Seckel Syndrome (MCPH‐SCKL) is a rare genetic disorder which causes morphological changes throughout the body. Some of the most commonly reported changes are those present within the cranium and mandible such as microcephaly, a beak‐like nose with convex nasal ridge, and mandibular deformities such as micrognathia. However, these clinical terms are insufficiently precise for proper diagnosis or to understand the distortions in physiology that take place with the disease. Therefore, quantification of the features of the skull are necessary to further explain this pathology, and comparisons to normal variation will help to understand the degree to which the anatomy is affected. Our hypothesis is that MCPH‐SCKL will demonstrate a dramatic deviation from a normal distribution of craniums and mandibles.In this experiment: A patient diagnosed with MCPH‐SCKL underwent hi‐resolution CT imaging at voxel dimensions of approximately 1.117 mm3. This sample was manually segmented using 3D Slicer for the cranium, cranial vault, mandible without the alveolar bone and teeth, and atlas vertebrae. Each segment was used to perform radiomics analysis to produce shape features. In addition, rulers were used to analyze 2D distances from landmarks. The patient was also compared to similar segmentations and analysis results from ten patients without MCPH‐SCKL (representing a normal population). A power test was used to evaluate the results to ensure proper sample size given the results. Statistical shape models of the mandible were also used to establish a mean model for normal variation (figure 1), and compared used full and partial Procrustes analysis to demonstrate volume and natural shape differences between a normal population and MCPH‐SCKL.Seckel Syndrome is classified as a member of the microcephaly family of pathologies, however, our results demonstrate that the overall volume of the skull is not as significantly decreased as the cranial vault itself, which may provide the catalyst for Chiari Type I malformations. The mandible, likewise, is severely altered by Seckel Syndrome; the mandible’s volume decreases 44% and demonstrates altered physical proportions. Finally, the osteological measurements of the facial features demonstrated inconsistent findings between different anatomical structures, providing evidence that Seckel Syndrome may have a variable effect on the different bones and tissues of the skull.In conclusion, this project demonstrates the degree of morphological changes that can be associated with MCPH‐SCKL. This helps us to better understand the effects of the disease on the cranium, brain, and jaw. In addition, this may provide clinicians with better diagnostic criteria for MCPH‐SCKL and may provide better prognostic options for symptom management.A mean mesh created from N=10 meshes using statistical shape modelling. Procrustes was used to align the meshes by the landmarks of the mandibular condyles, coranoid processes, mandibular angles, and mental protuberance. Parametric non‐rigid registration was used to create correspondence afterwords,, and PCA was used to build the statistical shape model. The MCPH‐SCKL patient mandible was then aligned using the same landmarks.Figure 1