|Classification and external resources|
|OMIM||609192 610168 608967 610380|
Loeys–Dietz syndrome is a autosomal dominant genetic syndrome discovered in 2005 which has many features similar to Marfan syndrome, but which is caused by mutations in the genes encoding transforming growth factor beta receptor 1 (TGFBR1) or 2 (TGFBR2).
There are currently two forms of Loeys–Dietz syndrome which are further subdivided into another two forms. The table below will better summarize this:
|1A||TGFBR1||9q22||609192||Also known as Furlong disease|
|2B||TGFBR2||3p22||610380||Previously known as Marfan syndrome type 2|
|3||SMAD3||613795||Also known as Aneurysms-osteoarthritis syndrome|
A de novo mutation in TGFB3, a ligand of the TGF ß pathway, was identified in an individual with a syndrome presenting partially overlapping symptoms with Marfan Syndrome and Loeys-Dietz Syndrome.
The main clinical characteristics include:
- Widely spaced eyes (orbital hypertelorism)
- Cleft palate or bifid uvula (a split in the tissue that hangs down in the back of the throat)
- Aortic and arterial aneurysms/dissections with tortuosity (corkscrew structure) of the arteries.
Other findings can include:
- Scoliosis or Kyphosis
- Indented or protruding chest wall (pectus excavatum or pectus carinatum)
- Contractures of fingers and toes (camptodactyly)
- Long fingers and lax joints
- Club foot
- Premature fusion of the skull bones (craniosynostosis)
- Joint hypermobility
- Congenital heart problems including patent ductus arteriosus (connection between the aorta and the lung circulation) and atrial septal defect (connection between heart chambers)
- Translucency of the skin with velvety texture
- Abnormal junction of the brain and medulla (Arnold-Chiari malformation)
- Bicuspid aortic valves
Many of the physical findings typical in Loeys–Dietz syndrome are also found in Marfan syndrome cases, including increased risk of ascending aortic aneurysm and aortic dissection, abnormally long limbs and fingers, and dural ectasia (a gradual stretching and weakening of the dura mater that can cause abdominal and leg pain). However, it also has some additional traits not typical of Marfan patients, including widely spaced eyes, a split uvula in the back of the throat, and skin findings such as easy bruising or abnormal scars.
As there is no known cure, Loeys–Dietz syndrome is a lifelong condition. Due to the high risk of death from aortic aneurysm rupture, patients should be followed closely to monitor aneurysm formation, which can then be corrected with interventional radiology orvascular surgery.
Previous research in laboratory mice has suggested that the angiotensin II receptor antagonist losartan, which appears to block TGF-beta activity, can slow or halt the formation of aortic aneurysms in Marfan syndrome. A large clinical trial sponsored by the National Institutes of Health is currently underway to explore the use of losartan to prevent aneurysms in Marfan syndrome patients. Both Marfan syndrome and Loeys–Dietz syndrome are associated with increased TGF-beta signaling in the vessel wall. Therefore, losartan also holds promise for the treatment of Loeys–Dietz syndrome.
- Loeys BL, Schwarze U, Holm T, et al (2006). "Aneurysm syndromes caused by mutations in the TGF-beta receptor". N. Engl. J. Med. 355 (8): 788–98. doi:10.1056/NEJMoa055695. PMID 16928994.
- LeMaire SA, Pannu H, Tran-Fadulu V, Carter SA, Coselli JS, Milewicz DM (2007). "Severe aortic and arterial aneurysms associated with a TGFBR2 mutation". Nature clinical practice. Cardiovascular medicine 4 (3): 167–71. doi:10.1038/ncpcardio0797. PMC 2561071. PMID 17330129.
- Loeys BL, Chen J, Neptune ER, et al (March 2005). "A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2". Nat. Genet. 37 (3): 275–81. doi:10.1038/ng1511. PMID 15731757.
- Rienhoff HY, Yeo C-Y, Morissette R, Khrebtukova I, Melnick J, Luo S, Leng N, Kim Y-J, Schroth G, Westwick J, Vogel H, McDonnell N, Hall JG, Whitman M. 2013. A mutation in TGFB3 associated with a syndrome of low muscle mass, growth retardation, distal arthrogryposis, and clinical features overlapping with Marfan and Loeys–Dietz syndrome. Am J Med Genet Part A. 161A:2040–2046.
- Loeys-Dietz Syndrome Foundation
- orphan.net LDS-Syndrome
- GeneReview/NIH/UW entry on Loeys-Dietz Syndrome
- Loeys-Dietz Syndrome Canada
- Cleft Lip and Palate Foundation of Smiles