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Genetics of Mitochondrial Disease with Focus on Movement Disorders

  • Chapter
Movement Disorder Genetics

Abstract

There is increasing awareness that mitochondrial disorders with involvement of the central nervous system may also manifest with movement disorders. Movement disorders most frequently manifesting in mitochondrial disorders are ataxia, parkinsonism, dystonia, choreoathetosis, cerebral palsy, and non-Parkinson’s tremor. More rarely, myoclonus, restless leg syndrome, tic disorders, or stereotypy disorders were described in mitochondrial disorders. Syndromic as well as nonsyndromic mitochondrial disorders may present with movement disorders. Frequently, the movement disorder is not the only clinical manifestation but one among others. It may be the dominant phenotypic feature or an ancillary manifestation. Clinical manifestations other than movement disorders may result from additional affection of the central nervous system, the eyes, the ears, the endocrine organs, the heart, the guts, the kidneys, the skin, or the bone marrow. Genes most frequently mutated in mitochondrial movement disorders are POLG1, twinkle, tRNAs, and respiratory chain complex I subunit genes. Treatment of movement disorders in mitochondrial disorders is not at variance from treatment of movement disorders in other patients, but therapy may be less beneficial than in non-mitochondrial patients.

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Abbreviations

ACO2:

Aconitase-2 gene

ADCK3:

AarF domain containing kinase-3

ANT1:

ADP/ATP translokase-1

ARSAL:

Autosomal recessive spastic ataxia with leukoencephalopathy

CABC1:

Chaperone activity of bc1 complex gene (synonymous with ADCK3)

CNS:

Central nervous system

CoQ:

Coenzyme Q

COX:

Cytochrome c oxidase

CPEO:

Chronic progressive external ophthalmoplegia

CSF:

Cerebrospinal fluid

DDS:

Deafness diabetes syndrome

DNA:

Desoxynucleic acid

DYTCA:

Dystonia cerebellar ataxia syndrome

HSD10:

Hydroxysteroid dehydrogenase 10

IMMP2L:

Inner mitochondrial membrane peptidase-2-like

IOSCA:

Infantile-onset spinocerebellar ataxia

LHON:

Leber’s hereditary optic neuropathy

MELAS:

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes

MERRF:

Myoclonic epilepsy with ragged-red fibers syndrome

MHBD:

2-Methyl-3-hydroxybutyryl-CoA dehydrogenase

MID:

Mitochondrial disorder

MILS:

Maternally inherited Leigh syndrome

MPV17:

Mitochondrial inner membrane protein

MR1:

Myofibrillogenesis regulator 1 gene

MRI:

Magnetic resonance imaging

mtDNA:

Mitochondrial DNA

MTS:

Mitochondria-targeted sequence

NARP:

Neuropathy, ataxia, retinitis pigmentosa syndrome

nDNA:

Nuclear DNA

PCH:

Pontocerebellar hypoplasia

POLG1:

Polymerase gamma-1

RARS2:

Mitochondrial arginyl-transfer RNA synthetase gene

RCC:

Respiratory chain complex

SANDO:

Sensory ataxia neuropathy dysarthria and ophthalmoplegia

TACO1:

Translational activator of cytochrome-c-oxidase gene

tRNA:

Transfer ribonucleic acid

UPDRS:

Unified Parkinson’s Disease Rating Scale

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Authors and Affiliations

  1. Krankenanstalt Rudolfstiftung (KAR), Vienna, 1180, Austria

    Josef Finsterer MD, PhD

  2. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Saudi Arabia

    Salma Majid Wakil PhD

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  1. Josef Finsterer MD, PhD
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  2. Salma Majid Wakil PhD
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Correspondence to Josef Finsterer MD, PhD .

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Editors and Affiliations

  1. Department of Neurology, University Hospital Kiel, Kiel, Germany

    Susanne A. Schneider

  2. Department of Molecular Neuroscience, University College London, Institute of Neurology, London, United Kingdom

    José M. Tomás Brás

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Finsterer, J., Wakil, S.M. (2015). Genetics of Mitochondrial Disease with Focus on Movement Disorders. In: Schneider, S., Brás, J. (eds) Movement Disorder Genetics. Springer, Cham. https://doi.org/10.1007/978-3-319-17223-1_18

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