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Parkinson disease 24, autosomal dominant, susceptibility to(PARK24)

MedGen UID:
1794179
Concept ID:
C5561969
Finding
Synonyms: PARK24; PARKINSON DISEASE 24, AUTOSOMAL DOMINANT, SUSCEPTIBILITY TO
 
Gene (location): PSAP (10q22.1)
 
Monarch Initiative: MONDO:0859183
OMIM®: 619491

Definition

Parkinson disease-24 (PARK24) is an autosomal dominant disorder characterized by classic Parkinson disease features, including adult onset, asymmetric limb involvement initially, and slowly progressive motor dysfunction. PARK24 shows incomplete penetrance, consistent with the presence of the PSAP mutation being a susceptibility factor for development of the disease (Oji et al., 2020). For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see 168600. [from OMIM]

Clinical features

From HPO
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
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 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.

Recent clinical studies

Etiology

Gustavsson EK, Follett J, Trinh J, Barodia SK, Real R, Liu Z, Grant-Peters M, Fox JD, Appel-Cresswell S, Stoessl AJ, Rajput A, Rajput AH, Auer R, Tilney R, Sturm M, Haack TB, Lesage S, Tesson C, Brice A, Vilariño-Güell C, Ryten M, Goldberg MS, West AB, Hu MT, Morris HR, Sharma M, Gan-Or Z, Samanci B, Lis P, Periñan MT, Amouri R, Ben Sassi S, Hentati F; Global Parkinson's Genetics Program (GP2), Tonelli F, Alessi DR, Farrer MJ
Lancet Neurol 2024 Jun;23(6):603-614. Epub 2024 Apr 10 doi: 10.1016/S1474-4422(24)00121-2. PMID: 38614108Free PMC Article
Emekli I, Tepgeç F, Samancı B, Toksoy G, Hasanoğulları Kına G, Tüfekçioğlu Z, Başaran S, Bilgiç B, Gürvit IH, Emre M, Uyguner ZO, Hanagasi HA
Parkinsonism Relat Disord 2021 Dec;93:35-39. Epub 2021 Nov 3 doi: 10.1016/j.parkreldis.2021.10.024. PMID: 34781237
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
Cobb SA, Wider C, Ross OA, Mata IF, Adler CH, Rajput A, Rajput AH, Wu RM, Hauser R, Josephs KA, Carr J, Gwinn K, Heckman MG, Aasly JO, Lynch T, Uitti RJ, Wszolek ZK, Kapatos G, Farrer MJ
Mov Disord 2009 Oct 30;24(14):2070-5. doi: 10.1002/mds.22729. PMID: 19735094
Lev N, Melamed E
Isr Med Assoc J 2001 Jun;3(6):435-8. PMID: 11433638

Diagnosis

Gustavsson EK, Follett J, Trinh J, Barodia SK, Real R, Liu Z, Grant-Peters M, Fox JD, Appel-Cresswell S, Stoessl AJ, Rajput A, Rajput AH, Auer R, Tilney R, Sturm M, Haack TB, Lesage S, Tesson C, Brice A, Vilariño-Güell C, Ryten M, Goldberg MS, West AB, Hu MT, Morris HR, Sharma M, Gan-Or Z, Samanci B, Lis P, Periñan MT, Amouri R, Ben Sassi S, Hentati F; Global Parkinson's Genetics Program (GP2), Tonelli F, Alessi DR, Farrer MJ
Lancet Neurol 2024 Jun;23(6):603-614. Epub 2024 Apr 10 doi: 10.1016/S1474-4422(24)00121-2. PMID: 38614108Free PMC Article
Fan TS, Wu RM, Chen PL, Chen TF, Li HY, Lin YH, Chen CY, Chen ML, Tai CH, Lin HI, Lin CH
Parkinsonism Relat Disord 2016 Dec;33:36-43. Epub 2016 Sep 7 doi: 10.1016/j.parkreldis.2016.09.008. PMID: 27628070
Funayama M, Ohe K, Amo T, Furuya N, Yamaguchi J, Saiki S, Li Y, Ogaki K, Ando M, Yoshino H, Tomiyama H, Nishioka K, Hasegawa K, Saiki H, Satake W, Mogushi K, Sasaki R, Kokubo Y, Kuzuhara S, Toda T, Mizuno Y, Uchiyama Y, Ohno K, Hattori N
Lancet Neurol 2015 Mar;14(3):274-82. Epub 2015 Feb 4 doi: 10.1016/S1474-4422(14)70266-2. PMID: 25662902
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
Hedera P, Fang JY, Phibbs F, Cooper MK, Charles PD, Davis TL
Mov Disord 2009 Nov 15;24(15):2285-8. doi: 10.1002/mds.22772. PMID: 19795470

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

Prognosis

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

Gustavsson EK, Follett J, Trinh J, Barodia SK, Real R, Liu Z, Grant-Peters M, Fox JD, Appel-Cresswell S, Stoessl AJ, Rajput A, Rajput AH, Auer R, Tilney R, Sturm M, Haack TB, Lesage S, Tesson C, Brice A, Vilariño-Güell C, Ryten M, Goldberg MS, West AB, Hu MT, Morris HR, Sharma M, Gan-Or Z, Samanci B, Lis P, Periñan MT, Amouri R, Ben Sassi S, Hentati F; Global Parkinson's Genetics Program (GP2), Tonelli F, Alessi DR, Farrer MJ
Lancet Neurol 2024 Jun;23(6):603-614. Epub 2024 Apr 10 doi: 10.1016/S1474-4422(24)00121-2. PMID: 38614108Free 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
Stamelou M, Charlesworth G, Cordivari C, Schneider SA, Kägi G, Sheerin UM, Rubio-Agusti I, Batla A, Houlden H, Wood NW, Bhatia KP
Mov Disord 2014 Jun;29(7):928-34. Epub 2014 Jan 17 doi: 10.1002/mds.25802. PMID: 24442708Free PMC Article

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