The ontogeny of Robin sequence

Am J Med Genet A. 2018 Jun;176(6):1349-1368. doi: 10.1002/ajmg.a.38718. Epub 2018 Apr 25.


The triad of micrognathia, glossoptosis, and concomitant airway obstruction defined as "Robin sequence" (RS) is caused by oropharyngeal developmental events constrained by a reduced stomadeal space. This sequence of abnormal embryonic development also results in an anatomical configuration that might predispose the fetus to a cleft palate. RS is heterogeneous and many different etiologies have been described including syndromic, RS-plus, and isolated forms. For an optimal diagnosis, subsequent treatment and prognosis, a thorough understanding of the embryology and pathogenesis is necessary. This manuscript provides an update about our current understanding of the development of the mandible, tongue, and palate and possible mechanisms involved in the development of RS. Additionally, we provide the reader with an up-to-date summary of the different etiologies of this phenotype and link this to the embryologic, developmental, and genetic mechanisms.

Keywords: Pierre Robin sequence; Robin sequence; cleft palate; embryology; genetics; glossoptosis; micrognathia.

Publication types

  • Review

MeSH terms

  • Female
  • Gene Expression Regulation, Developmental*
  • Humans
  • Mandible / embryology*
  • Palate / embryology*
  • Pierre Robin Syndrome / etiology*
  • Pierre Robin Syndrome / physiopathology
  • Pregnancy
  • Tongue / embryology*