Orthostatic tremor, progressive external ophthalmoplegia, and twinkle

Margherita Milone, Bryan T. Klassen, Megan L. Landsverk, Richard H. Haas, Lee Jun Wong

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

IMPORTANCE: Orthostatic tremor (OT) is a high-frequency (13-18 Hz) leg tremor occurring in standing position. Orthostatic tremor has an unknown pathophysiologic mechanism. It is thought to be sporadic but siblings with OT from 3 unrelated families were reported. No mutations have been reported in OT. We describe a patient with OT carrying a C10orf2 TWINKLE mutation to highlight the possible association of OT with mitochondrial dysfunction and mutations in the mitochondrial replicative helicase Twinkle. OBSERVATIONS: A man in his late 60s had ptosis and tremor on standing for 30 years, followed by development of progressive external ophthalmoplegia. Polygraphic recordings revealed an orthostatic synchronic tremor with 17.5-Hz frequency. Electromyography/nerve conduction studies showed evidence for a mild myopathy and associated mild axonal sensorimotor peripheral neuropathy. Muscle biopsy revealed ragged red fibers; mild cerebral atrophy was evident by magnetic resonance imaging. Molecular analysis revealed a novel heterozygous missense mutation at an evolutionarily conserved residue of the C10orf2 TWINKLE gene. CONCLUSIONS AND RELEVANCE: Although the incidental association of OT and C10orf2 TWINKLE mutation is possible, the simultaneous onset of OT and eyelid ptosis at a much younger age than usually observed for OT raises the possibility of mitochondrial dysfunction and loss of mitochondrial DNA integrity in the pathogenesis of OT.

Original languageEnglish (US)
Pages (from-to)1429-1431
Number of pages3
JournalJAMA neurology
Volume70
Issue number11
DOIs
StatePublished - Nov 2013

ASJC Scopus subject areas

  • Clinical Neurology

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