1. Gastroenterology (GI) Basics
Kathleen J. Motil, M.D., Ph.D.
USDA Children’s Nutrition Research Center
Baylor College of Medicine
Houston, TX 77030

2. Disclosures
I am a Section Editor for Up-To-Date, Inc., an electronic textbook of medicine.
I do not have relevant financial relationships with the manufacturers of commercial products and/or providers of commercial services discussed in this presentation.
I will not discuss unapproved or investigative use of a commercial product or device in my presentation.

3. Parental Concerns
“My daughter eats all of the time, but she doesn’t gain weight.”
“My daughter screams constantly. I know something is wrong.”
“My daughter’s stomach is full of air. It must hurt.”
“My daughter won’t go to the bathroom unless I give her something. I don’t want her to become addicted.”

4. Objectives
Recognize problems related to GI dysmotility in Rett syndrome
Recognize “trigger” signs to call your physician
Understand the reason for selected GI tests
Understand approaches to treat GI dysmotility in Rett syndrome

5. GI Problems in Rett Syndrome
Feeding difficulty %
Chewing dysfunction %
Swallowing dysfunction %
Gastrointestinal dysmotility %
Gastroesophageal reflux %
Delayed gastric emptying %
Biliary tract disease %
Gas bloating ?
Constipation %
Motil KJ, J Pediatr Gastroenterol Nutr, 2012

6. Enteric Nervous System
MeCP2 found throughout GI tract
MeCP2 found specifically in enteric nervous tissue
MeCP2 found throughout development of GI tract
GI dysmotility in Rett syndrome mediated directly through ENS dysfunction because of abnormal MECP2 (protein)
Wahba G, Neurogastroenterol Motil, 2015

7. Chew/Swallow Dysfunction
Definition: poor jaw movement, tongue mobility/propulsion, delayed initiation of swallow, pooling of food in sinuses, laryngeal liquid penetration/aspiration
Trigger: Meals > 30 min, choking with meals, poor weight gain
Test: OT/Speech assessment, Swallow function study, BMI
Treatment: OT/Speech therapy, alternative feeding methods

8. Gastroesophageal Reflux
Definition: involuntary reverse passage of acid, food from stomach to esophagus/mouth due to poor motility of esophagus, LES, stomach
Trigger: irritability, vomiting, night awakening, feeding refusal, wheezing
Test: Medical history, UGI series, upper endoscopy/biopsy, gastric emptying scan
Treatment: dietary, position, medications (PPI, prokinetic), surgery (fundoplication)

9. Biliary Tract Disease Definition: three disorders
Cholecystitis (inflammation)
Cholelithiasis (gallstones)
Biliary dyskinesia (dysmotility)
Trigger: abdominal pain, jaundice, vomiting
Test: AUS, HIDA scan
Treatment: surgery (cholecystectomy)

10. Gas Bloating
Definition: gas trapping due to air swallowing (bruxism, breath holding, hyperventilation) or bacterial fermentation of undigested CHO
Trigger: abdominal distention, discomfort
Test: blood (celiac disease), stool (giardiasis, H pylori), H2 breath test (lactose intolerance, SBBO), AXR (constipation)
Treatment: diet (↓ CHO/sorbitol, gluten-free, lactase enzyme), medications (simethicone, antibiotics, laxatives, probiotics)

11. Constipation
Definition: defecation difficulty, bowel movements < 2x/week,
Trigger: large or pebble hard stool, blood on stool, abdominal pain,  gas, poor appetite, vomiting, UTI, diarrhea
Test: Medical history, abdominal/rectal exam; AXR, barium enema, rectal manometry/biopsy, colonoscopy/biopsy
Treatment: diet ( fiber, sorbitol), medications (softener/pusher laxatives, probiotics, suppositories, enemas) surgery (cecostomy, appendicostomy), physical activity

12. Gastrointestinal Crises
Severely ill, abdominal pain, abdominal distention, vomiting
Surgical emergencies (stomach, intestines)
Volvulus (twisting)
Intussusception (sliding)
Perforation (hole)
Cause of abdominal crises unknown
Air swallowing alone does not result in intestinal perforation
Chronic constipation, megacolon may increase risk for obstruction
Not unique to Rett Syndrome

13. Future Research Enteric nervous system Intestinal microbiome
Role of MECP2 in synaptic transmission, neurotransmitter synthesis and activity
Differences in genotype-phenotype outcomes
Intestinal microbiome
Patterns of microbial colonization, metabolic end-products

14. Summary
GI problems (chewing/swallowing difficulties, feeding refusal, gastroesophageal reflux, delayed gastric emptying, gas bloating, constipation) commonly found in RTT
GI problems caused by dysmotility of GI tract, presumably due to abnormalities in enteric nervous system
Any symptom that causes parental concern should be evaluated by a physician
Treatment strategies should be discussed with a physician to improve symptoms, avoid complications, improve quality of life