To whom should patients with suspected Ehlers-Danlos syndrome (EDS) be referred for evaluation and management?

Referral Pathway for Suspected Ehlers-Danlos Syndrome

Patients with suspected EDS should be referred to a medical geneticist as the primary specialist for definitive diagnosis and classification. 1, 2

Primary Referral: Medical Genetics

Medical geneticists serve as the cornerstone for EDS evaluation because they possess specialized expertise in inherited connective tissue disorders and can coordinate appropriate genetic testing and multidisciplinary care. 1, 2 This is particularly critical because EDS presents with overlapping features with multiple other connective tissue disorders including Marfan syndrome, Loeys-Dietz syndrome, and familial thoracic aortic aneurysm, requiring expert differentiation. 1

For hypermobile EDS (hEDS)—the most common subtype affecting 80-90% of EDS patients—diagnosis remains entirely clinical since no causative genes have been identified, making the clinical expertise of a medical geneticist essential. 2

Urgent Subspecialty Referrals Based on Clinical Presentation

Vascular Surgery (URGENT if vascular EDS suspected)

• Refer immediately to vascular surgery if you suspect vascular EDS (thin translucent skin with visible veins, family history of arterial rupture or sudden death, easy bruising). 1, 2
• Vascular EDS carries a median survival of only 48 years with life-threatening arterial rupture risk, requiring urgent COL3A1 genetic testing and surveillance imaging protocols. 2
• Critical pitfall: Avoid invasive vascular procedures in suspected vascular EDS patients, as fatal complications from arterial fragility have been reported. 2

Cardiology (Essential for all EDS types)

• All suspected EDS patients require echocardiography to evaluate aortic root diameter, as 25-33% of hypermobile and classic EDS patients develop aortic root dilation. 2, 3
• Cardiologists manage surveillance protocols: annual echocardiograms if aortic root <4.5 cm, every 6 months if >4.5 cm or growth >0.5 cm/year. 2, 3
• For patients with normal aortic dimensions, repeat imaging every 2-3 years until adult height is reached. 4, 3

Gastroenterology (High priority for hEDS)

• Refer to gastroenterology given that up to 98% of hEDS patients experience GI manifestations including gastroparesis, functional bowel disorders, and pelvic floor dysfunction. 2, 4
• Gastroenterologists can screen using the Beighton score and apply 2017 hEDS diagnostic criteria, potentially identifying cases before formal genetics evaluation. 2
• They manage specialized testing including anorectal manometry (50% have pelvic floor dysfunction), gastric emptying studies (30% have delayed emptying), and celiac screening (20% prevalence in hEDS). 4

Rheumatology

• Rheumatologists evaluate joint hypermobility using the Beighton scale (score ≥5/9 required for adults under 50, ≥4/9 for those over 50, ≥6/9 for prepubertal children). 2, 4
• They differentiate EDS from other rheumatologic conditions presenting with joint hypermobility and chronic pain. 2

Ophthalmology

• A dilated slit-lamp examination by an ophthalmologist is essential to exclude ectopia lentis, which would shift diagnosis toward Marfan syndrome rather than EDS. 1, 3
• This examination must be performed with pupils fully dilated by an ophthalmologist experienced with connective tissue disorders. 1

Secondary Referrals for Symptom Management

Pain Management Specialist

• Pain management consultation is crucial for patients with chronic pain, which affects the majority of EDS patients. 4, 3
• Pain specialists prescribe neuromodulators (tricyclic antidepressants, SNRIs, gabapentin, pregabalin) while avoiding opioids, which should never be used for chronic or abdominal pain in EDS. 2, 4

Physical Medicine and Rehabilitation

• Physical therapy with myofascial release techniques is necessary before patients can participate in low-resistance exercise programs to improve joint stability. 4, 3
• Orthopedic surgery should be delayed in favor of physical therapy and bracing due to poor outcomes in EDS patients compared to the general population. 4, 3

Neurology (for autonomic dysfunction)

• Neurologists evaluate for postural orthostatic tachycardia syndrome (POTS), which commonly complicates hEDS and requires postural vital sign testing (heart rate increase ≥30 beats/min within 10 minutes of standing). 2, 4

Allergy/Immunology (if mast cell symptoms present)

• Refer to allergy specialists if patients present with episodic multisystem symptoms (flushing, urticaria, wheezing) suggesting mast cell activation syndrome, which affects up to 10% of hEDS patients. 2, 4
• Baseline serum tryptase should be obtained before referral, with diagnostic threshold of 20% increase above baseline plus 2 ng/mL during symptom flares. 2

Coordination of Care

The medical geneticist serves as the hub for coordinating this multidisciplinary team, ensuring appropriate subspecialty involvement based on EDS subtype and individual patient manifestations. 2, 4 Genetic counseling before mutation screening is paramount due to complex financial, insurance, familial, and social implications. 2

Common pitfall: Referring only to cardiology or rheumatology without genetics involvement often results in missed diagnoses or misclassification, as these specialists may not be familiar with the 13 distinct EDS subtypes and their specific management requirements. 1, 5