SMAD6 and craniosynostosis: More recently, mutations in Zic family member 1 (ZIC1); SMAD family member 6 (SMAD6); HECT, UBA and WWE domain-containing 1, E3 ubiquitin protein ligase (HUWE1); and smoothened, frizzled class receptor (SMO) have been identified as causal in the development of craniosynostosis.