title: Familial effects on the clinical course of multiple sclerosis.
abstract: BACKGROUND
  Familial factors influence susceptibility to multiple sclerosis (MS) but it is unknown whether there are additional effects on the natural history of the disease.
  
  
  METHODS
  We evaluated 1,083 families with > or =2 first-degree relatives with MS for concordance of age at onset, clinical course, and disease severity and investigated transmission patterns of these clinical features in affected parent-child pairs.
  
  
  RESULTS
  There is concordance for age at onset for all families (correlation coefficient 0.14; p < 0.001), as well as for affected siblings (correlation coefficient 0.15; p < 0.001), and affected parent-child pairs (correlation coefficient 0.12; p = 0.03) when each is evaluated separately. Concordance for year of onset is present among affected siblings (correlation coefficient 0.18; p < 0.001) but not the parent-child group (correlation coefficient 0.08; p = 0.15). The clinical course is similar between siblings (kappa 0.12; p < 0.001) but not affected parents and their children (kappa -0.04; p = 0.09). This influence on the natural history is present in all clinical subgroups of relapsing-remitting, and primary and secondary progressive MS, reflecting a familial effect on episodic and progressive phases of the disease. There is no concordance for disease severity within any of the considered family groups (correlation coefficients: all families analyzed together, 0.02, p = 0.53; affected sibling group, 0.02, p = 0.61; affected parent-child group, 0.02, p = 0.69). Furthermore, there are no apparent transmission patterns of any of the investigated clinical features in affected parent-child pairs and no evidence for anticipation or effects of genetic loading.
  
  
  CONCLUSIONS
  Familial factors do not significantly affect eventual disease severity. However, they increase the probability of a progressive clinical course, either from onset or after a phase of relapsing remitting disease. The familial effect is more likely to reflect genetic than environmental conditions. The results are relevant for counseling patients and have implications for the design of studies seeking to identify factors that influence the natural history of the disease.
authors.affiliation: Department of Clinical Neuroscience, University of Cambridge Clinical School, Addenbrooke's Hospital, Box 165, Cambridge CB2 2QQ, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Hensiek
authors.forename: S R
authors.initials: SR
authors.lastname: Seaman
authors.forename: L F
authors.initials: LF
authors.lastname: Barcellos
authors.forename: A
authors.initials: A
authors.lastname: Oturai
authors.forename: M
authors.initials: M
authors.lastname: Eraksoi
authors.forename: E
authors.initials: E
authors.lastname: Cocco
authors.forename: L
authors.initials: L
authors.lastname: Vecsei
authors.forename: G
authors.initials: G
authors.lastname: Stewart
authors.forename: B
authors.initials: B
authors.lastname: Dubois
authors.forename: J
authors.initials: J
authors.lastname: Bellman-Strobl
authors.forename: M
authors.initials: M
authors.lastname: Leone
authors.forename: O
authors.initials: O
authors.lastname: Andersen
authors.forename: K
authors.initials: K
authors.lastname: Bencsik
authors.forename: D
authors.initials: D
authors.lastname: Booth
authors.forename: E G
authors.initials: EG
authors.lastname: Celius
authors.forename: H F
authors.initials: HF
authors.lastname: Harbo
authors.forename: S L
authors.initials: SL
authors.lastname: Hauser
authors.forename: R
authors.initials: R
authors.lastname: Heard
authors.forename: J
authors.initials: J
authors.lastname: Hillert
authors.forename: K-M
authors.initials: KM
authors.lastname: Myhr
authors.forename: M G
authors.initials: MG
authors.lastname: Marrosu
authors.forename: J R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: C
authors.initials: C
authors.lastname: Rajda
authors.forename: S J
authors.initials: SJ
authors.lastname: Sawcer
authors.forename: P S
authors.initials: PS
authors.lastname: Sørensen
authors.forename: F
authors.initials: F
authors.lastname: Zipp
authors.forename: D A S
authors.initials: DA
authors.lastname: Compston
mesh_terms: D000328:Adult; D018450:Disease Progression; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000235:genetics*; D010375:Pedigree; D015995:Prevalence; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors