Gastrointestinal Symptoms and Channelopathy-Associated Epilepsy

J Pediatr. 2021 Oct:237:41-49.e1. doi: 10.1016/j.jpeds.2021.06.034. Epub 2021 Jun 26.


Objective: To determine the prevalence of and identify factors associated with gastrointestinal (GI) symptoms among children with channelopathy-associated developmental and epileptic encephalopathy (DEE).

Study design: Parents of 168 children with DEEs linked to SCN1A (n = 59), KCNB1 (n = 31), or KCNQ2 (n = 78) completed online CLIRINX surveys about their children's GI symptoms. Our analysis examined the prevalence, frequency, and severity of GI symptoms, as well as DEE type, functional mobility, feeding difficulties, ketogenic diet, antiseizure medication, autism spectrum disorder (ASD), and seizures. Statistical analyses included the χ2 test, Wilcoxon rank-sum analysis, and multiple logistic regression.

Results: GI symptoms were reported in 92 of 168 patients (55%), among whom 63 of 86 (73%) reported daily or weekly symptoms, 29 of 92 (32%) had frequent or serious discomfort, and 13 of 91 (14%) had frequent or serious appetite disturbances as a result. The prevalence of GI symptoms varied across DEE cohorts with 44% of SCN1A-DEE patients, 35% of KCNB1-DEE patients, and 71% of KCNQ2-DEE patients reporting GI symptoms in the previous month. After adjustment for DEE type, current use of ketogenic diet (6% reported), and gastrostomy tube (13% reported) were both associated with GI symptoms in a statistically, but not clinically, significant manner (P < .05). Patient age, functional mobility, feeding difficulties, ASD, and seizures were not clearly associated with GI symptoms. Overall, no individual antiseizure medication was significantly associated with GI symptoms across all DEE cohorts.

Conclusions: GI symptoms are common and frequently severe in patients with DEE.

Keywords: constipation; gastrointestinal dysmotility; voltage-gated potassium channel; voltage-gated sodium channel.

MeSH terms

  • Adolescent
  • Brain Diseases / complications*
  • Brain Diseases / genetics
  • Brain Diseases / therapy
  • Channelopathies / complications*
  • Channelopathies / genetics
  • Channelopathies / therapy
  • Child
  • Child, Preschool
  • Epilepsy / complications*
  • Epilepsy / genetics
  • Epilepsy / therapy
  • Female
  • Gastrointestinal Diseases / diagnosis
  • Gastrointestinal Diseases / epidemiology
  • Gastrointestinal Diseases / etiology*
  • Genetic Markers
  • Health Surveys
  • Humans
  • Infant
  • KCNQ2 Potassium Channel / genetics
  • Logistic Models
  • Male
  • NAV1.1 Voltage-Gated Sodium Channel / genetics
  • Prevalence
  • Risk Factors
  • Severity of Illness Index
  • Shab Potassium Channels / genetics


  • Genetic Markers
  • KCNB1 protein, human
  • KCNQ2 Potassium Channel
  • KCNQ2 protein, human
  • NAV1.1 Voltage-Gated Sodium Channel
  • SCN1A protein, human
  • Shab Potassium Channels