title: Prospective screening for subtelomeric rearrangements in children with mental retardation of unknown aetiology: the Amsterdam experience.
abstract: OBJECTIVE
  The frequency of subtelomeric rearrangements in patients with unexplained mental retardation (MR) is uncertain, as most studies have been retrospective and case retrieval may have been biased towards cases more likely to have a chromosome anomaly. To ascertain the frequency of cytogenetic anomalies, including subtelomeric rearrangements, we prospectively screened a consecutive cohort of cases with unexplained MR in an academic tertiary centre.
  
  
  METHODS
  Inclusion criteria were: age <18 years at referral, IQ<85, no aetiological diagnosis after complete examination, which included karyotyping with high resolution banding (HRB).
  
  
  RESULTS
  In 266 karyotyped children, anomalies were detected in 20 (7.5%, seven numerical, 13 structural); 39 cases were analysed by FISH for specific interstitial microdeletions, and anomalies were found in nine (23%). FISH analyses for subtelomeric microdeletions were performed in 184 children (44% moderate-profound MR, 51% familial MR), and one rearrangement (0.5%) was identified in a non-familial MR female with mild MR (de novo deletion 12q24.33-qter). The number of probable polymorphisms was considerable: 2qter (n=7), Xpter (n=3), and Ypter (n=1). A significantly higher total number of malformations and minor anomalies was present in the cytogenetic anomaly group compared to the group without cytogenetic anomalies.
  
  
  CONCLUSIONS
  The total frequency of cytogenetic anomalies in this prospective study was high (1:10), but the frequency of subtelomeric rearrangements was low. The most likely explanations are the high quality of HRB cytogenetic studies and the lack of clinical selection bias. Conventional cytogenetic analyses, combined with targeted microdeletion testing, remain the single most effective way of additional investigation in mentally retarded children, also in a tertiary centre.
authors.affiliation: Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: C D M
authors.initials: CD
authors.lastname: van Karnebeek
authors.forename: C
authors.initials: C
authors.lastname: Koevoets
authors.forename: S
authors.initials: S
authors.lastname: Sluijter
authors.forename: E K
authors.initials: EK
authors.lastname: Bijlsma
authors.forename: D F M C
authors.initials: DF
authors.lastname: Smeets
authors.forename: E J
authors.initials: EJ
authors.lastname: Redeker
authors.forename: R C M
authors.initials: RC
authors.lastname: Hennekam
authors.forename: J M N
authors.initials: JM
authors.lastname: Hoovers
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D027042:Chromosomes, Artificial, P1 Bacteriophage / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000209:etiology* / Q000235:genetics*; D008297:Male; D008677:Metaphase / Q000235:genetics; D009426:Netherlands; D009693:Nucleic Acid Hybridization; D011446:Prospective Studies; D020080:Tandem Repeat Sequences / Q000235:genetics; D016615:Telomere / Q000235:genetics*