Soft tissue nasal asymmetry as an indicator of orofacial cleft predisposition

Am J Med Genet A. 2018 Jun;176(6):1296-1303. doi: 10.1002/ajmg.a.38688. Epub 2018 Apr 16.

Abstract

The biological relatives of offspring with nonsyndromic orofacial clefts have been shown to exhibit distinctive facial features, including excess asymmetry, which are hypothesized to indicate the presence of genetic risk factors. The significance of excess soft tissue nasal asymmetry in at-risk relatives is unclear and was examined in the present study. Our sample included 164 unaffected parents from families with a history of orofacial clefting and 243 adult controls. Geometric morphometric methods were used to analyze the coordinates of 15 nasal landmarks collected from three-dimensional facial surface images. Following generalized Procrustes analysis, Procrustes ANOVA and MANOVA tests were applied to determine the type and magnitude of nasal asymmetry present in each group. Group differences in mean nasal asymmetry were also assessed via permutation testing. We found that nasal asymmetry in both parents and controls was directional in nature, although the magnitude of the asymmetry was greater in parents. This was confirmed with permutation testing, where the mean nasal asymmetry was significantly different (p < .0001) between parents and controls. The asymmetry was greatest for midline structures and the nostrils. When subsets of parents were subsequently analyzed and compared (parents with bilateral vs. unilateral offspring; parents with left vs. right unilateral offspring), each group showed a similar pattern of asymmetry and could not be distinguished statistically. Thus, the side of the unilateral cleft (right vs. left) in offspring was not associated with the direction of the nasal asymmetry in parents.

Keywords: cleft lip and palate; geometric morphometrics; shape variation; stereophotogrammetry.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Case-Control Studies
  • Cleft Palate / genetics*
  • Facial Asymmetry / diagnostic imaging*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Nose / abnormalities
  • Nose / diagnostic imaging
  • Parents