Figure 8.

Multiple developmental disruptions may underlie pediatric dysphagia. One possibility, supported by some of the observations in the LgDel mouse model of 22q11DS summarized in this review, is that feeding and swallowing dysfunction arises due to disruptions of hindbrain patterning. These disruptions then compromise hindbrain motor neuron differentiation as well as neural crest specification that is key for cranial nerve growth, appropriate sensory and motor innervation as well as morphogenesis of oropharyngeal structures critical for optimal feeding and swallowing. A second possibility is that pediatric dysphagia is primarily a disorder of disrupted craniofacial/oropharyngeal development due to altered patterning and differentiation of cranial mesendoderm and ectodermal placodes—independent of any significant, primary involvement of the central nervous system or neuroectodermal derivatives. These changes would lead primarily to oropharyngeal morphogenetic anomalies that would alter feeding and swallowing mechanics, with only secondary changes in motor or sensory innervation and circuit function—some of which might be compensatory for the peripheral dysmorphology. We note that these two possible general mechanisms are not mutually exclusive. Indeed mutations, teratogens, or maternal stress might alter both in parallel, modifying normal central/peripheral interactions leading to pathogenesis that results in pediatric dysphagia.