Patterns of Dysphagia and Airway Protection in Infants with 22q11.2‐Deletion Syndrome

Abstract

Objective: 22q11.2-deletion syndrome is a genetic condition that affects 1:3000 births. In addition to cardiac anomalies and immunosuppression, individuals with 22q11.2-deletion syndrome can have feeding difficulties from birth resulting in failure to thrive and infections. This study aims to characterize the dysphagia seen in infants with 22q11.2-deletion syndrome. Methods: This is a retrospective chart review of infants with 22q11.2-deletion syndrome who underwent videofluoroscopic swallow studies (VFSS) from June 1, 2008 to January 1, 2018 at a tertiary children's hospital. Demographic data and VFSS findings were collected. Results: Forty-four patients were identified, 52% were females, and mean age at VFSS was 71 days. In their lifetime, 30% of the patients had at least 1 episode of pneumonia, 66% had NG-tube placement and 41% required G-tube placement. 93% had oral-phase dysphagia, and 89% had pharyngeal-phase dysphagia. Twenty-two patients (50%) demonstrated evidence of penetration. Eighteen patients (41%) showed tracheal aspiration. Of the patients that showed tracheal aspiration, 83% of them aspirated "silently." Three patients (7%) had upper esophageal sphincter (UES) opening dysfunction. Conclusion: Vast majority of the infants with 22q11.2-deletion syndrome referred for swallow studies demonstrated evidence of dysphagia in both oral and pharyngeal phases with deficits in swallow physiology not yet documented in other studies. Importantly, more than 80% of these infants showed evidence of "silent" tracheal aspiration, which can lead to recurrent pneumonia and significant morbidity if overlooked. Prompt recognition is paramount in these infants to intervene early and reduce long-term complications and also develop targeted interventions.

Persistent Feeding and Swallowing Deficits in a Mouse Model of 22q11.2 Deletion Syndrome

“…Some behavioral sex differences have been described in individuals with 22q11DS: males tend to be more withdrawn, have more somatic complaints, and are more likely to have anxiety and depression than females (22). Nevertheless, the incidence of dysphagia and other airway abnormalities in 22q11DS does not differ between males and females (1,10,(23)(24)(25)(26). In addition, our previous research with adult C57BL/6J mice revealed no significant differences in swallowing function between sexes (13).…”

Variations in maternal vitamin A intake modifies phenotypes in a mouse model of 22q11.2 deletion syndrome

“…Features of 22q11DS vary widely even in individuals with the same deletion (McDonald‐McGinn et al, 2015). While cardiac and craniofacial dysmorphology as well as a broad range of behavioral disabilities are among the most well‐known features of 22q11DS, almost all 22q11DS patients exhibit some degree of feeding and swallowing problems during childhood, a disorder known as pediatric dysphagia (Dyce et al, 2002; Eicher et al, 2000; Grasso et al, 2018; Jones, Tracy, Perryman, & Arganbright, 2018; Maggadottir & Sullivan, 2013; McDonald‐McGinn et al, 2015; Wong et al, 2019). Infants with 22q11DS gag, regurgitate and aspirate during feedings and have difficulties advancing the volume of feeds (Dyce et al, 2002; Eicher et al, 2000).…”

“…Infants with 22q11DS gag, regurgitate and aspirate during feedings and have difficulties advancing the volume of feeds (Dyce et al, 2002; Eicher et al, 2000). Aspiration during swallowing is a major factor contributing to frequent respiratory, sinus and ear infections observed in 22q11DS patients (Eicher et al, 2000; Grasso et al, 2018; Jones et al, 2018; Maggadottir & Sullivan, 2013; Wong et al, 2019). Approximately half of children with 22q11DS exhibit difficulties with feeding after the first year of age and a third struggle with advancing to textured foods (Eicher et al, 2000).…”

Mechanisms of larynx and vocal fold development and pathogenesis

“…These data confirmed that mesenchymal Tbx1 is necessary for pharyngeal arch development (Zhang, Huynh and Baldini, 2006) and mutation in Tbx1 gene is closely associated with the etiology of DiGeorge syndrome. In patients, DiGeorge syndrome, or velo-cardio-facial syndrome, is linked with the 22q11.2 microdeletion (Wong et al, 2019), which alters Tbx1 gene expression (Lipson et al, 1991;Chieffo et al, 1997;Morrow et al, 2018). Besides congenital heart defects and craniofacial malformations, these patients exhibit a wide range of laryngeal abnormalities including laryngeal webs (the most frequent anomaly), subglottic stenosis, laryngomalacia and/or atrophic VF (Fokstuen S, Bottani A, Medeiros PF, Antonarakis SE, Stoll C, 1997; Ebert et al, 2018).…”