Auricular Vagal Nerve Stimulation for Hypermobile Ehlers-Danlos Syndrome

Inclusion Criteria:

• Children aged 10-18 years old

• Children with functional upper GI complaints and clinical suspicion for hEDS or HSDas well as a Beighton score of at least 4/9

• Children with functional upper GI complaints and clinical suspicion for ANSdysfunction

• De-identified data from our prior studies (IRB #689519 and IRB #1064187) of patientswith functional GI disorders who do NOT meet criteria for hEDS will be used as acomparison group

• Children who are English-speaking and lack other explanation for symptoms

• Children willing to participate and consent to this study (for children, have aparent willing to participate)

Exclusion Criteria:

A) Exclusion Criteria applying to all participants:

• Medically complex children or those who take a medication or suffer from a diseasethat can explain symptoms will be excluded from participation in the study.

• Adult subjects, children or their parents who have significant developmental delay (will be excluded due to difficulties in accurately completing the questionnairesand assessing symptoms)

• Patients with findings of organic disease such as peptic ulcer disease, H.pylorigastritis, celiac disease, inflammatory bowel disease, allergic disorders, metabolicdisorder or any other chronic condition or medication that may cause chronic GIsymptoms will be excluded from the study.

• Patients who are treated with a new drug affecting the central nervous system in thetwo weeks prior to enrollment will also be excluded.

• Pregnancy (evaluating MD screens patients as they normally would during a clinicvisit (by questioning) and would only perform urine pregnancy test if clinicallyindicated (absence of menstrual period or other symptoms concerning for pregnancy)

• Chronic alcohol/illicit drug use and/or smoking.

B) Exclusion Criteria for subjects undergoing pVNS therapy:

• Severe dermatological condition or active infection of external or middle ear

• Implanted electrical device

C) Exclusion Criteria for subjects undergoing aVNS therapy:

• Hearing impaired

• Sight impaired without correction

• Seizure disorder

D) Exclusion Criteria for subjects undergoing gastric motor function sub-study:

• Patients with pacemakers, metal clips used in previous surgery or other device whichare not compatible with MRI scanning

• Claustrophobia or inability to lie still in the scanner

• Orthodontic braces or permanent retainers

• Patients who are unable to tolerate noise produced by the MRI

• Egg allergy or anticipated inability to complete a standardized egg meal

E) Exclusion Criteria for subjects undergoing HepGI Biobank specimen collection sub-study:

• Bleeding disorder for the specific biopsies

• Recent antibiotic usage for fecal sample

• Significant anemia or clinical status which will not allow safe blood draw requiredfor blood collection

• Refusal of blood collection or to provide DNA sample

• Inability or unwillingness on the individual (or parent/legal guardian) to provideclinical or family history.