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FGFR1, FGFR2, FGFR3 & TWIST1 related craniosynostosis panel - The craniosynostosis syndromes are a group of disorders sharing the premature fusion of one or more sutures of the skull. Often additional anomalies are associated. There are seven craniosynostosis syndromes caused by mutations in three fibroblast growth factor receptor genes: FGFR1, FGFR2 and FGFR3. They include Apert syndrome (MIM 101200), Beare-Stevenson cutis gyrata syndrome (BSTVS; MIM 123790), Crouzon syndrome (MIM 123500), Crouzon syndrome with acanthosis nigricans (CAN; MIM 612247), Jackson-Weiss syndrome (JWS; MIM123150), Muenke Syndrome (MNKES; MIM 602849) and Pfeiffer syndrome (MIM 101600). All are autosomal dominant. Penetrance varies with the specific craniosynostosis type. Many FGFR mutations are associated with advanced paternal age. Craniosynostosis, type 1 (CRS1; MIM 123100) is an autosomal dominant disorder caused by mutations in the TWIST1 gene. TWIST1 encodes a helix-loop-helix transcription factor (Twist-related protein 1) whose downstream targets include FGFRs, RUNX2 and osteoblast marker genes. Craniosynostosis without additional findings is the defining feature of CRS1. Intelligence is reported to be normal and the skull is reported to have a beaten copper appearance. Penetrance is apparently not complete as some carriers of TWIST1 mutations have been reported to be unaffected. Mutations in the TWIST1 gene also cause Saethre-Chotzen syndrome (SCS; MIM 101400) and Robinow-Sorauf syndrome (MIM 180750).