Within-family associations and disease progression in familial multiple sclerosis

Objective: To address the differences in disease progression between familial and sporadic multiple scleroris (MS) and the association within sib-pairs.

Methods: 48 sibling pairs and 98 controls from a databank of 445 sporadic MS-patients, randomly pair-matched for age, gender, clinical course and disease duration were included. In 33 available sibling-pairs follow-up data were collected prospectively Outcome parameters included baseline expanded disability status scale (EDSS), age at onset, mono- or multifocal onset and disease progression. For analyses within-group distributions were described and compared, using Wilcoxon's signed-rank statistics for categorical differences, and t-statistics for continous variables. Relative frequencies of categories were tested by McNemar's test, and within sibling-pair associations using an intraclass correlation coefficient. Statistical tests were performed 2-sided at the 5% level using UNIVARIATE and FREQ SAS software 9.1.

Results: Disease onset was slightly earlier (29.01 vs. 29.44 years, p=0.492) and multifocal onset significantly more often (p=0.0052) in familial than sporadic MS. Notably, a substantial within-pair correlation for disease progression could be observed (rho=0.40; r2=0.16, p=0.0062). However, there was neither a difference in baseline EDSS, nor in EDSS progression between the groups.

Conclusions: Familial MS differs from sporadic cases with respect to age at onset and multifocal involvement as first clinical event. The progression rate of one out of two affected siblings may provide as a predictor for the other sib. However, prognosis over a six-year follow-up concerning the EDSS was similar in both groups. Larger longitudinal studies are required to find clinical, genetic, immunological or therapeutic implications.