Definition
Autosomal dominant connective tissue disorder of TGF-beta signalling causing aggressive arterial aneurysm and dissection with craniofacial and skeletal features.
Classification
- Type 1, TGFBR1
- Type 2, TGFBR2
- Type 3, SMAD3, also called aneurysm osteoarthritis syndrome
- Type 4, TGFB2
- Type 5, TGFB3
Clinical Features
- Triad of arterial tortuosity, hypertelorism and bifid uvula or cleft palate
- Aortic dissection at smaller diameters and younger ages than Marfan syndrome
- Aneurysms throughout the arterial tree, including head and neck vessels
- Craniosynostosis, malar hypoplasia, retrognathia and blue sclerae
- Skeletal overlap with Marfan syndrome
- Pectus deformity
- Scoliosis
- Joint laxity and arachnodactyly
- Pes planus
- Dural ectasia
- Features favouring Loeys-Dietz over Marfan syndrome
- No ectopia lentis
- Cervical spine instability
- Clubfoot
- Early onset osteoarthritis in SMAD3 disease
- Translucent skin, easy bruising and wide scars
- Osteoporosis and fragility fractures
Investigations
- Heritable thoracic aortic disease gene panel
- Echocardiography at diagnosis and during follow up
- Head to pelvis MR or CT angiography at diagnosis
- Flexion and extension cervical spine radiographs to detect instability
Differential Diagnosis
- Marfan syndrome
- Vascular Ehlers-Danlos syndrome
- Shprintzen-Goldberg syndrome
- Arterial tortuosity syndrome
Management
- Blood pressure control. Beta blocker or angiotensin receptor blocker to slow aortic growth
- Early aortic surgery. Lower root diameter thresholds than Marfan syndrome, guided by subtype and family history
- Cervical fusion. Symptomatic or progressive cervical instability
- Scoliosis surgery. Planned for dural ectasia, pseudarthrosis and vascular fragility, see scoliosis in Marfan syndrome
- Foot surgery. Clubfoot and symptomatic pes planus
- Vascular imaging before major surgery. Arterial fragility and aneurysms raise operative risk
References
- Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, Xu FL, Myers LA, Spevak PJ, Cameron DE, De Backer J, Hellemans J, Chen Y, Davis EC, Webb CL, Kress W, Coucke P, Rifkin DB, De Paepe AM, Dietz HC. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 2005, 37(3), 275-81. PubMed
- MacCarrick G, Black JH, Bowdin S, El-Hamamsy I, Frischmeyer-Guerrerio PA, Guerrerio AL, Sponseller PD, Loeys B, Dietz HC. Loeys-Dietz syndrome. A primer for diagnosis and management. Genet Med. 2014, 16(8), 576-87. PubMed
- Meester JAN, Verstraeten A, Schepers D, Alaerts M, Van Laer L, Loeys BL. Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Ann Cardiothorac Surg. 2017, 6(6), 582-94. PubMed
Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 19 October 2026.