05/06/2026
Genetic testing guidelines for connective tissue conditions (like Ehlers-Danlos, Marfan, and related disorders) are still fairly conservative—and for good reason. Testing everyone isn’t always helpful.
But emerging research suggests we may be missing important diagnoses if we rely too heavily on classic features alone.
Recent studies have found:
• Up to 26% of patients diagnosed with hypermobile EDS had a different or additional genetic condition identified
• Around 9% of patients had clearly actionable genetic results, with even more showing uncertain but potentially meaningful findings
• In children who didn’t fully meet criteria, ~22% still had a genetic diagnosis
We also know that some genetic conditions can present subtly—or not at all—until something serious happens.
So what does this mean?
👉 Not that everyone needs genetic testing
👉 But that in the right situations, testing can provide clarity, guide care, and sometimes change management entirely
Situations where testing may be worth considering:
• Multiple connective tissue features (even without family history)
• Early or more severe symptoms
• When ruling out other genetic conditions would impact care
This is where genetic counseling matters.
Because the goal isn’t more testing—it’s the right testing, for the right person, at the right time.
References:
1. 2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.
Journal of the American College of Cardiology. 2022. Isselbacher EM, Preventza O, Hamilton Black Iii J, et al.Guideline
2. Spontaneous Coronary Artery Dissection: Current State of the Science: A Scientific Statement From the American Heart Association.
Circulation. 2018. Hayes SN, Kim ESH, Saw J, et al.Guideline
3. Hypermobile Ehlers-Danlos Syndrome: Diagnostic Challenges and the Role of Genetic Testing.
Genes. 2025. Forghani I, See J, McGonigle WC.New
4. Next-Generation Sequencing and Analysis of Consecutive Patients Referred for Connective Tissue Disorders.
American Journal of Medical Genetics. Part A. 2022. Steinle J, Hossain WA, Veatch OJ, Strom SP, Butler MG.
5. Diagnostic Outcomes for Molecular Genetic Testing in Children With Suspected Ehlers-Danlos Syndrome.
American Journal of Medical Genetics. Part A. 2022. Damseh N, Dupuis L, O'Connor C, et al.
6. Precision Medicine Approaches to Vascular Disease: JACC Focus Seminar 2/5.
Journal of the American College of Cardiology. 2021. Miller CL, Kontorovich AR, Hao K, et al.
7. Genetic Testing for Heritable Cardiovascular Diseases in Pediatric Patients: A Scientific Statement From the American Heart Association.
Circulation. Genomic and Precision Medicine. 2021. Landstrom AP, Kim JJ, Gelb BD, et al.Guideline
8. Heritable Thoracic Aortic Disease Overview.
GeneReviews® [Internet]. 2023. Milewicz DM, Cecchi AC
9. Genetic Complexity of Diagnostically Unresolved Ehlers-Danlos Syndrome.
Journal of Medical Genetics. 2024. Vandersteen AM, Weerakkody RA, Parry DA, et al.
10. The Role of Genetic Testing in Children Requiring Surgery for Ectopia Lentis.
Genes. 2023. Musleh M, Bull A, Linton E, et al.
11. Cardiovascular Management of Aortopathy in Children: A Scientific Statement From the American Heart Association.
Circulation. 2024. Morris SA, Flyer JN, Yetman AT, et al.Guideline