S14-08 SESSION 14: FACIOCRANIOSYNOSTOSIS – PART III A COMPREHENSIVE PHENOTYPIC STUDY OF ERF-RELATED CRANIOSYNOSTOSIS

Introduction: Heterozygous mutations in the ERF gene cause a form of craniosynostosis thought to account for about 2% of all syndromic presentations. Reports have implicated ERF mutations in both single and multi-sutural synostosis, Chiari-1 malformation, facial dysmorphism, speech & language delay, learning difficulties and behavioral problems but our understanding of the phenotypic variations is incomplete, which has implications for diagnosis and management. The purpose of this study was to establish a comprehensive phenotypic description of ERF-related craniosynostosis and appreciate the phenotypic variations. Methods: We conducted a study of 36 patients with an ERF mutation. The findings presented include data from 16 unrelated probands and 20 additional family members sharing the mutations. Results: All 16 probands and 7 additional family members had confirmed craniosynostosis. The synostotic pattern included the sagittal and lambdoid sutures (Mercedes-Benz pattern) in 7 cases, with 7 additional cases exhibiting pansynostosis. Craniosynostosis was often insidious and progressive with a median presentation of 42 months, by which time papilledema was present in two cases and was associated with permanent visual loss. Ten probands had raised intracranial pressure (ICP) and/or Chiari-1 malformation at presentation, all of whom underwent cranial remodeling surgery. Facial dysmorphism (where present) took the form of orbital hypertelorism, mild exorbitism and malar hypoplasia with a class I occlusal relationship. Speech delay, poor gross and/or fine motor control, hyperactivity and poor concentration were common. Variable expressivity and non-penetrance among genetically affected relatives was encountered. Conclusion: These observations form a comprehensive phenotypic profile of ERF-related craniosynostosis. Importantly, the most common synostotic variants (sagittal with bi-lambdoid and pansynostosis) result in a relatively normal head shape. Consequently, late presentations are typical, by which time raised ICP, and the consequences thereof, may be manifest. A low threshold for investigation and management of raised ICP is warranted in these patients.