Craniofacial Dysmorphology Associated with Phelan-McDermid Syndrome using Three-Dimensional Morphometrics

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This research seeks to characterize the craniofacial dysmorphology associated with Phelan-McDermid syndrome (PMS) (OMIM #606232), a genetic disorder that has been diagnosed in over 1500 individuals. The craniofacial dysmorphology associated with PMS has not been well established. The literature reports a variety of characteristics, including bulbous nose, ear anomalies, full lips, epicanthal folds, macrocephaly, dolicocephaly, high arch palate, full cheeks, periorbitial fullness, pointed chin, wide nasal bridge, long pholtrum, malar hypoplasia, microcephaly, deep set eyes, and flat midface. Our study will include a larger patient population that will provide an understanding of how these dysmorphic features vary in frequency and intensity associated with PMS. The research will use geometric morphometric approaches to allow the variation to be more precisely defined and visualized, so that a more specific and universal understanding of “bulbous nose”, for instance, will emerge. This research will provide a more precise and systematic study of the phenotype associated with PMS with a focus on the facial dysmorphology then has been completed before. The project will optimize the synergies available through cross-disciplinary collaborations between clinicians, developmental biologists, and anatomists thus advancing understanding of PMS cranial dysmorphology beyond what would result if these scientists were working in isolation. The research model will capitalize on clinical expertise of PMS, anatomical science to quantify the dysmorphology, and developmental biology to explore developmental models for characterizing PMS. The initial diagnosis of PMS by clinical geneticists is often based on a characteristic pattern of physical features observed in a patient. To provide a quantitative assessment of the craniofacial dysmorphology associated with PMS, geometric morphometric approaches will provide greater insights into the mean morphology associated with the syndrome along with an evaluation of the variation associated with age, sex, and ancestry differences. Dysmorphology can be evaluated using anatomical landmarks placed within a three-dimensional coordinate system and through dense surface models of the craniofacial complex. This study will advance diagnosis and treatment of PMS in the following ways: (1) Precisely characterize craniofacial dysmorphologies associated with PMS; (2) determine the variation associated by PMS in the patient population; (3) quantify the effects of sex and ancestry associated with the dysmorphologies observed in PMS; and (4) define the impact on growth associated with PMS in the craniofacial complex and within craniofacial regions.