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This chapter discusses the genetics/genetic epidemiology of pediatric multiple sclerosis (MS) as largely derived from information on adults, and draws attention to needed areas of research on pediatric MS, including etiology, pathogenesis, natural history, response to therapy, recovery from relapse, cognition, and activities of daily living. The first direct evidence for a relationship between genes and MS susceptibility came in 1972, when Jersild et al reported an association between human leukocyte antigen (HLA) system alleles and MS. MS is not a monogenic disease and thus recurrence risk data for relatives of patients are based on empiric data rather than strict theoretical models. Recurrence risk data are collected by taking a family history and documenting affected and unaffected statuses among family members of index cases. MS in Northern Europeans has been associated with extended major histocompatibility complex (MHC) haplotypes.