Loeys–Dietz syndrome
Loeys–Dietz syndrome | |
---|---|
Other names | Aortic aneurysm syndrome due to TGF-beta receptors anomalies |
This condition is inherited in an autosomal dominant manner[1] | |
Pronunciation | |
Specialty | Cardiology, rheumatology, medical genetics |
Loeys–Dietz syndrome (LDS) is an
There are five types of the syndrome, labelled types I through V, which are distinguished by their genetic cause. Type 1, Type 2, Type 3, Type 4 and Type 5 are caused by
Loeys–Dietz syndrome was identified and characterized by pediatric geneticists Bart Loeys and Harry "Hal" Dietz at Johns Hopkins University in 2005.
Signs and symptoms
There is considerable variability in the phenotype of Loeys–Dietz syndrome, from mild features to severe systemic abnormalities. The primary manifestations of Loeys–Dietz syndrome are arterial tortuosity (winding course of blood vessels), widely spaced eyes (
There is overlap in the manifestations of Loeys–Dietz and Marfan syndromes, 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). Findings of hypertelorism (widely spaced eyes), bifid or split uvula, and skin findings such as easy bruising or abnormal scars may distinguish Loeys–Dietz from Marfan syndrome.[citation needed]
Affected individuals often develop immune system related problems such as allergies to food, asthma, hay fever, and inflammatory disorders such as eczema or inflammatory bowel disease.[citation needed]
Findings of Loeys–Dietz syndrome may include:[citation needed]
- Skeletal/spinal malformations: craniosynostosis, Scoliosis, spinal instability and spondylolisthesis, Kyphosis
- Sternal abnormalities: pectus excavatum, pectus carinatum
- Contractures of fingers and toes (camptodactyly)
- Long fingers and lax joints
- Weakened or missing eye muscles (strabismus)
- 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
- Criss-crossed pulmonary arteries
Cause
Types (old nomenclature)
Several genetic causes of Loeys–Dietz syndrome have been identified. A de novo mutation in
Type | Gene | Locus | OMIM |
Description |
1A | TGFBR1 |
9q22 | 609192 | Also known as Furlong disease |
1B | TGFBR2 |
3p22 | 610168 | |
2A | TGFBR1 | 9q22 | 608967 | |
2B | TGFBR2 | 3p22 | 610380 | Previously known as Marfan syndrome type 2 |
3 | SMAD3 |
15q22.33 | 613795 | Also known as Aneurysms-osteoarthritis syndrome |
4 | TGFB2 |
1q41 | 614816 | |
5 | TGFB3 |
14q24.3 | 615582 | |
6 | SMAD2 | 18q21.1 | 619656 |
Diagnosis
Diagnosis involves consideration of physical features and genetic testing. Presence of split uvula is a differentiating characteristic from Marfan Syndrome, as well as the severity of the heart defects. Loeys–Dietz Syndrome patients have more severe heart involvement and it is advised that they be treated for enlarged aorta earlier due to the increased risk of early rupture in Loeys–Dietz patients. Because different people express different combinations of symptoms and the syndrome was first identified in 2005, many doctors may not be aware of its existence.[citation needed]
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
If an increased heart rate is present, a cardioselective beta-1 blocker, with or without losartan, is sometimes prescribed to reduce the heart rate to prevent any extra pressure on the tissue of the aorta. Likewise, strenuous physical activity is discouraged in patients, especially weight lifting and contact sports.[9]
Epidemiology
The incidence of Loeys–Dietz syndrome is unknown; however, Type 1 and 2 appear to be the most common.[6]
References
- ^ "Loeys Dietz syndrome". Orphanet. Archived from the original on 30 July 2017. Retrieved 27 July 2017.
- ^ "Research and Treatment | Loeys-Dietz Syndrome". Johns Hopkins Medicine. 10 August 2018. Archived from the original on 2021-12-19. Retrieved 8 November 2020.
- PMID 16928994.
- PMID 17330129.
- S2CID 24499542.
- ^ NLMGenetics Home Reference
- ^ "Loeys-Dietz Syndrome". The Marfan Foundation. 27 June 2013.
- ^ 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.
- PMID 20301312.
Further reading
- Bertoli-Avella, A. M; Gillis, E; Morisaki, H; Verhagen, J. M. A; De Graaf, B. M; Van De Beek, G; Gallo, E; Kruithof, B. P. T; Venselaar, H; Myers, L. A; Laga, S; Doyle, A. J; Oswald, G; Van Cappellen, G. W. A; Yamanaka, I; Van Der Helm, R. M; Beverloo, B; De Klein, A; Pardo, L; Lammens, M; Evers, C; Devriendt, K; Dumoulein, M; Timmermans, J; Bruggenwirth, H. T; Verheijen, F; Rodrigus, I; Baynam, G; Kempers, M; et al. (2015). "Mutations in a TGF-β ligand, TGFB3, cause syndromic aortic aneurysms and dissections". Journal of the American College of Cardiology. 65 (13): 1324–1336. PMID 25835445.