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X-linked dystonia parkinsonism: epidemiology, genetics, clinical features, diagnosis, and treatment

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Abstract

X-linked dystonia parkinsonism (XDP) is a rare X-linked recessive degenerative movement disorder that only affects Filipino descent, predominantly males. Its underlying cause is associated with the genetic alterations in the TAF1/DYT3 multiple transcription system. SINE-VNTR-Alu (SVA) retrotransposon insertion was suggested to be the responsible genetic mutation. Clinically, it initially presents as focal dystonia and generalizes within years. Parkinsonism arises years later and coexists with dystonia. Nonmotor symptoms like cognitive impairment and mood disorders are also common among XDP patients. XDP diagnosis relies on clinical history and physical examination. On imaging, abnormalities of the striatum, such as atrophy, are widely seen and can explain the clinical presentations with a three-model pathway of the striatum. Treatments aim for symptomatic relief of dystonia and parkinsonism and to prevent complications. Oral medications, chemo-denervation, and surgery are used in XDP patients. This review summarizes the currently important information regarding XDP, providing a synoptic overview and understanding of XDP for future studies.

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References

  1. Lee LV, Pascasio FM, Fuentes FD, Viterbo GH (1976) Torsion dystonia in panay, Philippines. Adv Neurol 14:137–151

    CAS  PubMed  Google Scholar 

  2. Rosales RL (2010) X-linked dystonia Parkinsonism: clinical phenotype, genetics and therapeutics. J Movem Disord 3(2):32–38. https://doi.org/10.14802/jmd.10009

    Article  Google Scholar 

  3. Lee LV, Munoz EL, Tan KT, Reyes MT (2001) Sex linked recessive dystonia Parkinsonism of panay, Philippines (XDP). Mol Pathol 54(6):362–368

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Evidente VGH (2005) X-linked dystonia-Parkinsonism. In: Adam MP et al (eds) GeneReviews. University of Washington, Seattle

    Google Scholar 

  5. Lee LV, Maranon E, Demaisip C, Peralta O, Borres-Icasiano R, Arancillo J, Rivera C, Munoz E, Tan K, Reyes MT (2002) The natural history of sex-linked recessive dystonia parkinsonism of Panay, Philippines (XDP). Parkinsonism Relat Disord 9(1):29–38. https://doi.org/10.1016/s1353-8020(02)00042-1

    Article  PubMed  Google Scholar 

  6. Domingo A, Lee LV, Brüggemann N, Freimann K, Kaiser FJ, Jamora RDG, Rosales RL, Klein C, Westenberger A (2014) Woman with x-linked recessive dystonia-parkinsonism: Clue to the epidemiology of parkinsonism in Filipino women? JAMA Neurol 71(9):1177–1180. https://doi.org/10.1001/jamaneurol.2014.56

    Article  PubMed  Google Scholar 

  7. Plummer C, Bradfield J, Singleton AB, Hernandez D, Singleton AA, O’sullivan J (2005) First case report of X linked dystonia Parkinsonism (XDP) or“lubag”in Australia. J Clin Neurosci 12(8):945–946. https://doi.org/10.1016/j.jocn.2004.10.012

    Article  CAS  PubMed  Google Scholar 

  8. Lee LV, Rivera C, Teleg RA, Dantes MB, Pasco PMD, Jamora RDG, Arancillo J, Villareal-Jordan RF, Rosales RL, Demaisip C, Maranon E, Peralta O, Borres R, Tolentino C, Monding MJ, Sarcia S (2011) The unique phenomenology of sex-linked dystonia parkinsonism (XDP, DYT3, “Lubag”). Int J Neurosci 121(Suppl 1):3–11. https://doi.org/10.3109/00207454.2010.526728

    Article  PubMed  Google Scholar 

  9. Evidente VGH, Nolte D, Niemann S, Advincula J, Mayo MC, Natividad FF, Müller U (2004) Phenotypic and molecular analyses of X-linked dystonia-parkinsonism (“lubag”) in women. Arch Neurol 61(12):1956–1959. https://doi.org/10.1001/archneur.61.12.1956

    Article  PubMed  Google Scholar 

  10. Nolte D, Niemann S, Müller U (2003) Specific sequence changes in multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism. Proc Natl Acad Sci USA 100(18):10347–10352. https://doi.org/10.1073/pnas.1831949100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Makino S, Kaji R, Ando S, Tomizawa M, Yasuno K, Goto S, Matsumoto S, Tabuena MD, Maranon E, Dantes M, Lee LV, Ogasawara K, Tooyama I, Akatsu H, Nishimura M, Tamiya G (2007) Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism. Am J Hum Genet 80(3):393–406. https://doi.org/10.1086/512129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Snyder M, Gerstein M (2003) Genomics. Defining genes in the genomics era. Science 300(5617):258–260. https://doi.org/10.1126/science.1084354

    Article  CAS  PubMed  Google Scholar 

  13. Thomas MC, Chiang CM (2006) The general transcription machinery and general cofactors. Crit Rev Biochem Mol Biol 41(3):105–178. https://doi.org/10.1080/10409230600648736

    Article  CAS  PubMed  Google Scholar 

  14. Aneichyk T, Hendriks WT, Yadav R, Shin D, Gao D, Vaine CA, Collins RL, Domingo A, Currall B, Stortchevoi A, Multhaupt-Buell T, Penney EB, Cruz L, Dhakal J, Brand H, Hanscom C, Antolik C, Dy M, Ragavendran A, Underwood J, Cantsilieris S, Munson KM, Eichler EE, Acuña P, Go C, Jamora RDG, Rosales RL, Church DM, Williams SR, Garcia S, Klein C, Müller U, Wilhelmsen KC, Timmers HTM, Sapir Y, Wainger BJ, Henderson D, Ito N, Weisenfeld N, Jaffe D, Sharma N, Breakefield XO, Ozelius LJ, Bragg DC, Talkowski ME (2018) Dissecting the causal mechanism of X-linked dystonia-Parkinsonism by integrating genome and transcriptome assembly. Cell 172(5):897-909.e21. https://doi.org/10.1016/j.cell.2018.02.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Herzfeld T, Nolte D, Müller U (2007) Structural and functional analysis of the human TAF1/DYT3 multiple transcript system. Mamm Genome 18(11):787–795. https://doi.org/10.1007/s00335-007-9063-z

    Article  CAS  PubMed  Google Scholar 

  16. Pasco PMD, Ison CV, Muňoz EL, Magpusao NS, Cheng AE, Tan KT, Lo RW, Teleg RA, Dantes MB, Borres R, Maranon E, Demaisip C, Reyes MVT, Lee LV (2011) Understanding XDP through imaging, pathology, and genetics. Int J Neurosci 121(Suppl 1):12–17. https://doi.org/10.3109/00207454.2010.526729

    Article  CAS  PubMed  Google Scholar 

  17. Wilhelmsen KC, Moskowitz CB, Weeks DE, Neystat M, Nygaard TG, Clark L, Dancoup M, Sobrevega EE, Rosales R, Gamez GL, Pacioles O, Perez M, Fahn S (1998) Molecular genetic analysis of Lubag. Adv Neurol 78:341–348

    CAS  PubMed  Google Scholar 

  18. Domingo A, Westenberger A, Lee LV, Brænne I, Liu T, Vater I, Rosales R, Jamora RD, Pasco PM, Cutiongco-Dela Paz EM, Freimann K, Schmidt TG, Dressler D, Kaiser FJ, Bertram L, Erdmann J, Lohmann K, Klein C (2015) New insights into the genetics of X-linked dystonia-parkinsonism (XDP, DYT3). Eur J Hum Genet 23(10):1334–1340. https://doi.org/10.1038/ejhg.2014.292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Krause C, Schaake S, Grütz K, Sievert H, Reyes CJ, König IR, Laabs BH, Jamora RD, Rosales RL, Diesta CCE, Pozojevic J, Gemoll T, Westenberger A, Kaiser FJ, Klein C, Kirchner H (2020) DNA methylation as a potential molecular mechanism in X-linked dystonia-Parkinsonism. Mov Disord 35(12):2220–2229. https://doi.org/10.1002/mds.28239

    Article  CAS  PubMed  Google Scholar 

  20. Westenberger A, Reyes CJ, Saranza G, Dobricic V, Hanssen H, Domingo A, Laabs BH, Schaake S, Pozojevic J, Rakovic A, Grütz K, Begemann K, Walter U, Dressler D, Bauer P, Rolfs A, Münchau A, Kaiser FJ, Ozelius LJ, Jamora RD, Rosales RL, Diesta CCE, Lohmann K, König IR, Brüggemann N, Klein C (2019) A hexanucleotide repeat modifies expressivity of X-linked dystonia parkinsonism. Ann Neurol 85(6):812–822. https://doi.org/10.1002/ana.25488

    Article  CAS  PubMed  Google Scholar 

  21. Petrozziello T, Dios AM, Mueller KA, Vaine CA, Hendriks WT, Glajch KE, Mills AN, Mangkalaphiban K, Penney EB, Ito N, Fernandez-Cerado C, Legarda GPA, Velasco-Andrada MS, Acuña PJ, Ang MA, Muñoz EL, Diesta CCE, Macalintal-Canlas R, Acuña G, Sadri-Vakili G (2020) SVA insertion in X-linked Dystonia Parkinsonism alters histone H3 acetylation associated with TAF1 gene. PLoS ONE 15(12):e0243655. https://doi.org/10.1371/journal.pone.0243655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Herzfeld T, Nolte D, Grznarova M, Hofmann A, Schultze JL, Müller U (2013) X-linked dystonia parkinsonism syndrome (XDP, lubag): Disease-specific sequence change DSC3 in TAF1/DYT3 affects genes in vesicular transport and dopamine metabolism. Hum Mol Genet 22(5):941–951. https://doi.org/10.1093/hmg/dds499

    Article  CAS  PubMed  Google Scholar 

  23. Petrozziello T, Mills AN, Vaine CA, Penney EB, Fernandez-Cerado C, Legarda GPA, Velasco-Andrada MS, Acuña PJ, Ang MA, Muñoz EL, Diesta CCE, Macalintal-Canlas R, Acuña-Sunshine G, Ozelius LJ, Sharma N, Bragg DC, Sadri-Vakili G (2020) Neuroinflammation and histone H3 citrullination are increased in X-linked dystonia Parkinsonism post-mortem prefrontal cortex. Neurobiol Dis 144:105032. https://doi.org/10.1016/j.nbd.2020.105032

    Article  CAS  PubMed  Google Scholar 

  24. Vaine CA, Shin D, Liu C, Hendriks WT, Dhakal J, Shin K, Sharma N, Bragg DC (2017) X-linked dystonia-Parkinsonism patient cells exhibit altered signaling via nuclear factor-kappa B. Neurobiol Dis 100:108–118. https://doi.org/10.1016/j.nbd.2016.12.016

    Article  CAS  PubMed  Google Scholar 

  25. Pauly MG, Ruiz López M, Westenberger A, Saranza G, Brüggemann N, Weissbach A, Rosales RL, Diesta CC, Jamora RDG, Reyes CJ, Madoev H, Petkovic S, Ozelius LJ, Klein C, Domingo A (2020) Expanding data collection for the MDSGene database: X-linked dystonia-parkinsonism as use case example. Mov Disord 35(11):1933–1938. https://doi.org/10.1002/mds.28289

    Article  PubMed  Google Scholar 

  26. Sprenger A, Hanssen H, Hagedorn I, Prasuhn J, Rosales RL, Jamora RDG, Diesta CC, Domingo A, Klein C, Brüggemann N, Helmchen C (2019) Eye movement deficits in X-linked dystonia-parkinsonism are related to striatal degeneration. Parkinsonism Relat Disord 61:170–178. https://doi.org/10.1016/j.parkreldis.2018.10.016

    Article  PubMed  Google Scholar 

  27. Ng AR, Jamora RDG, Rosales RL (2021) X-linked dystonia Parkinsonism: crossing a new threshold. J Neural Transm 128(4):567–573. https://doi.org/10.1007/s00702-021-02324-0

    Article  PubMed  Google Scholar 

  28. Evidente VGH, Gwinn-Hardy K, Hardy J, Hernandez D, Singleton A (2002) X-linked dystonia (“Lubag”) presenting predominantly with parkinsonism: a more benign phenotype? Mov Disord 17(1):200–202. https://doi.org/10.1002/mds.1263

    Article  PubMed  Google Scholar 

  29. Evidente VGH, Advincula J, Esteban R, Pasco P, Alfon JA, Natividad FF, Cuanang J, Luis AS, Gwinn-Hardy K, Hardy J, Hernandez D, Singleton A (2002) Phenomenology of “Lubag” or X-linked dystonia-parkinsonism. Mov Disord 17(6):1271–1277. https://doi.org/10.1002/mds.10271

    Article  PubMed  Google Scholar 

  30. Bittel DC, Theodoro MF, Kibiryeva N, Fischer W, Talebizadeh Z, Butler MG (2008) Comparison of X-chromosome inactivation patterns in multiple tissues from human females. J Med Genet 45(5):309–313. https://doi.org/10.1136/jmg.2007.055244

    Article  CAS  PubMed  Google Scholar 

  31. Kristiansen M, Knudsen GPS, Bathum L, Naumova AK, Sørensen TIA, Brix TH, Svendsen AJ, Christensen K, Kyvik KO, Ørstavik KH (2005) Twin study of genetic and aging effects on X chromosome inactivation. Eur J Hum Genet 13(5):599–606. https://doi.org/10.1038/sj.ejhg.5201398

    Article  CAS  PubMed  Google Scholar 

  32. Song PC, Le H, Acuna P, De Guzman JKP, Sharma N, Francouer TN, Dy ME, Go CL (2020) Voice and swallowing dysfunction in X-linked dystonia Parkinsonism. Laryngoscope 130(1):171–177. https://doi.org/10.1002/lary.27897

    Article  PubMed  Google Scholar 

  33. Song SA, Go CL, Acuna PB, De Guzman JKP, Sharma N, Song PC (2020) Progressive decline in voice and voice-related quality of life in X-linked dystonia Parkinsonism. J Voice S0892–1997(20):30428–30438. https://doi.org/10.1016/j.jvoice.2020.11.014

    Article  Google Scholar 

  34. Zaninotto AL, de Guzman JK, Stipancic KL, Perry BJ, Supnet ML, Go C, Sharma N, Green JR (2021) Speech and swallowing deficits in X-linked dystonia-Parkinsonism. Parkinsonism Relat Disord 89:105–110. https://doi.org/10.1016/j.parkreldis.2021.07.006

    Article  CAS  PubMed  Google Scholar 

  35. Kawarai T, Morigaki R, Kaji R, Goto S (2017) Clinicopathological phenotype and genetics of X-linked dystonia-Parkinsonism (XDP; DYT3; Lubag). Brain Sci 7(7):E72. https://doi.org/10.3390/brainsci7070072

    Article  CAS  Google Scholar 

  36. Jamora RDG, Ledesma LK, Domingo A, Cenina ARF, Lee LV (2014) Nonmotor features in sex-linked dystonia Parkinsonism. Neurodegener Dis Manag 4(3):283–289. https://doi.org/10.2217/nmt.14.16

    Article  PubMed  Google Scholar 

  37. Jamora RDG, Suratos CTR, Bautista JEC, Ramiro GMI, Westenberger A, Klein C, Ledesma LK (2021) Neurocognitive profile of patients with X-linked dystonia-parkinsonism. J Neural Transm 128(5):671–678. https://doi.org/10.1007/s00702-021-02317-z

    Article  PubMed  Google Scholar 

  38. Morigaki R, Nakataki M, Kawarai T, Lee LV, Teleg RA, Tabuena MDP, Mure H, Sako W, Pasco PMD, Nagahiro S, Iga J, Ohmori T, Goto S, Kaji R (2013) Depression in X-linked dystonia-parkinsonism: a case-control study. Parkinsonism Relat Disord 19(9):844–846. https://doi.org/10.1016/j.parkreldis.2013.04.027

    Article  PubMed  Google Scholar 

  39. Evidente VGH, Esteban RP, Hernandez JL, Natividad FF, Advincula J, Gwinn-Hardy K, Hardy J, Singleton A (2004) Smell testing is abnormal in “lubag” or X-linked dystonia-parkinsonism: a pilot study. Parkinsonism Relat Disord 10(7):407–410. https://doi.org/10.1016/j.parkreldis.2004.04.011

    Article  PubMed  Google Scholar 

  40. Gillian LS (2013) Pathological gambling in X-linked dystonia Parkinsonism. J Addict Med 7(4):299–301. https://doi.org/10.1097/ADM.0b013e31828ee8a2

    Article  PubMed  Google Scholar 

  41. Jamora RDG, Cenina ARF, Teleg RA, Lee LV (2015) Suicidality among patients with sex-linked dystonia-Parkinsonism (XDP). Acta Med Philipp 49(1):Article 1. https://doi.org/10.47895/amp.v49i1.1009

    Article  Google Scholar 

  42. Camargos S, Cardoso F (2016) Understanding dystonia: diagnostic issues and how to overcome them. Arq Neuropsiquiatr 74(11):921–936. https://doi.org/10.1590/0004-282X20160140

    Article  PubMed  Google Scholar 

  43. Moghimi N, Jabbari B, Szekely AM (2014) Primary dystonias and genetic disorders with dystonia as clinical feature of the disease. Eur J Paediatr Neurol 18(1):79–105. https://doi.org/10.1016/j.ejpn.2013.05.015

    Article  PubMed  Google Scholar 

  44. Klein C, Lohmann K, Marras C, Münchau A (1993) Hereditary dystonia overview. In: Adam MP et al (eds) GeneReviews. University of Washington, Seattle

    Google Scholar 

  45. Diestro JDB, Ang MAC, Mondia MWL, Pasco PMD (2018) Validation of a questionnaire for distinguishing X-linked dystonia Parkinsonism from its mimics. Front Neurol 9:830. https://doi.org/10.3389/fneur.2018.00830

    Article  PubMed  PubMed Central  Google Scholar 

  46. Stephen CD, Go CL, Acuna P, Sharma N (2020) Phasic knee bending dystonic and Parkinsonian gait: a characteristic finding in X-linked dystonia Parkinsonism. Mov Disord Clini Pract 7(4):448–452. https://doi.org/10.1002/mdc3.12929

    Article  Google Scholar 

  47. Diestro JDB, Pasco PMD, Lee LV, Center the XSG of the PCM (2017) Validation of a screening questionnaire for X-linked dystonia Parkinsonism: the first phase of the population-based prevalence study of X-linked dystonia Parkinsonism in Panay. Neurol Clin Neurosci 5(3):79–85. https://doi.org/10.1111/ncn3.12113

    Article  Google Scholar 

  48. Al Ali J, Vaine CA, Shah S, Campion L, Hakoum A, Supnet ML, Acuña P, Aldykiewicz G, Multhaupt-Buell T, Ganza NGM, Lagarde JBB, De Guzman JK, Go C, Currall B, Trombetta B, Webb PK, Talkowski M, Arnold SE, Cheah PS, Breakefield XO (2021) TAF1 transcripts and neurofilament light chain as biomarkers for X-linked dystonia-Parkinsonism. Mov Disord 36(1):206–215. https://doi.org/10.1002/mds.28305

    Article  CAS  PubMed  Google Scholar 

  49. Bragg DC, Mangkalaphiban K, Vaine CA, Kulkarni NJ, Shin D, Yadav R, Dhakal J, Ton ML, Cheng A, Russo CT, Ang M, Acuña P, Go C, Franceour TN, Multhaupt-Buell T, Ito N, Müller U, Hendriks WT, Breakefield XO, Ozelius LJ (2017) Disease onset in X-linked dystonia-parkinsonism correlates with expansion of a hexameric repeat within an SVA retrotransposon in TAF1. Proc Natl Acad Sci USA 114(51):E11020–E11028. https://doi.org/10.1073/pnas.1712526114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Hanssen H, Heldmann M, Prasuhn J, Tronnier V, Rasche D, Diesta CC, Domingo A, Rosales RL, Jamora RD, Klein C, Münte TF, Brüggemann N (2018) Basal ganglia and cerebellar pathology in X-linked dystonia-Parkinsonism. Brain: A J Neurol 141(10):2995–3008. https://doi.org/10.1093/brain/awy222

    Article  Google Scholar 

  51. Hanssen H, Prasuhn J, Heldmann M, Diesta CC, Domingo A, Göttlich M, Blood AJ, Rosales RL, Jamora RDG, Münte TF, Klein C, Brüggemann N (2019) Imaging gradual neurodegeneration in a basal ganglia model disease. Ann Neurol 86(4):517–526. https://doi.org/10.1002/ana.25566

    Article  CAS  PubMed  Google Scholar 

  52. Eidelberg D, Takikawa S, Wilhelmsen K, Dhawan V, Chaly T, Robeson W, Dahl R, Margouleff D, Greene P, Hunt A (1993) Positron emission tomographic findings in Filipino X-linked dystonia-Parkinsonism. Ann Neurol 34(2):185–191. https://doi.org/10.1002/ana.410340214

    Article  CAS  PubMed  Google Scholar 

  53. Waters CH, Takahashi H, Wilhelmsen KC, Shubin R, Snow BJ, Nygaard TG, Moskowitz CB, Fahn S, Calne DB (1993) Phenotypic expression of X-linked dystonia-Parkinsonism (lubag) in two women. Neurology 43(8):1555–1558. https://doi.org/10.1212/wnl.43.8.1555

    Article  CAS  PubMed  Google Scholar 

  54. Tackenberg B, Metz A, Unger M, Schimke N, Passow S, Hoeffken H, Hoffmann GF, Müller U, Nolte D, Oertel WH, Eggert K, Möller JC (2007) Nigrostriatal dysfunction in X-linked dystonia-parkinsonism (DYT3). Mov Disord 22(6):900–902. https://doi.org/10.1002/mds.21462

    Article  PubMed  Google Scholar 

  55. Brüggemann N, Rosales RL, Waugh JL, Blood AJ, Domingo A, Heldmann M, Jamora RD, Münchau A, Münte TF, Lee LV, Buchmann I, Klein C (2017) Striatal dysfunction in X-linked dystonia-parkinsonism is associated with disease progression. Eur J Neurol 24(5):680–686. https://doi.org/10.1111/ene.13256

    Article  PubMed  Google Scholar 

  56. Walter U, Rosales R, Rocco A, Westenberger A, Domingo A, Go CL, Brüggemann N, Klein C, Lee LV, Dressler D (2017) Sonographic alteration of substantia Nigra is related to parkinsonism-predominant course of X-linked dystonia-parkinsonism. Parkinsonism Relat Disord 37:43–49. https://doi.org/10.1016/j.parkreldis.2017.01.006

    Article  PubMed  Google Scholar 

  57. Arasaratnam CJ, Singh-Bains MK, Waldvogel HJ, Faull RLM (2021) Neuroimaging and neuropathology studies of X-linked dystonia Parkinsonism. Neurobiol Dis 148:105186. https://doi.org/10.1016/j.nbd.2020.105186

    Article  CAS  PubMed  Google Scholar 

  58. Berg D, Godau J, Riederer P, Gerlach M, Arzberger T (2010) Microglia activation is related to substantia Nigra echogenicity. J Neural Transm 117(11):1287–1292. https://doi.org/10.1007/s00702-010-0504-6

    Article  CAS  PubMed  Google Scholar 

  59. Goto S, Lee LV, Munoz EL, Tooyama I, Tamiya G, Makino S, Ando S, Dantes MB, Yamada K, Matsumoto S, Shimazu H, Kuratsu J, Hirano A, Kaji R (2005) Functional anatomy of the basal ganglia in X-linked recessive dystonia-Parkinsonism. Ann Neurol 58(1):7–17. https://doi.org/10.1002/ana.20513

    Article  PubMed  Google Scholar 

  60. Goto S, Kawarai T, Morigaki R, Okita S, Koizumi H, Nagahiro S, Munoz EL, Lee LV, Kaji R (2013) Defects in the striatal neuropeptide Y system in X-linked dystonia-Parkinsonism. Brain 136(Pt 5):1555–1567. https://doi.org/10.1093/brain/awt084

    Article  PubMed  Google Scholar 

  61. Graybiel AM, Canales JJ, Capper-Loup C (2000) Levodopa-induced dyskinesias and dopamine-dependent stereotypies: a new hypothesis. Trends Neurosci 23(10 Suppl):S71-77. https://doi.org/10.1016/s1471-1931(00)00027-6

    Article  CAS  PubMed  Google Scholar 

  62. Evidente VGH, Evidente DH, Ortega SC, Levine TD, Freeman R, Gibbons CH (2022) X-linked dystonia-Parkinsonism (“Lubag”) may present with peripheral Synucleinopathy. Mov Disord 37(1):130–136. https://doi.org/10.1002/mds.28801

    Article  CAS  PubMed  Google Scholar 

  63. Pasco PMD, Jamora RDG, Rosales RL, Diesta CCE, Ng AR, Teleg RA, Go CL, Lee L, Fernandez HH (2017) Validation of the XDP-MDSP rating scale for the evaluation of patients with X-linked dystonia-Parkinsonism. NPJ Parkinson’s Disease 3:24. https://doi.org/10.1038/s41531-017-0026-0

    Article  PubMed  PubMed Central  Google Scholar 

  64. Jamora RDG, Diesta CCE, Pasco PMD, Lee LV (2011) Oral pharmacological treatment of X-linked dystonia Parkinsonism: successes and failures. Int J Neurosci 121(Suppl 1):18–21. https://doi.org/10.3109/00207454.2010.544433

    Article  CAS  PubMed  Google Scholar 

  65. Evidente VGH (2002) Zolpidem improves dystonia in “Lubag” or X-linked dystonia-Parkinsonism syndrome. Neurology 58(4):662–663. https://doi.org/10.1212/wnl.58.4.662

    Article  PubMed  Google Scholar 

  66. Rosales RL, Santos MMDD, Ng AR, Teleg R, Dantes M, Lee LV, Fernandez HH (2011) The broadening application of chemodenervation in X-linked dystonia-parkinsonism (Part I): muscle afferent block versus botulinum toxin-A in cervical and limb dystonias. Int J Neurosci 121(Suppl 1):35–43. https://doi.org/10.3109/00207454.2010.544435

    Article  CAS  PubMed  Google Scholar 

  67. Aguilar JA, Vesagas TS, Jamora RD, Teleg RA, Ledesma L, Rosales RL, Fernandez HH, Lee LV (2011) The promise of deep brain stimulation in X-linked dystonia Parkinsonism. Int J Neurosci 121(Suppl 1):57–63. https://doi.org/10.3109/00207454.2010.541573

    Article  PubMed  Google Scholar 

  68. Abejero JEE, Jamora RDG, Vesagas TS, Teleg RA, Rosales RL, Anlacan JP, Velasquez MS, Aguilar JA (2019) Long-term outcomes of pallidal deep brain stimulation in X-linked dystonia Parkinsonism (XDP): Up to 84 months follow-up and review of literature. Parkinsonism Relat Disord 60:81–86. https://doi.org/10.1016/j.parkreldis.2018.09.022

    Article  PubMed  Google Scholar 

  69. Brüggemann N, Domingo A, Rasche D, Moll CKE, Rosales RL, Jamora RDG, Hanssen H, Münchau A, Graf J, Weissbach A, Tadic V, Diesta CC, Volkmann J, Kühn A, Münte TF, Tronnier V, Klein C (2019) Association of pallidal neurostimulation and outcome predictors with X-linked dystonia Parkinsonism. JAMA Neurol 76(2):211–216. https://doi.org/10.1001/jamaneurol.2018.3777

    Article  PubMed  Google Scholar 

  70. Kilbane C, Witt J, Galifianakis NB, Glass GA, Volz M, Heath S, Starr PA, Ostrem JL (2018) Long-term outcomes of bilateral pallidal deep brain stimulation for X-linked dystonia and Parkinsonism. Stereotact Funct Neurosurg 96(5):320–326. https://doi.org/10.1159/000492823

    Article  PubMed  Google Scholar 

  71. Oyama G, Fernandez HH, Foote KD, Zeilman P, Hwynn N, Jacobson CE, Malaty IA, Rodriguez RL, Okun MS (2010) Differential response of dystonia and parkinsonism following globus pallidus internus deep brain stimulation in X-linked dystonia-parkinsonism (Lubag). Stereotact Funct Neurosurg 88(5):329–333. https://doi.org/10.1159/000319961

    Article  PubMed  PubMed Central  Google Scholar 

  72. Chang WC, Taira T, Jamora RDG, Chiu PY, Lin W (2019) First Experience with MR-guided focused ultrasound in the treatment of X-linked dystonia-Parkinsonism (XDP). Movement Disorders 34 (suppl 2)

  73. Jamora RDG, Chang WC, Taira T (2021) Transcranial magnetic resonance-guided focused ultrasound in X-linked dystonia-Parkinsonism. Life 11(5):392. https://doi.org/10.3390/life11050392

    Article  PubMed  PubMed Central  Google Scholar 

  74. Umemoto G, Furuya H (2020) Management of dysphagia in patients with Parkinson’s disease and related disorders. Intern Med 59(1):7–14. https://doi.org/10.2169/internalmedicine.2373-18

    Article  PubMed  Google Scholar 

  75. De Roxas RC, Jamora RDG (2019) Cost-analysis of the different treatment modalities in X-linked dystonia-Parkinsonism. Front Neurol 10:500. https://doi.org/10.3389/fneur.2019.00500

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Medical Science, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Hok Leong Chin & Chia-Yi Lin

  2. Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

    Oscar Hou-In Chou

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  1. Hok Leong Chin
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  2. Chia-Yi Lin
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  3. Oscar Hou-In Chou
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Contributions

HLC: literature review, figures, tables, data analysis and interpretation, manuscript drafting, and critical revision of manuscript. CYL: literature review, data analysis and interpretation, manuscript drafting, and critical revision of manuscript. OHIC: study conception, study supervision, project planning, data interpretation, manuscript drafting, and critical revision of manuscript.

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Correspondence to Oscar Hou-In Chou.

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Chin, H.L., Lin, CY. & Chou, O.HI. X-linked dystonia parkinsonism: epidemiology, genetics, clinical features, diagnosis, and treatment. Acta Neurol Belg 123, 45–55 (2023). https://doi.org/10.1007/s13760-022-02144-3

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