Loey's Dietz syndrome: Difference between revisions
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{{Infobox_Disease | | {{Infobox_Disease | | ||
Name = Loeys-Dietz syndrome | | Name = Loeys-Dietz syndrome | | ||
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{{CMG}} | {{CMG}} | ||
==Overview== | |||
'''Loeys-Dietz syndrome''' is a recently-discovered [[autosomal dominant]] genetic [[syndrome]] which has many features similar to [[Marfan syndrome]], but which is caused by [[mutation]]s in the genes encoding [[transforming growth factor]] beta receptor 1 (''[[TGFBR1]]'') or 2 (''[[TGFBR2]]'').<ref>{{cite journal |author=Loeys BL, Schwarze U, Holm T, ''et al'' |title=Aneurysm syndromes caused by mutations in the TGF-beta receptor |journal=N. Engl. J. Med. |volume=355 |issue=8 |pages=788–98 |year=2006 |pmid=16928994 |doi=10.1056/NEJMoa055695}}</ref><ref>{{cite journal |author=LeMaire SA, Pannu H, Tran-Fadulu V, Carter SA, Coselli JS, Milewicz DM |title=Severe aortic and arterial aneurysms associated with a TGFBR2 mutation |journal=Nature clinical practice. Cardiovascular medicine |volume=4 |issue=3 |pages=167–71 |year=2007 |pmid=17330129 |doi=10.1038/ncpcardio0797 |url=http://www.nature.com/ncpcardio/journal/v4/n3/full/ncpcardio0797.html |pmc=2561071}}</ref><ref name="pmid15731757">{{cite journal |author=Loeys BL, Chen J, Neptune ER, ''et al'' |title=A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2 |journal=Nat. Genet. |volume=37 |issue=3 |pages=275–81 |year=2005 |month=March |pmid=15731757 |doi=10.1038/ng1511}}</ref> | '''Loeys-Dietz syndrome''' is a recently-discovered [[autosomal dominant]] genetic [[syndrome]] which has many features similar to [[Marfan syndrome]], but which is caused by [[mutation]]s in the genes encoding [[transforming growth factor]] beta receptor 1 (''[[TGFBR1]]'') or 2 (''[[TGFBR2]]'').<ref>{{cite journal |author=Loeys BL, Schwarze U, Holm T, ''et al'' |title=Aneurysm syndromes caused by mutations in the TGF-beta receptor |journal=N. Engl. J. Med. |volume=355 |issue=8 |pages=788–98 |year=2006 |pmid=16928994 |doi=10.1056/NEJMoa055695}}</ref><ref>{{cite journal |author=LeMaire SA, Pannu H, Tran-Fadulu V, Carter SA, Coselli JS, Milewicz DM |title=Severe aortic and arterial aneurysms associated with a TGFBR2 mutation |journal=Nature clinical practice. Cardiovascular medicine |volume=4 |issue=3 |pages=167–71 |year=2007 |pmid=17330129 |doi=10.1038/ncpcardio0797 |url=http://www.nature.com/ncpcardio/journal/v4/n3/full/ncpcardio0797.html |pmc=2561071}}</ref><ref name="pmid15731757">{{cite journal |author=Loeys BL, Chen J, Neptune ER, ''et al'' |title=A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2 |journal=Nat. Genet. |volume=37 |issue=3 |pages=275–81 |year=2005 |month=March |pmid=15731757 |doi=10.1038/ng1511}}</ref> | ||
==Historical Perspective== | |||
It was identified and characterized by [[United States of America|American]] physician Harry C. Dietz and [[Belgium|Belgian]] physician Bart L. Loeys, for whom it is named. | It was identified and characterized by [[United States of America|American]] physician Harry C. Dietz and [[Belgium|Belgian]] physician Bart L. Loeys, for whom it is named. | ||
== | ==Classification== | ||
There are currently two forms of Loeys-Dietz syndrome which are further subdivided into another two forms | There are currently two forms of Loeys-Dietz syndrome which are further subdivided into another two forms as shown in the table below: | ||
{| class="wikitable" | {| class="wikitable" | ||
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|} | |} | ||
== | ==Pathophysiology== | ||
===Associated Conditions=== | |||
*[[Congenital heart disease]]s including [[patent ductus arteriosus]] (connection between the aorta and the lung circulation) and [[atrial septal defect]] (connection between heart chambers) | |||
*Abnormal junction of the brain and medulla ([[Arnold-Chiari malformation]]) | |||
*[[Bicuspid aortic valves]] | |||
==Differentiating Loey's Dietz Syndrome from other Disorders== | |||
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 [[bruise|bruising]] or abnormal [[scar]]s. | |||
==Diagnosis== | |||
===Physical Examination=== | |||
====General Appearance==== | |||
*[[Scoliosis]] | |||
====Skin==== | |||
*Translucency of the skin with velvety texture | |||
====Head==== | |||
*Widely spaced eyes (orbital [[hypertelorism]]) | *Widely spaced eyes (orbital [[hypertelorism]]) | ||
*[[Cleft palate]] or [[bifid uvula]] (a split in the tissue that hangs down in the back of the throat) | *[[Cleft palate]] or [[bifid uvula]] (a split in the tissue that hangs down in the back of the throat) | ||
====Cardiac==== | |||
*Indented or protruding chest wall ([[pectus excavatum]] or [[pectus carinatum]]) | |||
====Extremities==== | |||
*Contractures of fingers and toes ([[camptodactyly]]) | *Contractures of fingers and toes ([[camptodactyly]]) | ||
*Long fingers and lax joints | *Long fingers and lax joints | ||
| Line 55: | Line 69: | ||
*Premature fusion of the skull bones ([[craniosynostosis]]) | *Premature fusion of the skull bones ([[craniosynostosis]]) | ||
*Joint hypermobility | *Joint hypermobility | ||
===Imaging Findings=== | |||
Aortic and arterial aneurysms/dissections with [[tortuosity]] (corkscrew structure) of the arteries. | |||
==Treatment== | ==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]]. | 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]]. | ||
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==References== | ==References== | ||
{{ | {{Reflist|2}} | ||
==External links== | ==External links== | ||
Revision as of 21:38, 21 October 2012
| Loeys-Dietz syndrome | |
| OMIM | below See below |
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| DiseasesDB | 34032 |
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Aortic aneurysm Microchapters |
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Diagnosis |
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Treatment |
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Loey's Dietz syndrome On the Web |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
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][3]
Historical Perspective
It was identified and characterized by American physician Harry C. Dietz and Belgian physician Bart L. Loeys, for whom it is named.
Classification
There are currently two forms of Loeys-Dietz syndrome which are further subdivided into another two forms as shown in the table below:
| 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 |
Pathophysiology
Associated Conditions
- Congenital heart diseases including patent ductus arteriosus (connection between the aorta and the lung circulation) and atrial septal defect (connection between heart chambers)
- Abnormal junction of the brain and medulla (Arnold-Chiari malformation)
- Bicuspid aortic valves
Differentiating Loey's Dietz Syndrome from other Disorders
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.
Diagnosis
Physical Examination
General Appearance
Skin
- Translucency of the skin with velvety texture
Head
- Widely spaced eyes (orbital hypertelorism)
- Cleft palate or bifid uvula (a split in the tissue that hangs down in the back of the throat)
Cardiac
- Indented or protruding chest wall (pectus excavatum or pectus carinatum)
Extremities
- Contractures of fingers and toes (camptodactyly)
- Long fingers and lax joints
- Club foot
- Premature fusion of the skull bones (craniosynostosis)
- Joint hypermobility
Imaging Findings
Aortic and arterial aneurysms/dissections with tortuosity (corkscrew structure) of the arteries.
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.
See also
References
- ↑ 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. (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. Unknown parameter
|month=ignored (help)
External links
- 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
Template:Receptor deficiencies id:Sindrom Loeys-Dietz