Familial effects on the clinical course of multiple sclerosis

A. E. Hensiek, S. R. Seaman, L. F. Barcellos, A. Oturai, M. Eraksoi, E. Cocco, L. Vécsei, G. Stewart, B. Dubois, J. Bellman-Strobl, M. Leone, O. Andersen, K. Bencsik, D. Booth, E. G. Celius, H. F. Harbo, S. L. Hauser, R. Heard, J. Hillert, K. M. MyhrM. G. Marrosu, J. R. Oksenberg, C. Rajda, S. J. Sawcer, P. S. Sørensen, F. Zipp, D. A S Compston

Research output: Contribution to journalArticle

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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 ≥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.

Original languageEnglish
Pages (from-to)376-383
Number of pages8
JournalNeurology
Volume68
Issue number5
DOIs
Publication statusPublished - Jan 2007

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Multiple Sclerosis
Siblings
Chronic Progressive Multiple Sclerosis
Age of Onset
Natural History
Counseling
Parents

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hensiek, A. E., Seaman, S. R., Barcellos, L. F., Oturai, A., Eraksoi, M., Cocco, E., ... Compston, D. A. S. (2007). Familial effects on the clinical course of multiple sclerosis. Neurology, 68(5), 376-383. https://doi.org/10.1212/01.wnl.0000252822.53506.46

Familial effects on the clinical course of multiple sclerosis. / Hensiek, A. E.; Seaman, S. R.; Barcellos, L. F.; Oturai, A.; Eraksoi, M.; Cocco, E.; Vécsei, L.; Stewart, G.; Dubois, B.; Bellman-Strobl, J.; Leone, M.; Andersen, O.; Bencsik, K.; Booth, D.; Celius, E. G.; Harbo, H. F.; Hauser, S. L.; Heard, R.; Hillert, J.; Myhr, K. M.; Marrosu, M. G.; Oksenberg, J. R.; Rajda, C.; Sawcer, S. J.; Sørensen, P. S.; Zipp, F.; Compston, D. A S.

In: Neurology, Vol. 68, No. 5, 01.2007, p. 376-383.

Research output: Contribution to journalArticle

Hensiek, AE, Seaman, SR, Barcellos, LF, Oturai, A, Eraksoi, M, Cocco, E, Vécsei, L, Stewart, G, Dubois, B, Bellman-Strobl, J, Leone, M, Andersen, O, Bencsik, K, Booth, D, Celius, EG, Harbo, HF, Hauser, SL, Heard, R, Hillert, J, Myhr, KM, Marrosu, MG, Oksenberg, JR, Rajda, C, Sawcer, SJ, Sørensen, PS, Zipp, F & Compston, DAS 2007, 'Familial effects on the clinical course of multiple sclerosis', Neurology, vol. 68, no. 5, pp. 376-383. https://doi.org/10.1212/01.wnl.0000252822.53506.46
Hensiek AE, Seaman SR, Barcellos LF, Oturai A, Eraksoi M, Cocco E et al. Familial effects on the clinical course of multiple sclerosis. Neurology. 2007 Jan;68(5):376-383. https://doi.org/10.1212/01.wnl.0000252822.53506.46
Hensiek, A. E. ; Seaman, S. R. ; Barcellos, L. F. ; Oturai, A. ; Eraksoi, M. ; Cocco, E. ; Vécsei, L. ; Stewart, G. ; Dubois, B. ; Bellman-Strobl, J. ; Leone, M. ; Andersen, O. ; Bencsik, K. ; Booth, D. ; Celius, E. G. ; Harbo, H. F. ; Hauser, S. L. ; Heard, R. ; Hillert, J. ; Myhr, K. M. ; Marrosu, M. G. ; Oksenberg, J. R. ; Rajda, C. ; Sawcer, S. J. ; Sørensen, P. S. ; Zipp, F. ; Compston, D. A S. / Familial effects on the clinical course of multiple sclerosis. In: Neurology. 2007 ; Vol. 68, No. 5. pp. 376-383.
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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 ≥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.",
author = "Hensiek, {A. E.} and Seaman, {S. R.} and Barcellos, {L. F.} and A. Oturai and M. Eraksoi and E. Cocco and L. V{\'e}csei and G. Stewart and B. Dubois and J. Bellman-Strobl and M. Leone and O. Andersen and K. Bencsik and D. Booth and Celius, {E. G.} and Harbo, {H. F.} and Hauser, {S. L.} and R. Heard and J. Hillert and Myhr, {K. M.} and Marrosu, {M. G.} and Oksenberg, {J. R.} and C. Rajda and Sawcer, {S. J.} and S{\o}rensen, {P. S.} and F. Zipp and Compston, {D. A S}",
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T1 - Familial effects on the clinical course of multiple sclerosis

AU - Hensiek, A. E.

AU - Seaman, S. R.

AU - Barcellos, L. F.

AU - Oturai, A.

AU - Eraksoi, M.

AU - Cocco, E.

AU - Vécsei, L.

AU - Stewart, G.

AU - Dubois, B.

AU - Bellman-Strobl, J.

AU - Leone, M.

AU - Andersen, O.

AU - Bencsik, K.

AU - Booth, D.

AU - Celius, E. G.

AU - Harbo, H. F.

AU - Hauser, S. L.

AU - Heard, R.

AU - Hillert, J.

AU - Myhr, K. M.

AU - Marrosu, M. G.

AU - Oksenberg, J. R.

AU - Rajda, C.

AU - Sawcer, S. J.

AU - Sørensen, P. S.

AU - Zipp, F.

AU - Compston, D. A S

PY - 2007/1

Y1 - 2007/1

N2 - 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 ≥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.

AB - 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 ≥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.

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