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Parkinson disease 5, autosomal dominant, susceptibility to(PARK5)

MedGen UID:
462249
Concept ID:
C3150899
Finding
Synonyms: Parkinson disease 5; Parkinson disease 5, susceptibility to
 
Gene (location): UCHL1 (4p13)
 
Monarch Initiative: MONDO:0013340
OMIM®: 613643

Definition

Parkinson's disease is a progressive disorder of the nervous system. The disorder affects several regions of the brain, especially an area called the substantia nigra that controls balance and movement.

Often the first symptom of Parkinson's disease is trembling or shaking (tremor) of a limb, especially when the body is at rest. Typically, the tremor begins on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet, and face. Other characteristic symptoms of Parkinson's disease include rigidity or stiffness of the limbs and torso, slow movement (bradykinesia) or an inability to move (akinesia), and impaired balance and coordination (postural instability). These symptoms worsen slowly over time.

Parkinson's disease can also affect emotions and thinking ability (cognition). Some affected individuals develop psychiatric conditions such as depression and visual hallucinations. People with Parkinson's disease also have an increased risk of developing dementia, which is a decline in intellectual functions including judgment and memory.

Generally, Parkinson's disease that begins after age 50 is called late-onset disease. The condition is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 are sometimes referred to as juvenile-onset Parkinson's disease. [from MedlinePlus Genetics]

Clinical features

From HPO
Bradykinesia
MedGen UID:
115925
Concept ID:
C0233565
Sign or Symptom
Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement).
Postural instability
MedGen UID:
334529
Concept ID:
C1843921
Finding
A tendency to fall or the inability to keep oneself from falling; imbalance. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, Use of the retropulsion test includes a rapid balance perturbation in the backward direction, and the number of balance correcting steps (or total absence thereof) is used to rate the degree of postural instability. Healthy subjects correct such perturbations with either one or two large steps, or without taking any steps, hinging rapidly at the hips while swinging the arms forward as a counterweight. In patients with balance impairment, balance correcting steps are often too small, forcing patients to take more than two steps. Taking three or more steps is generally considered to be abnormal, and taking more than five steps is regarded as being clearly abnormal. Markedly affected patients continue to step backward without ever regaining their balance and must be caught by the examiner (this would be called true retropulsion). Even more severely affected patients fail to correct entirely, and fall backward like a pushed toy soldier, without taking any corrective steps.
Parkinsonism with favorable response to dopaminergic medication
MedGen UID:
375989
Concept ID:
C1846868
Disease or Syndrome
Parkinsonism is a clinical syndrome that is a feature of a number of different diseases, including Parkinson disease itself, other neurodegenerative diseases such as progressive supranuclear palsy, and as a side-effect of some neuroleptic medications. Some but not all individuals with Parkinsonism show responsiveness to dopaminergic medication defined as a substantial reduction of amelioration of the component signs of Parkinsonism (including mainly tremor, bradykinesia, rigidity, and postural instability) upon administration of dopaminergic medication.
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.

Professional guidelines

PubMed

Krygowska-Wajs A, Kachergus JM, Hulihan MM, Farrer MJ, Searcy JA, Booij J, Berendse HW, Wolters ECh, Wszolek ZK
J Neural Transm (Vienna) 2005 Nov;112(11):1487-502. Epub 2005 Mar 23 doi: 10.1007/s00702-005-0290-8. PMID: 15785861
Nichols WC, Pankratz N, Hernandez D, Paisán-Ruíz C, Jain S, Halter CA, Michaels VE, Reed T, Rudolph A, Shults CW, Singleton A, Foroud T; Parkinson Study Group-PROGENI investigators
Lancet 2005 Jan 29-Feb 4;365(9457):410-2. doi: 10.1016/S0140-6736(05)17828-3. PMID: 15680455

Recent clinical studies

Etiology

Cherian A, Divya KP
Acta Neurol Belg 2020 Dec;120(6):1297-1305. Epub 2020 Aug 19 doi: 10.1007/s13760-020-01473-5. PMID: 32813147
Zhao Y, Qin L, Pan H, Liu Z, Jiang L, He Y, Zeng Q, Zhou X, Zhou X, Zhou Y, Fang Z, Wang Z, Xiang Y, Yang H, Wang Y, Zhang K, Zhang R, He R, Zhou X, Zhou Z, Yang N, Liang D, Chen J, Zhang X, Zhou Y, Liu H, Deng P, Xu K, Xu K, Zhou C, Zhong J, Xu Q, Sun Q, Li B, Zhao G, Wang T, Chen L, Shang H, Liu W, Chan P, Xue Z, Wang Q, Guo L, Wang X, Xu C, Zhang Z, Chen T, Lei L, Zhang H, Wang C, Tan J, Yan X, Shen L, Jiang H, Zhang Z, Hu Z, Xia K, Yue Z, Li J, Guo J, Tang B
Brain 2020 Jul 1;143(7):2220-2234. doi: 10.1093/brain/awaa167. PMID: 32613234
Reed X, Bandrés-Ciga S, Blauwendraat C, Cookson MR
Neurobiol Dis 2019 Apr;124:230-239. Epub 2018 Nov 15 doi: 10.1016/j.nbd.2018.11.012. PMID: 30448284Free PMC Article
Lill CM
Mol Cell Probes 2016 Dec;30(6):386-396. Epub 2016 Nov 4 doi: 10.1016/j.mcp.2016.11.001. PMID: 27818248
Bonifati V
Parkinsonism Relat Disord 2014 Jan;20 Suppl 1:S23-8. doi: 10.1016/S1353-8020(13)70009-9. PMID: 24262182

Diagnosis

Zhao Y, Qin L, Pan H, Liu Z, Jiang L, He Y, Zeng Q, Zhou X, Zhou X, Zhou Y, Fang Z, Wang Z, Xiang Y, Yang H, Wang Y, Zhang K, Zhang R, He R, Zhou X, Zhou Z, Yang N, Liang D, Chen J, Zhang X, Zhou Y, Liu H, Deng P, Xu K, Xu K, Zhou C, Zhong J, Xu Q, Sun Q, Li B, Zhao G, Wang T, Chen L, Shang H, Liu W, Chan P, Xue Z, Wang Q, Guo L, Wang X, Xu C, Zhang Z, Chen T, Lei L, Zhang H, Wang C, Tan J, Yan X, Shen L, Jiang H, Zhang Z, Hu Z, Xia K, Yue Z, Li J, Guo J, Tang B
Brain 2020 Jul 1;143(7):2220-2234. doi: 10.1093/brain/awaa167. PMID: 32613234
Sciacca P, Giacchi V, Mattia C, Greco F, Smilari P, Betta P, Distefano G
BMC Cardiovasc Disord 2014 May 9;14:66. doi: 10.1186/1471-2261-14-66. PMID: 24884933Free PMC Article
Lin CH, Tzen KY, Yu CY, Tai CH, Farrer MJ, Wu RM
J Biomed Sci 2008 Sep;15(5):661-7. Epub 2008 Jun 4 doi: 10.1007/s11373-008-9260-0. PMID: 18523869
Pankratz N, Foroud T
Genet Med 2007 Dec;9(12):801-11. doi: 10.1097/gim.0b013e31815bf97c. PMID: 18091429
Pankratz N, Nichols WC, Uniacke SK, Halter C, Rudolph A, Shults C, Conneally PM, Foroud T; Parkinson Study Group
Am J Hum Genet 2002 Jul;71(1):124-35. Epub 2002 Jun 7 doi: 10.1086/341282. PMID: 12058349Free PMC Article

Therapy

Sciacca P, Giacchi V, Mattia C, Greco F, Smilari P, Betta P, Distefano G
BMC Cardiovasc Disord 2014 May 9;14:66. doi: 10.1186/1471-2261-14-66. PMID: 24884933Free PMC Article
Young JE, Vilariño-Güell C, Lin SC, Wszolek ZK, Farrer MJ
Mayo Clin Proc 2009 Feb;84(2):134-8. doi: 10.4065/84.2.134. PMID: 19181647Free PMC Article
Ichinose H, Suzuki T, Inagaki H, Ohye T, Nagatsu T
Biol Chem 1999 Dec;380(12):1355-64. doi: 10.1515/BC.1999.175. PMID: 10661862

Prognosis

Smaili I, Tesson C, Regragui W, Bertrand H, Rahmani M, Bouslam N, Benomar A, Brice A, Lesage S, Bouhouche A
J Mol Neurosci 2021 Jan;71(1):142-152. Epub 2020 Jun 16 doi: 10.1007/s12031-020-01635-3. PMID: 32557143
Lahut S, Gispert S, Ömür Ö, Depboylu C, Seidel K, Domínguez-Bautista JA, Brehm N, Tireli H, Hackmann K, Pirkevi C, Leube B, Ries V, Reim K, Brose N, den Dunnen WF, Johnson M, Wolf Z, Schindewolf M, Schrempf W, Reetz K, Young P, Vadasz D, Frangakis AS, Schröck E, Steinmetz H, Jendrach M, Rüb U, Başak AN, Oertel W, Auburger G
Dis Model Mech 2017 May 1;10(5):619-631. Epub 2017 Jan 20 doi: 10.1242/dmm.028035. PMID: 28108469Free PMC Article
Lill CM
Mol Cell Probes 2016 Dec;30(6):386-396. Epub 2016 Nov 4 doi: 10.1016/j.mcp.2016.11.001. PMID: 27818248
Mata IF, Davis MY, Lopez AN, Dorschner MO, Martinez E, Yearout D, Cholerton BA, Hu SC, Edwards KL, Bird TD, Zabetian CP
Am J Med Genet B Neuropsychiatr Genet 2016 Oct;171(7):925-30. Epub 2016 Apr 25 doi: 10.1002/ajmg.b.32452. PMID: 27111571Free PMC Article
Sciacca P, Giacchi V, Mattia C, Greco F, Smilari P, Betta P, Distefano G
BMC Cardiovasc Disord 2014 May 9;14:66. doi: 10.1186/1471-2261-14-66. PMID: 24884933Free PMC Article

Clinical prediction guides

Santos-Lobato BL, Schumacher-Schuh A, Mata IF, Letro GH, Braga-Neto P, Brandão PRP, Godeiro-Junior CO, Coletta MVD, Camargos ST, Borges V, Rieder CRM, Tumas V
Arq Neuropsiquiatr 2021 Jul;79(7):612-623. doi: 10.1590/0004-282X-anp-2020-0409. PMID: 34468500
Reed X, Bandrés-Ciga S, Blauwendraat C, Cookson MR
Neurobiol Dis 2019 Apr;124:230-239. Epub 2018 Nov 15 doi: 10.1016/j.nbd.2018.11.012. PMID: 30448284Free PMC Article
Lill CM
Mol Cell Probes 2016 Dec;30(6):386-396. Epub 2016 Nov 4 doi: 10.1016/j.mcp.2016.11.001. PMID: 27818248
Prestel J, Sharma M, Leitner P, Zimprich A, Vaughan JR, Dürr A, Bonifati V, De Michele G, Hanagasi HA, Farrer M, Hofer A, Asmus F, Volpe G, Meco G, Brice A, Wood NW, Müller-Myhsok B, Gasser T; European Consortium on Genetic Susceptibility in Parkinson's Disease (GSPD)
Eur J Hum Genet 2005 Feb;13(2):193-7. doi: 10.1038/sj.ejhg.5201317. PMID: 15523496
Hicks AA, Pétursson H, Jónsson T, Stefánsson H, Jóhannsdóttir HS, Sainz J, Frigge ML, Kong A, Gulcher JR, Stefánsson K, Sveinbjörnsdóttir S
Ann Neurol 2002 Nov;52(5):549-55. doi: 10.1002/ana.10324. PMID: 12402251

Recent systematic reviews

Santos-Lobato BL, Schumacher-Schuh A, Mata IF, Letro GH, Braga-Neto P, Brandão PRP, Godeiro-Junior CO, Coletta MVD, Camargos ST, Borges V, Rieder CRM, Tumas V
Arq Neuropsiquiatr 2021 Jul;79(7):612-623. doi: 10.1590/0004-282X-anp-2020-0409. PMID: 34468500

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