FREM1 and Fraser syndrome: Whilst the phenotype of rafels further extends the homology of the role of the Fraser complex proteins in AER morphogenesis, it is noteworthy that a recent report has described human patients bearing FREM1 mutations which display bifid nose and anorectal malformations but not the classic Fraser syndactyly, cryptophthalmos or ablepharon, although they do show renal agenesis similar to the Fraser syndrome patients [36].