title: Sibling disability risk at onset and during disease progression in familial multiple sclerosis.
abstract: BACKGROUND
  The objective of this study was to address the differences in onset and disease progression between familial and sporadic multiple sclerosis (MS) and the association within sibling pairs.
  
  
  METHODS
  Ninety-eight siblings and their controls were included from a database of 763 sporadic MS-patients, randomly pair-matched for age, gender, clinical course, disease duration and treatment. Sixty-eight available siblings completed a prospective six-year follow-up. Outcome parameters included baseline Expanded Disability Status Scale (EDSS), age at onset, mono- or multifocal onset, disease progression and conversion to secondary progression of initially relapsing-remitting MS. For statistical analyses Wilcoxon's signed-rank statistics for categorical differences, t-statistics for continuous variables, McNemar's test for relative frequencies of categories, intra-class correlations for within sibling-pair associations, or Kaplan-Meier analysis for survival analyses were used; all two-sided at the 5% level.
  
  
  RESULTS
  Disease onset was slightly earlier (29.01 vs. 29.44 years, p = 0.0492) and multifocal onset significantly more often (p = 0.0052) in familial than in sporadic MS. Notably, a substantial within sibling-pair correlation for disease progression (rho = 0.40; p = 0.0062) as well as a higher risk for siblings than for controls to convert into secondary progression (0.545 vs. 0.227; p = 0.018) could be observed.
  
  
  CONCLUSIONS
  Familial MS differs from sporadic cases with respect to age at onset, multifocal involvement as first clinical event, and conversion into secondary progression. The progression rate of one out of two affected siblings may act as a predictor for the other sib.
authors.affiliation: Philipps-University, Department of Neurology, Clinical Neuroimmunology Group, Marburg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Wellek
authors.forename: Catharina
authors.initials: C
authors.lastname: Korsukewitz
authors.forename: Jan P
authors.initials: JP
authors.lastname: Bach
authors.forename: Sabine
authors.initials: S
authors.lastname: Schock
authors.forename: Christian
authors.initials: C
authors.lastname: Eienbröker
authors.forename: Florian
authors.initials: F
authors.lastname: Seitz
authors.forename: Anna
authors.initials: A
authors.lastname: Spengler
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmer
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schlegel
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.forename: Norbert
authors.initials: N
authors.lastname: Sommer
authors.forename: Björn
authors.initials: B
authors.lastname: Tackenberg
mesh_terms: D000328:Adult; D017668:Age of Onset; D016208:Databases, Factual; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D012306:Risk; D035781:Siblings