title: Hard to swallow: Developmental biological insights into pediatric dysphagia.
abstract: 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.
authors.affiliation: Institute for Neuroscience, The George Washington University School of Medicine and Health Sciences, Washington D.C., USA; Department of Pharmacology and Physiology, George Washington University, School of Medicine and Health Sciences, Washington D.C., USA.
authors.forename: Anthony-Samuel
authors.initials: AS
authors.lastname: LaMantia
authors.affiliation: Institute for Neuroscience, The George Washington University School of Medicine and Health Sciences, Washington D.C., USA; Department of Anatomy and Regenerative Biology, George Washington University, School of Medicine and Health Sciences, Washington D.C., USA.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Moody
authors.affiliation: Institute for Neuroscience, The George Washington University School of Medicine and Health Sciences, Washington D.C., USA; Department of Pharmacology and Physiology, George Washington University, School of Medicine and Health Sciences, Washington D.C., USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Maynard
authors.affiliation: Institute for Neuroscience, The George Washington University School of Medicine and Health Sciences, Washington D.C., USA; Department of Pharmacology and Physiology, George Washington University, School of Medicine and Health Sciences, Washington D.C., USA.
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Karpinski
authors.affiliation: Institute for Neuroscience, The George Washington University School of Medicine and Health Sciences, Washington D.C., USA; Center for Neuroscience Research, Children's National Health System, Washington D.C., USA.
authors.forename: Irene E
authors.initials: IE
authors.lastname: Zohn
authors.affiliation: Institute for Neuroscience, The George Washington University School of Medicine and Health Sciences, Washington D.C., USA; Department of Pharmacology and Physiology, George Washington University, School of Medicine and Health Sciences, Washington D.C., USA.
authors.forename: David
authors.initials: D
authors.lastname: Mendelowitz
authors.affiliation: Institute for Neuroscience, The George Washington University School of Medicine and Health Sciences, Washington D.C., USA; Department of Pharmacology and Physiology, George Washington University, School of Medicine and Health Sciences, Washington D.C., USA.
authors.forename: Norman H
authors.initials: NH
authors.lastname: Lee
authors.affiliation: Institute for Neuroscience, The George Washington University School of Medicine and Health Sciences, Washington D.C., USA; Department of Anatomy and Regenerative Biology, George Washington University, School of Medicine and Health Sciences, Washington D.C., USA.
authors.forename: Anastas
authors.initials: A
authors.lastname: Popratiloff
mesh_terms: D000818:Animals; D002648:Child; D003680:Deglutition Disorders / Q000473:pathology*; D004195:Disease Models, Animal; D048788:Growth and Development; D006801:Humans; D008954:Models, Biological; D009415:Nerve Net / Q000503:physiopathology
keywords: 22q11.2 Deletion/DiGeorge Syndrome; Brainstem circuitry; Cranial nerves; Hindbrain patterning; Oropharyngeal morphogenesis; Pediatric dysphagia