Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis

The overall goal of this project is to determine whether well-established environmental and
genetic risk factors for adult onset MS play an important role in susceptibility to
pediatric-onset MS. Our study design is based on the hypothesis that genetic influences,
specifically variation at HLA-DRB1 and other confirmed non-MHC MS loci, as well as
environmental exposures including EBV infection and tobacco smoke, contribute to disease
risk. In addition, we will also examine the relationship between serum levels of 25(OH)
vitamin D3 and prior vitamin D status, and risk for pediatric onset MS. Finally, we will
investigate whether specific G x E, and other multivariable relationships influencing risk
exist for pediatric-onset MS. There are 16 collaborating sites other than UCSF that will
enroll cases and controls for this study.

Children are eligible for this study as cases if:

- They have MS or clinically isolated syndrome (CIS):

- MS: As defined by the 2010 McDonald criteria for diagnosis of MS (Polman 2010),

- CIS: A first demyelinating event indicating high risk for MS (i.e., one clinical
event involving the spinal cord, the optic nerve, the brainstem or cerebellum, or
occasionally the hemispheres) and at least 2 silent T2 bright areas on a brain or
spinal cord MRI (at least one must be in the brain); AND

- They are three years of age or older; AND

- Disease onset occurred before 18 years of age.

Patients are not eligible for study participation if:

- Disease onset occurred more than 4 years prior to the opportunity to enroll; OR

- They have had an organ transplant; OR

- They are known to have neuromyelitis optica (NMO).

Children are not eligible to participate as pediatric controls if:

- They are two years of age or younger; OR

- They are 22 years of age or older; OR

- They are known to have MS or another demyelinating disease (for example, neuromyelitis
optica or acute disseminated encephalomyelitis); OR

- They have a biological family member who has been enrolled as a control; OR

- They have an immediate, biological family member (parent/sibling) who has been
diagnosed with MS; OR

- They have an autoimmune disorder (except asthma or eczema); OR

- They have had an organ transplant; OR

- They have a chronic neurological condition with major disability (this does not
include, for example, migraine, controlled seizures, and mild learning disabilities
such as ADD or ADHD).