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Chapter 29 - Genetic Parkinsonisms

from Section 2: - Hypokinetic Movement Disorders

Published online by Cambridge University Press:  07 January 2025

By
Jaroslaw Dulski ,
Shinsuke Fujioka  and
Zbigniew K. Wszolek
Edited by
Erik Ch. Wolters  and
Christian R. Baumann
Erik Ch. Wolters
Affiliation:
Universität Zürich
Christian R. Baumann
Affiliation:
Universität Zürich
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Summary

Parkinsonism is used to describe a clinical syndrome of bradykinesia, rest tremor, rigidity and postural instability, and is present in a many sporadic and genetic disorders. The most common cause of parkinsonism is Parkinson’s disease (PD). Typical parkinsonism is characterized by asymmetry, slow progression, and excellent L-Dopa response, whereas atypical parkinsonism is parkinsonism with additional features (oculomotor abnormalities, myoclonus, cerebellar and pyramidal signs, ataxia), faster progression, and poor L-Dopa response. The genetic landscape of parkinsonism may be divided into monogenic variants; oligo- and polygenic forms of (a)typical parkinsonism; and intermediate variants with incomplete penetrance and low frequency. Typical and atypical parkinsonisms are reviewed, presenting and discussing 101 genes and loci associated with parkinsonism, classified based on phenotype into autosomal-dominant typical parkinsonisms, autosomal-recessive (a)typical parkinsonisms, other genetic forms of (a)typical parkinsonisms, and genetic syndromes with features of atypical parkinsonism. Genetic susceptibility and issues related to diagnostic genetic tests are also discussed.

Keywords

Autosomal-dominant genetic forms of parkinsonismsautosomal-recessive forms of parkinsonismsother genetic forms of parkinsonismsgenetic forms of disorders with features of parkinsonism
Type
Chapter
Information
International Compendium of Movement Disorders , pp. 347 - 367
Publisher: Cambridge University Press
Print publication year: 2025

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References

Balestrino, R, Schapira, AHV. Parkinson disease. Eur J Neurol 2020;27(1):27–42.CrossRefGoogle ScholarPubMed
Hall, A, Bandres-Ciga, S, Diez-Fairen, M, Quinn, JP, Billingsley, KJ. Genetic risk profiling in Parkinson’s disease and utilizing genetics to gain insight into disease-related biological pathways. Int J Mol Sci. 2020;21(19):7332.CrossRefGoogle ScholarPubMed
Trinh, J, Zeldenrust, FMJ, Huang, J, et al. Genotype–phenotype relations for the Parkinson’s disease genes SNCA, LRRK2, VPS35: MDSGene systematic review. Mov Disord 2018;33(12):1857–1870.CrossRefGoogle ScholarPubMed
Deng, H, Wang, P, Jankovic, J. The genetics of Parkinson disease. Ageing Res Rev 2018;42:72–85.CrossRefGoogle ScholarPubMed
Lai, D, Alipanahi, B, Fontanillas, P, et al. Genomewide association studies of LRRK2 modifiers of Parkinson’s disease. Ann Neurol 2021;90(1):76–88.CrossRefGoogle ScholarPubMed
Lunati, A, Lesage, S, Brice, A. The genetic landscape of Parkinson’s disease. Rev Neurol (Paris) 2018;174(9):628–643.CrossRefGoogle ScholarPubMed
Reed, X, Bandres-Ciga, S, Blauwendraat, C, Cookson, MR. The role of monogenic genes in idiopathic Parkinson’s disease. Neurobiol Dis 2019;124:230–239.CrossRefGoogle ScholarPubMed
Chen, Y, Cen, Z, Zheng, X, et al. LRP10 in autosomal-dominant Parkinson’s disease. Mov Disord 2019;34(6):912–916.CrossRefGoogle ScholarPubMed
Puschmann, A. New genes causing hereditary Parkinson’s disease or parkinsonism. Curr Neurol Neurosci Rep 2017;17(9):66.CrossRefGoogle ScholarPubMed
Lee, JS, Kanai, K, Suzuki, M, et al. Arylsulfatase A, a genetic modifier of Parkinson’s disease, is an alpha-synuclein chaperone. Brain 2019;142(9):2845–2859.CrossRefGoogle Scholar
Oji, Y, Hatano, T, Ueno, SI, et al. Variants in saposin D domain of prosaposin gene linked to Parkinson’s disease. Brain 2020;143(4):1190–1205.CrossRefGoogle ScholarPubMed
Kasten, M, Hartmann, C, Hampf, J, et al. Genotype–phenotype relations for the Parkinson’s disease genes Parkin, PINK1, DJ1: MDSGene systematic review. Mov Disord 2018;33(5):730–741.CrossRefGoogle ScholarPubMed
Kumar, S, Abbas, MM, Govindappa, ST, et al. Compound heterozygous variants in Wiskott–Aldrich syndrome like (WASL) gene segregating in a family with early onset Parkinson’s disease. Parkinsonism Relat Disord 2021;84:61–67.CrossRefGoogle Scholar
Riboldi, GM, Di Fonzo, AB. GBA, Gaucher disease, and Parkinson’s disease: from genetic to clinic to new therapeutic approaches. Cells 2019;8(4):364.CrossRefGoogle ScholarPubMed
Arienti, F, Lazzeri, G, Vizziello, M, et al. Unravelling genetic factors underlying corticobasal syndrome: a systematic review. Cells. 2021;10(1):171.CrossRefGoogle ScholarPubMed
Labbe, C, Heckman, MG, Lorenzo-Betancor, O, et al. MAPT haplotype diversity in multiple system atrophy. Parkinsonism Relat Disord 2016;30:40–45.CrossRefGoogle ScholarPubMed
Wen, Y, Zhou, Y, Jiao, B, Shen, L. Genetics of progressive supranuclear palsy: a review. J Parkinsons Dis 2021;11(1):93–105.CrossRefGoogle ScholarPubMed
Deutschlander, AB, Konno, T, Soto-Beasley, AI, et al. Association of MAPT subhaplotypes with clinical and demographic features in Parkinson’s disease. Ann Clin Transl Neurol 2020;7(9):1557–1563.CrossRefGoogle ScholarPubMed
de Boer, EMJ, Orie, VK, Williams, T, et al. TDP-43 proteinopathies: a new wave of neurodegenerative diseases. J Neurol Neurosurg Psychiatry 2021;92(1):86–95.CrossRefGoogle Scholar
Dulski, J, Cerquera-Cleves, C, Milanowski, L, et al. Clinical, pathological and genetic characteristics of Perry disease – new cases and literature review. Eur J Neurol 2021;28(12):4010–4021.CrossRefGoogle ScholarPubMed
Siuda, J, Fujioka, S, Wszolek, ZK. Parkinsonian syndrome in familial frontotemporal dementia. Parkinsonism Relat Disord 2014;20(9):957–964.CrossRefGoogle ScholarPubMed
Bourinaris, T, Houlden, H. C9orf72 and its relevance in parkinsonism and movement disorders: a comprehensive review of the literature. Mov Disord Clin Pract 2018;5(6):575–585.CrossRefGoogle ScholarPubMed
Chitramuthu, BP, Bennett, HPJ, Bateman, A. Progranulin: a new avenue towards the understanding and treatment of neurodegenerative disease. Brain 2017;140(12):3081–3104.CrossRefGoogle ScholarPubMed
Di Lazzaro, G, Magrinelli, F, Estevez-Fraga, C, et al. X-linked parkinsonism: phenotypic and genetic heterogeneity. Mov Disord 2021;36(7):1511–1525.CrossRefGoogle ScholarPubMed
Boot, E, Bassett, AS, Marras, C. 22q11.2 Deletion syndrome-associated Parkinson’s disease. Mov Disord Clin Pract 2019;6(1):11–16.CrossRefGoogle ScholarPubMed
Figura, M, Geremek, M, Milanowski, LM, et al. Movement disorders associated with chromosomal aberrations diagnosed in adult patients. Neurol Neurochir Pol 2021;55(3):300–305.CrossRefGoogle ScholarPubMed
Araujo, FMM, Junior, WM, Tomaselli, PJ, et al. SPG15: a rare correlation with atypical juvenile parkinsonism responsive to levodopa. Mov Disord Clin Pract 2020;7(7):842–844.CrossRefGoogle ScholarPubMed
Leuzzi, V, Nardecchia, F, Pons, R, Galosi, S. Parkinsonism in children: clinical classification and etiological spectrum. Parkinsonism Relat Disord 2021;82:150–157.CrossRefGoogle ScholarPubMed
Hsieh, PC, Wang, CC, Tsai, CL, et al. POLG R964C and GBA L444P mutations in familial Parkinson’s disease: case report and literature review. Brain Behav 2019;9(5):e01281.CrossRefGoogle ScholarPubMed
Mehta, SH, Dickson, DW, Morgan, JC, et al. Juvenile onset Parkinsonism with “pure nigral” degeneration and POLG1 mutation. Parkinsonism Relat Disord 2016;30:83–85.CrossRefGoogle ScholarPubMed
Konno, T, Ross, OA, Teive, HAG, et al. DCTN1-related neurodegeneration: Perry syndrome and beyond. Parkinsonism Relat Disord 2017;41:14–24.CrossRefGoogle ScholarPubMed
Gatto, EM, Rojas, GJ, Nemirovsky, SI, et al. A novel mutation in PSEN1 (p.Arg41Ser) in an Argentinian woman with early onset Parkinsonism. Parkinsonism Relat Disord 2020;77:21–25.CrossRefGoogle Scholar
Synofzik, M. Parkinsonism in neurodegenerative diseases predominantly presenting with ataxia. Int Rev Neurobiol 2019;149:277–298.CrossRefGoogle ScholarPubMed
Park, H, Kim, HJ, Jeon, BS. Parkinsonism in spinocerebellar ataxia. Biomed Res Int 2015;2015:125273.CrossRefGoogle ScholarPubMed
Hanna Al-Shaikh, R, Wernick, AI, Strongosky, AJ, et al. Spinocerebellar ataxia type 6 family with phenotypic overlap with multiple system atrophy. Neurol Neurochir Pol 2020;54(4):350–355.CrossRefGoogle ScholarPubMed
Pollini, L, Galosi, S, Tolve, M, et al. KCND3-related neurological disorders: from old to emerging clinical phenotypes. Int J Mol Sci 2020;21(16):5802.CrossRefGoogle ScholarPubMed
Ser, MH, Tekgul, S, Gunduz, A, et al. Ataxia telangiectasia like disorder: another dopa-responsive disorder look-alike? Parkinsonism Relat Disord 2020;74:22–24.CrossRefGoogle ScholarPubMed
Weissbach, A, Saranza, G, Domingo, A. Combined dystonias: clinical and genetic updates. J Neural Transm (Vienna) 2021;128(4):417–429.CrossRefGoogle ScholarPubMed
Weissbach, A, Wittke, C, Kasten, M, Klein, C. ‘Atypical’ Parkinson’s disease – genetic. Int Rev Neurobiol 2019;149:207–235.CrossRefGoogle ScholarPubMed
Hedera, P. Wilson’s disease: a master of disguise. Parkinsonism Relat Disord 2019;59:140–145.CrossRefGoogle ScholarPubMed
Niemann, N, Jankovic, J. Juvenile parkinsonism: differential diagnosis, genetics, and treatment. Parkinsonism Relat Disord 2019;67:74–89.CrossRefGoogle ScholarPubMed
Anagianni, S, Tuschl, K. Genetic disorders of manganese metabolism. Curr Neurol Neurosci Rep 2019;19(6):33.CrossRefGoogle ScholarPubMed
Reilmann, R. Parkinsonism in Huntington’s disease. Int Rev Neurobiol 2019;149:299–306.CrossRefGoogle ScholarPubMed
Bally, JF, Camargos, S, Oliveira Dos Santos, C, et al. DYT-TUBB4A (DYT4 dystonia): new clinical and genetic observations. Neurology 2021;96(14):e1887–e1897.CrossRefGoogle ScholarPubMed
Chen, J, Luo, S, Li, N, et al. A novel missense mutation of the CSF1R gene causes incurable CSF1R-related leukoencephalopathy: case report and review of literature. Int J Gen Med 2020;13:1613–1620.CrossRefGoogle ScholarPubMed
Ramirez, J, Dilliott, AA, Binns, MA, et al. Parkinson’s disease, NOTCH3 genetic variants, and white matter hyperintensities. Mov Disord 2020;35(11):2090–2095.CrossRefGoogle ScholarPubMed
Horvath, R, Kley, RA, Lochmuller, H, Vorgerd, M. Parkinson syndrome, neuropathy, and myopathy caused by the mutation A8344G (MERRF) in tRNALys. Neurology 2007;68(1):56–58.CrossRefGoogle ScholarPubMed
Balicza, P, Bencsik, R, Lengyel, A, et al. Novel dominant MPAN family with a complex genetic architecture as a basis for phenotypic variability. Neurol Genet 2020;6(5):e515.CrossRefGoogle ScholarPubMed
Annesi, G, Gagliardi, M, Iannello, G, et al. Mutational analysis of COASY in an Italian patient with NBIA. Parkinsonism Relat Disord 2016;28:150–151.CrossRefGoogle Scholar
Ebrahimi-Fakhari, D, Van Karnebeek, C, Munchau, A. Movement disorders in treatable inborn errors of metabolism. Mov Disord 2019;34(5):598–613.CrossRefGoogle ScholarPubMed
Kresojevic, N, Mandic-Stojmenovic, G, Dobricic, V, et al. Very late-onset Niemann Pick type C disease: example of progressive supranuclear palsy look-alike disorder. Mov Disord Clin Pract 2020;7(2):211–214.CrossRefGoogle ScholarPubMed
Ebrahimi-Fakhari, D, Hildebrandt, C, Davis, PE, et al. The spectrum of movement disorders in childhood-onset lysosomal storage diseases. Mov Disord Clin Pract 2018;5(2):149–155.CrossRefGoogle ScholarPubMed
Cherian, A, Divya, KP, Paramasivan, NK, Krishnan, S. Pearls & Oy-sters: levodopa-responsive adult NCL (type B Kufs disease) due to CLN6 mutation. Neurology 2021;96(21):e2662–e2665.CrossRefGoogle ScholarPubMed
Tian, Y, Wang, JL, Huang, W, et al. Expansion of human-specific GGC repeat in neuronal intranuclear inclusion disease-related disorders. Am J Hum Genet 2019;105(1):166–176.CrossRefGoogle ScholarPubMed
de Gusmao, CM, Stone, S, Waugh, JL, et al. VAC14 gene-related parkinsonism–dystonia with response to deep brain stimulation. Mov Disord Clin Pract 2019;6(6):494–497.CrossRefGoogle ScholarPubMed
Park, J, Park, ST, Kim, J, Kwon, KY. A case report of adult-onset Alexander disease clinically presenting as Parkinson’s disease: is the comorbidity associated with genetic susceptibility? BMC Neurol 2020;20(1):27.CrossRefGoogle Scholar
Introne, WJ, Westbroek, W, Groden, CA, et al. Neurologic involvement in patients with atypical Chediak-Higashi disease. Neurology 2017;88(7):e57–e65.CrossRefGoogle ScholarPubMed
Flokas, ME, Tomani, M, Agdere, L, Brown, B. Triple A syndrome (Allgrove syndrome): improving outcomes with a multidisciplinary approach. Pediatric Health Med Ther 2019;10:99–106.CrossRefGoogle ScholarPubMed
Vroegindeweij, LHP, Langendonk, JG, Langeveld, M, et al. New insights in the neurological phenotype of aceruloplasminemia in Caucasian patients. Parkinsonism Relat Disord 2017;36:33–40.CrossRefGoogle ScholarPubMed
Kumar, N, Rizek, P, Sadikovic, B, Adams, PC, Jog, M. Movement disorders associated with hemochromatosis. Can J Neurol Sci 2016;43(6):801–808.CrossRefGoogle ScholarPubMed
Bohlega, S, Abusrair, AH, Al-Ajlan, FS, et al. Patterns of neurological manifestations in Woodhouse–Sakati syndrome. Parkinsonism Relat Disord 2019;69:99–103.CrossRefGoogle ScholarPubMed
Dulski, J, Sulek, A, Krygier, M, Radziwonik, W, Slawek, J. False-negative tests in Huntington’s disease: a new variant within primer hybridization site. Eur J Neurol 2021;28(6):2103–2105.CrossRefGoogle ScholarPubMed

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