Phenotypic variability and gastrointestinal manifestations/interventions for growth in NAA10‐related neurodevelopmental syndrome

Abstract

AbstractOur study of 61 children with NAA10‐related neurodevelopmental syndrome, an X‐linked disorder due to NAA10 gene variants, demonstrated a high prevalence of growth failure, with weight and height percentiles often in the failure‐to‐thrive diagnostic range; however, dramatic weight fluctuations and phenotypic variability is evidenced in the growth parameters of this population. Although never previously explored in depth, the gastrointestinal pathology associated with NAA10‐related neurodevelopmental syndrome includes feeding difficulties in infancy, dysphagia, GERD/silent reflux, vomiting, constipation, diarrhea, bowel incontinence, and presence of eosinophils on esophageal endoscopy, in order from most to least prevalent. Additionally, the gastrointestinal symptom profile for children with this syndrome has been expanded to include eosinophilic esophagitis, cyclic vomiting syndrome, Mallory Weiss tears, abdominal migraine, esophageal dilation, and subglottic stenosis. Although the exact cause of poor growth in NAA10‐related neurodevelopmental syndrome probands is unclear and the degree of contribution to this problem by GI symptomatology remains uncertain, an analysis including nine G‐tube or GJ‐tube fed probands demonstrates that G/GJ‐tubes are overall efficacious with respect to improvements in weight gain and caregiving. The choice to insert a gastrostomy or gastrojejunal tube to aid with weight gain is often a challenging decision to make for parents, who may alternatively choose to rely on oral feeding, caloric supplementation, calorie tracking, and feeding therapy. In this case, if NAA10‐related neurodevelopmental syndrome children are not tracking above the failure to thrive (FTT) range past 1 year of age despite such efforts, the treating physicians should be consulted regarding possibly undergoing G‐tube placement to avoid prolonged growth failure. If G‐tubes are not immediately inducing weight gain after insertion, recommendations could include altering formula, increasing caloric input, or exchanging a G‐tube for a GJ‐tube by means of a minimally invasive procedure.