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Genotype-phenotype correlations of 39 patients with Cornelia De Lange syndrome: the Dutch experience
  1. Z A Bhuiyan1,
  2. M Klein2,
  3. P Hammond3,
  4. A van Haeringen4,
  5. M M A M Mannens1,
  6. I Van Berckelaer-Onnes2,
  7. R C M Hennekam5
  1. 1Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
  2. 2Department of Clinical Child and Adolescent Studies, Faculty of Social and Behavioural Sciences, University of Leiden, Leiden, The Netherlands
  3. 3Eastman Dental Institute, UCL, London, UK
  4. 4Department of Clinical Genetics, UMCL, Leiden, The Netherlands
  5. 5Clinical and Molecular Genetics Unit, Institute of Child Health, UCL, London, UK and Department of Paediatrics, Academic Medical Centre, Amsterdam, The Netherlands
  1. Correspondence to:
 Dr R C M Hennekam
 Clinical and Molecular Genetics Unit, Institute of Child Health, UCL, 30 Guilford Street, London WC1N 1EH, UK; r.hennekam{at}


Background: Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly syndrome characterised by a distinctive facial appearance, prenatal and postnatal growth deficiency, psychomotor delay, behavioural problems, and malformations of the upper extremities. Recently mutations in NIPBL, the human homologue of the Drosophila Nipped-B gene, were found to cause CdLS. Mutations have been found in 39% of reported cases.

Methods: Patients were enrolled in the study and classified into one of four groups based on clinical examination: classic, mild, possible, or definitively not CdLS. Three dimensional photography was taken of 20 subjects, and compared between groups. Behaviour was assessed with specific attention to autism. We searched for mutations in NIPBL and correlated genotype with phenotype.

Results: : We found mutations in 56% of cases.

Conclusions: Truncating mutations were generally found to cause a more severe phenotype but this correlation was not absolute. Three dimensional facial imaging demonstrated the potential for classifying facial features. Behavioural problems were highly correlated with the level of adaptive functioning, and also included autism. No correlation of behaviour with the type of mutation was found

  • 3D, three dimensional
  • CdLS, Cornelia de Lange syndrome
  • DBC, Developmental Behaviour Checklist
  • DHPLC, denaturing high performance liquid chromatography
  • DISCO, Diagnostic Interview for Social and Communication Disorders
  • DSM, dense surface model
  • NLS, nuclear localisation signal
  • VABS, Vineland Adaptive Behaviour Scale
  • Cornelia de Lange syndrome
  • behaviour
  • 3D scanning
  • genotype-phenotype correlations

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  • Published Online First 19 October 2005

  • Competing interests: there are no competing interests