Hard to swallow: Developmental biological insights into pediatric dysphagia

Document Type

Journal Article

Publication Date

1-1-2016

Journal

Developmental Biology

Volume

409

Issue

2

DOI

10.1016/j.ydbio.2015.09.024

Keywords

22q11.2 Deletion/DiGeorge Syndrome; Brainstem circuitry; Cranial nerves; Hindbrain patterning; Oropharyngeal morphogenesis; Pediatric dysphagia

Abstract

© 2015. Pediatric dysphagia-feeding and swallowing difficulties that begin at birth, last throughout childhood, and continue into maturity-is one of the most common, least understood complications in children with developmental disorders. We argue that a major cause of pediatric dysphagia is altered hindbrain patterning during pre-natal development. Such changes can compromise craniofacial structures including oropharyngeal muscles and skeletal elements as well as motor and sensory circuits necessary for normal feeding and swallowing. Animal models of developmental disorders that include pediatric dysphagia in their phenotypic spectrum can provide mechanistic insight into pathogenesis of feeding and swallowing difficulties. A fairly common human genetic developmental disorder, DiGeorge/22q11.2 Deletion Syndrome (22q11DS) includes a substantial incidence of pediatric dysphagia in its phenotypic spectrum. Infant mice carrying a parallel deletion to 22q11DS patients have feeding and swallowing difficulties that approximate those seen in pediatric dysphagia. Altered hindbrain patterning, craniofacial malformations, and changes in cranial nerve growth prefigure these difficulties. Thus, in addition to craniofacial and pharyngeal anomalies that arise independently of altered neural development, pediatric dysphagia may result from disrupted hindbrain patterning and its impact on peripheral and central neural circuit development critical for feeding and swallowing. The mechanisms that disrupt hindbrain patterning and circuitry may provide a foundation to develop novel therapeutic approaches for improved clinical management of pediatric dysphagia.

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