U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Autosomal dominant Parkinson disease 8(PARK8)

MedGen UID:
339628
Concept ID:
C1846862
Disease or Syndrome
Synonyms: LRRK2-Related Parkinson Disease; Parkinson disease 8; Parkinson disease 8, susceptibility to
 
Gene (location): LRRK2 (12q12)
 
Monarch Initiative: MONDO:0011764
OMIM®: 607060

Definition

LRRK2 Parkinson disease (PD) is characterized by features consistent with idiopathic PD: initial motor features of slowly progressive asymmetric tremor at rest and/or bradykinesia, cogwheel muscle rigidity, postural instability, and gait abnormalities that may include festination and freezing. Certain nonmotor symptoms in LRRK2-PD, especially REM sleep behavior disorder and cognitive decline, may occur at similar or slightly reduced frequency compared to typical idiopathic* PD. Onset is generally after age 50, although early-onset (in the 20s) and late-onset (in the 90s) disease has been described. * Idiopathic PD refers to the presence of signs and symptoms of PD for which the etiology is currently unknown and in which there is no known family history of PD. [from GeneReviews]

Additional description

From MedlinePlus Genetics
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.  https://medlineplus.gov/genetics/condition/parkinsons-disease

Clinical features

From HPO
Lewy bodies
MedGen UID:
43126
Concept ID:
C0085200
Cell Component
Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of Lewy bodies is the histological marker of the degenerative changes in LEWY BODY DISEASE and PARKINSON DISEASE but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex.
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).
Resting tremor
MedGen UID:
66697
Concept ID:
C0234379
Sign or Symptom
A resting tremor occurs when muscles are at rest and becomes less noticeable or disappears when the affected muscles are moved. Resting tremors are often slow and coarse.
Parkinsonism
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
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.
Substantia nigra gliosis
MedGen UID:
337668
Concept ID:
C1846865
Finding
Focal proliferation of glial cells in the substantia nigra.
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.
Hyposmia
MedGen UID:
473584
Concept ID:
C2364082
Finding
A decreased sensitivity to odorants (that is, a decreased ability to perceive odors).
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

Fernández-Ramos JA, De la Torre-Aguilar MJ, Quintáns B, Pérez-Navero JL, Beyer K, López-Laso E; Spanish Segawa Disease Research group
Parkinsonism Relat Disord 2022 Jan;94:67-78. Epub 2021 Nov 25 doi: 10.1016/j.parkreldis.2021.11.014. PMID: 34890878
Mehta SG, Khare M, Ramani R, Watts GD, Simon M, Osann KE, Donkervoort S, Dec E, Nalbandian A, Platt J, Pasquali M, Wang A, Mozaffar T, Smith CD, Kimonis VE
Clin Genet 2013 May;83(5):422-31. Epub 2012 Oct 4 doi: 10.1111/cge.12000. PMID: 22909335Free PMC Article
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

Recent clinical studies

Etiology

Sung YJ, Yang C, Norton J, Johnson M, Fagan A, Bateman RJ, Perrin RJ, Morris JC, Farlow MR, Chhatwal JP, Schofield PR, Chui H, Wang F, Novotny B, Eteleeb A, Karch C, Schindler SE, Rhinn H, Johnson ECB, Oh HS, Rutledge JE, Dammer EB, Seyfried NT, Wyss-Coray T, Harari O, Cruchaga C
Sci Transl Med 2023 Jul 5;15(703):eabq5923. doi: 10.1126/scitranslmed.abq5923. PMID: 37406134Free PMC Article
Ettinger S
Curr Nutr Rep 2022 Dec;11(4):643-652. Epub 2022 Aug 26 doi: 10.1007/s13668-022-00435-y. PMID: 36018501
Chen YP, Yu SH, Zhang GH, Hou YB, Gu XJ, Ou RW, Shen Y, Song W, Chen XP, Zhao B, Cao B, Zhang LY, Sun MM, Liu FF, Wei QQ, Liu KC, Lin JY, Yang TM, Yang J, Wu Y, Jiang Z, Liu J, Cheng YF, Xiao Y, Su WM, Feng F, Cai YY, Li SR, Hu T, Yuan XQ, Zhou QQ, Shao N, Ma S, Shang HF
Eur J Neurol 2022 Nov;29(11):3218-3228. Epub 2022 Aug 4 doi: 10.1111/ene.15509. PMID: 35861376
Nussbaum RL
Cold Spring Harb Perspect Med 2018 Jun 1;8(6) doi: 10.1101/cshperspect.a024109. PMID: 28213435Free PMC Article
Sanna G, Del Giudice MG, Crosio C, Iaccarino C
Biochem Soc Trans 2012 Oct;40(5):1117-22. doi: 10.1042/BST20120117. PMID: 22988875

Diagnosis

Fernández-Ramos JA, De la Torre-Aguilar MJ, Quintáns B, Pérez-Navero JL, Beyer K, López-Laso E; Spanish Segawa Disease Research group
Parkinsonism Relat Disord 2022 Jan;94:67-78. Epub 2021 Nov 25 doi: 10.1016/j.parkreldis.2021.11.014. PMID: 34890878
Loeffler DA, Aasly JO, LeWitt PA, Coffey MP
J Parkinsons Dis 2019;9(3):467-488. doi: 10.3233/JPD-191630. PMID: 31322581Free PMC Article
Weng YC, Wang CC, Wu YR
Brain Behav 2018 Feb;8(2):e00906. Epub 2018 Jan 20 doi: 10.1002/brb3.906. PMID: 29484265Free PMC Article
Alcalay RN, Levy OA, Waters CC, Fahn S, Ford B, Kuo SH, Mazzoni P, Pauciulo MW, Nichols WC, Gan-Or Z, Rouleau GA, Chung WK, Wolf P, Oliva P, Keutzer J, Marder K, Zhang X
Brain 2015 Sep;138(Pt 9):2648-58. Epub 2015 Jun 27 doi: 10.1093/brain/awv179. PMID: 26117366Free PMC Article
Nygaard TG
Curr Opin Neurol 1995 Aug;8(4):310-3. doi: 10.1097/00019052-199508000-00011. PMID: 7582048

Therapy

Fernández-Ramos JA, De la Torre-Aguilar MJ, Quintáns B, Pérez-Navero JL, Beyer K, López-Laso E; Spanish Segawa Disease Research group
Parkinsonism Relat Disord 2022 Jan;94:67-78. Epub 2021 Nov 25 doi: 10.1016/j.parkreldis.2021.11.014. PMID: 34890878
Weng YC, Wang CC, Wu YR
Brain Behav 2018 Feb;8(2):e00906. Epub 2018 Jan 20 doi: 10.1002/brb3.906. PMID: 29484265Free PMC Article
Kang JF, Luo Y, Tang BS, Wan CM, Yang Y, Li K, Liu ZH, Sun QY, Xu Q, Yan XX, Guo JF
Sci Rep 2016 Oct 3;6:34502. doi: 10.1038/srep34502. PMID: 27694831Free PMC Article
Schulte EC, Stahl I, Czamara D, Ellwanger DC, Eck S, Graf E, Mollenhauer B, Zimprich A, Lichtner P, Haubenberger D, Pirker W, Brücke T, Bereznai B, Molnar MJ, Peters A, Gieger C, Müller-Myhsok B, Trenkwalder C, Winkelmann J
PLoS One 2013;8(11):e79145. Epub 2013 Nov 11 doi: 10.1371/journal.pone.0079145. PMID: 24244438Free PMC Article
Nygaard TG
Curr Opin Neurol 1995 Aug;8(4):310-3. doi: 10.1097/00019052-199508000-00011. PMID: 7582048

Prognosis

Vöglein J, Paumier K, Jucker M, Preische O, McDade E, Hassenstab J, Benzinger TL, Noble JM, Berman SB, Graff-Radford NR, Ghetti B, Farlow MR, Chhatwal J, Salloway S, Xiong C, Karch CM, Cairns N, Mori H, Schofield PR, Masters CL, Goate A, Buckles V, Fox N, Rossor M, Chrem P, Allegri R, Ringman JM, Höglinger G, Steiner H, Dieterich M, Haass C, Laske C, Morris JC, Bateman RJ, Danek A, Levin J; Dominantly Inherited Alzheimer Network
Brain 2019 May 1;142(5):1429-1440. doi: 10.1093/brain/awz050. PMID: 30897203Free PMC Article
Alcalay RN, Levy OA, Waters CC, Fahn S, Ford B, Kuo SH, Mazzoni P, Pauciulo MW, Nichols WC, Gan-Or Z, Rouleau GA, Chung WK, Wolf P, Oliva P, Keutzer J, Marder K, Zhang X
Brain 2015 Sep;138(Pt 9):2648-58. Epub 2015 Jun 27 doi: 10.1093/brain/awv179. PMID: 26117366Free PMC Article
Schulte EC, Stahl I, Czamara D, Ellwanger DC, Eck S, Graf E, Mollenhauer B, Zimprich A, Lichtner P, Haubenberger D, Pirker W, Brücke T, Bereznai B, Molnar MJ, Peters A, Gieger C, Müller-Myhsok B, Trenkwalder C, Winkelmann J
PLoS One 2013;8(11):e79145. Epub 2013 Nov 11 doi: 10.1371/journal.pone.0079145. PMID: 24244438Free PMC Article
Jankovic J, Madisetty J, Vuong KD
Pediatrics 2004 Nov;114(5):1203-5. doi: 10.1542/peds.2004-0031. PMID: 15520096
Gouider-Khouja N, Belal S, Hamida MB, Hentati F
Neurology 2000 Apr 25;54(8):1603-9. doi: 10.1212/wnl.54.8.1603. PMID: 10762501

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
Wilson H, Dervenoulas G, Pagano G, Koros C, Yousaf T, Picillo M, Polychronis S, Simitsi A, Giordano B, Chappell Z, Corcoran B, Stamelou M, Gunn RN, Pellecchia MT, Rabiner EA, Barone P, Stefanis L, Politis M
Lancet Neurol 2019 Aug;18(8):748-759. Epub 2019 Jun 19 doi: 10.1016/S1474-4422(19)30140-1. PMID: 31229470
Vöglein J, Paumier K, Jucker M, Preische O, McDade E, Hassenstab J, Benzinger TL, Noble JM, Berman SB, Graff-Radford NR, Ghetti B, Farlow MR, Chhatwal J, Salloway S, Xiong C, Karch CM, Cairns N, Mori H, Schofield PR, Masters CL, Goate A, Buckles V, Fox N, Rossor M, Chrem P, Allegri R, Ringman JM, Höglinger G, Steiner H, Dieterich M, Haass C, Laske C, Morris JC, Bateman RJ, Danek A, Levin J; Dominantly Inherited Alzheimer Network
Brain 2019 May 1;142(5):1429-1440. doi: 10.1093/brain/awz050. PMID: 30897203Free PMC Article
Conedera S, Apaydin H, Li Y, Yoshino H, Ikeda A, Matsushima T, Funayama M, Nishioka K, Hattori N
Neurobiol Aging 2016 Apr;40:192.e1-192.e5. Epub 2016 Jan 14 doi: 10.1016/j.neurobiolaging.2016.01.003. PMID: 26882974
Schulte EC, Stahl I, Czamara D, Ellwanger DC, Eck S, Graf E, Mollenhauer B, Zimprich A, Lichtner P, Haubenberger D, Pirker W, Brücke T, Bereznai B, Molnar MJ, Peters A, Gieger C, Müller-Myhsok B, Trenkwalder C, Winkelmann J
PLoS One 2013;8(11):e79145. Epub 2013 Nov 11 doi: 10.1371/journal.pone.0079145. PMID: 24244438Free PMC Article

Recent systematic reviews

Fereshtehnejad SM, Saleh PA, Oliveira LM, Patel N, Bhowmick S, Saranza G, Kalia LV
Neurol Sci 2023 Mar;44(3):947-959. Epub 2022 Nov 28 doi: 10.1007/s10072-022-06516-8. PMID: 36441344Free PMC Article
Wu MC, Chang YY, Chen YF, Lan MY, Chen PL, Tai CH, Lin CH
J Formos Med Assoc 2022 Jan;121(1 Pt 2):375-380. Epub 2021 Jun 4 doi: 10.1016/j.jfma.2021.05.017. PMID: 34092466
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
Samukawa M, Hirano M, Saigoh K, Kawai S, Hamada Y, Takahashi D, Nakamura Y, Kusunoki S
Cerebellum 2019 Feb;18(1):76-84. doi: 10.1007/s12311-018-0955-0. PMID: 29916049

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...