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Familial effects on the clinical course of multiple sclerosis

Item Type:Article
Title:Familial effects on the clinical course of multiple sclerosis
Creators Name:Hensiek, A.E. and Seaman, S.R. and Barcellos, L.F. and Oturai, A. and Eraksoi, M. and Cocco, E. and Vecsei, L. and Stewart, G. and Dubois, B. and Bellman-Strobl, J. and Leone, M. and Andersen, O. and Bencsik, K. and Booth, D. and Celius, E.G. and Harbo, H.F. and Hauser, S.L. and Heard, R. and Hillert, J. and Myhr, K.M. and Marrosu, M.G. and Oksenberg, J.R. and Rajda, C. and Sawcer, S.J. and Sorensen, P.S. and Zipp, F. and Compston, D.A.S.
Abstract:BACKGROUND: Familial factors influence susceptibility to multiple sclerosis (MS) but it is unknown whether there are additional effects on the natural history of the disease. METHOD: We evaluated 1,083 families with > or = 2 first-degree relatives with MS for concordance of age at onset, clinical course, and disease severity and investigated transmission patterns of these clinical features in affected parent-child pairs. RESULTS: There is concordance for age at onset for all families (correlation coefficient 0.14; p < 0.001), as well as for affected siblings (correlation coefficient 0.15; p < 0.001), and affected parent-child pairs (correlation coefficient 0.12; p = 0.03) when each is evaluated separately. Concordance for year of onset is present among affected siblings (correlation coefficient 0.18; p < 0.001) but not the parent-child group (correlation coefficient 0.08; p = 0.15). The clinical course is similar between siblings (kappa 0.12; p < 0.001) but not affected parents and their children (kappa -0.04; p = 0.09). This influence on the natural history is present in all clinical subgroups of relapsing-remitting, and primary and secondary progressive MS, reflecting a familial effect on episodic and progressive phases of the disease. There is no concordance for disease severity within any of the considered family groups (correlation coefficients: all families analyzed together, 0.02, p = 0.53; affected sibling group, 0.02, p = 0.61; affected parent-child group, 0.02, p = 0.69). Furthermore, there are no apparent transmission patterns of any of the investigated clinical features in affected parent-child pairs and no evidence for anticipation or effects of genetic loading. CONCLUSION: Familial factors do not significantly affect eventual disease severity. However, they increase the probability of a progressive clinical course, either from onset or after a phase of relapsing remitting disease. The familial effect is more likely to reflect genetic than environmental conditions. The results are relevant for counseling patients and have implications for the design of studies seeking to identify factors that influence the natural history of the disease.
Keywords:Disease Progression, Genetic Predisposition to Disease, Heterozygote, Multiple Sclerosis, Pedigree, Prevalence, Risk Assessment, Risk Factors
Publisher:American Academy of Neurology
Page Range:376-383
Date:30 January 2007
Official Publication:https://doi.org/10.1212/01.wnl.0000252822.53506.46
PubMed:View item in PubMed

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