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Prospective screening for subtelomeric rearrangements in children with mental retardation of unknown aetiology: the Amsterdam experience
  1. C D M van Karnebeek1,
  2. C Koevoets1,
  3. S Sluijter1,
  4. E K Bijlsma1,
  5. D F M C Smeets3,
  6. E J Redeker1,
  7. R C M Hennekam1,2,
  8. J M N Hoovers1
  1. 1Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands
  2. 2Department of Paediatrics/Emma Children’s Hospital, Academic Medical Centre, Amsterdam, The Netherlands
  3. 3Department of Human Genetics, University Medical Centre, Nijmegen, The Netherlands
  1. Correspondence to:
 Dr J M N Hoovers, Department of Clinical Genetics, Academic Medical Centre, PO Box 22700, 1100 DE Amsterdam, The Netherlands;


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.

  • mental retardation
  • prospective
  • screening
  • subtelomeric
  • MR, mental retardation
  • HRB, high resolution banding
  • VNTR, variable number of tandem repeats
  • HR-CGH, high resolution comparative genomic hybridisation
  • BAC, bacterial artificial chromosome
  • PAC, P1 derived artificial chromosome

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