The Influence of trisomy 21 on facial form and variability

John M. Starbuck, Theodore M. Cole, Roger H. Reeves, Joan T. Richtsmeier

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Triplication of chromosome 21 (trisomy 21) results in Down syndrome (DS), the most common live-born human aneuploidy. Individuals with DS have a unique facial appearance that can include form changes and altered variability. Using 3D photogrammatic images, 3D coordinate locations of 20 anatomical landmarks, and Euclidean Distance Matrix Analysis methods, we quantitatively test the hypothesis that children with DS (n = 55) exhibit facial form and variance differences relative to two different age-matched (4–12 years) control samples of euploid individuals: biological siblings of individuals with DS (n = 55) and euploid individuals without a sibling with DS (n = 55). Approximately 36% of measurements differ significantly between DS and DS-sibling samples, whereas 46% differ significantly between DS and unrelated control samples. Nearly 14% of measurements differ significantly in variance between DS and DS sibling samples, while 18% of measurements differ significantly in variance between DS and unrelated euploid control samples. Of those measures that showed a significant difference in variance, all were relatively increased in the sample of DS individuals. These results indicate that faces of children with DS are quantitatively more similar to their siblings than to unrelated euploid individuals and exhibit consistent, but slightly increased variation with most individuals falling within the range of normal variation established by euploid samples. These observations provide indirect evidence of the strength of the genetic underpinnings of the resemblance between relatives and the resistance of craniofacial development to genetic perturbations caused by trisomy 21, while underscoring the complexity of the genotype–phenotype map.

Original languageEnglish (US)
Pages (from-to)2861-2872
Number of pages12
JournalAmerican Journal of Medical Genetics, Part A
Issue number11
StatePublished - Nov 2017


  • Down syndrome
  • Euclidean Distance Matrix Analysis (EDMA)
  • gene-dosage imbalance
  • human facial variation
  • morphometric

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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