Genotype-phenotype correlations in Cornelia de Lange syndrome: Behavioral characteristics and changes with age

Research output: Contribution to journalArticlepeer-review


  • Jessica Penhallow
  • Morad Ansari
  • Stephanie Barton
  • David Bourn
  • David R FitzPatrick
  • Judith Goodship
  • Peter Hammond
  • Catherine Roberts
  • Alice Welham

Colleges, School and Institutes

External organisations

  • Cerebra Centre for Neurodevelopmental Disorders, School of Psychology, University of Birmingham, Birmingham B15 2TT, UK.
  • University of Edinburgh, The
  • Northern Regional Genetics Service, Institute of Genetic Medicine, Newcastle upon Tyne, UK.
  • University of Oxford


Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder associated with unusual facial features, limb abnormalities, a wide range of health conditions, and intellectual disability. Mutations in five genes that encode (SMC1A, SMC3, RAD21) or regulate (NIPBL, HDAC8) the cohesin complex have been identified in up to 70% of individuals. Genetic cause remains unknown for a proportion of individuals. There is substantial heterogeneity in all aspects of CdLS but very little is known about what predicts phenotypic heterogeneity. In this study, we evaluated genotype-phenotype associations in 34 individuals with CdLS. Participants with NIPBL mutations had significantly lower self help skills and were less likely to have verbal skills relative to those who were negative for the NIPBL mutation. No significant differences were identified between the groups in relation to repetitive behavior, mood, interest and pleasure, challenging behavior, activity, impulsivity, and characteristics of autism spectrum disorder whilst controlling differences in self help skills. Significant correlations indicating lower mood, interest and pleasure, and increased insistence on sameness with older age were identified for those who were NIPBL mutation positive. The findings suggest similarities in the behavioral phenotype between those with and without the NIPBL mutation once differences in self help skills are controlled for. However, there may be subtle differences in the developmental trajectory of these behaviors according to genetic mutation status in CdLS.


Original languageEnglish
JournalAmerican Journal of Medical Genetics. Part A
Early online date19 Apr 2017
Publication statusE-pub ahead of print - 19 Apr 2017


  • Journal Article, behavioral phenotype , CdLS , Cornelia de Lange syndrome , genotype–phenotype correlation