Rapidly Progressive Multisutural Craniosynostosis in a Patient With Jackson-Weiss Syndrome and a De Novo Pathogenic Variant.

Little is currently known about the mechanisms by which pathogenic variants of produce changes in the FGFR protein and influence the clinical presentation of affected individuals. We report on a patient with a de novo pathogenic variant of and a phenotype consistent with Jackson-Weiss syndrome who presented with delayed, rapidly progressive multisutural craniosynostosis and associated medical complications. Using 3-dimensional modeling of the FGFR protein, we provide evidence that this variant resulted in abnormal dimerization and constitutive activation of FGFR, leading to the Jackson-Weiss phenotype. Knowledge regarding the correlation between genotype and phenotype of persons with -related craniosynostosis has the potential to allow for anticipation of medical complications, institution of early treatment, and improved clinical outcomes.