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Vanishing white matter disease with different faces

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Abstract

Purpose

The goal of this study was to better understand vanishing white matter (VWM) disease, which is one of the most common hereditary white matter disorders, and its relationship to radiologic features, genetic analyses, and clinical findings.

Methods

We performed a study on 11 patients to describe the clinical and neuroimaging features of VWM. Patients were grouped into “infantile,” “early childhood,” and “juvenile” based on their onset age. EIF2B1–5 genes encoding five subunits of eukaryotic translation initiation factor 2B (eIF2B) were analyzed in all patients with clinically suspected VWM disease.

Results

In brain magnetic resonance imaging (MRI), all patients showed white matter abnormalities with various degrees. The initial clinical presentation in five of patients was ataxia, with severe refractory epilepsy in three patients. In children with infantile-onset VWM, a rapid deterioration of motor function was detected, and the frequency of epilepsy was higher. Two patients showed manifestations of end-stage VWM disease, and one of them had chronic subdural hematoma. One of our patients and his father were diagnosed with Brugada syndrome. Sequencing of the exons and exon-intron boundaries of the EIF2B1–5 genes revealed mutations in the genes EIF2B5 (5 cases), EIF2B3 (3 cases), and EIF2B4 (2 cases). We also found a novel mutation in one patient: c.323_325delGAA in the EIF2B1 gene.

Conclusions

In this study, in addition to classical clinical and radiological findings, we wanted to emphasize that we may be confronted with refractory epilepsy (early infancy), cardiac problems, and intracranial complications that may occur in advanced stages.

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References

  1. Bugiani M, Boor I, Powers JM, Scheper GC, van der Knaap MS (2010) Leukoencephalopathy with vanishing white matter: a review. J Neuropathol Exp Neurol 69(10):987–996

    Article  Google Scholar 

  2. van der Knaap MS, Fogli A, Boespflug-Tanguy O, Abbink TEM, Schiffmann R (1993-2019) Childhood ataxia with central nervous system hypomyelination / vanishing white matter. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A (eds) GeneReviews®. University of Washington, Seattle, WA

  3. van der Knaap MS, Pronk JC, Scheper GC (2006) Vanishing white matter disease. Lancet Neurol 5(5):413–423. https://doi.org/10.1016/S1474-4422(06)70440-9

    Article  PubMed  Google Scholar 

  4. Fogli A, Dionisi-Vici C, Deodato F, Bartuli A, Boespflug-Tanguy O, Bertini E (2002) A severe variant of childhood ataxia with central hypomyelination/vanishing white matter leukoencephalopathy related to EIF21B5 mutation. Neurology 59(12):1966–1968

    Article  CAS  Google Scholar 

  5. van der Knaap MS, van Berkel CG, Herms J, van Coster R, Baethmann M, Naidu S, Boltshauser E, Willemsen MA, Plecko B, Hoffmann GF, Proud CG, Scheper GC, Pronk JC (2003) eIF2B-related disorders: antenatal onset and involvement of multiple organs. Am J Hum Genet 73(5):1199–1207. https://doi.org/10.1086/379524

    Article  PubMed  PubMed Central  Google Scholar 

  6. Maletkovic J, Schiffmann R, Gorospe JR, Gordon ES, Mintz M, Hoffman EP, Alper G, Lynch DR, Singhal BS, Harding C, Amartino H, Brown CM, Chan A, Renaud D, Geraghty M, Jensen L, Senbil N, Kadom N, Nazarian J, Yuanjian F, Zuyi W, Hartka T, Morizono H, Vanderver A (2008) Genetic and clinical heterogeneity in eIF2B-related disorder. J Child Neurol 23(2):205–215. https://doi.org/10.1177/0883073807308705

    Article  PubMed  Google Scholar 

  7. Proud CG (2012) Vanishing white matter: the next 10 years. Future Neurol 7(1):81–92

    Article  CAS  Google Scholar 

  8. Zhang H, Dai L, Chen N, Zang L, Leng X, Du L, Wang J, Jiang Y, Zhang F, Wu X, Wu Y (2015) Fifteen novel EIF2B1-5 mutations identified in Chinese children with leukoencephalopathy with vanishing white matter and a long term follow-up. PLoS One 10(3):e0118001. https://doi.org/10.1371/journal.pone.0118001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. van der Knaap MS, Barth PG, Gabreels FJ, Franzoni E, Begeer JH, Stroink H, Rotteveel JJ, Valk J (1997) A new leukoencephalopathy with vanishing white matter. Neurology 48(4):845–855

    Article  Google Scholar 

  10. Gunel MK, Mutlu A, Tarsuslu T, Livanelioglu A (2009) Relationship among the Manual Ability Classification System (MACS), the Gross Motor Function Classification System (GMFCS), and the functional status (WeeFIM) in children with spastic cerebral palsy. Eur J Pediatr 168(4):477–485. https://doi.org/10.1007/s00431-008-0775-1

    Article  PubMed  Google Scholar 

  11. Zhou L, Zhang H, Chen N, Zhang Z, Liu M, Dai L, Wang J, Jiang Y, Wu Y (2018) Similarities and differences between infantile and early childhood onset vanishing white matter disease. J Neurol 265(6):1410–1418. https://doi.org/10.1007/s00415-018-8851-6

    Article  PubMed  Google Scholar 

  12. Turon-Vinas E, Pineda M, Cusi V, Lopez-Laso E, Del Pozo RL, Gutierrez-Solana LG, Moreno DC, Sierra-Corcoles C, Olabarrieta-Hoyos N, Madruga-Garrido M, Aguirre-Rodriguez J, Gonzalez-Alvarez V, O’Callaghan M, Muchart J, Armstrong-Moron J (2014) Vanishing white matter disease in a spanish population. J Cent Nerv Syst Dis 6:59–68. https://doi.org/10.4137/JCNSD.S13540

    Article  PubMed  PubMed Central  Google Scholar 

  13. Fogli A, Schiffmann R, Bertini E, Ughetto S, Combes P, Eymard-Pierre E, Kaneski CR, Pineda M, Troncoso M, Uziel G, Surtees R, Pugin D, Chaunu MP, Rodriguez D, Boespflug-Tanguy O (2004) The effect of genotype on the natural history of eIF2B-related leukodystrophies. Neurology 62(9):1509–1517

    Article  CAS  Google Scholar 

  14. Alorainy IA, Patenaude YG, O’Gorman AM, Black DN, Meagher-Villemure K (1999) Cree leukoencephalopathy: neuroimaging findings. Radiology 213(2):400–406

    Article  CAS  Google Scholar 

  15. Fogli A, Wong K, Eymard-Pierre E, Wenger J, Bouffard JP, Goldin E, Black DN, Boespflug-Tanguy O, Schiffmann R (2002) Cree leukoencephalopathy and CACH/VWM disease are allelic at the EIF2B5 locus. Ann Neurol 52(4):506–510. https://doi.org/10.1002/ana.10339

    Article  CAS  PubMed  Google Scholar 

  16. Labauge P, Horzinski L, Ayrignac X, Blanc P, Vukusic S, Rodriguez D, Mauguiere F, Peter L, Goizet C, Bouhour F, Denier C, Confavreux C, Obadia M, Blanc F, de Seze J, Fogli A, Boespflug-Tanguy O (2009) Natural history of adult-onset eIF2B-related disorders: a multi-centric survey of 16 cases. Brain 132(Pt 8):2161–2169. https://doi.org/10.1093/brain/awp171

    Article  PubMed  Google Scholar 

  17. Schiffmann R, van der Knaap MS (2009) Invited article: an MRI-based approach to the diagnosis of white matter disorders. Neurology 72(8):750–759. https://doi.org/10.1212/01.wnl.0000343049.00540.c8

    Article  PubMed  PubMed Central  Google Scholar 

  18. Tedeschi G, Schiffmann R, Barton NW, Shih HH, Gospe SM Jr, Brady RO, Alger JR, Di Chiro G (1995) Proton magnetic resonance spectroscopic imaging in childhood ataxia with diffuse central nervous system hypomyelination. Neurology 45(8):1526–1532

    Article  CAS  Google Scholar 

  19. van der Lei HD, Steenweg ME, Barkhof F, de Grauw T, d’Hooghe M, Morton R, Shah S, Wolf N, van der Knaap MS (2012) Characteristics of early MRI in children and adolescents with vanishing white matter. Neuropediatrics 43(1):22–26. https://doi.org/10.1055/s-0032-1307456

    Article  PubMed  Google Scholar 

  20. Wilson CJ, Pronk JC, Van der Knaap MS (2005) Vanishing white matter disease in a child presenting with ataxia. J Paediatr Child Health 41(1–2):65–67. https://doi.org/10.1111/j.1440-1754.2005.00540.x

    Article  CAS  PubMed  Google Scholar 

  21. Singh RR, Livingston J, Lim M, Berry IR, Siddiqui A (2017) An unusual neuroimaging finding and response to immunotherapy in a child with genetically confirmed vanishing white matter disease. Eur J Paediatr Neurol 21(2):410–413. https://doi.org/10.1016/j.ejpn.2016.08.012

    Article  PubMed  Google Scholar 

  22. Patay Z (2005) Diffusion-weighted MR imaging in leukodystrophies. Eur Radiol 15(11):2284–2303. https://doi.org/10.1007/s00330-005-2846-2

    Article  PubMed  Google Scholar 

  23. Barros SR, Parreira SCR, Miranda AFB, Pereira AMB, Campos NMP (2018) New insights in vanishing white matter disease: isolated bilateral optic neuropathy in adult onset disease. J Neuroophthalmol 38(1):42–46. https://doi.org/10.1097/WNO.0000000000000565

    Article  PubMed  Google Scholar 

  24. Ding XQ, Bley A, Ohlenbusch A, Kohlschutter A, Fiehler J, Zhu W, Lanfermann H (2012) Imaging evidence of early brain tissue degeneration in patients with vanishing white matter disease: a multimodal MR study. J Magn Reson Imaging 35(4):926–932. https://doi.org/10.1002/jmri.23517

    Article  PubMed  Google Scholar 

  25. van der Lei HD, Steenweg ME, Bugiani M, Pouwels PJ, Vent IM, Barkhof F, van Wieringen WN, van der Knaap MS (2012) Restricted diffusion in vanishing white matter. Arch Neurol 69(6):723–727. https://doi.org/10.1001/archneurol.2011.1658

    Article  PubMed  Google Scholar 

  26. Van Haren K, van der Voorn JP, Peterson DR, van der Knaap MS, Powers JM (2004) The life and death of oligodendrocytes in vanishing white matter disease. J Neuropathol Exp Neurol 63(6):618–630. https://doi.org/10.1093/jnen/63.6.618

    Article  PubMed  Google Scholar 

  27. Pronk JC, van Kollenburg B, Scheper GC, van der Knaap MS (2006) Vanishing white matter disease: a review with focus on its genetics. Ment Retard Dev Disabil Res Rev 12(2):123–128. https://doi.org/10.1002/mrdd.20104

    Article  PubMed  Google Scholar 

  28. Venter JC (2019) http://provean.jcvi.org/index.php. J Creig Venter. Accessed 14/5/2019

  29. LEVY N (2019) http://www.umd.be/HSF/. Aix Marseille Universite. Accessed 14/5/2019

  30. Schwarz JM, Cooper DN, Schuelke M, Seelow D (2014) MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods 11(4):361–362. https://doi.org/10.1038/nmeth.2890

    Article  CAS  Google Scholar 

  31. Scali O, Di Perri C, Federico A (2006) The spectrum of mutations for the diagnosis of vanishing white matter disease. Neurol Sci 27(4):271–277. https://doi.org/10.1007/s10072-006-0683-y

    Article  CAS  PubMed  Google Scholar 

  32. Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Brignole M, Giordano U, Giovannini T, Menozzi C, Bloise R, Crotti L, Terreni L, Schwartz PJ (2000) Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: a prospective evaluation of 52 families. Circulation 102(20):2509–2515

    Article  CAS  Google Scholar 

  33. Iglesias DG, Rubín J, Pérez D, Morís C, Calvo D (2019) Insights for stratification of risk in Brugada syndrome. Eur Cardiol 14(1):45–49. https://doi.org/10.15420/ecr.2018.31.2

    Article  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Radiology, Faculty of Medicine, Pamukkale University, Denizli, Turkey

    Gülay Güngör

  2. Department of Pediatric Neurology, Faculty of Medicine, Pamukkale University, 20100, Denizli, Turkey

    Olcay Güngör

  3. Department of Medical Genetics, Necip Fazıl City Hospital, Kahramanmaras, Turkey

    Seda Çakmaklı

  4. Department of Pediatric Neurology, Ümraniye Training and Research Hospital, İstanbul, Turkey

    Hülya Maraş Genç

  5. Department of Pediatric Neurology, Faculty of Medicine, Medical Park University, Samsun, Turkey

    Hülya İnce

  6. Department of Medical Genetics, Faculty of Medicine, Bezmialem Vakıf University, İstanbul, Turkey

    Gözde Yeşil

  7. Department of Pediatric Neurology, Faculty of Medicine, Medipol University, İstanbul, Turkey

    Cengiz Dilber

  8. Department of Pediatric Neurology, Marash Life Hospital, Kahramanmaraş, Turkey

    Kürşad Aydın

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  1. Gülay Güngör
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Contributions

GG, OG, and SÇ were involved in the design of this study. OG, Hİ, CD, KA, and HMG contributed to the analysis of the data. GG, OG, and SÇ contributed to the writing the manuscript. All authors critically reviewed and approved the final manuscript.

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Correspondence to Olcay Güngör.

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Güngör, G., Güngör, O., Çakmaklı, S. et al. Vanishing white matter disease with different faces. Childs Nerv Syst 36, 353–361 (2020). https://doi.org/10.1007/s00381-019-04334-6

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  • DOI: https://doi.org/10.1007/s00381-019-04334-6

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