title: Efficacy of cascade testing for fragile X syndrome.
abstract: OBJECTIVE
  Fragile X syndrome is the most common cause of mental retardation from a single gene defect, transmitted in an X-linked semidominant fashion. Cloning of the gene responsible for fragile X syndrome has made it possible to identify carriers who are at risk of giving birth to a child with fragile X syndrome. One of the proposed strategies for identifying carriers is cascade testing, in which relatives of a patient with fragile X syndrome (the index case) are tested. Because the effectiveness of this type of testing is unknown, the objective of this study was to develop a simulation model for studying the consequences of cascade testing for fragile X syndrome.
  
  
  METHODS
  With this model, 100,000 five-generation pedigrees were simulated to assess the maximum number of carriers that would be detected for three scenarios: (a) only first degree relatives of the index case are tested; (b) relatives up to the third degree are tested; (c) relatives up to the fifth degree are tested.
  
  
  RESULTS
  In the start-up phase of the testing programme, 18% of couples who will have a fragile X syndrome child are detected. After this phase the (stabilised) cascade testing programme detects 7% of undetected couples who would have a fragile X syndrome child if only first degree relatives were tested, 12% if first to third degree relatives were tested, and 15% if first to fifth degree relatives were tested. To detect 90% of all premutation and full mutation carriers at least eight consecutive generations need to be tested.
  
  
  CONCLUSIONS
  The results of our analysis show that cascade testing is not very effective in detecting carriers.
authors.affiliation: Department of Public Health, Faculty of Medicine, Erasmus University Rotterdam, The Netherlands.
authors.forename: M F
authors.initials: MF
authors.lastname: Wildhagen
authors.forename: T A
authors.initials: TA
authors.lastname: van Os
authors.forename: J J
authors.initials: JJ
authors.lastname: Polder
authors.forename: L P
authors.initials: LP
authors.lastname: ten Kate
authors.forename: J D
authors.initials: JD
authors.lastname: Habbema
mesh_terms: D003661:Decision Support Techniques; D005260:Female; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics*; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D018911:Trinucleotide Repeats