Genetic factors and the founder effect explain familial MS in Sardinia

Objective: To estimate the presence of familial aggregation and determine the contribution of genetic factors to familial clustering of MS in patients coming from Sardinia, a Mediterranean island considered a genetically homogeneous, isolated area having high disease incidence and prevalence. Methods: Recurrence risk in siblings of 901 Sardinian patients and factors influencing risk (patient and sibling sex, patient age at onset, sibling birth cohort, and presence of affected relatives other than siblings) were examined. The presence of distant familial relationships among patients was evaluated by tracing the extended pedigrees of all patients with MS born in one Sardinian village. Results: Twenty-three brothers and 36 sisters of the 2,971 siblings were affected with MS. Recurrence risk was greater in siblings of index patients with onset age less than 30 years ( p p Conclusions: Data from this study indicate that MS familial aggregation in Sardinians is influenced by genetic factors and that founder effect and the isolation of Sardinia can be considered causes of the enrichment of “etiologic” MS genes.