J Neurol Neurosurg Psychiatry 2001
Dec;71(6):757-61
Chataway J, Mander A, Robertson
N, Sawcer S, Deans J, Fraser M, Broadley S, Clayton D, Compston A.
University of Cambridge Neurology
unit, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK.
OBJECTIVES:
To assess the potential contribution
of genetic factors to clinical phenotype in multiple sclerosis.
METHODS:
Using 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.
RESULTS:
Adjusted 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 (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 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 (kappa=0.11
(95% CI 0.04 to 0.19)), progression (kappa=0.09 (95% CI 0.01 to 0.18))
and handicap (kappa=0.08 (95% CI 0.02 to 0.14)).
CONCLUSIONS:
Within 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.
PMID: 11723196 [PubMed - in process]