SFRP4 and Pyle disease: Mutations in the Secreted Frizzled-Related 4 gene (SFRP4) were shown to be responsible for Pyle’s disease in 20169 and three independent confirmations have subsequently been reported.10–12 SFRP4 is a secreted WNT decoy receptor, structurally related to WNT Frizzled receptors, that binds WNTs to inhibit both canonical and non-canonical WNT signaling.13–16