title: Identical Twins Discordant for Metopic Craniosynostosis: Evidence of Epigenetic Influences.
abstract: Craniosynostosis, or premature fusion of the cranial sutures, occurs in approximately 1 in 2500 live births. The genetic causes and molecular basis of these disorders have greatly expanded over the last 2 decades, with numerous causative and contributory mutations having been identified. The role of fibroblast growth factor receptor (FGFR) mutations in the etiology of certain eponymous forms of craniosynostosis is now well elucidated; the most common syndromes associated with craniosynostosis are Pfeifer (FGFR1, FGFR2), Apert (FGFR2), Crouzon (FGFR2), Saethre-Chotzen (TWIST1), Jackson-Weiss (FGFR2), Greig (GL13), and Muenke (FGFR3) syndromes. Although pathological expression of these mutations often results in bilateral coronal craniosynostosis, single suture fusions (typically unilateral coronal synostosis) or multiple suture craniosynostosis are possible.The majority of patients diagnosed with craniosynostosis lack an identifiable syndrome or genetic mutation. The etiopathogenesis of these "nonsyndromic" forms of craniosynostosis is believed to involve a complex interplay of genetics, epigenetics, and environmental factors. Evaluation of genes implicated in nonsyndromic craniosynostosis has been conflicting; some evidence demonstrates an interplay between genetic and epigenetic influences while others do not. Certain environmental factors such as teratogenic levels of retinoic acid, maternal metabolic and hematologic disorders, and head growth constraint in utero may increase the likelihood of developing craniosynostosis, but these associations are again tenuous.The authors present 1 of 2 genetically confirmed identical twins discordant for metopic craniosynostosis. The implications of this case are clear: epigenetic influences, environmental influences, or both played a role in the development of this premature suture fusion.
authors.affiliation: *Division of Neurosurgery, Children's National Health System †The George Washington University School of Medicine and Health Sciences, Washington, DC ‡Department of Neurosurgery, Mayo Clinic Hospital, Rochester, MN §Division of Laboratory Medicine, Children's National Health System, Washington, DC ||TLC Perinatal, Silver Spring, MD ¶Division of Plastic and Reconstructive Surgery, Children's National Health System, Washington, DC.
authors.forename: Suresh N
authors.initials: SN
authors.lastname: Magge
authors.forename: Kendall
authors.initials: K
authors.lastname: Snyder
authors.forename: Aparna
authors.initials: A
authors.lastname: Sajja
authors.forename: Tiffani A
authors.initials: TA
authors.lastname: DeFreitas
authors.forename: Sean E
authors.initials: SE
authors.lastname: Hofherr
authors.forename: Richard E
authors.initials: RE
authors.lastname: Broth
authors.forename: Robert F
authors.initials: RF
authors.lastname: Keating
authors.forename: Gary F
authors.initials: GF
authors.lastname: Rogers
mesh_terms: D003398:Craniosynostoses / Q000601:surgery*; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007223:Infant; D014430:Twins, Monozygotic