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Saethre-Chotzen syndrome (SCS; MIM 101400) is an autosomal dominant disorder. SCS is mainly caused by loss of function mutations in the TWIST1 gene, or a specific gain-of-function mutation in the FGFR3 gene. TWIST1 encodes a helix-loop-helix transcription factor (Twist-related protein 1) whose downstream targets include fibroblast growth factor receptors, RUNX2 and osteoblast marker genes. The findings are variable and may include craniosynostosis involving the coronal (frequent), lambdoid and metopic sutures. Other findings may included asymmetry of the orbits, low-set and abnormally shaped ears, a long thin and pointed or beaked nose, syndactyly of the fingers and toes, bifid terminal phalanges of digits 2 and 3, congenital heart defects and cleft palate. The FGFR3 mutation, Pro250Arg, is the same mutation that causes Muenke syndrome (MNKES; MIM 602849). Features that help distinguish SCS from Muenke syndrome include a low-set frontal hairline, gross ptosis of the eyelids, small ears with various abnormalities, syndactyly, a dilated parietal foramen, broad great toes, bifid distal phalanges, increased intracranial hypertension and normal mental development, except in the case of patients with large TWIST1 deletions who have been associated with learning disability. In contrast, mental delay and sensorineural hearing loss are typically associated with Muenke syndrome. Robinow-Sorauf syndrome (MIM 180750) is also caused by mutations in the TWIST1 gene and clinical findings are similar to SCS. Robinow-Sorauf syndrome may not be a distinct disorder, but may belong to the phenotypic spectrum of SCS. Saethre-Chotzen syndrome with eyelid abnormalities is another variant caused by TWIST1 mutations. Patients have moderate to severe ptosis and eyelid malformations but may not have craniosynostosis. The incidence of the Saethre-Chotzen syndrome is estimated to be 1:25,000 to 1:50,000.