Craniofacial Dysmorphology Associated With Phelan– McDermid Syndrome Using Three‐Dimensional Morphometrics

Phelan-McDermid syndrome (PMS) frequently presents with distinctive facial features, although a typical facial phenotype for this condition has not been well characterized. Facial dysmorphology assessments can be subjective, depending on the experience and training of the clinical geneticist conducting the patient evaluation. In this investigation, we sought to quantitatively assess craniofacial features in Phelan-McDermid syndrome. Three-dimension (3D) morphometric assessment was conducted of 100 children and young adults diagnosed with PMS and 536 age- and sex-matched typically developing subjects obtained from the FaceBase consortium. The data were analyzed using principal component analysis (PCA), Procrustes MANOVA, and canonical variates analysis (CVA). We found that people with PMS aged 3-32 years have quantitatively distinctive craniofacial features compared to age- and sex-matched normed people. We observed an elongated face, a pointed chin, a flattened midface, and nasal expansion as characteristic of the PMS facial phenotype. Further, distinct growth patterns were observed, with children ages 3-6 and 7-12 years having more rapid growth compared to matched normed samples. While people with PMS have distinctive facial features, individual variation is the greatest contribution to facial variation. Quantitative assessment of craniofacial features paired with genotype can further our understanding of genetic contributions to craniofacial development.