Multiple sclerosis in sibling pairs: an analysis of 250 families

Objectives-To assess the potential contribution of genetic factors to clini cal phenotype in multiple sclerosis. Methods-Using a cohort of 262 pairs of coaffected siblings from 250 familie s with multiple sclerosis, intersibling concordance analysis was used to ex plore underlying genetic mechanisms in disease pathogenesis by assessing pa rameters of disease course, clinical presentation, age and year of onset, a nd measures of disability and handicap. Results-Adjusted intraclass correlation coefficients were not significant f or either age of onset or for year of first symptom. One third of sibling p airs were concordant for presenting symptom (81/262), a result that was non -significant. However, course type was identical in 50% of the sibling pair s (kappa =0.17 (95% confidence interval (95% CI) 0.08 to 0.26)) indicating a significant result. Severity of the disease at assessment, using the Kurt zke and CAMBS scales, demonstrated that whereas there was no agreement for relapse rate in the previous year within the sibship, there was significant concordance for measures of disability (kappa =0.11 (95% CI 0.04 to 0.19)) , progression (kappa =0.09 (95% CI 0.01 to 0.18)) and handicap (kappa0.08 ( 95% CI 0.02 to 0.14)). Conclusions-Within a sibship, the clinical presentation tends to be differe nt. However, once established, concordance is more likely to be seen for th e ultimate course, leading in the end to similar disability and handicap sc ores. These results are consistent with the hypothesis that genes influence both disease susceptibility and evolution in multiple sclerosis.