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Dopa‐Responsive Parkinsonism in a Patient With Homozygous RFC1 Expansions
2020; Wiley; Volume: 35; Issue: 10 Linguagem: Inglês
10.1002/mds.28286
ISSN1531-8257
AutoresGabriel da Silva Schmitt, Alberto Martínez, Felipe Franco da Graça, Fabrício Diniz de Lima, Luciana Cardoso Bonadia, Bárbara Juarez Amorim, Anamarli Nucci, Marcondes C. França,
Tópico(s)Neurological disorders and treatments
ResumoMovement DisordersVolume 35, Issue 10 p. 1889-1890 Letters: Published ArticleFree Access Dopa-Responsive Parkinsonism in a Patient With Homozygous RFC1 Expansions Gabriel da Silva Schmitt MD, Gabriel da Silva Schmitt MD Neuromuscular Division, Department of Neurology, University of Campinas, Campinas, BrazilSearch for more papers by this authorAlberto R.M. Martinez MD, PhD, Alberto R.M. Martinez MD, PhD Neuromuscular Division, Department of Neurology, University of Campinas, Campinas, BrazilSearch for more papers by this authorFelipe F. da Graça MD, Felipe F. da Graça MD Neuromuscular Division, Department of Neurology, University of Campinas, Campinas, BrazilSearch for more papers by this authorFabrício Diniz de Lima MD, MSc, Fabrício Diniz de Lima MD, MSc orcid.org/0000-0002-9946-6032 Neuromuscular Division, Department of Neurology, University of Campinas, Campinas, BrazilSearch for more papers by this authorLuciana C. Bonadia PhD, Luciana C. Bonadia PhD Department of Medical Genetics and Genomic Medicine, University of Campinas, Campinas, BrazilSearch for more papers by this authorBárbara Juarez Amorim MD, PhD, Bárbara Juarez Amorim MD, PhD Nuclear Medicine Division, Department of Radiology, University of Campinas, Campinas, BrazilSearch for more papers by this authorAnamarli Nucci MD, PhD, Anamarli Nucci MD, PhD Neuromuscular Division, Department of Neurology, University of Campinas, Campinas, BrazilSearch for more papers by this authorMarcondes Cavalcante França Jr. MD, PhD, Corresponding Author Marcondes Cavalcante França Jr. MD, PhD mcfrancajr@uol.com.br Neuromuscular Division, Department of Neurology, University of Campinas, Campinas, Brazil Correspondence to: Marcondes Cavalcante França, Department of Neurology, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126. Cidade Universitaria “Zeferino Vaz,” Campinas, SP 13083-887, Brazil; E-mail: mcfrancajr@uol.com.brSearch for more papers by this author Gabriel da Silva Schmitt MD, Gabriel da Silva Schmitt MD Neuromuscular Division, Department of Neurology, University of Campinas, Campinas, BrazilSearch for more papers by this authorAlberto R.M. Martinez MD, PhD, Alberto R.M. Martinez MD, PhD Neuromuscular Division, Department of Neurology, University of Campinas, Campinas, BrazilSearch for more papers by this authorFelipe F. da Graça MD, Felipe F. da Graça MD Neuromuscular Division, Department of Neurology, University of Campinas, Campinas, BrazilSearch for more papers by this authorFabrício Diniz de Lima MD, MSc, Fabrício Diniz de Lima MD, MSc orcid.org/0000-0002-9946-6032 Neuromuscular Division, Department of Neurology, University of Campinas, Campinas, BrazilSearch for more papers by this authorLuciana C. Bonadia PhD, Luciana C. Bonadia PhD Department of Medical Genetics and Genomic Medicine, University of Campinas, Campinas, BrazilSearch for more papers by this authorBárbara Juarez Amorim MD, PhD, Bárbara Juarez Amorim MD, PhD Nuclear Medicine Division, Department of Radiology, University of Campinas, Campinas, BrazilSearch for more papers by this authorAnamarli Nucci MD, PhD, Anamarli Nucci MD, PhD Neuromuscular Division, Department of Neurology, University of Campinas, Campinas, BrazilSearch for more papers by this authorMarcondes Cavalcante França Jr. MD, PhD, Corresponding Author Marcondes Cavalcante França Jr. MD, PhD mcfrancajr@uol.com.br Neuromuscular Division, Department of Neurology, University of Campinas, Campinas, Brazil Correspondence to: Marcondes Cavalcante França, Department of Neurology, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126. Cidade Universitaria “Zeferino Vaz,” Campinas, SP 13083-887, Brazil; E-mail: mcfrancajr@uol.com.brSearch for more papers by this author First published: 17 October 2020 https://doi.org/10.1002/mds.28286Citations: 1 Relevant conflicts of interest/financial disclosures: : Nothing to report. Funding agencies:: This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo Grants 2013/26410-0 and 2013/01766-7. AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat We read the letter titled “RFC1 Intronic Repeat Expansions Absent in Pathologically Confirmed Multiple Systems Atrophy” published online in April 20201 with great interest. In light of that letter, we would like to expand the phenotypic spectrum of RFC1 expansion-related disorders by reporting dopa-responsive parkinsonism in a 63-year-old woman. She developed parkinsonian symptoms in her early 50s, characterized by bradykinesia, resting tremor, and stiffness. The patient was started on levodopa as a symptomatic therapy with overt gait improvement (Video S1). Approximately 1 year later, she noticed oscillopsia and sensory complaints described as asymmetrical limb paresthesia that became confluent and associated with decreased vibration as well as proprioceptive sensation leading to gait unsteadiness. Head impulse test demonstrated absent vestibulo-ocular reflex bilaterally. A 20-year dry cough history was also reported. Brain magnetic resonance imaging and laboratory workup were unremarkable. Nerve conduction studies showed diffuse abnormalities restricted to sensory nerves, quantitative sudomotor axonal reflex was normal, and heart rate variability revealed incipient cardiac dysautonomia. Dopamine transporter scan highlighted a marked reduction of dopaminergic transporters in the bilateral striatum (Fig. 1A). Whole-exome sequencing failed to identify relevant variants, but triplet-repeat primed polymerase chain reaction detected biallelic (AAGGGn) intronic RFC1 expansions (Fig. 1C). FIG. 1Open in figure viewerPowerPoint Dopamine transporter scan with 99mTc-TRODAT-1 (axial slices) showing marked reduction on bilateral striatum in the patient (A) and normal tracer uptake in a healthy control (B). RFC1 electropherogram showing pentanucleotide expansion (C). [Color figure can be viewed at wileyonlinelibrary.com] Since the description of biallelic intronic RFC1 expansions as the underlying cause for cerebellar ataxia with neuropathy and vestibular areflexia syndrome in 2019, the full phenotypic spectrum related to this genetic abnormality remains to be determined.1-3 Herein we report a patient with RFC1 expansions leading to cerebellar ataxia with neuropathy and vestibular areflexia syndrome and dopa-responsive parkinsonism as part of her clinical picture. Although different cohorts involving patients with parkinsonism in the context of multiple system atrophy failed to demonstrate intronic RFC1 expansions as a causative factor,1, 3 we hypothesize that parkinsonism could be related to RFC1 in our patient. Indeed, the absence of autonomic features (with normal quantitative sudomotor axonal reflex) and hypo/anosmia combined with the lack of rapid eye movement behavior disorder all argue against the diagnosis of classical Parkinson's disease. Her benign clinical course without motor fluctuations more than a decade after levodopa start is also atypical. Lastly, the simultaneous occurrence of 2 rare conditions—homozygous RFC1 expansions and young-onset parkinsonism—just by chance would be possible but, rather, improbable. This description, although anecdotic, raises the possibility that dopa-responsive parkinsonism is part of the RFC1 clinical spectrum. Further studies in young-onset parkinsonian patients should be done to validate this assumption. Author Roles (1) Research project: A. Conception, B. Organization, C. Execution; (2) Manuscript: A. Writing of the first draft, B. Review and Critique. G.S.S.: 1B, 1C, 2A A.R.M.M.: 1A, 1B, 2B F.F.G.: 1A, 2B F.D.L.: 1A, 2B L.C.B.: 1B, 1C, 2B B.J.A.: 1C, 2B A.N.: 1A, 2B M.C.F.: 1A, 1B, 2B Supporting Information Filename Description mds28286-sup-0001-Video.mp4MPEG-4 video, 6.6 MB Video S1: A video highlighting the described patient in prelevodopa and postlevodopa treatment. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. References 1Sullivan R, Yau WY, Chelban V, et al. RFC1 Intronic repeat expansions absent in pathologically confirmed multiple systems atrophy. Mov Disord 2020; 35: 1277– 1279. Wiley Online LibraryPubMedWeb of Science®Google Scholar 2Cortese A, Tozza S, Yau WY, et al. Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. Brain 2020; 143: 480– 490. CrossrefPubMedWeb of Science®Google Scholar 3Fan Y, Zhang S, Yang J, et al. No biallelic intronic AAGGG repeat expansion in RFC1 was found in patients with late-onset ataxia and MSA. Parkinsonism Relat Disord 2020; 73: 1– 2. PubMedWeb of Science®Google Scholar Citing Literature Volume35, Issue10October 2020Pages 1889-1890 This article also appears in:Special Collection: COVID-19 Resources FiguresReferencesRelatedInformation
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