A proposal for classification of entities combining vascular malformations and deregulated growth

Charlene E. U. Oduber, Chantal M. A. M. van der Horst, J. Henk Sillevis Smitt, Mark J. C. Smeulders, Vibhu Mendiratta, John I. Harper, Maurice A. M. van Steensel, Raoul C. M. Hennekam*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Agreement on terminology and nomenclature is fundamental and essential for effective exchange of information between clinicians and researchers. An adequate terminology to describe all patients showing vascular malformations combined with deregulated growth is at present not available. Objectives: To propose a classification of patients with vascular malformations, not restricted to the face, and growth disturbances based on simple, clinically visible characteristics, on which clinicians and researchers can comment and which should eventually lead to an internationally accepted classification. Methods: Rooted in our joint experience we established a classification of vascular malformation not limited to the face, with growth disturbances. It is based on the nature and localization of the vascular malformations; the nature, localization and timing of growth disturbances; the nature of co-localization of the vascular malformations and growth disturbances; the presence or absence of other features. Subsequently a mixed (experienced and non-experienced) group of observers evaluated 146 patients (106 from the Netherlands; 40 from the UK) with vascular malformations and disturbed growth, using the classification. Inter-observer variability was assessed by estimating the Intra-Class Correlation (ICC) coefficient and its 95% confidence interval. Results: We defined 6 subgroups within the group of entities with vascular malformation-deregulated growth. Scoring the patients using the proposed classification yielded a high inter-observer reproducibility (ICC varying between 0.747 and 0.895 for all levels of flow). Conclusions: The presently proposed classification was found to be reliable and easy to use for patients with vascular malformations with growth disturbances. We invite both clinicians and researchers to comment on the classification, in order to improve it further. This way we may obtain our final aim of an internationally accepted classification of patients, which should facilitate both clinical treatment and care of, as well as research into the molecular background of entities combining vascular malformation and deregulated growth.
Original languageEnglish
Pages (from-to)262-271
JournalEuropean Journal of Medical Genetics
Issue number3
Publication statusPublished - 2011


  • Vascular diseases
  • Angiomatosis
  • Angio-osteo-hypertrophy
  • Overgrowth
  • Hypotrophy
  • Asymmetry
  • Klippel-Trenaunay syndrome
  • Bockenheimer syndrome
  • Van Lohuizen syndrome
  • Cutis marmorata telangiectatica congenita
  • Proteus syndrome
  • Phenotype
  • Subclassification

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