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Parkinson disease 17(PARK17)

MedGen UID:
481763
Concept ID:
C3280133
Disease or Syndrome
Synonym: PARK17
 
Gene (location): VPS35 (16q11.2)
 
Monarch Initiative: MONDO:0013625
OMIM®: 614203

Definition

VPS35-related Parkinson disease (VPS35-PD) is defined as Parkinson disease caused by heterozygous VPS35 pathogenic variants. Currently, the only known VPS35 variant with confirmed pathogenicity is c.1858G>A (p.Asp620Asn). Except for a younger age of onset, VPS35-PD is clinically indistinguishable from Parkinson disease of unknown cause (so-called sporadic Parkinson disease). Variability among 50 individuals reported with molecularly confirmed VPS35-PD includes age of onset (mean: 51.0±8.7 years; range: 34-68 years), Parkinson subtype (tremor, akinetic rigid, mixed), first motor symptom, course of the disease (unilateral onset and slow disease progression are typical; dyskinesia and motor fluctuations may occur), and presence/absence of neuropsychiatric manifestations (including depression, schizophrenia, learning difficulties, mild cognitive impairment, and dementia). [from GeneReviews]

Additional descriptions

From OMIM
Parkinson disease-17 is an autosomal dominant, adult-onset form of the disorder. It is phenotypically similar to idiopathic Parkinson disease (summary by Wider et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of Parkinson disease (PD), see 168600.  http://www.omim.org/entry/614203
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
Dyskinesia
MedGen UID:
8514
Concept ID:
C0013384
Disease or Syndrome
A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Akinesia
MedGen UID:
43218
Concept ID:
C0085623
Finding
Inability to initiate changes in activity or movement and to perform ordinary volitional movements rapidly and easily.
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.
Parkinsonian disorder
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.
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.
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

Mele B, Van S, Holroyd-Leduc J, Ismail Z, Pringsheim T, Goodarzi Z
BMJ Open 2020 Sep 9;10(9):e037632. doi: 10.1136/bmjopen-2020-037632. PMID: 32907903Free PMC Article
McKeith IG, Ferman TJ, Thomas AJ, Blanc F, Boeve BF, Fujishiro H, Kantarci K, Muscio C, O'Brien JT, Postuma RB, Aarsland D, Ballard C, Bonanni L, Donaghy P, Emre M, Galvin JE, Galasko D, Goldman JG, Gomperts SN, Honig LS, Ikeda M, Leverenz JB, Lewis SJG, Marder KS, Masellis M, Salmon DP, Taylor JP, Tsuang DW, Walker Z, Tiraboschi P; prodromal DLB Diagnostic Study Group
Neurology 2020 Apr 28;94(17):743-755. Epub 2020 Apr 2 doi: 10.1212/WNL.0000000000009323. PMID: 32241955Free PMC Article
Espay AJ, Aybek S, Carson A, Edwards MJ, Goldstein LH, Hallett M, LaFaver K, LaFrance WC Jr, Lang AE, Nicholson T, Nielsen G, Reuber M, Voon V, Stone J, Morgante F
JAMA Neurol 2018 Sep 1;75(9):1132-1141. doi: 10.1001/jamaneurol.2018.1264. PMID: 29868890Free PMC Article

Recent clinical studies

Etiology

De Pablo-Fernández E, Lees AJ, Holton JL, Warner TT
JAMA Neurol 2019 Apr 1;76(4):470-479. doi: 10.1001/jamaneurol.2018.4377. PMID: 30640364Free PMC Article
Ferreira RM, Alves WMGDC, de Lima TA, Alves TGG, Alves Filho PAM, Pimentel CP, Sousa EC, Cortinhas-Alves EA
Arq Neuropsiquiatr 2018 Aug;76(8):499-506. doi: 10.1590/0004-282X20180071. PMID: 30231121
Giardini M, Nardone A, Godi M, Guglielmetti S, Arcolin I, Pisano F, Schieppati M
Neural Plast 2018;2018:5614242. Epub 2018 Mar 7 doi: 10.1155/2018/5614242. PMID: 29706993Free PMC Article
Canning CG, Sherrington C, Lord SR, Close JC, Heritier S, Heller GZ, Howard K, Allen NE, Latt MD, Murray SM, O'Rourke SD, Paul SS, Song J, Fung VS
Neurology 2015 Jan 20;84(3):304-12. Epub 2014 Dec 31 doi: 10.1212/WNL.0000000000001155. PMID: 25552576Free PMC Article
Li F, Harmer P, Fitzgerald K, Eckstrom E, Stock R, Galver J, Maddalozzo G, Batya SS
N Engl J Med 2012 Feb 9;366(6):511-9. doi: 10.1056/NEJMoa1107911. PMID: 22316445Free PMC Article

Diagnosis

Höglinger GU, Adler CH, Berg D, Klein C, Outeiro TF, Poewe W, Postuma R, Stoessl AJ, Lang AE
Lancet Neurol 2024 Feb;23(2):191-204. doi: 10.1016/S1474-4422(23)00404-0. PMID: 38267191
Mele B, Van S, Holroyd-Leduc J, Ismail Z, Pringsheim T, Goodarzi Z
BMJ Open 2020 Sep 9;10(9):e037632. doi: 10.1136/bmjopen-2020-037632. PMID: 32907903Free PMC Article
Gazerani P
Int J Mol Sci 2019 Aug 23;20(17) doi: 10.3390/ijms20174121. PMID: 31450864Free PMC Article
De Pablo-Fernández E, Lees AJ, Holton JL, Warner TT
JAMA Neurol 2019 Apr 1;76(4):470-479. doi: 10.1001/jamaneurol.2018.4377. PMID: 30640364Free PMC Article
Giardini M, Nardone A, Godi M, Guglielmetti S, Arcolin I, Pisano F, Schieppati M
Neural Plast 2018;2018:5614242. Epub 2018 Mar 7 doi: 10.1155/2018/5614242. PMID: 29706993Free PMC Article

Therapy

Mele B, Van S, Holroyd-Leduc J, Ismail Z, Pringsheim T, Goodarzi Z
BMJ Open 2020 Sep 9;10(9):e037632. doi: 10.1136/bmjopen-2020-037632. PMID: 32907903Free PMC Article
Deuel LM, Seeberger LC
Neurotherapeutics 2020 Oct;17(4):1434-1455. doi: 10.1007/s13311-020-00900-y. PMID: 32785848Free PMC Article
Pazzaglia C, Imbimbo I, Tranchita E, Minganti C, Ricciardi D, Lo Monaco R, Parisi A, Padua L
Physiotherapy 2020 Mar;106:36-42. Epub 2019 Dec 23 doi: 10.1016/j.physio.2019.12.007. PMID: 32026844
Gazerani P
Int J Mol Sci 2019 Aug 23;20(17) doi: 10.3390/ijms20174121. PMID: 31450864Free PMC Article
Kwok JYY, Kwan JCY, Auyeung M, Mok VCT, Lau CKY, Choi KC, Chan HYL
JAMA Neurol 2019 Jul 1;76(7):755-763. doi: 10.1001/jamaneurol.2019.0534. PMID: 30958514Free PMC Article

Prognosis

Alberts JL, Rosenfeldt AB
J Parkinsons Dis 2020;10(s1):S21-S27. doi: 10.3233/JPD-202100. PMID: 32925109Free PMC Article
De Pablo-Fernández E, Lees AJ, Holton JL, Warner TT
JAMA Neurol 2019 Apr 1;76(4):470-479. doi: 10.1001/jamaneurol.2018.4377. PMID: 30640364Free PMC Article
Dorsey ER, Sherer T, Okun MS, Bloem BR
J Parkinsons Dis 2018;8(s1):S3-S8. doi: 10.3233/JPD-181474. PMID: 30584159Free PMC Article
Groveman BR, Orrù CD, Hughson AG, Raymond LD, Zanusso G, Ghetti B, Campbell KJ, Safar J, Galasko D, Caughey B
Acta Neuropathol Commun 2018 Feb 9;6(1):7. doi: 10.1186/s40478-018-0508-2. PMID: 29422107Free PMC Article
Hoehn MM, Yahr MD
Neurology 1967 May;17(5):427-42. doi: 10.1212/wnl.17.5.427. PMID: 6067254

Clinical prediction guides

Gandhi P, Steele CM
Am J Speech Lang Pathol 2022 Jan 18;31(1):463-485. Epub 2021 Dec 10 doi: 10.1044/2021_AJSLP-21-00145. PMID: 34890260Free PMC Article
Pazzaglia C, Imbimbo I, Tranchita E, Minganti C, Ricciardi D, Lo Monaco R, Parisi A, Padua L
Physiotherapy 2020 Mar;106:36-42. Epub 2019 Dec 23 doi: 10.1016/j.physio.2019.12.007. PMID: 32026844
Giardini M, Nardone A, Godi M, Guglielmetti S, Arcolin I, Pisano F, Schieppati M
Neural Plast 2018;2018:5614242. Epub 2018 Mar 7 doi: 10.1155/2018/5614242. PMID: 29706993Free PMC Article
Wu PL, Lee M, Huang TT
PLoS One 2017;12(7):e0181515. Epub 2017 Jul 27 doi: 10.1371/journal.pone.0181515. PMID: 28749970Free PMC Article
Li F, Harmer P, Fitzgerald K, Eckstrom E, Stock R, Galver J, Maddalozzo G, Batya SS
N Engl J Med 2012 Feb 9;366(6):511-9. doi: 10.1056/NEJMoa1107911. PMID: 22316445Free PMC Article

Recent systematic reviews

Ernst M, Folkerts AK, Gollan R, Lieker E, Caro-Valenzuela J, Adams A, Cryns N, Monsef I, Dresen A, Roheger M, Eggers C, Skoetz N, Kalbe E
Cochrane Database Syst Rev 2023 Jan 5;1(1):CD013856. doi: 10.1002/14651858.CD013856.pub2. PMID: 36602886Free PMC Article
Allen NE, Canning CG, Almeida LRS, Bloem BR, Keus SH, Löfgren N, Nieuwboer A, Verheyden GS, Yamato TP, Sherrington C
Cochrane Database Syst Rev 2022 Jun 6;6(6):CD011574. doi: 10.1002/14651858.CD011574.pub2. PMID: 35665915Free PMC Article
Gamborg M, Hvid LG, Dalgas U, Langeskov-Christensen M
Acta Neurol Scand 2022 May;145(5):504-528. Epub 2022 Jan 8 doi: 10.1111/ane.13579. PMID: 34997759
Barrio C, Arias-Sánchez S, Martín-Monzón I
Psychoneuroendocrinology 2022 Mar;137:105640. Epub 2021 Dec 17 doi: 10.1016/j.psyneuen.2021.105640. PMID: 34942539
Wu PL, Lee M, Huang TT
PLoS One 2017;12(7):e0181515. Epub 2017 Jul 27 doi: 10.1371/journal.pone.0181515. PMID: 28749970Free PMC Article

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