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Autosomal recessive early-onset Parkinson disease 7(PARK7)

MedGen UID:
344049
Concept ID:
C1853445
Disease or Syndrome
Synonym: Parkinson disease 7
 
Gene (location): PARK7 (1p36.23)
 
Monarch Initiative: MONDO:0011658
OMIM®: 606324

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
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
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.
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 tremor
MedGen UID:
66696
Concept ID:
C0234378
Sign or Symptom
A type of tremors that is triggered by holding a limb in a fixed position.
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.
Psychotic episodes
MedGen UID:
90930
Concept ID:
C0338614
Mental or Behavioral Dysfunction
Periods of time during which an individual experiences significant disturbances in their thoughts, perceptions, emotions, and behavior, resulting in a loss of touch with reality. These episodes are hallmark features of psychotic disorders such as schizophrenia, schizoaffective disorder, and certain forms of bipolar disorder.
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.
Brisk reflexes
MedGen UID:
382164
Concept ID:
C2673700
Finding
Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal.
Leg dystonia
MedGen UID:
1671070
Concept ID:
C4732775
Sign or Symptom
A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the legs.
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.
Blepharospasm
MedGen UID:
599
Concept ID:
C0005747
Disease or Syndrome
A focal dystonia that affects the muscles of the eyelids and brow, associated with involuntary recurrent spasm of both eyelids.

Recent clinical studies

Etiology

Skou LD, Johansen SK, Okarmus J, Meyer M
Cells 2024 Feb 6;13(4) doi: 10.3390/cells13040296. PMID: 38391909Free PMC Article
Bakhit Y, Ibrahim MO, Tesson C, Elhassan AA, Ahmed MA, Alebeed MA, Elrasheed SM, Omar MA, Abubaker R, Eltom K, Shaheen MT, Ibrahim YA, Almak ME, Ali HA, Abugrain AA, Almahal MA, MohamedSharif AA, Tahir MY, Malik SM, Eldirdiri Abdelrahman H, Khidir RJ, Mohamed MT, Abdalla A, Elsayed LEO, Lesage S, Corvol JC, Seidi O, Wüllner U
Parkinsonism Relat Disord 2023 Jun;111:105401. Epub 2023 Apr 25 doi: 10.1016/j.parkreldis.2023.105401. PMID: 37150071
Jia Y, Kim RQ, Kooij R, Ovaa H, Sapmaz A, Geurink PP
J Med Chem 2022 Oct 13;65(19):13288-13304. Epub 2022 Sep 23 doi: 10.1021/acs.jmedchem.2c01113. PMID: 36149939Free PMC Article
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
Gu X, Li C, Chen Y, Ou R, Cao B, Wei Q, Hou Y, Zhang L, Song W, Zhao B, Wu Y, Shang H
Neurobiol Aging 2020 Oct;94:311.e1-311.e4. Epub 2020 May 13 doi: 10.1016/j.neurobiolaging.2020.05.005. PMID: 32507414

Diagnosis

Sarasola LI, Del Torrent CL, Pérez-Arévalo A, Argerich J, Casajuana-Martín N, Chevigné A, Fernández-Dueñas V, Ferré S, Pardo L, Ciruela F
Biomed Pharmacother 2022 Dec;156:113896. Epub 2022 Oct 21 doi: 10.1016/j.biopha.2022.113896. PMID: 36279718
Li JY, Li NN, Wang L, Peng JX, Duan LR, Chen CL, Peng R
J Neurol 2021 Jun;268(6):2223-2227. Epub 2021 Jan 25 doi: 10.1007/s00415-021-10405-z. PMID: 33491134
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
Ahfeldt T, Ordureau A, Bell C, Sarrafha L, Sun C, Piccinotti S, Grass T, Parfitt GM, Paulo JA, Yanagawa F, Uozumi T, Kiyota Y, Harper JW, Rubin LL
Stem Cell Reports 2020 Jan 14;14(1):75-90. Epub 2020 Jan 2 doi: 10.1016/j.stemcr.2019.12.005. PMID: 31902706Free PMC Article
Lücking CB, Dürr A, Bonifati V, Vaughan J, De Michele G, Gasser T, Harhangi BS, Meco G, Denèfle P, Wood NW, Agid Y, Brice A; French Parkinson's Disease Genetics Study Group; European Consortium on Genetic Susceptibility in Parkinson's Disease
N Engl J Med 2000 May 25;342(21):1560-7. doi: 10.1056/NEJM200005253422103. PMID: 10824074

Therapy

Chen XB, Zhu HY, Bao K, Jiang L, Zhu H, Ying MD, He QJ, Yang B, Sheng R, Cao J
Acta Pharmacol Sin 2021 Jul;42(7):1160-1170. Epub 2021 Jan 25 doi: 10.1038/s41401-020-00600-5. PMID: 33495517Free PMC Article
Hijioka M, Inden M, Yanagisawa D, Kitamura Y
Biol Pharm Bull 2017;40(5):548-552. doi: 10.1248/bpb.b16-01006. PMID: 28458339
Halder T, Raj J, Sharma V, Das P
Neurosci Lett 2015 Sep 25;605:29-33. Epub 2015 Aug 14 doi: 10.1016/j.neulet.2015.08.021. PMID: 26282903
Shan Y, Akram A, Amatullah H, Zhou DY, Gali PL, Maron-Gutierrez T, González-López A, Zhou L, Rocco PR, Hwang D, Albaiceta GM, Haitsma JJ, dos Santos CC
Antioxid Redox Signal 2015 Mar 10;22(8):651-68. Epub 2015 Jan 19 doi: 10.1089/ars.2014.5987. PMID: 25401197Free PMC Article
Gao X, Ning Y
Drugs Today (Barc) 2011 Mar;47(3):215-22. doi: 10.1358/dot.2011.47.3.1519657. PMID: 21494699

Prognosis

Wang Z, Song Y, Zhu W, Wang X, Li X, Xu F, Si L, Yao T, Zhu J, Lai H, Li W, Lin F, Wang C
Parkinsonism Relat Disord 2021 Jul;88:62-67. Epub 2021 Jun 10 doi: 10.1016/j.parkreldis.2021.06.005. PMID: 34144229
Miyahara K, Takano N, Yamada Y, Kazama H, Tokuhisa M, Hino H, Fujita K, Barroga E, Hiramoto M, Handa H, Kuroda M, Ishikawa T, Miyazawa K
Sci Rep 2021 Apr 22;11(1):8735. doi: 10.1038/s41598-021-87698-7. PMID: 33888730Free PMC Article
Lorenzo-Betancor O, Lin YH, Samii A, Jayadev S, Kim HM, Longfellow K, Distad BJ, Yearout D, Mata IF, Zabetian CP
Parkinsonism Relat Disord 2020 Nov;80:142-147. Epub 2020 Sep 22 doi: 10.1016/j.parkreldis.2020.09.035. PMID: 33002721Free PMC Article
Simón-Sánchez J, Kilarski LL, Nalls MA, Martinez M, Schulte C, Holmans P; International Parkinson's Disease Genomics Consortium; Wellcome Trust Case Control Consortium, Gasser T, Hardy J, Singleton AB, Wood NW, Brice A, Heutink P, Williams N, Morris HR
PLoS One 2012;7(3):e28787. Epub 2012 Mar 12 doi: 10.1371/journal.pone.0028787. PMID: 22427796Free PMC Article
Hague S, Rogaeva E, Hernandez D, Gulick C, Singleton A, Hanson M, Johnson J, Weiser R, Gallardo M, Ravina B, Gwinn-Hardy K, Crawley A, St George-Hyslop PH, Lang AE, Heutink P, Bonifati V, Hardy J, Singleton A
Ann Neurol 2003 Aug;54(2):271-4. doi: 10.1002/ana.10663. PMID: 12891685

Clinical prediction guides

Nam Y, Na J, Ma SX, Park H, Park H, Lee E, Kim H, Jang SM, Ko HS, Kim S
Genes Genomics 2024 May;46(5):519-529. Epub 2024 Mar 9 doi: 10.1007/s13258-024-01506-w. PMID: 38460098
Miyahara K, Takano N, Yamada Y, Kazama H, Tokuhisa M, Hino H, Fujita K, Barroga E, Hiramoto M, Handa H, Kuroda M, Ishikawa T, Miyazawa K
Sci Rep 2021 Apr 22;11(1):8735. doi: 10.1038/s41598-021-87698-7. PMID: 33888730Free PMC Article
Tan AH, Lohmann K, Tay YW, Lim JL, Ahmad-Annuar A, Ramli N, Chin YT, Mawardi AS, Azmi K, Aziz ZA, Puvanarajah SD, Bauer P, Klein C, Rolfs A, Lim SY
Parkinsonism Relat Disord 2020 Oct;79:34-39. Epub 2020 Aug 19 doi: 10.1016/j.parkreldis.2020.08.015. PMID: 32861104
Ahfeldt T, Ordureau A, Bell C, Sarrafha L, Sun C, Piccinotti S, Grass T, Parfitt GM, Paulo JA, Yanagawa F, Uozumi T, Kiyota Y, Harper JW, Rubin LL
Stem Cell Reports 2020 Jan 14;14(1):75-90. Epub 2020 Jan 2 doi: 10.1016/j.stemcr.2019.12.005. PMID: 31902706Free PMC Article
Gao X, Ning Y
Drugs Today (Barc) 2011 Mar;47(3):215-22. doi: 10.1358/dot.2011.47.3.1519657. PMID: 21494699

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