Autosomal-dominant and autosomal-recessive form of Juvenile parkinsonism – part I

Authors

Keywords:

Juvenile parkinsonism, Parkinson's disease, atypical parkinsonism, Parkin, levodopa

Abstract

Juvenile parkinsonism (JP) is a rare, heterogeneous and often familial syndrome characterized by the manifestation of parkinsonism in patients under 21 years of age. The clinical picture may resemble that of idiopathic Parkinson's disease (PD), but there is often an atypical and complex phenotype, with other predominant motor symptoms (dystonia, choreoathetosis, spasticity, myoclonus, ataxia), cognitive and behavioural problems. Mutations in various genes are described in patients with juvenile parkinsonism, the Parkin gene being the most common. Patients with Parkin, PINK1 and DJ1 mutations have a similar phenotype that resembles that of idiopathic PD, although the disease often has an earlier onset and slower progression of the symptoms. Autosomal-dominant forms of JP are characterized by incomplete penetrance, a mean age of onset most often in the fifth decade and good response to dopaminergic treatment.
Pathological variants in LRRK2 and VPS35 have been demonstrated in patients with parkinsonism resembling the idiopathic form of PD, whereas mutations in SNCA have been described in cases of atypical parkinsonism. Usually, a good or excellent initial response to levodopa is observed, although this is complicated by levodopa-induced dyskinesias and motor fluctuations

References

Anwar, A., Saleem, S., Akhtar,. A, Ashraf, S., Ahmed, M.F. Juvenile Parkinson Disease. Cureus. 2019, 17, 11, e5409. 2. Alcalay, R., Caccappolo, E., Mejia-Santana, H., Tang, M., Rosado, L., Ross, B., Verbitsky, M., Kisselev, S., Louis, E., Comella, C., Colcher, A., Jennings, D., Nance, M., Bressman, S., Scott, W., Tanner, C., Mickel, S., Andrews, H., Waters, C., Fahn, S., Cote, L., Frucht, S., Ford, B., Rezak, M., Novak, K., Friedman, J., Pfeiffer, R., Marsh, L., Hiner, B., Siderowf, A., Ottman, R., Marder, K., Clark, L.. Frequency of known mutations in earlyonset Parkinson disease: implication for genetic counseling: the consortium on risk for early onset Parkinson disease study. Arch Neurol, 2010, 67, 9, 1116-1122.

Al-Rumayyan, A., Klein, C., Alfadhel, M. Early-Onset Parkinsonism: Case Report and Review of the Literature. Pediatr Neurol, 2017, 67, 102-106.

Behrens, M., Brüggemann, N., Chana, P., Venegas, P., Kägi, M., Parrao, T., Orellana, P., Garrido, C., Rojas, C., Hauke, J., Hahnen, E., González, R., Seleme, N., Fernández, V., Schmidt, A., Binkofski, F., Kömpf, D., Kubisch, C., Hagenah, J., Klein, C., Ramirez, A. Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations. Mov Disord, 2010, 25, 12, 1929-1937.

Bonifati, V., De Michele, G., Lücking, C., Dürr, A., Fabrizio, E., Ambrosio, G., Vanacore, N., De Mari, M., Marconi, R., Capus, L., Breteler, M., Gasser, T., Oostra, B., Wood, N., Agid, Y., Filla, A., Meco, G., Brice, A.; Italian, P. Genetics Study Group, French PD Genetics Study Group, European Consortium on Genetic Susceptibility in PD. The parkin gene and its phenotype. Italian PD Genetics Study Group, French PD Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease. Neurol Sci, 2001, 22, 1, 51-52.

Cardoso, F., Camargos, S. Juvenile parkinsonism: a heterogeneous entity. Eur J Neurol, 2000, 7, 5, 467-471.

Crosiers, D., Ceulemans, B., Meeus, B., Nuytemans, K., Pals, P., Van Broeckhoven, C., Cras, P., Theuns, J. Juvenile dystonia-parkinsonism and dementia caused by a novel ATP13A2 frameshift mutation. Parkinsonism Relat Disord, 2011, 17, 2, 135-138.

Fang, Y., Mao, F., Zhu, M., Li, X. Compound heterozygous mutations in PARK2 causing early-onset Parkinson disease: A case report. Medicine (Baltimore), 2019, 98, 5, e14228.

Ferraris, A. Valente, E., Bentivoglio, A. Prevalence and Phenotypic Spectrum of PINK1 Mutations in Parkinson’s Disease. US Neurology, 2009, 5, 1, 34-37.

Funayama, M., Li, Y., Tsoi, T., Lam, C., Ohi, T., Yazawa, S., Uyama, E., Djaldetti, R., Melamed, E., Yoshino, H., Imamichi, Y., Takashima, H., Nishioka, K., Sato, K., Tomiyama, H., Kubo, S., Mizuno, Y., Hattori, N. Familial Parkinsonism with digenic parkin and PINK1 mutations. Mov Disord, 2008, 23, 10, 1461-1465.

Garcia-Cazorla, A., Duarte, S. Parkinsonism and inborn errors of metabolism. J Inherit Metab Dis, 2014, 37, 4, 627-642.

Gasser, T. Genetics of Parkinson's disease. Curr Opin Neurol, 2005, 18, 4, 363-369.

Guadagnolo, D., Piane, M., Torrisi, M., Pizzuti, A., Petrucci, S. Genotype-Phenotype Correlations in Monogenic Parkinson Disease: A Review on Clinical and Molecular Findings. Front Neurol, 2021, 12, 648588.

Hedrich, K., Djarmati, A., Schäfer, N., Hering, R., Wellenbrock, C., Weiss, P., Hilker, R., Vieregge, P., Ozelius, L., Heutink, P., Bonifati, V., Schwinger, E., Lang, A., Noth, J., Bressman, S., Pramstaller, P., Riess, O., Klein, C. DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease. Neurology, 2004, 62, 3, 389-394.

Kann, M., Jacobs, H., Mohrmann K. Role of parkin mutations in 111 community-based patients with early-onset parkinsonism. Ann Neurol, 2002, 51, 621-625.

Kasten, M., Hartmann, C., Hampf, J., Schaake, S., Westenberger, A., Vollstedt, E., Balck, A., Domingo, A., Vulinovic, F., Dulovic, M., Zorn, I., Madoev, H., Zehnle, H., Lembeck, C., Schawe, L., Reginold, J., Huang, J., König, I., Bertram, L., Marras, C., Lohmann, K., Lill, C., Klein, C. Genotype-Phenotype Relations for the Parkinson's Disease Genes Parkin, PINK1, DJ1: MDSGene Systematic Review. Mov Disord, 2018, 33, 5, 730-741.

Khan, N., Graham, E., Critchley, P., Schrag, A., Wood, N., Lees, A., Bhatia, K., Quinn. Parkin disease: a phenotypic study of a large case series. Brain, 2003, 126, Pt 6, 1279-1292.

Kiely, A., Asi, Y., Kara, E., Limousin, P., Ling, H., Lewis, P., Proukakis, C., Quinn, N., Lees, A., Hardy, J., Revesz, T., Houlden, H., Holton, J. α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson's disease and multiple system atrophy? Acta Neuropathol, 2013, 125, 5, 753-769.

Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., Shimizu, N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature, 1998, 392 6676, 605-608.

Kirola, L., Behari, M., Shishir, C., Thelma, B.. Identification of a novel homozygous mutation Arg459Pro in SYNJ1 gene of an Indian family with autosomal recessive juvenile Parkinsonism. Parkinsonism Relat Disord, 2016, 31, 124-128.

Lesage, S., Anheim, M., Letournel, F. et al. G51D α-synuclein mutation causes a novel parkinsonian-pyramidal syndrome. Ann Neurol, 2013, 73, 4, 459-471.

Lohmann, E., Periquet, M., Bonifati, V., Wood, N., De Michele, G., Bonnet, A., Fraix, V., Broussolle, E., Horstink, M., Vidailhet, M., Verpillat, P., Gasser, T., Nicholl, D., Teive, H., Raskin, S., Rascol, O., Destée, A., Ruberg, M., Gasparini, F., Meco, G., Agid, Y., Durr, A., Brice, A.; French Parkinson's Disease Genetics Study Group; European Consortium on Genetic Susceptibility in Parkinson's Disease. How much phenotypic variation can be attributed to parkin genotype? Ann Neurol, 2003, 54, 2, 176-185.

Leuzzi, V., Nardecchia, F., Pons, R., Galosi, S. Parkinsonism in children: Clinical classification and etiological spectrum. Parkinsonism Relat Disord, 2021, 82, 150-157.

Liu, X., Le, W. Profiling Non-motor Symptoms in Monogenic Parkinson's Disease. Front Aging Neurosci, 2020, 12, 591183.

Lücking, C., Dürr, A., Bonifati, V., Vaughan, J., De Michele, G., Gasser, T., Harhangi, B., Meco, G., Denèfle, P., Wood, N., Agid, Y., Brice, A., French Parkinson's Disease Genetics Study Group, European Consortium on Genetic Susceptibility in Parkinson's Disease. Association between early-onset Parkinson's disease and mutations in the parkin gene. N Engl J Med, 2000, 342, 21, 1560-1567.

Marongiu, R., Ferraris, A., Ialongo, T., Michiorri, S., Soleti, F., Ferrari, F., Elia, A., Ghezzi, D., Albanese, A., Altavista, M., Antonini, A., Barone, P., Brusa, L., Cortelli, P., Martinelli, P., Pellecchia, M., Pezzoli, G., Scaglione, C., Stanzione, P., Tinazzi, M., Zecchinelli, A., Zeviani, M., Cassetta, E., Garavaglia, B., Dallapiccola, B., Bentivoglio, A., Valente, E.; Italian PD Study Group. PINK1 heterozygous rare variants: prevalence, significance and phenotypic spectrum. Hum Mutat, 2008, 29, 4, 565.

Marder, K., Tang, M., Mejia-Santana, H. et al. Predictors of parkin mutations in early-onset Parkinson disease: the consortium on risk for early-onset Parkinson disease study. Arch Neurol, 2010, 67, 6, 731-738.

Martikainen, M., Päivärinta, M., Hietala, M., Kaasinen, V. Clinical and imaging findings in Parkinson disease associated with the A53E SNCA mutation. Neurol Genet, 2015, 1, 4, e27.

Martí Massó, F., Ruiz-Martínez, J., Paisán-Ruiz, C., Gorostidi, A., Bergareche, C., Lopez de Munain, A., Alzualde, A., Pérez-Tur, J. Parkin and LRRK2/Dardarin Mutations in Early Onset Parkinson’s Disease in theBasque Country (Spain) Journal of Behavioral and Brain Science, 2015, 5, 101-108

Morales-Briceño, H., Mohammad, S., Post, B., Fois, A., Dale, R., Tchan, M., Fung, V. Clinical and neuroimaging phenotypes of genetic parkinsonism from infancy to adolescence. Brain, 2020, 1, 143, 3, 751-770.

Nichols, W., Pankratz, N., Marek, D., Pauciulo, M., Elsaesser, V., Halter, C., Rudolph, A., Wojcieszek, J., Pfeiffer, R., Foroud, T.; Parkinson Study Group-PROGENI Investigators. Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset. Neurology, 2009, 72, 4, 310-316.

Niemann, N., Jankovic, J. Juvenile parkinsonism: Differential diagnosis, genetics, and treatment. Parkinsonism Relat Disord, 2019, 67, 74-89.

Olszewska, D., McCarthy, A., Soto-Beasley, A., Walton, R., Ross, O., Lynch, T. PARKIN, PINK1, and DJ1 analysis in early-onset Parkinson's disease in Ireland. Ir J Med Sci, 2022, 191, 2, 901-907.

Olgiati, S., de Rosa, A., Quadri, M., Criscuolo, C., Breedveld, G., Picillo, M., Bonifati, V. PARK20 caused by SYNJ1 homozygous Arg258Gln mutation in a new Italian family. Neurogenetics, 2014, 15, 3, 183-188.

Periquet, M., Latouche, M., Lohmann, E., Rawal, N., De Michele, G., Ricard, S., Teive, H., Fraix, V., Vidailhet, M., Nicholl, D., Barone, P., Wood, N., Raskin, S., Deleuze, J., Agid, Y., Dürr, A., Brice, A.; French Parkinson's Disease Genetics Study Group; European Consortium on Genetic Susceptibility in Parkinson's Disease. Parkin mutations are frequent in patients with isolated early-onset parkinsonism. Brain, 2003, 126, Pt 6, 1271-1278.

Piredda, R., Desmarais, P., Masellis, M., Gasca-Salas, C. Cognitive and psychiatric symptoms in genetically determined Parkinson's disease: a systematic review. Eur J Neurol, 2020, 27, 2, 229-234.

Puschmann, A., Fiesel, F., Caulfield, T., Hudec, R., Ando, M., Truban, D., Hou, X., Ogaki, K., Heckman, M., James, E., Swanberg, M., Jimenez-Ferrer, I., Hansson, O., Opala, G., Siuda, J., Boczarska-Jedynak, M., Friedman, A., Koziorowski, D., Rudzińska-Bar, M., Aasly, J., Lynch, T., Mellick, G., Mohan, M., Silburn, P., Sanotsky, Y., Vilariño-Güell, C., Farrer, M., Chen, L., Dawson, V., Dawson, T., Wszolek, Z., Ross, O., Springer, W. Heterozygous PINK1 p.G411S increases risk of Parkinson's disease via a dominant-negative mechanism. Brain, 2017, 140, 1, 98-117.

Quinn, N., Critchley, P., Marsden, C. Young onset Parkinson's disease. Mov Disord, 1987, 2, 2, 73-91.

Riboldi, G., Frattini, E., Monfrini, E., Frucht, S., Di Fonzo, A. A Practical Approach to Early-Onset Parkinsonism. J Parkinsons Dis, 2022, 12, 1, 1-26.

Schrag, A., Schott, J.. Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism. Lancet Neurol, 2006, 5, 4, 355-363.

Schneider, S., Paisan-Ruiz, C., Quinn, N., Lees, A., Houlden, H., Hardy, J., Bhatia, K.. ATP13A2 mutations (PARK9) cause neurodegeneration with brain iron accumulation. Mov Disord, 2010, 25, 8, 979-984.

Shi, C., Zhang, S., Yang, Z., Yang, J., Shang, D., Mao, C., Liu, H., Hou, H., Shi,.M., Wu, J., Xu, Y.. A novel RAB39B gene mutation in X-linked juvenile parkinsonism with basal ganglia calcification. Mov Disord, 2016, 31, 12, 1905-1909.

Steinlechner, S., Stahlberg, J., Völkel, B., Djarmati, A., Hagenah, J., Hiller, A., Hedrich, K., König, I., Klein, C., Lencer, R.. Co-occurrence of affective and schizophrenia spectrum disorders with PINK1 mutations. J Neurol Neurosurg Psychiatry, 2007, 78, 5, 532-535.

Suleiman, J., Hamwi, N., El-Hattab, A. ATP13A2 novel mutations causing a rare form of juvenile-onset Parkinson disease. Brain Dev, 2018, 40, 9, 824-826.

Tokutake, T., Ishikawa, A., Yoshimura, N., Miyashita, A., Kuwano, R., Nishizawa, M., Ikeuchi, T. Clinical and neuroimaging features of patient with early-onset Parkinson's disease with dementia carrying SNCA p.G51D mutation. Parkinsonism Relat Disord, 2014, 20, 2, 262-264.

Tranchant, C., Koob, M., Anheim, M. Parkinsonian-Pyramidal syndromes: A systematic review. Parkinsonism Relat Disord, 2017, 39, 4-16.

Published

30.12.2023

How to Cite

Aleksandrova, I., Asenova, A., & Bojinova, V. (2023). Autosomal-dominant and autosomal-recessive form of Juvenile parkinsonism – part I. Bulgarian Neurology, 24(3), 101–106. Retrieved from https://www.nevrologiabg.com/journal/index.php/neurology/article/view/147

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