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Table 5. Parkinsonism associated with mutations in mitochondrial-related nDNA genes
Protein Clinical features of
Gene Mutation change parkinsonism Other clinical aspects Ref.
POLG c.2693T > C I898T Early onset rigidity, akinesia PEO, optic atrophy Ma et al. [84] 2019
c.2993C > T S998L
c.830A > T H277L Asymmetrical akinesia, PEO Sato et al. [73] 2011
c.2827C > T R943C rigidity
c.2864A > G Y955C Bilateral akinesia, rigidity PEO, myopathy Synofzik et al. [71] 2010
Asymmetrical tremor PEO, myopathy, neuropathy,
hypogonadism
c.3311C > G Akinesia, rigidity, tremor PEO, myopathy Betts-Henderson et al. [67] 2009
c.2542G > A G848S
c.1288A > T M430L Bilateral tremor, rigidity PEO, myopathy Invernizzi et al. [68] 2008
c.2752T > C W918L
c.2243G > C W748S Bilateral akinesia, rigidity, PEO, sensory and cerebellar Remes et al. [69] 2008
tremor ataxia
c.1389G > T S511N Bilateral akinesia, rigidity PEO, myopathy, neuropathy Hudson et al. [70] 2007
c.1532G > A
c.2839C > T R853N Bilateral akinesia, rigidity PEO, myopathy, dystonia Davidzon et al. [66] 2006
c.2491G > C G737R
c.2492A > G Y831C Symmetrical akinesia, rigidity, PEO, myopathy Mancuso M et al. [65] 2004
tremor
c.2864A > G Y955C Tremor and/or akinesia, rigidity PEO Luoma et al. 2004 [60] 2004
c.1402A > G N468D
c.313G > A
ANT1 c.865G > A A467T Bilateral akinesia, rigidity PEO, myopathy, neuropathy Galassi et al. [72] 2008
POLG c.1399G > A
POLG2 c.970-1G > C - Asymmetrical tremor and Sensory and cerebellar ataxia, Van Maldergem et al. [64] 2016
bradykinesia dementia, PEO
c.1192-8_1207dup24 - Camptocormia Lehmann Urban et al. [83] 2020
TWNK c.907C > T R3030W Asymmetrical tremor and PEO, myopathy Brandon et al. [77] 2013
akinesia, rigidity
c.1750G > A A359T Asymmetrical tremor and PEO, neuropathy Kiferle et al. [76] 2013
akinesia, rigidity
c.1031G > A R334Q Asymmetrical tremor, akinesia, PEO, neuropathy Vandenberghe et al. [75] 2009
rigidity
c.1121G > A R374Q Asymmetrical akinesia, rigidity, PEO Baloh et al. [61] 2007
tremor
OPA1 c.1462G > A G488R Akinesia, rigidity, tremor PEO, myopathy, neuropathy, Carelli et al. [62] 2015
c.1484C > T A495V dementia
MPV17 c.428T > G L143* Akinesia, rigidity, tremor PEO, myopathy, neuropathy Garone et al. [63] 2012
c.263A > T K88M
c.265A > T M89L
SPG7 c.1529C > T A510V bradykinesia, rest tremor, and Ataxia, PEO De la Casa-Fages et al. [78] 2019
rigidity
n.a. mtDNA MDels - Tremor, moderate bradykinesia PEO, neuropathy Wilcox et al. [79] 2007
n.a. mtDNA MDels - Asymmetrical akinesia, rigidity, - Siciliano et al. [81] 2001
rest tremor
n.a. mtDNA MDels - Asymmetrical akinesia, rigidity PEO, myopathy Casali et al. [82] 2001
n.a. mtDNA MDels - asymmetric rest tremor PEO, myopathy, neuropathy Chalmers et al. [80] 1996
akinesia, rigidity
PEO: progressive external ophthalmoplegia; mtDNA MDels: mitochondrial DNA multiple deletions; n.a.: not available

can mimic very well an idiopathic Parkinson disease (IPD) because age of onset, the asymmetric distribution
of motor symptoms, the efficacy of dopaminergic drugs, and the support of the imaging studies showing
nigrostriatal dysfunction are not dissimilar in these conditions. Nevertheless, reviewing the MP cases
reported thus far, it appears evident that MP may manifest earlier than IPD, and some additional clinical
features, rarely reported in IP, are indeed recurrent in MP. In fact, considering the reported cases with MP
due to mutations in mitochondrial-related nuclear genes impairing mtDNA maintenance [Table 5], it is quite
clear that external ophthalmoplegia is a common feature with frequent association with proximal myopathy
and less commonly neuropathy and ataxia.

According to these considerations, MP should be suspected in patients manifesting an akinetic syndrome
with PEO and myopathic signs.