-cM segment between D16S3131 and D16S408, the result confirming the previously defined PKCCR, but being unable to narrow it down. Although the mutation analysis of the 157 genes was unsuccessful at identifying any mutations that were shared by patients from the seven families, two nonsynonymous substitutions, i.e., 6186C>A in exon 3 of SCNN1G and 45842A>G in exon 29 of ITGAL, which were segregated with the disease in Families C and F, respectively, were not observed in more than 400 normal controls. Thus, one of the two genes, SCNN1G and ITGAL, could be causative for PKC, but we were not able to find any other mutations that explain the PKC phenotype.
Journal of Human Genetics 02/2007; 52(4):334-41. DOI:10.1007/s10038-007-0116-7 · 2.46 Impact Factor
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