Postnatal Progressive Craniosynostosis: An Unusual Case Presentation Leading to Cascade Diagnosis for Multiple...

NM_000141.5: FGFR2 c.1032G>A is a pathogenic variant that causes Crouzon syndrome through activation of a new donor splice site. This clinical report highlights the intrafamilial variability that can exist with this specific variant. The proband is a 4-year-old boy who initially presented with concern for seizures. Computed tomography and magnetic resonance imaging revealed pancraniosynostosis and Chiari 1 malformation. Papilledema on fundoscopic exam and copper beaten appearance of the skull on imaging both suggested the presence of elevated intracranial pressure. Genetic testing identified c.1032G>A (p.Ala344=) in FGFR2. Familial testing and genetic evaluation confirmed the same pathogenic variant in the father (age 25) and clinical diagnosis of Crouzon syndrome in the paternal grandmother (age 50). Both had only mild facial features, including hypertelorism and midface hypoplasia without other symptoms. This family illustrates a wide range of clinical phenotypes, including asymptomatic midface hypoplasia to progressive postnatal pancraniosynostosis with elevated intracranial pressure. Therefore, a high index of suspicion is indicated for mild cases with isolated midface hypoplasia and hypertelorism to achieve early diagnosis.