RFC1 Intronic Repeat Expansions Absent in Pathologically Confirmed Multiple Systems Atrophy

@article{Sullivan2020RFC1IR,
  title={RFC1 Intronic Repeat Expansions Absent in Pathologically Confirmed Multiple Systems Atrophy},
  author={Roisin Sullivan and Wai Yan Yau and Viorica Chelban and Salvatore Rossi and Emer O’connor and Nicholas W. Wood and Andrea Cortese and Henry Houlden},
  journal={Movement Disorders},
  year={2020},
  volume={35}
}
MSA is a rare neurodegenerative disorder involving cerebellar impairment, parkinsonism, and autonomic dysfunction that varies in presentation. The pathological hallmark of MSA is the accumulation of alpha-synuclein, which aggregates in mature oligodendrocytes that form glial cytoplasmic inclusions, defining it as a synucleinopathy. Based on the current diagnostic criteria, only 60% of clinical MSA cases meet the pathological criteria in a recent brain bank series. Because of the overlap in some… 
14 Citations
RFC1-related ataxia is a mimic of early multiple system atrophy
TLDR
Three cases with biallelic RFC1 expansions are presented: two clinically diagnosed with ‘probable’ MSA and one with 'probable' based on the SCDC for MSA, hypothesised that the recessive RFC1 expansion may be implicated in patients that atypically fit the diagnostic criteria for M SA.
RFC 1-related ataxia is a mimic of early multiple system atrophy
INTRODUCTION Multiple systems atrophy (MSA) is a rare neurodegenerative disorder combining varying presentations of cerebellar impairment, parkinsonism and autonomic dysfunction that relies on
CANVAS: a late onset ataxia due to biallelic intronic AAGGG expansions
TLDR
A protocol for RFC1 expansion screening is optimised which is described herein and the phenotype of CANVAS is expanded after analysing late-onset ataxia patients from around the world.
RFC1 CANVAS: the expanding phenotype
  • M. Reilly
  • Medicine
    Journal of Neurology, Neurosurgery, and Psychiatry
  • 2021
TLDR
The RFC1 expansion is reported in three patients with cerebellar ataxia, parkinsonism and autonomic dysfunction (and neuropathy in 2/3) out of a total of 207 patients with either possible or probable MSA and the authors conclude that there are clinical similarities between CANVAS and early MSA especially those with predominant Cerebellar involvement (MSAC).
Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort
TLDR
The study confirms the genetic heterogeneity of the CANVAS and that RFC1 repeat expansions should be searched for preferentially in case of unexplained ILOA associated with a sensory neuronopathy, but not particularly in patients classified as MSA-C.
Dopa‐Responsive Parkinsonism in a Patient With Homozygous RFC1 Expansions
TLDR
It is hypothesize that parkinsonism could be related to RFC1 in a patient with RFC1 expansions leading to cerebellar ataxia with neuropathy and vestibular areflexia syndrome and dopa-responsive parkinsonistan as part of her clinical picture, and raises the possibility that dopa/anosmia is part of the RFC1 clinical spectrum.
Dopa‐Responsive Parkinsonism in a Patient With Homozygous RFC1 Expansions
TLDR
The phenotypic spectrum of RFC1 expansion-related disorders is expanded by reporting dopa-responsive parkinsonism in a 63-year-old woman, characterized by bradykinesia, resting tremor, and stiffness.
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): genetic and clinical aspects
TLDR
Clinical examination identifies a sensory neuropathy or neuronopathy and bilaterally impaired vestibulo-ocular reflex in RFC1 disease, probably the most common cause of recessive ataxia.
CHRONOLOGICAL OVERVIEW OF CEREBELLAR ATAXIA WITH NEUROPATHY AND VESTIBULAR AREFLEXIA SYNDROME LITERATURE
Recent findings Recent advancements in the range of the clinical features of CANVAS have aided the development of a broader, more well-defined clinical diagnostic criteria. Additionally, the
Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease
TLDR
This study provides Class II evidence that RFC1 repeat expansions are associated with CANVAS and ACC, with RFC1 disease occurring across continents and as variable, overlapping clusters along a continuous multisystemic disease spectrum, including MSA-C-overlap.
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