Modeling age-specific facial development in Williams-Beuren-, Noonan-, and 22q11.2 deletion syndromes in cohorts of Czech patients aged 3-18 years: A cross-sectional three-dimensional geometric morphometry analysis of their facial gestalt

Am J Med Genet A. 2018 Dec;176(12):2604-2613. doi: 10.1002/ajmg.a.40659. Epub 2018 Oct 31.

Abstract

Three-dimensional (3D) virtual facial models facilitate genotype-phenotype correlations and diagnostics in clinical dysmorphology. Within cross-sectional analysis of both genders we evaluated facial features in representative cohorts of Czech patients with Williams-Beuren-(WBS; 12 cases), Noonan-(NS; 14), and 22q11.2 deletion syndromes (22q11.2DS; 20) and compared their age-related developmental trajectories to 21 age, sex and ethnically matched controls in 3-18 years of age. Using geometric morphometry statistically significant differences in facial morphology were found in all cases compared to controls. The dysmorphic features observed in WBS were specific and manifested in majority of cases. During ontogenesis, dysmorphic features associated with increased facial convexity become more pronounced whereas other typical features remained relatively stable. Dysmorphic features observed in NS cases were mostly apparent during childhood and gradually diminished with age. Facial development had a similar progress as in controls, while there has been increased growth of patients' nose and chin in adulthood. Facial characteristics observed in 22q11.2DS, except for hypoplastic alae nasi, did not correspond with the standard description of its facial phenotype because of marked facial heterogeneity of this clinical entity. Because of the sensitivity of 3D facial morphometry we were able to reach statistical significance even in smaller retrospective patient cohorts, which proves its clinical utility within the routine setting.

Keywords: 22q11.2 deletion syndrome; 3D facial gestalt analysis; 3D imaging; Noonan syndrome; Williams-Beuren syndrome; dysmorphology; facial shape and size; geometric morphometry; ontogenetic trajectory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Czech Republic
  • DiGeorge Syndrome / diagnosis*
  • DiGeorge Syndrome / genetics
  • Facies*
  • Female
  • Humans
  • Imaging, Three-Dimensional*
  • Male
  • Models, Anatomic*
  • Noonan Syndrome / diagnosis*
  • Noonan Syndrome / genetics
  • Williams Syndrome / diagnosis*
  • Williams Syndrome / genetics