Guideline sources The following summarized guidelines for the evaluation and management of Loeys-Dietz syndrome (LDS) are prepared by our editorial team based on guidelines from the Genetic Aortic Disorders Association Canada (GADA 2014) and the Society for Cardiovascular Angiography and Interventions (SCAI/STS/SVM/AATS/SCA/AHA/ACR/ACC/ASA/SIR 2010). 1 3 Guidelines 1. Diagnostic investigations Aortic imaging: as per AHA 2010 guidelines, obtain complete aortic imaging in patients with LDS or a confirmed genetic mutation known to predispose to aortic aneurysms and aortic dissections such as TGFBR1, TGFBR2, FBN1, ACTA2, or MYH11, at initial diagnosis and 6 months thereafter to establish if enlargement is occurring. B https://web.pathway.md/diseases/recmGDOkoYocifkBu 1/5 6/29/23, 5:54 AM Loeys-Dietz syndrome Pathway Duplex arterial screning: consider duplex arterial screening in presence of abnormal physical exam findings to identify arterial aneurysms or dissection. Cervical spine radiographs: obtain cervical spine XRs in the flexion and extension position at diagnosis to assess for instability. Manage per typical protocol. In children, if normal at baseline, consider repeat imaging at 3-5 year intervals through growth. DEXA scan: consider bone density measurement with DEXA scan in patients presenting with fractures in the absence of significant trauma. Food allergen testing: obtain food allergen testing for individuals experiencing reactions following food exposure. Evaluation for craniosynostosis: consider craniofacial referral with 3D CT for craniosynostosis in presence of skull asymmetry. Treat by typical protocol. 2. Medical management Antihypertensives: as per GADA 2014 guidelines, consider offering BP-lowering medication, such as ARB, ss-blocker, or ACEI. Bronchodilators: treat asthma with conservative use of bronchodilators along with other medications such as ICSs for chronic management. Beta-blockers: discuss BP medications in presence of asthma, as -blockers can exacerbate an asthma predisposition. Moisturizing creams: treat eczema with aggressive moisturizing and/or prescription ointments/topical creams. Medications to avoid: avoid prescribing medications that may negatively impact cardiovascular systems, including stimulant medications and vasoconstrictors for headache or migraine management. Self-injectable epinephrine: advise conservative use of Epi-Pen to treat exposure to food allergen. Management of rhinitis: prefer the use of antihistamines and/or intranasal steroids for chronic rhinitis symptoms. Management of arrythmias: manage AF or other arrhythmias per typical protocol. Mangement of GI disease: use typical protocols to diagnose, manage, and treat eosinophilic gastrointestinal disease and IBD. Management of constipation: consider PEG-3350 for treating constipation. Precede maintenance therapy with a clean-out if constipation has been longstanding or rectal impaction exists. Consider endoscopy and biopsy to evaluate for eosinophilic gastrointestinal disease and IBD if suspected clinically. Evaluate for cervical spine instability before endoscopy. https://web.pathway.md/diseases/recmGDOkoYocifkBu 2/5 6/29/23, 5:54 AM Loeys-Dietz syndrome Pathway 3. Nonpharmacologic interventions Exercise restrictions: advise exercise restrictions, including avoidance of contact or competitive sports, isometric exercises such as sit-ups, push-ups, pull-ups, or weight lifting, exercising to the point of exhaustion, and activities with routine blows to the chest or head. Physical therapy: perform routine occupational or physical therapy for joint hypermobility or hypotonia. Foot care/shoe inserts: consider advising hard shoe inserts or shoes with good arch support as they may help decrease lower extremity pain caused by significantly flat feet. Consider orthotics or other therapeutic bracing as indicated. Avoidance of allergens: treat food allergens by food avoidance and other typical protocols. Caloric supplementation: track weight/height and BMI curves. Have a low threshold for caloric supplementation if patient fails to thrive. Optimize and maintain BMI before any planned surgery. Calcium and vitamin D supplementation: monitor calcium intake and serum 25-hydroxyvitamin D periodically. Treat deficiency using regular protocols. Psychotherapy: administer psychotherapy to address psychosocial implications of diagnosis on the family. 4. Surgical interventions Aortic repair: as per AHA 2010 guidelines, consider surgical repair of the aorta in all adult patients with LDS or a confirmed TGFBR1 or TGFBR2 mutation and an internal aortic diameter of 4.2 cm by TEE, or an external diameter of 4.4 to 4.6 cm by CT and/or MRI. C Orthopedic procedures: treat clubfoot and contracture intervention per typical protocols. Hernia repair: perform hernia repair per typical protocol; consider mesh placement and be aware of potential significant scar tissue with multiple interventions. Pectus repair: discuss repair with general surgeon for appropriate timing. Consider avoiding performing in conjunction with aortic root replacement surgery. 5. Specific circumstances Pregnant patients: as per GADA 2014 guidelines, down titrate ARBs safely prior to pursuing pregnancy, with use of -blockade during pregnancy. Show 6 more 6. Patient education https://web.pathway.md/diseases/recmGDOkoYocifkBu 3/5 6/29/23, 5:54 AM Loeys-Dietz syndrome Pathway General couseling: consider preconception genetic counseling regarding autosomal-dominant inheritance, variable expressivity, and genetic testing options including preimplantation or prenatal testing. 7. Preventative measures Endocarditis prophylaxis: consider subacute bacterial endocarditis prophylaxis in those with artificial valves undergoing dental or other procedures expected to contaminate the blood stream. 8. Follow-up and surveillance Serial imaging assessment: consider obtaining yearly echocardiography; more frequently depending on severity of aortic disease. Surveillance vascular magnetic resonance imaging: obtain yearly MRI from the cerebrovascular circulation to the pelvis in patients with LDS. B Indications for specialist referral: consult with cardiothoracic surgery when approaching surgical thresholds for aortic root dimension. Clinical findings Past medical history Family history Aortic aneurysm Autosomal dominant inheritance Arnold-chiari malformation Musculoskeletal exam Atrial septal defect Congenital heart disease Camptodactyly Criss-crossed pulmonary arteries Club foot Joint hypermobility Genetic abnormality Kyphosis Patent ductus arteriosus Pectus carinatum Translucency of the skin with velvety texture Scoliosis Ocular exam Strabismus References 1. MacCarrick G, Black JH rd, Bowdin S et al. Loeys-Dietz syndrome: a primer for diagnosis and management. Genet Med. 2014 Aug;16 8 576 87. Open https://web.pathway.md/diseases/recmGDOkoYocifkBu 4/5 6/29/23, 5:54 AM Loeys-Dietz syndrome Pathway 2. Eric M Isselbacher, Ourania Preventza, James Hamilton Black rd et al. 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. Circulation. 2022 Nov 2. Open 3. Hiratzka LF, Bakris GL, Beckman JA et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation. 2010 Apr 6;121 13):e266 369. Open 4. Bradley S Kane, Kamran Shamsa. Preventing a Catastrophe: Increasing Awareness of Loeys-Dietz Syndrome. Tex Heart Inst J. 2019 Feb 1;46 1 41 43. Open 5. Christine Van Hemelrijk, Marjolijn Renard, Bart Loeys. The Loeys-Dietz syndrome: an update for the clinician. Curr Opin Cardiol. 2010 Nov;25 6 546 51. Open 6. Gretchen MacCarrick, James H Black rd, Sarah Bowdin et al. Loeys-Dietz syndrome: a primer for diagnosis and management. Genet Med. 2014 Aug;16 8 576 87. Open 7. J J J Aalberts, M P van den Berg, J E H Bergman et al. The many faces of aggressive aortic pathology: Loeys-Dietz syndrome. Neth Heart J. 2008 Sep;16 9 299 304. Open https://web.pathway.md/diseases/recmGDOkoYocifkBu 5/5