Skip to main content

Advertisement

SpringerLink
Log in

Paroxysmal Movement Disorders: Recent Advances

  • Movement Disorders (T. Simuni, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Recent advancements in next-generation sequencing (NGS) have enabled techniques such as whole exome sequencing (WES) and whole genome sequencing (WGS) to be used to study paroxysmal movement disorders (PMDs). This review summarizes how the recent genetic advances have altered our understanding of the pathophysiology and treatment of the PMDs. Recently described disease entities are also discussed.

Recent Findings

With the recognition of the phenotypic and genotypic heterogeneity that occurs amongst the PMDs, an increasing number of gene mutations are now implicated to cause the disorders. PMDs can also occur as part of a complex phenotype. The increasing complexity of PMDs challenges the way we view and classify them.

Summary

The identification of new causative genes and their genotype-phenotype correlation will shed more light on the underlying pathophysiology and will facilitate development of genetic testing guidelines and identification of novel drug targets for PMDs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Demirkiran M, Jankovic J. Paroxysmal dyskinesias: clinical features and classification. Ann Neurol. 1995;38(4):571–9.

    CAS  PubMed  Google Scholar 

  2. Meneret A, Roze E. Paroxysmal movement disorders: an update. Rev Neurol. 2016;172(8–9):433–45.

    CAS  PubMed  Google Scholar 

  3. Zhang XJ, Xu ZY, Wu YC, Tan EK. Paroxysmal movement disorders: recent advances and proposal of a classification system. Parkinsonism Relat Disord. 2019;59:131–139. https://doi.org/10.1016/j.parkreldis.2019.02.021

    Google Scholar 

  4. • Liu XR, Huang D, Wang J, Wang YF, Sun H, Tang B, et al. Paroxysmal hypnogenic dyskinesia is associated with mutations in the PRRT2 gene.. Neurol Genet. 2016;2(2):e66. https://doi.org/10.1212/NXG.0000000000000066. This paper describes two individuals with paroxysmal hypnogenic dyskinesia with PRRT2 mutations detected):e66.

    PubMed  PubMed Central  Google Scholar 

  5. Choi KD, Choi JH. Episodic ataxias: clinical and genetic features. J Mov Disord. 2016;9(3):129–35.

    PubMed  PubMed Central  Google Scholar 

  6. Cader MZ, Steckley JL, Dyment DA, McLachlan RS, Ebers GC. A genome-wide screen and linkage mapping for a large pedigree with episodic ataxia. Neurology. 2005;65(1):156–8.

    CAS  PubMed  Google Scholar 

  7. Kerber KA, Jen JC, Lee H, Nelson SF, Baloh RW. A new episodic ataxia syndrome with linkage to chromosome 19q13. Arch Neurol. 2007;64(5):749–52.

    PubMed  Google Scholar 

  8. Tomita H, Nagamitsu S, Wakui K, Fukushima Y, Yamada K, Sadamatsu M, et al. Paroxysmal kinesigenic choreoathetosis locus maps to chromosome 16p11.2-q12.1. Am J Hum Genet. 1999;65(6):1688–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Wang JL, Cao L, Li XH, Hu ZM, Li JD, Zhang JG, et al. Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesias. Brain. 2011;134(Pt 12):3493–501.

    PubMed  Google Scholar 

  10. Chen WJ, Lin Y, Xiong ZQ, Wei W, Ni W, Tan GH, et al. Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia. Nat Genet. 2011;43(12):1252–5.

    CAS  PubMed  Google Scholar 

  11. McGovern EM, Roze E, Counihan TJ. The expanding spectrum of paroxysmal movement disorders: update from clinical features to therapeutics. Curr Opin Neurol. 2018;31(4):491–7.

    PubMed  Google Scholar 

  12. Heron SE, Grinton BE, Kivity S, Afawi Z, Zuberi SM, Hughes JN, et al. PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome. Am J Hum Genet. 2012;90(1):152–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Ebrahimi-Fakhari D, Saffari A, Westenberger A, Klein C. The evolving spectrum of PRRT2-associated paroxysmal diseases. Brain J Neurol. 2015;138(Pt 12):3476–95.

    Google Scholar 

  14. Delcourt M, Riant F, Mancini J, Milh M, Navarro V, Roze E, et al. Severe phenotypic spectrum of biallelic mutations in PRRT2 gene. J Neurol Neurosurg Psychiatry. 2015;86(7):782–5.

    PubMed  Google Scholar 

  15. • Gardella E, Becker F, Moller RS, Schubert J, Lemke JR, Larsen LH, et al. Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation. Ann Neurol. 2016;79(3):428–36 Mutations in SCN8A are shown to result in the phenotype of benign infantile seizures and paroxysmal dyskinesia.

    CAS  PubMed  Google Scholar 

  16. •• Tian WT, Huang XJ, Mao X, Liu Q, Liu XL, Zeng S, et al. Proline-rich transmembrane protein 2-negative paroxysmal kinesigenic dyskinesia: clinical and genetic analyses of 163 patients. Mov Disord. 2018;33(3):459–67 A large cohort of PRRT2-negative PKD subjects undergo extensive genetic testing with new genetic mutations and genes implicated in the disorder.

    CAS  PubMed  Google Scholar 

  17. Yin XM, Lin JH, Cao L, Zhang TM, Zeng S, Zhang KL, et al. Familial paroxysmal kinesigenic dyskinesia is associated with mutations in the KCNA1 gene. Hum Mol Genet. 2018;27(4):625–37.

    CAS  PubMed  Google Scholar 

  18. Kostic VS, Petrovic IN. Brain calcification and movement disorders. Curr Neurol Neurosci Rep. 2017;17(1):2.

    PubMed  Google Scholar 

  19. Jiang YL, Yuan F, Yang Y, Sun XL, Song L, Jiang W. CHRNA4 variant causes paroxysmal kinesigenic dyskinesia and genetic epilepsy with febrile seizures plus? Seizure. 2018;56:88–91.

    PubMed  Google Scholar 

  20. Weber YG, Storch A, Wuttke TV, Brockmann K, Kempfle J, Maljevic S, et al. GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak. J Clin Invest. 2008;118(6):2157–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Gras D, Roze E, Caillet S, Meneret A, Doummar D, Billette de Villemeur T, et al. GLUT1 deficiency syndrome: an update. Rev Neurol. 2014;170(2):91–9.

    CAS  PubMed  Google Scholar 

  22. Leen WG, Klepper J, Verbeek MM, Leferink M, Hofste T, van Engelen BG, et al. Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder. Brain J Neurol. 2010;133(Pt 3):655–70.

    Google Scholar 

  23. Rotstein M, Engelstad K, Yang H, Wang D, Levy B, Chung WK, et al. Glut1 deficiency: inheritance pattern determined by haploinsufficiency. Ann Neurol. 2010;68(6):955–8.

    PubMed  PubMed Central  Google Scholar 

  24. Friedman J, Feigenbaum A, Chuang N, Silhavy J, Gleeson JG. Pyruvate dehydrogenase complex-E2 deficiency causes paroxysmal exercise-induced dyskinesia. Neurology. 2017;89(22):2297–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Olgiati S, Skorvanek M, Quadri M, Minneboo M, Graafland J, Breedveld GJ, et al. Paroxysmal exercise-induced dystonia within the phenotypic spectrum of ECHS1 deficiency. Mov Disord. 2016;31(7):1041–8. https://doi.org/10.1002/mds.26610.

    CAS  PubMed  Google Scholar 

  26. •• Erro R, Bhatia KP. Unravelling of the paroxysmal dyskinesias. J Neurol Neurosurg Psychiatry. 2018. A review article discussing genetic advances and limitations in the current classification system used in the paroxysmal dyskinesias.

  27. Leuzzi V, Di Sabato ML, Deodato F, Rizzo C, Boenzi S, Carducci C, et al. Vigabatrin improves paroxysmal dystonia in succinic semialdehyde dehydrogenase deficiency. Neurology. 2007;68(16):1320–1.

    CAS  PubMed  Google Scholar 

  28. Rainier S, Thomas D, Tokarz D, Ming L, Bui M, Plein E, et al. Myofibrillogenesis regulator 1 gene mutations cause paroxysmal dystonic choreoathetosis. Arch Neurol. 2004;61(7):1025–9.

    PubMed  Google Scholar 

  29. Chang FCF, Westenberger A, Dale RC, Smith M, Pall HS, Perez-Dueñas B, et al. Phenotypic insights intoADCY5-associated disease. Mov Disord. 2016;31(7):1033–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Breen DP, Högl B, Fasano A, Trenkwalder C, Lang AE. Sleep-related motor and behavioral disorders: recent advances and new entities. Mov Disord. 2018;33(7):1042–55.

    PubMed  Google Scholar 

  31. Carecchio M, Mencacci NE, Iodice A, Pons R, Panteghini C, Zorzi G, et al. ADCY5-related movement disorders: frequency, disease course and phenotypic variability in a cohort of paediatric patients. Parkinsonism Relat Disord. 2017;41:37–43.

    PubMed  PubMed Central  Google Scholar 

  32. Browne DL, Gancher ST, Nutt JG, Brunt ER, Smith EA, Kramer P, et al. Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. Nat Genet. 1994;8(2):136–40.

    CAS  PubMed  Google Scholar 

  33. Graves TD, Cha YH, Hahn AF, Barohn R, Salajegheh MK, Griggs RC, et al. Episodic ataxia type 1: clinical characterization, quality of life and genotype-phenotype correlation. Brain. 2014;137(Pt 4):1009–18.

    PubMed  PubMed Central  Google Scholar 

  34. D'Adamo MC, Hasan S, Guglielmi L, Servettini I, Cenciarini M, Catacuzzeno L, et al. New insights into the pathogenesis and therapeutics of episodic ataxia type 1. Front Cell Neurosci. 2015;9:317.

    PubMed  PubMed Central  Google Scholar 

  35. Graves TD, Rajakulendran S, Zuberi SM, Morris HR, Schorge S, Hanna MG, et al. Nongenetic factors influence severity of episodic ataxia type 1 in monozygotic twins. Neurology. 2010;75(4):367–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Nachbauer W, Nocker M, Karner E, Stankovic I, Unterberger I, Eigentler A, et al. Episodic ataxia type 2: phenotype characteristics of a novel CACNA1A mutation and review of the literature. J Neurol. 2014;261(5):983–91.

    CAS  PubMed  Google Scholar 

  37. Escayg A, De Waard M, Lee DD, Bichet D, Wolf P, Mayer T, et al. Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am J Hum Genet. 2000;66(5):1531–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Jen JC, Wan J, Palos TP, Howard BD, Baloh RW. Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures. Neurology. 2005;65(4):529–34.

    CAS  PubMed  Google Scholar 

  39. de Vries B, Mamsa H, Stam AH, Wan J, Bakker SL, Vanmolkot KR, et al. Episodic ataxia associated with EAAT1 mutation C186S affecting glutamate reuptake. Arch Neurol. 2009;66(1):97–101.

    PubMed  Google Scholar 

  40. Conroy J, McGettigan P, Murphy R, Webb D, Murphy SM, McCoy B, et al. A novel locus for episodic ataxia: UBR4 the likely candidate. Eur J Hum Genet. 2014;22(4):505–10.

    CAS  PubMed  Google Scholar 

  41. Schesny M, Joncourt F, Tarnutzer AA. Acetazolamide-responsive episodic ataxia linked to novel splice site variant in FGF14 gene. Cerebellum 2019.

  42. Choquet K, La Piana R, Brais B. A novel frameshift mutation in FGF14 causes an autosomal dominant episodic ataxia. Neurogenetics. 2015;16(3):233–6.

    CAS  PubMed  Google Scholar 

  43. Liu Z, Wadsworth P, Singh AK, Chen H, Wang P, Folorunso O, et al. Identification of peptidomimetics as novel chemical probes modulating fibroblast growth factor 14 (FGF14) and voltage-gated sodium channel 1.6 (Nav1.6) protein-protein interactions. Bioorg Med Chem Lett. 2019;29(3):413–9.

    CAS  PubMed  Google Scholar 

  44. • Pablo JL, Pitt GS. FGF14 is a regulator of KCNQ2/3 channels. Proc Natl Acad Sci U S A. 2017;114(1):154–9 A paper elucidating the function of FGF14 as a potassium channel regulator.

    CAS  PubMed  Google Scholar 

  45. Dale RC, Gardiner A, Antony J, Houlden H. Familial PRRT2 mutation with heterogeneous paroxysmal disorders including paroxysmal torticollis and hemiplegic migraine. Dev Med Child Neurol. 2012;54(10):958–60.

    PubMed  Google Scholar 

  46. Hao SS, Feng YH, Zhang GB, Wang AP, Wang F, Wang P. Neuropathophysiology of paroxysmal, systemic, and other related movement disorders. Eur Rev Med Pharmacol Sci. 2015;19(13):2452–60.

    PubMed  Google Scholar 

  47. Chen DH, Meneret A, Friedman JR, Korvatska O, Gad A, Bonkowski ES, et al. ADCY5-related dyskinesia: broader spectrum and genotype-phenotype correlations. Neurology. 2015;85(23):2026–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Raj Kumar K, Fung VS. ADCY5 identified as a novel cause of benign hereditary chorea. Mov Disord. 2015;30(13):1726.

    PubMed  Google Scholar 

  49. Barrett MJ, Williams ES, Chambers C, Dhamija R. Autosomal recessive inheritance of ADCY5-related generalized dystonia and myoclonus. Neurol Genet. 2017;3(5):193.

    PubMed  PubMed Central  Google Scholar 

  50. Douglas AG, Andreoletti G, Talbot K, Hammans SR, Singh J, Whitney A, et al. ADCY5-related dyskinesia presenting as familial myoclonus-dystonia. Neurogenetics. 2017;18(2):111–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Waalkens AJE, Vansenne F, van der Hout AH, Zutt R, Mourmans J, Tolosa E, et al. Expanding the ADCY5 phenotype toward spastic paraparesis: a mutation in the M2 domain. Neurol Genet. 2018;4(1):e214.

    PubMed  PubMed Central  Google Scholar 

  52. Gardella E, Marini C, Trivisano M, Fitzgerald MP, Alber M, Howell KB, et al. The phenotype of SCN8A developmental and epileptic encephalopathy. Neurology. 2018;91(12):e1112–e24.

    PubMed  Google Scholar 

  53. Veeramah KR, O'Brien JE, Meisler MH, Cheng X, Dib-Hajj SD, Waxman SG, et al. De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP. Am J Hum Genet. 2012;90(3):502–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Wagnon JL, Mencacci NE, Barker BS, Wengert ER, Bhatia KP, Balint B, et al. Partial loss-of-function of sodium channel SCN8A in familial isolated myoclonus. Hum Mutat. 2018;39(7):965–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Tsai MH, Chan CK, Chang YC, Yu YT, Chuang ST, Fan WL, et al. DEPDC5 mutations in familial and sporadic focal epilepsy. Clin Genet. 2017;92(4):397–404.

    CAS  PubMed  Google Scholar 

  56. Schwartz CE, May MM, Carpenter NJ, Rogers RC, Martin J, Bialer MG, et al. Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene. Am J Hum Genet. 2005;77(1):41–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Lemos RR, Ramos EM, Legati A, Nicolas G, Jenkinson EM, Livingston JH, et al. Update and mutational analysis of SLC20A2: a major cause of primary familial brain calcification. Hum Mutat. 2015;36(5):489–95.

    CAS  PubMed  Google Scholar 

  58. Tabarki B, AlMajhad N, AlHashem A, Shaheen R, Alkuraya FS. Homozygous KCNMA1 mutation as a cause of cerebellar atrophy, developmental delay and seizures. Hum Genet. 2016;135(11):1295–8.

    CAS  PubMed  Google Scholar 

  59. Leniger T, Kananura C, Hufnagel A, Bertrand S, Bertrand D, Steinlein OK. A new Chrna4 mutation with low penetrance in nocturnal frontal lobe epilepsy. Epilepsia. 2003;44(7):981–5.

    CAS  PubMed  Google Scholar 

  60. Pascual JM, Ronen GM. Glucose transporter type I deficiency (G1D) at 25 (1990-2015): presumptions, facts, and the lives of persons with this rare disease. Pediatr Neurol. 2015;53(5):379–93.

    PubMed  PubMed Central  Google Scholar 

  61. Steinberger D, Weber Y, Korinthenberg R, Deuschl G, Benecke R, Martinius J, et al. High penetrance and pronounced variation in expressivity of GCH1 mutations in five families with dopa-responsive dystonia. Ann Neurol. 1998;43(5):634–9.

    CAS  PubMed  Google Scholar 

  62. Cobb SA, Wider C, Ross OA, Mata IF, Adler CH, Rajput A, et al. GCH1 in early-onset Parkinson's disease. Mov Disord. 2009;24(14):2070–5.

    PubMed  Google Scholar 

  63. Heinzen EL, Swoboda KJ, Hitomi Y, Gurrieri F, Nicole S, de Vries B, et al. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nat Genet. 2012;44(9):1030–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Rosewich H, Thiele H, Ohlenbusch A, Maschke U, Altmuller J, Frommolt P, et al. Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study. Lancet Neurol. 2012;11(9):764–73.

    CAS  PubMed  Google Scholar 

  65. Demos MK, van Karnebeek CD, Ross CJ, Adam S, Shen Y, Zhan SH, et al. A novel recurrent mutation in ATP1A3 causes CAPOS syndrome. Orphanet J Rare Dis. 2014;9:15.

    PubMed  PubMed Central  Google Scholar 

  66. Brashear A, Dobyns WB, de Carvalho Aguiar P, Borg M, Frijns CJ, Gollamudi S, et al. The phenotypic spectrum of rapid-onset dystonia-parkinsonism (RDP) and mutations in the ATP1A3 gene. Brain. 2007;130(Pt 3):828–35.

    PubMed  Google Scholar 

  67. Dard R, Mignot C, Durr A, Lesca G, Sanlaville D, Roze E, et al. Relapsing encephalopathy with cerebellar ataxia related to an ATP1A3 mutation. Dev Med Child Neurol. 2015;57(12):1183–6.

    PubMed  Google Scholar 

  68. Sweadner KJ, Toro C, Whitlow CT, Snively BM, Cook JF, Ozelius LJ, et al. ATP1A3 mutation in adult rapid-onset ataxia. PLoS One. 2016;11(3):e0151429.

    PubMed  PubMed Central  Google Scholar 

  69. Paciorkowski AR, McDaniel SS, Jansen LA, Tully H, Tuttle E, Ghoneim DH, et al. Novel mutations in ATP1A3 associated with catastrophic early life epilepsy, episodic prolonged apnea, and postnatal microcephaly. Epilepsia. 2015;56(3):422–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Ciara E, Rokicki D, Halat P, Karkucinska-Wieckowska A, Piekutowska-Abramczuk D, Mayr J, et al. Difficulties in recognition of pyruvate dehydrogenase complex deficiency on the basis of clinical and biochemical features. The role of next-generation sequencing. Mol Genet Metab Rep. 2016;7:70–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Schiff M, Mine M, Brivet M, Marsac C, Elmaleh-Berges M, Evrard P, et al. Leigh’s disease due to a new mutation in the PDHX gene. Ann Neurol. 2006;59(4):709–14.

    CAS  PubMed  Google Scholar 

  72. Head RA, Brown RM, Zolkipli Z, Shahdadpuri R, King MD, Clayton PT, et al. Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency. Ann Neurol. 2005;58(2):234–41.

    CAS  PubMed  Google Scholar 

  73. Set KK, Ghosh D, Huq AHM, Luat AF. Episodic ataxia type 1 (K-channelopathy) manifesting as paroxysmal nonkinesogenic dyskinesia: expanding the phenotype. Mov Disord Clin Pract. 2017;4(5):784–6.

    PubMed  PubMed Central  Google Scholar 

  74. Ducros A, Denier C, Joutel A, Vahedi K, Michel A, Darcel F, et al. Recurrence of the T666M calcium channel CACNA1A gene mutation in familial hemiplegic migraine with progressive cerebellar ataxia. Am J Hum Genet. 1999;64(1):89–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat Genet. 1997;15(1):62–9.

    CAS  PubMed  Google Scholar 

  76. Vila-Pueyo M, Gene GG, Flotats-Bastardes M, Elorza X, Sintas C, Valverde MA, et al. A loss-of-function CACNA1A mutation causing benign paroxysmal torticollis of infancy. Eur J Paediatr Neurol. 2014;18(3):430–3.

    PubMed  Google Scholar 

  77. Damaj L, Lupien-Meilleur A, Lortie A, Riou E, Ospina LH, Gagnon L, et al. CACNA1A haploinsufficiency causes cognitive impairment, autism and epileptic encephalopathy with mild cerebellar symptoms. Eur J Hum Genet. 2015;23(11):1505–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Lv Y, Wang Z, Liu C, Cui L. Identification of a novel CACNA1A mutation in a Chinese family with autosomal recessive progressive myoclonic epilepsy. Neuropsychiatr Dis Treat. 2017;13:2631–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Jen JC, Wan J. Episodic ataxias. 2018;155:205–15.

  80. Kovermann P, Hessel M, Kortzak D, Jen JC, Koch J, Fahlke C, et al. Impaired K+ binding to glial glutamate transporter EAAT1 in migraine. Sci Rep. 2017;7(1):13913.

    PubMed  PubMed Central  Google Scholar 

  81. Miura S, Kosaka K, Fujioka R, Uchiyama Y, Shimojo T, Morikawa T, et al. Spinocerebellar ataxia 27 with a novel nonsense variant (Lys177X) in FGF14. Eur J Med Genet. 2019;62(3):172–6. https://doi.org/10.1016/j.ejmg.2018.07.005

    PubMed  Google Scholar 

  82. Gambardella A, Annesi G, De Fusco M, Patrignani A, Aguglia U, Annesi F, et al. A new locus for autosomal dominant nocturnal frontal lobe epilepsy maps to chromosome 1. Neurology. 2000;55(10):1467–71.

    CAS  PubMed  Google Scholar 

  83. Tinuper P, Bisulli F, Cross JH, Hesdorffer D, Kahane P, Nobili L, et al. Definition and diagnostic criteria of sleep-related hypermotor epilepsy. Neurology. 2016;86(19):1834–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. •• Morales-Briceño H, Chang FCF, Wong C, Mallawaarachchi A, Wolfe N, Pellegrino da Silva R, et al. Paroxysmal dyskinesias with drowsiness and thalamic lesions in GABA transaminase deficiency. Neurology. 2019;92(2):94–7 New disease entity of GABA transaminase deficiecy associated with the phenotype of paroxysmal dyskinesias occuring with drowsiness.

    PubMed  Google Scholar 

  85. Koenig MK, Hodgeman R, Riviello JJ, Chung W, Bain J, Chiriboga CA, et al. Phenotype of GABA-transaminase deficiency. Neurology. 2017;88(20):1919–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Waln O, Jankovic J. Paroxysmal movement disorders. Neurol Clin. 2015;33(1):137–52.

    PubMed  Google Scholar 

  87. •• Erro R, Bhatia KP, Espay AJ, Striano P. The epileptic and nonepileptic spectrum of paroxysmal dyskinesias: Channelopathies, synaptopathies, and transportopathies. Mov Disord. 2017;32(3):310–8. https://doi.org/10.1002/mds.26901. A review paper of the different pathogenic mechanisms implicated in the paroxysmal dyskinesias.

    PubMed  PubMed Central  Google Scholar 

  88. •• Fruscione F, Valente P, Sterlini B, Romei A, Baldassari S, Fadda M, et al. PRRT2 controls neuronal excitability by negatively modulating Na+ channel 1.2/1.6 activity. Brain. 2018;141(4):1000–16 A recently published paper shedding further light into PRRT2 function as a modulator of voltage-gated sodium channel activity.

    PubMed  PubMed Central  Google Scholar 

  89. Tan GH, Liu YY, Wang L, Li K, Zhang ZQ, Li HF, et al. PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by regulating synaptic transmission in cerebellum. Cell Res. 2018;28(1):90–110.

    CAS  PubMed  Google Scholar 

  90. Coleman J, Jouannot O, Ramakrishnan SK, Zanetti MN, Wang J, Salpietro V, et al. PRRT2 regulates synaptic fusion by directly modulating SNARE complex assembly. Cell Rep. 2018;22(3):820–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Yan H, Pablo JL, Pitt GS. FGF14 regulates presynaptic Ca2+ channels and synaptic transmission. Cell Rep. 2013;4(1):66–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Kim JH, Kim DW, Kim JB, Suh SI, Koh SB. Thalamic involvement in paroxysmal kinesigenic dyskinesia: a combined structural and diffusion tensor MRI analysis. Hum Brain Mapp. 2015;36(4):1429–41.

    PubMed  Google Scholar 

  93. Long Z, Xu Q, Miao HH, Yu Y, Ding MP, Chen H, et al. Thalamocortical dysconnectivity in paroxysmal kinesigenic dyskinesia: combining functional magnetic resonance imaging and diffusion tensor imaging. Mov Disord. 2017;32(4):592–600.

    CAS  PubMed  Google Scholar 

  94. Poston KL, Eidelberg D. Functional brain networks and abnormal connectivity in the movement disorders. Neuroimage. 2012;62(4):2261–70.

    PubMed  Google Scholar 

  95. Mark MD, Maejima T, Kuckelsberg D, Yoo JW, Hyde RA, Shah V, et al. Delayed postnatal loss of P/Q-type calcium channels recapitulates the absence epilepsy, dyskinesia, and ataxia phenotypes of genomic Cacna1a mutations. J Neurosci. 2011;31(11):4311–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Silveira-Moriyama L, Kovac S, Kurian MA, Houlden H, Lees AJ, Walker MC, et al. Phenotypes, genotypes, and the management of paroxysmal movement disorders. Dev Med Child Neurol. 2018;60(6):559–65.

    PubMed  Google Scholar 

  97. •• Montaut S, Tranchant C, Drouot N, Rudolf G, Guissart C, Tarabeux J, et al. Assessment of a targeted gene panel for identification of genes associated with movement disorders. JAMA Neurology. 2018;75(10):1234. This study evaluated the feasibiity of a targeted gene panel for the diagnosis of movement disorders.–45.

    PubMed  PubMed Central  Google Scholar 

  98. Bhatia KP. Paroxysmal dyskinesias. Mov Disord. 2011;26(6):1157–65.

    PubMed  Google Scholar 

  99. Labate A, Tarantino P, Viri M, Mumoli L, Gagliardi M, Romeo A, et al. Homozygous c.649dupC mutation in PRRT2 worsens the BFIS/PKD phenotype with mental retardation, episodic ataxia, and absences. Epilepsia. 2012;53(12):e196–9.

    PubMed  Google Scholar 

  100. Li F, Lin ZD, Hu Y, Li W, Xue CC, Poonit ND. Lamotrigine monotherapy for paroxysmal kinesigenic dyskinesia in children. Seizure. 2016;37:41–4.

    PubMed  Google Scholar 

  101. Horisawa S, Sumi M, Akagawa H, Kawamata T, Taira T. Thalamotomy for paroxysmal kinesigenic dyskinesias in a multiplex family. Eur J Neurol. 2017;24(10):e71–e2.

    CAS  PubMed  Google Scholar 

  102. Synofzik M, Schicks J, Lindig T, Biskup S, Schmidt T, Hansel J, et al. Acetazolamide-responsive exercise-induced episodic ataxia associated with a novel homozygous DARS2 mutation. J Med Genet. 2011;48(10):713–5.

    CAS  PubMed  Google Scholar 

  103. Alter AS, Engelstad K, Hinton VJ, Montes J, Pearson TS, Akman CI, et al. Long-term clinical course of Glut1 deficiency syndrome. J Child Neurol. 2015;30(2):160–9.

    PubMed  Google Scholar 

  104. McWilliam CA, Ridout CK, Brown RM, McWilliam RC, Tolmie J, Brown GK. Pyruvate dehydrogenase E2 deficiency: a potentially treatable cause of episodic dystonia. Eur J Paediatr Neurol. 2010;14(4):349–53.

    PubMed  Google Scholar 

  105. Leen WG, Mewasingh L, Verbeek MM, Kamsteeg EJ, van de Warrenburg BP, Willemsen MA. Movement disorders in GLUT1 deficiency syndrome respond to the modified Atkins diet. Mov Disord. 2013;28(10):1439–42.

    PubMed  Google Scholar 

  106. Mochel F, Hainque E, Gras D, Adanyeguh IM, Caillet S, Heron B, et al. Triheptanoin dramatically reduces paroxysmal motor disorder in patients with GLUT1 deficiency. J Neurol Neurosurg Psychiatry. 2016;87(5):550–3.

    PubMed  Google Scholar 

  107. Mahajan A, Constantinou J, Sidiropoulos C. ECHS1 deficiency-associated paroxysmal exercise-induced dyskinesias: case presentation and initial benefit of intervention. J Neurol. 2017;264(1):185–7.

    PubMed  Google Scholar 

  108. Dale RC, Melchers A, Fung VS, Grattan-Smith P, Houlden H, Earl J. Familial paroxysmal exercise-induced dystonia: atypical presentation of autosomal dominant GTP-cyclohydrolase 1 deficiency. Dev Med Child Neurol. 2010;52(6):583–6.

    PubMed  Google Scholar 

  109. Kumar A, Szekely A, Jabbari B. Effective treatment of paroxysmal nonkinesigenic dyskinesia with oxcarbazepine. Clin Neuropharmacol. 2016;39(4):201–5.

    CAS  PubMed  Google Scholar 

  110. Alemdar M, Iseri P, Selekler M, Komsuoglu SS. Levetiracetam-responding paroxysmal nonkinesigenic dyskinesia. Clin Neuropharmacol. 2007;30(4):241–4.

    PubMed  Google Scholar 

  111. Coulter DL, Donofrio P. Haloperidol for nonkinesiogenic paroxysmal dyskinesia. Arch Neurol. 1980;37(5):325–6.

    CAS  PubMed  Google Scholar 

  112. Loscher W, Richter A. Piracetam and levetiracetam, two pyrrolidone derivatives, exert antidystonic activity in a hamster model of paroxysmal dystonia. Eur J Pharmacol. 2000;391(3):251–4.

    CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Medical Research Council, Singapore.

Author information

Authors and Affiliations

  1. Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore

    Zheyu Xu, Louis C. S. Tan & Eng-King Tan

  2. Department of Clinical Translational Research, Singapore General Hospital, Bukit Merah, Singapore, Singapore

    Che-Kang Lim

  3. Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institute, Solna, Sweden

    Che-Kang Lim

  4. Duke-NUS Medical School, 8 College Rd, Singapore, 169857, Singapore

    Louis C. S. Tan & Eng-King Tan

Authors
  1. Zheyu Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Che-Kang Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Louis C. S. Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eng-King Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eng-King Tan.

Ethics declarations

Conflict of Interest

Eng-King Tan received honorarium for editorial duties for European Journal of Neurology and Parkinsonism related disorders. Zheyu Xu, Che-Kang Lim, and Louis CS Tan each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Movement Disorders

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, Z., Lim, CK., Tan, L.C.S. et al. Paroxysmal Movement Disorders: Recent Advances. Curr Neurol Neurosci Rep 19, 48 (2019). https://doi.org/10.1007/s11910-019-0958-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11910-019-0958-3

Keywords

Search

Navigation