Fine-grained facial phenotype-genotype analysis in Wolf-Hirschhorn syndrome

Eur J Hum Genet. 2012 Jan;20(1):33-40. doi: 10.1038/ejhg.2011.135. Epub 2011 Jul 27.


Wolf-Hirschhorn syndrome is caused by anomalies of the short arm of chromosome 4. About 55% of cases are due to de novo terminal deletions, 40% from unbalanced translocations and 5% from other abnormalities. The facial phenotype is characterized by hypertelorism, protruding eyes, prominent glabella, broad nasal bridge and short philtrum. We used dense surface modelling and pattern recognition techniques to delineate the milder facial phenotype of individuals with a small terminal deletion (breakpoint within 4p16.3) compared to those with a large deletion (breakpoint more proximal than 4p16.3). Further, fine-grained facial analysis of several individuals with an atypical genotype and/or phenotype suggests that multiple genes contiguously contribute to the characteristic Wolf-Hirschhorn syndrome facial phenotype.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Chromosome Deletion
  • Chromosomes, Human, Pair 4
  • Facial Asymmetry / diagnosis
  • Facial Asymmetry / genetics*
  • Female
  • Genetic Association Studies*
  • Humans
  • Hypertelorism / genetics
  • Image Processing, Computer-Assisted
  • Infant
  • Linear Models
  • Male
  • Pattern Recognition, Automated / methods
  • Phenotype*
  • Principal Component Analysis
  • Receptor, Fibroblast Growth Factor, Type 5 / genetics
  • Translocation, Genetic
  • Wolf-Hirschhorn Syndrome / diagnosis
  • Wolf-Hirschhorn Syndrome / genetics*
  • Young Adult


  • FGFRL1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 5