title: Heterozygous mutations in ERF cause syndromic craniosynostosis with multiple suture involvement.
abstract: Craniosynostosis is a clinically and genetically heterogeneous condition. Knowledge of the specific genetic diagnosis in patients presenting with this condition is important for surgical and medical management. The most common single gene causes of syndromic craniosynostosis are mutations in FGFR1, FGFR2, FGFR3, TWIST1, and EFNB1. Recently, a new single gene cause of craniosynostosis was published, together with phenotype data that highlight the clinical importance of making this specific molecular diagnosis. Phenotypic features of "ERF-related craniosynostosis" include sagittal or multiple-suture synostosis, Chiari malformation, and language delay. In order to determine the contribution of ERF mutations to genetically undiagnosed patients with craniosynostosis, we sequenced the coding regions of ERF in 40 patients with multi-suture or sagittal suture synostosis. We identified heterozygous ERF mutations in two individuals (5%). One mutation positive individual had pansynostosis, while the second had bilateral coronal and metopic synostosis. Both presented in infancy or childhood (age 3 months, and 6 years 9 months, respectively). One had CNS abnormalities including Chiari I malformation. Dysmorphic features included hypertelorism, proptosis, depressed nasal bridge, and retrognathia, in keeping with previously reported cases. The individuals did not require repeated cranial surgeries. ERF-related craniosynostosis should be suspected in patients presenting with multiple suture or sagittal synostosis.
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Ayeshah
authors.initials: A
authors.lastname: Chaudhry
authors.affiliation: Genome Diagnostics, Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Sabatini
authors.affiliation: Genome Diagnostics, Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Liping
authors.initials: L
authors.lastname: Han
authors.affiliation: Genome Diagnostics, Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Ray
authors.affiliation: Division of Plastic and Reconstructive Surgery, Centre for Craniofacial Careand Research, The Hospital for Sick Children.
authors.forename: Christopher
authors.initials: C
authors.lastname: Forrest
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bowdin
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003393:Cranial Sutures / Q000000981:diagnostic imaging / Q000473:pathology*; D003398:Craniosynostoses / Q000000981:diagnostic imaging / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics*; D013577:Syndrome; D014057:Tomography, X-Ray Computed
chemical_list: C107465:ERF protein, human; D012097:Repressor Proteins
keywords: ERF; craniosynostosis; phenotype