Facial Phenotypes and Subgroups in Children with Autism Spectrum Disorders

Background: The brain develops in concert and in coordination with the developing facial tissues, with each influencing the development of the other.  Autism spectrum disorders (ASD) result from alterations in the embryological brain, suggesting that the development of the face of children with ASD may result in subtle facial differences compared to typically-developing children. 

Objectives: The purpose of this study is to determine whether children with ASD display differences in facial phenotypes as compared to age-matched, typically-developing children.

Methods: The 3dMD Cranial system was used to acquire 3D stereophotogrammetric images for our study sample of 8-12 year old children diagnosed with essential ASD (N=60) and typically-developing children (N=69) following approved IRB protocols. Three-dimensional coordinates were recorded for 17 facial anthropometric landmarks from these images using 3dMD software.  Age-matched comparisons of facial morphology in the two groups were completed using Euclidean Distance Matrix Analysis (EDMA).

Results: First, we find that there are significant differences in facial morphology in children with ASD compared to typically-developing children.  Children with ASD have significantly broader orbits, philtrums, and mouths, and higher foreheads relative to typically-developing children.  Additionally, this group displays significantly less anteriorly prominent foreheads and nasal bridges relative to children with ASD.  Second, using a clustering technique, we also find a subgroup of children with ASD with facial morphology that differs from the majority of the children with ASD and the typically-developing children; this subgroup is defined by a superoinferiorly shorter midface.  None of these results were correlated with either age or measures of head size.

Conclusions: Children with ASD display a distinct facial phenotype from typically-developing children.  These differences may reflect alterations in the development of the brain during prenatal development in children with autism spectrum disorders.  There is also a subgroup of children with ASD who display a facial phenotype that is distinct from the majority of the children with ASD.  This subgroup may represent a different etiology compared to the larger group of children with ASD.  Further investigations into the brain morphology and correlations with clinical and behavioral phenotypes will help to elucidate the causes for and significance of these subtle phenotypic differences.