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Autosomal recessive juvenile Parkinson disease 2(PARK2; PDJ; EPDF)

MedGen UID:
401500
Concept ID:
C1868675
Disease or Syndrome
Synonyms: Juvenile parkinsonism; Parkin Type of Early-Onset Parkinson Disease; Parkin Type of Juvenile Parkinson Disease; Parkinson disease 2; Parkinson disease autosomal recessive, early onset; Parkinson disease, juvenile, autosomal recessive; Parkinson disease, juvenile, type 2; Parkinsonism, early onset, with diurnal fluctuation
 
Gene (location): PRKN (6q26)
 
Monarch Initiative: MONDO:0010820
OMIM®: 600116

Definition

Parkin type of early-onset Parkinson disease (PARK-Parkin) is characterized by the cardinal signs of Parkinson disease (PD): bradykinesia, resting tremor, and rigidity. The median age at onset is 31 years (range: 3-81 years). The disease is slowly progressive: disease duration of more than 50 years has been reported. Clinical findings vary; hyperreflexia is common. Lower-limb dystonia may be a presenting sign and cognitive decline appears to be no more frequent than in the general population. Dyskinesia as a result of treatment with levodopa frequently occurs. [from GeneReviews]

Additional description

From MedlinePlus Genetics
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.

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.

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 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.  https://medlineplus.gov/genetics/condition/parkinsons-disease

Clinical features

From HPO
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
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.
Hypokinesia
MedGen UID:
39223
Concept ID:
C0086439
Finding
Abnormally diminished motor activity. In contrast to paralysis, hypokinesia is not characterized by a lack of motor strength, but rather by a poverty of movement. The typical habitual movements (e.g., folding the arms, crossing the legs) are reduced in frequency.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Shuffling gait
MedGen UID:
68545
Concept ID:
C0231688
Finding
A type of gait (walking) characterized by by dragging one's feet along or without lifting the feet fully from the ground.
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.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
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.
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.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
Focal dystonia
MedGen UID:
149279
Concept ID:
C0743332
Disease or Syndrome
A type of dystonia that is localized to a specific part of the body.
Pill-rolling tremor
MedGen UID:
199684
Concept ID:
C0751564
Sign or Symptom
A type of resting tremor characterized by simultaneous rubbing movements of thumb and index fingers against each other.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
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.
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.
Cogwheel rigidity
MedGen UID:
57469
Concept ID:
C0151564
Sign or Symptom
A type of rigidity in which a muscle responds with cogwheellike jerks to the use of constant force in bending the limb (i.e., it gives way in little, repeated jerks when the muscle is passively stretched).

Professional guidelines

PubMed

Marino BLB, de Souza LR, Sousa KPA, Ferreira JV, Padilha EC, da Silva CHTP, Taft CA, Hage-Melim LIS
Mini Rev Med Chem 2020;20(9):754-767. doi: 10.2174/1389557519666191104110908. PMID: 31686637
Taylor JP, McKeith IG, Burn DJ, Boeve BF, Weintraub D, Bamford C, Allan LM, Thomas AJ, O'Brien JT
Lancet Neurol 2020 Feb;19(2):157-169. Epub 2019 Sep 10 doi: 10.1016/S1474-4422(19)30153-X. PMID: 31519472Free PMC Article
Atri A
Med Clin North Am 2019 Mar;103(2):263-293. doi: 10.1016/j.mcna.2018.10.009. PMID: 30704681

Recent clinical studies

Etiology

Leta V, Urso D, Batzu L, Lau YH, Mathew D, Boura I, Raeder V, Falup-Pecurariu C, van Wamelen D, Ray Chaudhuri K
J Neural Transm (Vienna) 2022 Sep;129(9):1119-1132. Epub 2022 Aug 29 doi: 10.1007/s00702-022-02536-y. PMID: 36036863Free PMC Article
Reichmann H, Csoti I, Koschel J, Lorenzl S, Schrader C, Winkler J, Wüllner U
J Neural Transm (Vienna) 2022 Sep;129(9):1235-1245. Epub 2022 May 23 doi: 10.1007/s00702-022-02509-1. PMID: 35606622Free PMC Article
Akdemir ÜÖ, Bora Tokçaer A, Atay LÖ
Turk J Med Sci 2021 Apr 30;51(2):400-410. doi: 10.3906/sag-2008-253. PMID: 33237660Free PMC Article
Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, Marras C, Bhudhikanok GS, Kasten M, Chade AR, Comyns K, Richards MB, Meng C, Priestley B, Fernandez HH, Cambi F, Umbach DM, Blair A, Sandler DP, Langston JW
Environ Health Perspect 2011 Jun;119(6):866-72. Epub 2011 Jan 26 doi: 10.1289/ehp.1002839. PMID: 21269927Free PMC Article
Lees AJ, Hardy J, Revesz T
Lancet 2009 Jun 13;373(9680):2055-66. doi: 10.1016/S0140-6736(09)60492-X. PMID: 19524782

Diagnosis

Bae YJ, Kim JM, Sohn CH, Choi JH, Choi BS, Song YS, Nam Y, Cho SJ, Jeon B, Kim JH
Radiology 2021 Aug;300(2):260-278. Epub 2021 Jun 8 doi: 10.1148/radiol.2021203341. PMID: 34100679
Akdemir ÜÖ, Bora Tokçaer A, Atay LÖ
Turk J Med Sci 2021 Apr 30;51(2):400-410. doi: 10.3906/sag-2008-253. PMID: 33237660Free PMC Article
Zhang PL, Chen Y, Zhang CH, Wang YX, Fernandez-Funez P
J Med Genet 2018 Feb;55(2):73-80. Epub 2017 Nov 18 doi: 10.1136/jmedgenet-2017-105047. PMID: 29151060
Bonifati V
Parkinsonism Relat Disord 2012 Jan;18 Suppl 1:S4-6. doi: 10.1016/S1353-8020(11)70004-9. PMID: 22166450
Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, Marras C, Bhudhikanok GS, Kasten M, Chade AR, Comyns K, Richards MB, Meng C, Priestley B, Fernandez HH, Cambi F, Umbach DM, Blair A, Sandler DP, Langston JW
Environ Health Perspect 2011 Jun;119(6):866-72. Epub 2011 Jan 26 doi: 10.1289/ehp.1002839. PMID: 21269927Free PMC Article

Therapy

McFarthing K, Rafaloff G, Baptista M, Mursaleen L, Fuest R, Wyse RK, Stott SRW
J Parkinsons Dis 2022;12(4):1073-1082. doi: 10.3233/JPD-229002. PMID: 35527571Free PMC Article
Zhang Y, Wu Q, Zhang L, Wang Q, Yang Z, Liu J, Feng L
Pharmacol Res 2019 Dec;150:104538. Epub 2019 Nov 9 doi: 10.1016/j.phrs.2019.104538. PMID: 31707034
Lang AE, Espay AJ
Mov Disord 2018 May;33(5):660-677. Epub 2018 Apr 11 doi: 10.1002/mds.27360. PMID: 29644751
Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, Marras C, Bhudhikanok GS, Kasten M, Chade AR, Comyns K, Richards MB, Meng C, Priestley B, Fernandez HH, Cambi F, Umbach DM, Blair A, Sandler DP, Langston JW
Environ Health Perspect 2011 Jun;119(6):866-72. Epub 2011 Jan 26 doi: 10.1289/ehp.1002839. PMID: 21269927Free PMC Article
Lees AJ, Hardy J, Revesz T
Lancet 2009 Jun 13;373(9680):2055-66. doi: 10.1016/S0140-6736(09)60492-X. PMID: 19524782

Prognosis

Reichmann H, Csoti I, Koschel J, Lorenzl S, Schrader C, Winkler J, Wüllner U
J Neural Transm (Vienna) 2022 Sep;129(9):1235-1245. Epub 2022 May 23 doi: 10.1007/s00702-022-02509-1. PMID: 35606622Free PMC Article
Cai R, Zhang Y, Simmering JE, Schultz JL, Li Y, Fernandez-Carasa I, Consiglio A, Raya A, Polgreen PM, Narayanan NS, Yuan Y, Chen Z, Su W, Han Y, Zhao C, Gao L, Ji X, Welsh MJ, Liu L
J Clin Invest 2019 Oct 1;129(10):4539-4549. doi: 10.1172/JCI129987. PMID: 31524631Free PMC Article
Postuma RB, Iranzo A, Hu M, Högl B, Boeve BF, Manni R, Oertel WH, Arnulf I, Ferini-Strambi L, Puligheddu M, Antelmi E, Cochen De Cock V, Arnaldi D, Mollenhauer B, Videnovic A, Sonka K, Jung KY, Kunz D, Dauvilliers Y, Provini F, Lewis SJ, Buskova J, Pavlova M, Heidbreder A, Montplaisir JY, Santamaria J, Barber TR, Stefani A, St Louis EK, Terzaghi M, Janzen A, Leu-Semenescu S, Plazzi G, Nobili F, Sixel-Doering F, Dusek P, Bes F, Cortelli P, Ehgoetz Martens K, Gagnon JF, Gaig C, Zucconi M, Trenkwalder C, Gan-Or Z, Lo C, Rolinski M, Mahlknecht P, Holzknecht E, Boeve AR, Teigen LN, Toscano G, Mayer G, Morbelli S, Dawson B, Pelletier A
Brain 2019 Mar 1;142(3):744-759. doi: 10.1093/brain/awz030. PMID: 30789229Free PMC Article
Zhang PL, Chen Y, Zhang CH, Wang YX, Fernandez-Funez P
J Med Genet 2018 Feb;55(2):73-80. Epub 2017 Nov 18 doi: 10.1136/jmedgenet-2017-105047. PMID: 29151060
Lees AJ, Hardy J, Revesz T
Lancet 2009 Jun 13;373(9680):2055-66. doi: 10.1016/S0140-6736(09)60492-X. PMID: 19524782

Clinical prediction guides

Hart A, Cordova-Rivera L, Barker F, Sayer AA, Granic A, Yarnall AJ
Neurol Sci 2023 Dec;44(12):4205-4217. Epub 2023 Aug 18 doi: 10.1007/s10072-023-07007-0. PMID: 37594550Free PMC Article
Sung YH, Kang SY
Neurol Sci 2022 Aug;43(8):4797-4802. Epub 2022 Mar 26 doi: 10.1007/s10072-022-06035-6. PMID: 35347528
Walker Z, Gandolfo F, Orini S, Garibotto V, Agosta F, Arbizu J, Bouwman F, Drzezga A, Nestor P, Boccardi M, Altomare D, Festari C, Nobili F; EANM-EAN Task Force for the recommendation of FDG PET for Dementing Neurodegenerative Disorders
Eur J Nucl Med Mol Imaging 2018 Jul;45(9):1534-1545. Epub 2018 May 19 doi: 10.1007/s00259-018-4031-2. PMID: 29779045Free PMC Article
Kalia LV
Parkinsonism Relat Disord 2018 Jan;46 Suppl 1:S19-S23. Epub 2017 Jul 24 doi: 10.1016/j.parkreldis.2017.07.023. PMID: 28781202
Fogel BL, Clark MC, Geschwind DH
Semin Neurol 2014 Apr;34(2):217-24. Epub 2014 Jun 25 doi: 10.1055/s-0034-1381738. PMID: 24963681Free PMC Article

Recent systematic reviews

Schindler A, Pizzorni N, Cereda E, Cosentino G, Avenali M, Montomoli C, Abbruzzese G, Antonini A, Barbiera F, Benazzo M, Benarroch E, Bertino G, Clavè P, Cortelli P, Eleopra R, Ferrari C, Hamdy S, Huckabee ML, Lopiano L, Marchese-Ragona R, Masiero S, Michou E, Occhini A, Pacchetti C, Pfeiffer RF, Restivo DA, Rondanelli M, Ruoppolo G, Sandrini G, Schapira A, Stocchi F, Tolosa E, Valentino F, Zamboni M, Zangaglia R, Zappia M, Tassorelli C, Alfonsi E
J Neurol Sci 2021 Nov 15;430:120008. Epub 2021 Sep 27 doi: 10.1016/j.jns.2021.120008. PMID: 34624796
Zhao N, Yang Y, Zhang L, Zhang Q, Balbuena L, Ungvari GS, Zang YF, Xiang YT
CNS Neurosci Ther 2021 Mar;27(3):270-279. Epub 2020 Dec 28 doi: 10.1111/cns.13549. PMID: 33372386Free PMC Article
Carey G, Görmezoğlu M, de Jong JJA, Hofman PAM, Backes WH, Dujardin K, Leentjens AFG
Mov Disord 2021 Feb;36(2):327-339. Epub 2020 Dec 2 doi: 10.1002/mds.28404. PMID: 33289195Free PMC Article
Pringsheim T, Jette N, Frolkis A, Steeves TD
Mov Disord 2014 Nov;29(13):1583-90. Epub 2014 Jun 28 doi: 10.1002/mds.25945. PMID: 24976103
Tomlinson CL, Patel S, Meek C, Herd CP, Clarke CE, Stowe R, Shah L, Sackley C, Deane KH, Wheatley K, Ives N
BMJ 2012 Aug 6;345:e5004. doi: 10.1136/bmj.e5004. PMID: 22867913Free PMC Article

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