title: Anticipation in familial cavernous angioma: ascertainment bias or genetic cause.
abstract: OBJECTIVE
  Anticipation has been linked to unstable trinucleotide repeats in many neurological disorders. We examined the hypothesis of genetic anticipation in familial cavernous angioma (FCA) of the central nervous system.
  
  
  METHODS
  The mean ASO of affected individuals was compared between successive generations in 55 families. Intergenerational pair-wise comparisons were employed to avoid several ascertainment biases. Regarding severity of disease both type of manifestation and number of cavernous angiomas were compared between generations.
  
  
  RESULTS
  The mean ASO decreased significantly both from the first to the second generation (31.6 vs 17.8 years; P = 0.000) and from the second to the third generation (17.8 vs 6.7 years; P = 0.002). The pair-wise comparisons also showed significantly earlier ASO. No clear evidence for anticipation with regard to severity of disease was found.
  
  
  CONCLUSIONS
  Molecular genetic studies will determine whether trinucleotide repeats are the underlying mechanism for our observation of anticipation in FCA.
authors.affiliation: Dartmouth College, Neurology, Hanover, New Hampshire, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Siegel
authors.forename: F
authors.initials: F
authors.lastname: Andermann
authors.forename: A
authors.initials: A
authors.lastname: Badhwar
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: M
authors.initials: M
authors.lastname: Dam
authors.forename: H C
authors.initials: HC
authors.lastname: Hopf
authors.forename: J
authors.initials: J
authors.lastname: Dichgans
authors.forename: M
authors.initials: M
authors.lastname: Sturzenegger
authors.forename: N J
authors.initials: NJ
authors.lastname: Hopf
authors.forename: N
authors.initials: N
authors.lastname: Yasui
authors.forename: F
authors.initials: F
authors.lastname: Stepper
authors.forename: M
authors.initials: M
authors.lastname: Killer
authors.forename: J A
authors.initials: JA
authors.lastname: Vanneste
authors.forename: N
authors.initials: N
authors.lastname: Acciarri
authors.forename: P
authors.initials: P
authors.lastname: Drigo
authors.forename: J
authors.initials: J
authors.lastname: Christensen
authors.forename: V
authors.initials: V
authors.lastname: Braun
authors.forename: D
authors.initials: D
authors.lastname: Könü
authors.forename: E
authors.initials: E
authors.lastname: Andermann
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D020132:Anticipation, Genetic; D015982:Bias; D016543:Central Nervous System Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D005260:Female; D006392:Hemangioma, Cavernous / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008297:Male