What gastrointestinal (GI) issues are associated with CHARGE syndrome?

Gastrointestinal Issues Associated with CHARGE Syndrome

Patients with CHARGE syndrome experience multiple gastrointestinal issues from mouth to anus, with over 90% requiring tube feeding early in life due to severe feeding difficulties and gut dysmotility. 1, 2

Common GI Manifestations in CHARGE Syndrome

Feeding and Swallowing Difficulties

• Oral-motor dysfunction due to cranial nerve abnormalities
• Weak sucking/chewing abilities 1
• Swallowing disorders leading to aspiration risk
• Nasopharyngeal reflux especially common in infants with submucous cleft palate 3

Upper GI Issues

• Gastroesophageal reflux disease (GERD) - extremely common 1, 2
• Esophageal dysmotility affecting food transit 3
• Oral aversion and sensory integration difficulties with solid foods 3

Lower GI Issues

• Constipation - reported as the most common GI challenge (30% of patients) 4
• Intestinal dysmotility - affecting the entire GI tract 2, 5
• Vomiting (19% of patients) and choking (17% of patients) 4

Structural Abnormalities

• Hernias (diaphragmatic, umbilical, inguinal)
• Less common congenital malformations including:
  • Esophageal atresia
  • Tracheoesophageal fistula
  • Intestinal malrotation/nonrotation
  • Intestinal atresia
  • Anal atresia/stenosis
  • Imperforate anus
  • Hirschsprung disease 3

Pathophysiology of GI Issues in CHARGE Syndrome

1. Cranial nerve dysfunction - particularly affecting vagal nerve projections to the GI tract 5
2. Neural crest cell formation abnormalities due to CHD7 gene mutations 1
3. Decreased and disorganized vagal projections to the gut, especially in the foregut 5
4. Contributing factors include:
   • Hypotonia
   • Structural abnormalities of the airway
   • Endocrine disorders (hypocalcemia, thyroid dysfunction) 3

Clinical Management Approach

Diagnostic Evaluation

• Complete physical examination including assessment for structural abnormalities
• Early evaluation by gastroenterology specialists 3
• Assessment for associated conditions (hypocalcemia, thyroid dysfunction)
• Monitoring for signs of aspiration or respiratory complications

Feeding Support

• Early feeding therapy at first sign of oral aversion 3
• Special feeding techniques and bottles used for children with cleft palate 3
• Tube feeding support (40-50% require nasogastric or gastrostomy tubes) 3
• Consider behavior analytic approaches for feeding difficulties 6

Medical Management

• GERD treatment with proton pump inhibitors 3
• Constipation management with:
  • Fiber supplementation
  • Osmotic laxatives (polyethylene glycol)
  • Stimulant laxatives when needed 7
• Careful nutrition reintroduction in malnourished patients (5-10 kcal/kg/day initially) 7

Surgical Interventions

• Nissen fundoplication for severe GERD 1
• Gastrostomy/jejunostomy for long-term feeding support 1
• Surgical correction of structural abnormalities when present

Long-term Considerations

• GI issues may persist into adolescence and adulthood
• Constipation often remains a lifelong problem requiring ongoing management 3
• Risk of obesity increases in adolescence, requiring attention to diet and physical activity 3
• Tube-fed individuals experience more problematic GI symptoms than those with partial or complete oral feeding 4

Pitfalls and Caveats

1. GI involvement is often overlooked due to focus on other severe medical issues 1
2. Prokinetic agents like domperidone and erythromycin show mixed responses in CHARGE syndrome 5
3. Refeeding syndrome risk when reintroducing nutrition after periods of malnutrition 7
4. Autoimmune GI diseases (celiac disease, inflammatory bowel disease) may coexist and require separate management 3

Early recognition and management of these GI issues is critical for improving quality of life and reducing morbidity and mortality in patients with CHARGE syndrome.