Gastrointestinal problems are common in Rett syndrome and related disorders, including reflux, constipation, and air swallowing. Gastrointestinal dysmotility can also lead to feeding difficulties and refractory constipation. Management of GI issues is challenging, and poor motility is not well understood. Further research is needed, especially regarding intestinal motility in these syndromes.

1. Gastrointestinal problems in
Rett and Rett-like disorders
Edwin Liu, MD
Taplin Endowed Chair for Celiac Disease
Director, Colorado Center for Celiac Disease
Professor of Pediatrics
Digestive Health Institute,Childrens’s Hospital Colorado

2. National Survey of Characteristics in Rett
Syndrome British Isle Rett Syndrome Survey (BIRSS)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Seizures Respiratory problem Cardiac problem GI problem
Cianfaglione R et all. AJMG 2015

3. North American RTT database: GI involvement
in Rett
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Dysmotility
Chewing/
Swallow Weight Growth
Bone
density
Biliary tract
Motil KJ et l. JPGN 2012

4. What are the common problems?
• Reflux
• Constipation
• Air swallowing (aerophagia)

5. Gastro-Esophageal Reflux
Regurgitation of stomach contents into the
esophagus
• Common symptoms:
• Vomiting
• Rumination
• Respiratory signs
• Weight loss
• Complications:
• Aspiration
• Esophagitis

6. Why does reflux occur?
• An incompetent lower sphincter
muscle
• Poor esophageal clearance of liquid
• Poor gastric function (persistently full
stomach)
Gastro-Esophageal Reflux

7. •Treatment
• Usually conservative initially:
• Acid suppression
• Sometimes fundoplication
• Sometimes jejunal feeds
Gastro-Esophageal Reflux

8. Constipation
• Occurs when the colon moves too slow,
or there is incomplete emptying of stool
• Needs to be monitored. What to look for:
• Firm stools
• Infrequent stools
• Large stools
• Constant soiling
• Hard lump in lower abdomen
• Streaks of blood in stool
• Pain with stooling

9. • Management:
• Encourage physical activity and regular
toileting
• Stool softeners
• Stimulant laxatives
• Sometimes suppositories or enemas
• Rarely manual disimpaction
Constipation

10. • Try to aim for daily soft stools. Prevent
retention of stool.
• If the stools are too firm, soften it using stool
softeners
• If the stools are still too infrequent, use a
stimulant laxative
• If there is incomplete emptying, use periodic
suppositories or enemas
Constipation

11. Aerophagia – air swallowing
• Characterized by:
• Severe abdominal distension
• Abdomen is flat in the morning, gets
progressively more distended while
awake
• Very gassy and uncomfortable
• Burping
• Repetitive movements of the mouth,
breath holding or hyperventilation
might be suggestive

12. • Behavioral modification – anxiety?
• Prevent constipation
• Gastric decompression
• Sometimes G-tube
• Rarely results in complications
Aerophagia – air swallowing

13. Gastrointestinal Dysmotility
• Esophageal dysmotility
• Gastric dysmotility
• Colonic dysmotility
• Generalized dysmotility

14. Esophageal dysmotility
• In one study, abnormal esophageal motility
was demonstrated in 75% of individuals
with Rett
• Poor relaxation of the LES
• High esophageal pressures
• Results in poor esophageal clearance and
reflux
• But in other children with neurologic
impairment, there can be low muscle tone of
the esophagus
Fortunato JE et al. Journal of Applied Research 2008

15. Poor esophageal motility leads to dysphagia
(difficulty swallowing) and worsening reflux
• Thirty-two children with Rett were studied by esophageal manometry
• In children with reflux or dysphagia symptoms, 1/3 of all swallows were
abnormal.
• In children with fundoplication, nearly ½ of all swallows were abnormal.
• No association between esophageal dysmotility and MECP2 mutations.
• Conclusions:
• Poor esophageal function is a common finding in Rett children with symptoms of
reflux and dysphagia.
• Esophageal manometry should be considered to screen Rett children for esophageal
motility dysfunction before anti-reflux procedures.
Fortunato JE et al. Pediatrics 2008

16. • Treatment includes management of reflux
• If esophageal muscle tone is increased,
medications to reduce high muscle tone
could help?
• G-Tube feeds to bypass the esophagus
Esophageal dysmotility

17. Gastric dysmotility
• Can lead to feeding intolerance
• Fullness
• Vomiting
• Bloating
• Discomfort
• More regurgitation
• Back-up of formula in G-tube feedings

18. • Treatment includes meds to try to speed
up the stomach
• Tube feeds past the stomach (GJ-tube
feeds)
Gastric dysmotility

19. Colonic dysmotility
• Slow transit in the colon. Has to be
distinguished from a problem of
poor relaxation of the outlet
(rectum).
• Can lead to constipation, bloating
• Sometimes leads to feeding
intolerance
• Treatment involves trying to treat
constipation, rarely more aggressive
surgical approaches needed.

20. How is CDKL5 different from Rett Syndrome?
• Data sourced from the International CDKL5 Disorder Database (CDD),
InterRett and the Australian Rett syndrome Database (ARSD)
• More GI problems in CDKL5 disorder than in Rett Syndrome overall
• Likelihood of finding GI problems increased with age
• No difference found based on CDKL5 mutation group
Mangatt M et al. Orphanet J Rare Dis 2016

21. GI problems in CDKL5
86% with a GI problem
• Constipation 71%
• Reflux 64%
• Air swallowing 27%
• G-tube or J-tube 29%
• Indications: feeding difficulties, poor weight gain, medications, poor
general health
• 20% were exclusively tube fed
• 80% had some degree of ability to eat and drink
• Over half who were orally fed experienced feeding difficulties (abnormal
swallowing, coughing)

22. What kind of tools to assess the GI tract?
• Endoscopy
• pH/impedance probe

23. Tools to assess the GI tract
• Sitzmarkers
• Abdominal x-rays

24. Tools to assess the GI tract
• Barium contrast studies
• Gastric emptying studies
• Intestinal manometry

25. Summary
Gastrointestinal complications are common in Rett syndrome
• Reflux
• Constipation
• Aerophagia (air swallowing)
• GI Dysmotility that can lead to feeding problems and refractory constipation
• Dysmotility is challenging to manage
• Poor weight gain
• May require enteral tube feedings
There is a lot that is not well understood in the GI tract in Rett syndrome
A lot of opportunities for research related to intestinal motility in particular