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Tumefactive lesions in retinal vasculopathy with cerebral leucoencephalopathy and systemic manifestations (RVCL-S): a role for neuroinflammation?
  1. Todd A. Hardy1,2,
  2. Stephanie Young3,
  3. Joanne S. Sy4,
  4. Alison F. Colley5,
  5. Gisela M. Terwindt6,
  6. Michel D. Ferrari6,
  7. Michael W. Hayes1,
  8. Suzanne Hodgkinson7
  1. 1 Department of Neurology, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
  2. 2 Brain and Mind Centre, University of Sydney, Camperdown, New South Wales, Australia
  3. 3 Department of Ophthalmology, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
  4. 4 Department of Anatomical Pathology, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
  5. 5 Department of Clinical Genetics, Liverpool Hospital, University of NSW, Liverpool, New South Wales, Australia
  6. 6 Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
  7. 7 Department of Neurology, Liverpool Hospital, University of NSW, Liverpool, New South Wales, Australia
  1. Correspondence to Dr Todd A. Hardy, Department of Neurology, Concord Repatriation General Hospital, Concord, NSW, 2139 Australia; thardy{at}med.usyd.edu.au

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Retinal vasculopathy with cerebral leucoencephalopathy and systemic manifestations (RVCL-S) is a rare, autosomal dominant condition caused by mutations in the TREX1 gene.1 2 Typically, vascular retinopathy becomes apparent in the fourth or fifth decade, soon followed by clinical manifestations of progressive focal and global brain disease. Brain imaging reveals ring-enhancing mass lesions and/or punctate hyperintense white matter lesions with or without nodular enhancement, often in combination with focal white matter calcifications. Many patients will also have, or develop, liver and kidney dysfunction, anaemia with or without gastrointestinal bleeding, hypertension, migraine and mild Raynaud’s phenomenon.2 We describe two brothers with genetically proven RVCL-S due to a mutation in the TREX1 gene (3688_3689insG) encoding the mutant protein V235fs. The clinical history, radiology, treatment and outcomes for the two brothers are presented in the online supplementary file 1 and as figure S1 in the online supplementary file 2.

Supplementary file 1

S1
[SP1.pdf]

Supplementary file 2

S2
[SP2.jpg]

In Case 1, multiple sclerosis (MS) with tumefactive demyelinating lesions, cerebral vasculitis and neoplasm were all considered as diagnostic possibilities until the patient’s brother also became symptomatic, indicating a possible genetic cause. The father of the two brothers was probably affected but confirmation is no longer possible. The consanguineous family history in our cases is unlikely to be significant as RVCL-S is an autosomal dominant rather than recessive condition. A recessive mutation in TREX1 causes Aicardi-Goutieres syndrome (AGS), which presents in the first year of life with acquired microcephaly, developmental delay, encephalopathy, spasticity and extrapyramidal signs. Like RVCL-S, AGS is notable for neuropathology demonstrating microangiopathy and microinfarction.

The MRI features of RVCL-S include periventricular white matter T2 hyperintensities, calcifications and infarcts.2 Tumefactive lesions are found in approximately …

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Footnotes

  • Contributors TAH and MWH conceived the idea for the article. TAH, SY and MWH drafted the manuscript. SY supplied fluorescein angiogram images and JSS the neuropathology. AFC reviewed the family history and suggested the diagnosis and GMT and MDF performed the confirmatory DNA analysis. All authors revised the manuscript critically for important intellectual content and gave final approval of the version to be published.

  • Funding This work received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Liverpool Hospital HREC.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement None.

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