Document Detail


Multiple sclerosis in sibling pairs: an analysis of 250 families.
MedLine Citation:
PMID:  11723196     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
J Chataway; A Mander; N Robertson; S Sawcer; J Deans; M Fraser; S Broadley; D Clayton; A Compston
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurology, neurosurgery, and psychiatry     Volume:  71     ISSN:  0022-3050     ISO Abbreviation:  J. Neurol. Neurosurg. Psychiatr.     Publication Date:  2001 Dec 
Date Detail:
Created Date:  2001-11-27     Completed Date:  2001-12-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985191R     Medline TA:  J Neurol Neurosurg Psychiatry     Country:  England    
Other Details:
Languages:  eng     Pagination:  757-61     Citation Subset:  IM    
Affiliation:
University of Cambridge Neurology Unit, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK.
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MeSH Terms
Descriptor/Qualifier:
Activities of Daily Living
Age of Onset
Analysis of Variance
Cohort Studies
Confounding Factors (Epidemiology)
Disabled Persons / classification
Disease Progression
Female
Genetic Predisposition to Disease / classification,  epidemiology,  genetics*
Genetic Testing
Great Britain / epidemiology
Humans
Male
Multiple Sclerosis, Chronic Progressive / classification,  epidemiology,  genetics*,  physiopathology
Multiple Sclerosis, Relapsing-Remitting / classification,  epidemiology,  genetics*,  physiopathology
Pedigree*
Registries
Severity of Illness Index
Time Factors
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