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August 30, 2016; 87 (9 Supplement 2) Article

Environmental and genetic factors in pediatric inflammatory demyelinating diseases

Emmanuelle Waubant, Anne-Louise Ponsonby, Maura Pugliatti, Heather Hanwell, Ellen M. Mowry, Rogier Q. Hintzen
First published August 29, 2016, DOI: https://doi.org/10.1212/WNL.0000000000003029
Emmanuelle Waubant
From the Pediatric MS Center (E.W.), UCSF Benioff Children's Hospital; Neurology Department (E.W.), UCSF, San Francisco, CA; Murdoch Children's Research Institute (A.-L.P.), Royal Children's Hospital, University of Melbourne, Australia; Department of Biomedical and Specialty Surgical Sciences (M.P.), University of Ferrara, Italy; Neurosciences and Mental Health (H.H.), The Hospital for Sick Children, Toronto, Canada; Department of Neurology (E.M.M.), Johns Hopkins, Baltimore, MD; and MS Center ErasMS, Department of Neurology (R.Q.H.), Erasmus MC, Rotterdam, the Netherlands.
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Anne-Louise Ponsonby
From the Pediatric MS Center (E.W.), UCSF Benioff Children's Hospital; Neurology Department (E.W.), UCSF, San Francisco, CA; Murdoch Children's Research Institute (A.-L.P.), Royal Children's Hospital, University of Melbourne, Australia; Department of Biomedical and Specialty Surgical Sciences (M.P.), University of Ferrara, Italy; Neurosciences and Mental Health (H.H.), The Hospital for Sick Children, Toronto, Canada; Department of Neurology (E.M.M.), Johns Hopkins, Baltimore, MD; and MS Center ErasMS, Department of Neurology (R.Q.H.), Erasmus MC, Rotterdam, the Netherlands.
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Maura Pugliatti
From the Pediatric MS Center (E.W.), UCSF Benioff Children's Hospital; Neurology Department (E.W.), UCSF, San Francisco, CA; Murdoch Children's Research Institute (A.-L.P.), Royal Children's Hospital, University of Melbourne, Australia; Department of Biomedical and Specialty Surgical Sciences (M.P.), University of Ferrara, Italy; Neurosciences and Mental Health (H.H.), The Hospital for Sick Children, Toronto, Canada; Department of Neurology (E.M.M.), Johns Hopkins, Baltimore, MD; and MS Center ErasMS, Department of Neurology (R.Q.H.), Erasmus MC, Rotterdam, the Netherlands.
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Heather Hanwell
From the Pediatric MS Center (E.W.), UCSF Benioff Children's Hospital; Neurology Department (E.W.), UCSF, San Francisco, CA; Murdoch Children's Research Institute (A.-L.P.), Royal Children's Hospital, University of Melbourne, Australia; Department of Biomedical and Specialty Surgical Sciences (M.P.), University of Ferrara, Italy; Neurosciences and Mental Health (H.H.), The Hospital for Sick Children, Toronto, Canada; Department of Neurology (E.M.M.), Johns Hopkins, Baltimore, MD; and MS Center ErasMS, Department of Neurology (R.Q.H.), Erasmus MC, Rotterdam, the Netherlands.
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Ellen M. Mowry
From the Pediatric MS Center (E.W.), UCSF Benioff Children's Hospital; Neurology Department (E.W.), UCSF, San Francisco, CA; Murdoch Children's Research Institute (A.-L.P.), Royal Children's Hospital, University of Melbourne, Australia; Department of Biomedical and Specialty Surgical Sciences (M.P.), University of Ferrara, Italy; Neurosciences and Mental Health (H.H.), The Hospital for Sick Children, Toronto, Canada; Department of Neurology (E.M.M.), Johns Hopkins, Baltimore, MD; and MS Center ErasMS, Department of Neurology (R.Q.H.), Erasmus MC, Rotterdam, the Netherlands.
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Rogier Q. Hintzen
From the Pediatric MS Center (E.W.), UCSF Benioff Children's Hospital; Neurology Department (E.W.), UCSF, San Francisco, CA; Murdoch Children's Research Institute (A.-L.P.), Royal Children's Hospital, University of Melbourne, Australia; Department of Biomedical and Specialty Surgical Sciences (M.P.), University of Ferrara, Italy; Neurosciences and Mental Health (H.H.), The Hospital for Sick Children, Toronto, Canada; Department of Neurology (E.M.M.), Johns Hopkins, Baltimore, MD; and MS Center ErasMS, Department of Neurology (R.Q.H.), Erasmus MC, Rotterdam, the Netherlands.
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Citation
Environmental and genetic factors in pediatric inflammatory demyelinating diseases
Emmanuelle Waubant, Anne-Louise Ponsonby, Maura Pugliatti, Heather Hanwell, Ellen M. Mowry, Rogier Q. Hintzen
Neurology Aug 2016, 87 (9 Supplement 2) S20-S27; DOI: 10.1212/WNL.0000000000003029

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Abstract

The onset of multiple sclerosis (MS) occurs in childhood in about 5% of all patients with MS. The disease in adults has a complex genetic and environmental inheritability. One of the main risk factors, also confirmed in pediatric MS, is HLA DRB1*1501. In addition to genetic factors, a large part of disease susceptibility in adults is conferred by environmental risk factors such as low vitamin D status, exposure to cigarette smoking, and remote Epstein-Barr virus (EBV) infection. In children, both exposure to cigarette smoking and prior EBV infection have been reported consistently as risk factors for MS. The role of vitamin D remains to be confirmed in this age category. Finally, although very likely critical in disease processes, few gene–environment interactions and epigenetic changes have been reported for adult and pediatric MS susceptibility. Of interest, some of the risk factors for MS have also been associated with disease course modification, such as low 25(OH) vitamin D serum levels in pediatric and adult MS. Age is also a clear disease modifier of clinical, CSF, and MRI phenotype in children with the disease. Finally, although much has yet to be unraveled regarding molecular processes at play in MS, there is a larger gap in our knowledge of genetic and environmental risk factors for pediatric neuromyelitis optica spectrum disorders and acute disseminated encephalomyelitis and only collaborative studies will answer those questions.

GLOSSARY

25(OH)D=
25-hydroxyvitamin D;
ADS=
acquired demyelinating syndromes;
BMI=
body mass index;
CIS=
clinically isolated syndromes;
CMV=
cytomegalovirus;
EBV=
Epstein-Barr virus;
GWAS=
genome-wide association studies;
HLA=
human leukocyte antigen;
HSV=
herpes simplex virus;
MS=
multiple sclerosis;
NMO=
neuromyelitis optica

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received August 19, 2015.
  • Accepted in final form June 28, 2016.
  • © 2016 American Academy of Neurology
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  • Article
    • Abstract
    • GLOSSARY
    • ENVIRONMENTAL RISK FACTORS FOR PEDIATRIC MS SUSCEPTIBILITY OTHER THAN VITAMIN D
    • ENVIRONMENTAL FACTORS AS DISEASE MODIFIERS OF PEDIATRIC MS
    • GENETIC RISK FACTORS FOR PEDIATRIC MS SUSCEPTIBILITY AND DISEASE MODIFICATION
    • GENE–GENE AND GENE–ENVIRONMENT INTERACTIONS IN PEDIATRIC MS SUSCEPTIBILITY
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