• ABSTRACT
    • The literature does not offer any review of the pathogenesis of the clinical features of syndromes with Pierre Robin sequence (PRS). The senior author (MMA) proposed a hypothesis that SOX9 and its interactions may play a key role in this pathogenesis. The current review aims to test this hypothesis.
  • METHODS
    • Three literature searches were made: the first aimed to document the main syndromes associated with PRS; and the second was to document the main functions of SOX9 in development; and the third was to investigate if SOX9 and its interactions may play a role in the pathogenesis.
  • RESULTS
    • SOX9 is the main positive regulator in the development of the mandibular cartilage and it also enhances collagen type II (the main collagen type in cartilage) expression in the mandibular cartilage. Furthermore, SOX9 participates in neural crest development, binds to the exon junction complex, and participates in sex determination. The interactions of SOX9 could explain the pathogenesis of the clinical features of syndromic PRS. These included interactions with collagen type II (in Strickler syndrome), exon junction complex (in Richier-Costa-Periera syndrome), glucose (in Catel-Manzke syndrome), RNA-binding proteins (in TARP syndrome), and the spliceosome (in cerebra-costo-mandibular syndrome). Finally, SOX9 mutations cause campomelic dysplasia.
  • CONCLUSIONS
    • The review supports the hypothesis of the participation of SOX9 in the pathogenesis of the clinical features of syndromic and nonsyndromic PRS. This should guide future research on the topic.