Browsing by Author "Heuckeroth, Robert O."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Down syndrome mouse models have an abnormal enteric nervous system
    (American Society for Clinical Investigation, 2019-04-18) Schill, Ellen M.; Wright, Christina M.; Jamil, Alisha; LaCombe, Jonathan M.; Roper, Randall J.; Heuckeroth, Robert O.; Biology, School of Science
    Children with trisomy 21 (Down syndrome [DS]) have a 130-fold increased incidence of Hirschsprung Disease (HSCR), a developmental defect where the enteric nervous system (ENS) is missing from distal bowel (i.e., distal bowel is aganglionic). Treatment for HSCR is surgical resection of aganglionic bowel, but many children have bowel problems after surgery. Post-surgical problems like enterocolitis and soiling are especially common in children with DS. To determine how trisomy 21 affects ENS development, we evaluated the ENS in two DS mouse models, Ts65Dn and Tc1. These mice are trisomic for many chromosome 21 homologous genes, including Dscam and Dyrk1a, which are hypothesized to contribute to HSCR risk. Ts65Dn and Tc1 mice have normal ENS precursor migration at E12.5 and almost normal myenteric plexus structure as adults. However, Ts65Dn and Tc1 mice have markedly reduced submucosal plexus neuron density throughout the bowel. Surprisingly, the submucosal neuron defect in Ts65Dn mice is not due to excess Dscam or Dyrk1a, since normalizing copy number for these genes does not rescue the defect. These findings suggest the possibility that the high frequency of bowel problems in children with DS and HSCR may occur because of additional unrecognized problems with ENS structure.
  • Thumbnail Image
    Item
    Hypothyroidism is a rare cause of isolated constipation
    (Wolters Kluwer, 2012-02) Bennett Jr., William E.; Heuckeroth, Robert O.; Department of Pediatrics, IU School of Medicine
    The prevalence of constipation in children is high and accounts for a large percentage of pediatric and pediatric gastroenterology visits. Thyroid testing is frequently ordered to evaluate constipation and other gastrointestinal complaints in children. We reviewed all patients with thyroid testing ordered by our pediatric gastroenterology division over a five-year period. We found 873 patients on whom thyroid testing was performed, and 56 had evidence of hypothyroidism. Nine patients had constipation and clinically significant hypothyroidism in this group. However, only one child had constipation as their sole presenting symptom. The contribution of occult hypothyroidism to isolated constipation in children may have been previously overestimated.