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Revista de investigación clínica

versión On-line ISSN 2564-8896versión impresa ISSN 0034-8376

Rev. invest. clín. vol.71 no.2 Ciudad de México mar./abr. 2019  Epub 12-Abr-2021

https://doi.org/10.24875/ric.19002979 

Letter to the editor

Letter to the Editor

I. de Boer1 

A.M.J.M. van den Maagdenberg1  2 

G.M. Terwindt1  * 

1Department of Neurology, Leiden University Medical Center, Leiden, Netherlands

2Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands


Dear Editor,

Recently, Monroy-Jaramillo et al.1 described a new family with a disorder now known as retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S)2. RVCL-S is a monogenetic small vessel disease caused by C-terminal frameshift mutations in TREX13. The auteurs confirm phenotypic variability in RVCL-S but inaccurately claim a large number of pre-manifest mutation carriers2. In general, RVCL-S is often underdiagnosed as not all necessary diagnostic tests are performed. In a large study with 78 patients from 11 unrelated families, neuroimaging reveals white matter lesions with or without nodular enhancement (97%), rim-enhancing mass lesions (84%), and calcifications (52%). Clinical brain symptomatology was found in 90%, including focal neurological deficits (68%), migraine (59%), cognitive impairment (56%), psychiatric disturbances (42%), and seizures (17%). Systemic features included liver disease (78%), anemia (74%), nephropathy (61%), hypertension (60%), Raynaud’s phenomenon (40%), and gastrointestinal bleeding (27%)2 (Fig. 1). Therefore, we advise follow-up with diagnostic laboratory, ophthalmological, and neuro-radiological screening of RVCL-S mutation carriers but strongly object against biopsies because these have no added value. We would like to stress that disease status can be reliably made based on genetic testing and clinical and radiological findings alone. We would strongly argue against withholding a diagnosis to (potential) mutation carriers, especially as this is relevant for their brain, eyes, and systemic condition and, if followed up regularly, may prevent unnecessary invasive tests and allows for timely ophthalmological treatment to prevent blindness at a young age.

Figure 1 Clinical course of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S). Symptoms of RVCL2,4 derived from cross-sectional investigation of RVCL-S patients (aged 18-65 years). Vascular retinopathy and Raynaud’s phenomenon are the earliest symptoms presenting from age 20 onward. Kidney disease becomes manifest from around the age of 35 years, followed by liver disease, anemia, and, in some mutation carriers, migraine and subclinical hypothyroidism, all from age 40. Cerebral and cognitive deficits usually started mildly around age 50, associated with increasing volume of white matter hyperintensities and intracerebral mass lesions, and becoming severe and ultimately lethal around the age of 60-65 years. 

REFERENCES

1. Monroy-Jaramillo N, Cerón A, León E, et al. Phenotypic variability in a Mexican mestizo family with retinal vasculopathy with cerebral leukodystrophy and TREX1 mutation p.V235Gfs*6. Rev Invest Clin. 2018;70:68-75. [ Links ]

2. Stam AH, Kothari PH, Shaikh A, et al. Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. Brain. 2016;139:2909-22. [ Links ]

3. Richards A, van den Maagdenberg AM, Jen JC, et al. C-terminal truncations in human 3'-5'DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nat Genet. 2007;39:1068-70. [ Links ]

4. Pelzer N, Hoogeveen ES, Haan J, et al. Systemic features of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations:a monogenic small vessel disease. J Intern Med. 2018;[Epub ahead of print]. [ Links ]

Received: February 01, 2019; Accepted: February 12, 2019

* Corresponding author: Gisela M. Terwindt Department of Neurology Leiden University Medical Center Albinusdreef, 2 PO Box 9600, 2300 RC Leiden, the Netherlands E-mail: g.m.terwindt@lumc.nl

Creative Commons License Revista de Investigación Clínica. Published by Permanyer. This is an open ccess article under the CC BY-NC-ND license