We identified high confidence variants, thereby providing a clinical genetic diagnosis, for 18 children ascertained for CAS, revealing 15 genes that have not previously been associated with this severe speech disorder (ARHGEF9, BRPF1, DDX3X, DIP2C, ERF, HRNPNK, KDM5C, PHF21A, PURA, RBFOX3, SETBP1, SETD1A, SETD1B, SHANK3, SPAST, TAOK2, TRIP12, ZBTB18). Here, SPAST is linked to speech disorder.