Multiple sclerosis in sibling pairs: an analysis of 250 families
J Chatawaya, A Manderb, N Robertsona c, S Sawcera, J Deansa, M Frasera, S Broadleya, D Claytonb, A Compstona d
a University
of Cambridge Neurology unit, Addenbrooke's Hospital, Hills Road,
Cambridge, CB2 2QQ, UK, b MRC Biostatistics Unit,
Institute of Public Health, University Forvie Site, Robinson Way,
Cambridge, CB2 2SR, UK, c University Department of Neurology, University
Hospital of Wales, Heath Park, Cardiff, CF4 4XN, UK, d ED Adrian
Building, University Forvie Site, Robinson Way, Cambridge, CB2
2SR, UK
Correspondence to: Dr A Compston alastair.compston{at}medschl.cam.ac.uk
Received 19 January
2001 and in revised form 16 July 2001;
Accepted 20 July
2001
OBJECTIVES
To assess
the potential contribution of genetic factors to clinical phenotype in
multiple sclerosis.
METHODSUsing a cohort
of 262 pairs of coaffected siblings from 250 families with multiple
sclerosis, intersibling concordance analysis was used to explore
underlying genetic mechanisms in disease pathogenesis by assessing
parameters of disease course, clinical presentation, age and year of
onset, and measures of disability and handicap.
RESULTSAdjusted
intraclass correlation coefficients were not significant for either age
of onset or for year of first symptom. One third of sibling pairs were
concordant for presenting symptom (81/262), a result that was
non-significant. However, course type was identical in 50% of the
sibling pairs (
=0.17 (95% confidence interval (95% CI) 0.08 to
0.26)) indicating a significant result. Severity of the disease at
assessment, using the Kurtzke 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 (=0.11 (95% CI 0.04 to 0.19)), progression (=0.09
(95% CI 0.01 to 0.18)) and handicap (=0.08 (95% CI 0.02 to 0.14)).
CONCLUSIONSWithin a
sibship, the clinical presentation tends to be different. However, once
established, concordance is more likely to be seen for the ultimate
course, leading in the end to similar disability and handicap scores.
These results are consistent with the hypothesis that genes influence
both disease susceptibility and evolution in multiple sclerosis.
Keywords: multiple sclerosis; sibling pair; concordance
© 2001 by Journal of Neurology, Neurosurgery, and Psychiatry
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