Experimental Aspects of the Pathogenesis of Robin Sequence

Objective The Pierre Robin Sequence (PRS) is a good example of disturbed embryonic development of the secondary palate involving insufficient mandibular growth, failed forward tongue movement, and, in the case of a cleft, impeded fusion of the secondary palate. Discussion continues regarding which of the involved pathogenetic factors is the primary cause of the induced cascade of signs: insufficient mandibular growth or failed descent of the tongue. Design Forty-five randomly selected, 18-day-old formalin-fixed A/WySn mouse fetuses were investigated. The strain is known to have a basic genetic defect and as much as 44% clefts in the offspring. Twenty-four fetuses in the group had a cleft palate. Mandible position was measured relative to the head and to the presence or absence of a cleft. Cleft width and tongue position were also determined. Thirty-eight NMRI mouse fetuses of the same age served as controls. Results All A/WySn fetuses showed marked mandibular retrognathia, which was more severe in the cleft group (p < .05), but there was no correlation between the degree of retrognathia and cleft width. The median cleft width was 3.4 mm (1.6 through 6.3 mm). The tongue was in the cleft in all 12 fetuses with wide clefts (>3.4 mm wide), and free in the oral cavity in the other 12. Tongue position did not influence the degree of retrognathia (p < .05). Moreover, the tongue was free in all fetuses with severe retrognathia. Conclusion The results support the primary role of retroposition of the mandible in the development of cardinal symptoms of Pierre Robin Sequence.