Hypermobile Ehlers-Danlos Syndrome (hEDS) is the Most Likely Diagnosis
This 8-year-old patient with documented delayed gastric emptying, chronic abdominal pain, functional constipation, significant joint hypermobility, and a family history of aortic dissection/esophageal rupture in a young relative should be urgently evaluated for Ehlers-Danlos Syndrome, specifically both hypermobile and vascular subtypes. The constellation of GI dysmotility, hypermobility, and catastrophic vascular events in a first-degree relative creates a critical diagnostic imperative that supersedes metabolic workup at this stage.
Critical Family History Analysis
The paternal relative's death at a young age from aortic dissection AND esophageal rupture is pathognomonic for vascular EDS (vEDS), not hypermobile EDS 1, 2, 3. This dual arterial and GI rupture pattern is the hallmark presentation of vEDS, which carries autosomal dominant inheritance with 50% transmission risk 3. While the child's hypermobility suggests hEDS, the family history mandates urgent vEDS exclusion first, as this is a life-threatening condition with median survival of 48 years and 25% mortality by age 20 from arterial or organ rupture 2, 3.
The metabolic disorder hypothesis is significantly less likely given the specific pattern of confirmed gastroparesis, documented hypermobility, and the pathognomonic family vascular history. Metabolic disorders do not explain the joint findings or the family's vascular catastrophes.
Immediate Diagnostic Algorithm
Phase 1: Urgent Vascular EDS Exclusion (Within 1-2 Weeks)
COL3A1 gene mutation testing must be ordered immediately as the definitive diagnostic test for vascular EDS 4. This is non-negotiable given the family history 2, 3.
Multi-gene panel testing covering COL3A1, COL5A1, COL5A2, TGFBR1, TGFBR2, and PLOD1 should be ordered simultaneously to capture other arteriopathy-associated EDS subtypes 4.
Baseline serum tryptase level should be obtained now to help distinguish myeloproliferative variants and assess for mast cell activation syndrome (MCAS), which commonly co-occurs with hEDS 4.
MR angiography of head, neck, thorax, abdomen, and pelvis should be performed to assess for arterial tortuosity, aneurysms, or dissections before any invasive procedures 4. This is critical because arteriography is absolutely contraindicated in vEDS due to vessel fragility 2.
Phase 2: Clinical hEDS Diagnosis (Concurrent)
While awaiting genetic results, formally assess for hypermobile EDS using the Beighton scale 1, 4:
Beighton score ≥5 is required (score each: passive 5th finger dorsiflexion >90°, thumb to forearm apposition, elbow hyperextension >10°, knee hyperextension >10°, palms flat on floor with knees extended) 1, 4.
Document skin characteristics: soft/velvety texture with normal or slightly increased extensibility, absence of fragility 1.
Assess for minor criteria: recurrent joint dislocations, chronic joint/limb pain, easy bruising, functional bowel disorders (which this patient clearly has), high narrow palate, dental crowding 1.
Echocardiogram to evaluate aortic root is mandatory, as 25-33% of hEDS patients develop aortic root dilation 1, 4. Repeat every 2-3 years until adult height if normal 1.
Phase 3: GI-Specific Workup (Already Partially Complete)
The patient's gastric emptying study confirming >80% retention and functional constipation align perfectly with hEDS 1, 5:
Celiac disease testing was appropriately performed (negative), as celiac risk is elevated in hEDS/POTS 1.
Anorectal manometry, balloon expulsion test, or defecography should be performed given the severe constipation, as pelvic floor dysfunction prevalence is extremely high in hEDS 1.
Postural vital signs should be measured (heart rate increase ≥30 bpm within 10 minutes of standing) to screen for POTS, which affects the majority of hEDS patients and worsens gastroparesis 1, 6, 7.
Phase 4: MCAS Evaluation (If Indicated)
MCAS testing should only be pursued if the patient has multisystem symptoms beyond GI (flushing, urticaria, wheezing, anaphylaxis-like episodes) 1, 6, 7.
Do NOT perform routine MCAS testing for isolated GI symptoms, as validated clinical tests for mast cell-mediated abdominal pain are lacking 1.
Immediate Symptom Management While Awaiting Diagnosis
Gastroparesis Management
Continue the prokinetic agent that previously provided "significant improvement" (likely metoclopramide based on context) 6, 7. The pharmacy refill issue causing symptom recurrence confirms its efficacy.
Implement a gastroparesis diet: 5-6 small frequent meals daily, low fat (<40g/day), low fiber, prioritize liquid calories 6, 7.
Add ondansetron 4-8mg as needed for breakthrough nausea 7.
Constipation Management
Polyethylene glycol 3350 (17g daily) as first-line osmotic laxative 7.
Continue current regimen but optimize dosing based on response 1.
POTS Management (If Confirmed)
Increase fluid intake to 2-3 liters daily and salt intake to 10-12 grams daily for volume expansion 6, 7.
Lower body compression garments (30-40 mmHg) during upright activities 6.
Critical Medications to AVOID
Never use NSAIDs - they worsen GI symptoms in hEDS and trigger MCAS 7.
Never use opioids for chronic abdominal pain - they cause narcotic bowel syndrome and worsen gastroparesis and constipation 1, 7.
Why Metabolic Workup is Secondary
The "selective vegetarianism" is likely a consequence of gastroparesis-induced food aversion and fear of eating, not a primary metabolic cause 6, 7. The documented delayed gastric emptying, hypermobility, and family vascular history create a coherent EDS picture that metabolic disorders cannot explain. Metabolic testing would be reasonable only after EDS evaluation is complete and if symptoms persist despite appropriate EDS-directed management.
Referral Strategy
Medical genetics consultation is mandatory for definitive EDS diagnosis and classification, genetic counseling regarding inheritance patterns, and coordination of family screening 4.
Cardiology referral for echocardiogram interpretation and surveillance planning 1, 4.
Consider autonomic testing (tilt table) if POTS screening is positive 1, 4.
Nutrition consultation is essential to prevent avoidant/restrictive food intake disorder (ARFID) development, which is common in this population with chronic GI symptoms 6, 7.
Common Pitfalls to Avoid
Do not perform invasive procedures (arteriography, unnecessary endoscopy) until vEDS is excluded, as vessel/tissue fragility can cause fatal complications 2, 3.
Do not dismiss the family history - the specific pattern of aortic dissection plus esophageal rupture is virtually diagnostic of vEDS in that relative 2, 3.
Do not implement restrictive diets without nutritional guidance - this population is highly vulnerable to disordered eating 6, 7.
Do not order whole-genome sequencing for hEDS - no causative genes have been identified, making this wasteful 4.