Dkk1 has been shown to modulate Wnt activity during head morphogenesis in mice54 in which a de novo deleterious missense variant, p.Arg120Leu, has been identified in two unrelated individuals with Chiari malformation type I (MIM: 118420) and, in one of them, hydrocephalus,55 phenotypes also observed in one (I-6, Table 1) of the affected individuals with macrocephaly. The gene discussed is DKK1; the disease is Chiari malformation type I.