Loeys-Dietz syndrome

Loeys-Dietz syndrome is a recently-discovered autosomal dominant genetic syndrome 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).^[1][2] It was identified and characterized by American physician Harry C. Dietz and Belgian physician Bart L. Loeys, for whom it is named.

Additional recommended knowledge

Essential Laboratory Skills Guide

How to ensure accurate weighing results every day?

What is the Correct Way to Check Repeatability in Balances?

Symptoms

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
• 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.

Treatment

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 vascular 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.

References

1. ^ 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.
2. ^ 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. PMID 17330129.

3. 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, Backer JD, Hellemans J, Chen Y, Davis EC, Webb CL, Kress W, Coucke P, Rifkin DB, De Paepe AM, Dietz HC. 2005. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat. Genet 37:275-281.