Loeys-Dietz syndrome: Difference between revisions

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==Overview==
==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]]''). It is characterized by numerous site of aneurysms in the aorta (outpouchings in the weakened areas) in children <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}}</ref>. These aneurysms are more prone to rupture at a smaller diameter, putting the children at risk for major internal bleeding or dying if they are not detected and treated in a timely manner.
'''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]]''). It is characterized by numerous site of aneurysms in the aorta (outpouchings in the weakened areas) in children <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}}</ref><ref>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.</ref>. These aneurysms are more prone to rupture at a smaller diameter, putting the children at risk for major internal bleeding or dying if they are not detected and treated in a timely manner.


==Historical Perspective==
==Historical Perspective==
Line 29: Line 28:
* LDS type I - Presence of craniofacial involvement
* LDS type I - Presence of craniofacial involvement
* LDS type II - Absence of craniofacial involvement
* LDS type II - Absence of craniofacial involvement
==Pathophysiology==
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
*[[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==
==Diagnosis==
Line 39: Line 44:


===Physical Examination===
===Physical Examination===
====Skin====
*Translucency of the skin with velvety texture
====Bones and Joints====
====Bones and Joints====
*[[Scoliosis]]
*[[Scoliosis]]
Line 47: Line 55:
*Premature fusion of the skull bones ([[craniosynostosis]])
*Premature fusion of the skull bones ([[craniosynostosis]])
*Joint hypermobility
*Joint hypermobility
====Skin====
*Translucency of the skin with velvety texture
====Neurological examination====
*Abnormal junction of the brain and medulla ([[Arnold-Chiari malformation]])


====Heart====
====Heart====
*Murmurs:
*Murmurs:
**Systolic ejection murmur: Bicuspid Aortic valves
**Systolic ejection murmur: [[Bicuspid Aortic valve]]s
**Machinery murmur: Congenital heart problems including [[patent ductus arteriosus]] (connection between the aorta and the lung circulation)
**Machinery murmur: Congenital heart problems including [[patent ductus arteriosus]] (connection between the aorta and the lung circulation)
**Early or mid-diastolic murmur: [[atrial septal defect]] (connection between heart chambers)
**Early or mid-diastolic murmur: [[atrial septal defect]] (connection between heart's atrial chambers)


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:
====Neurological examination====
*Abnormally long limbs and fingers
*Abnormal junction of the brain and medulla ([[Arnold-Chiari malformation]])
*[[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.


==Treatment==
==Treatment==
Line 70: Line 70:


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 Loeys-Dietz patients.
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 Loeys-Dietz patients.
==2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guideline Recommendations: Evaluation and Management of Acute Thoracic Aortic Disease (DO NOT EDIT)<ref name="pmid20233780">{{cite journal |author=Hiratzka LF, Bakris GL, Beckman JA, ''et al.'' |title=2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine |journal=[[Circulation]] |volume=121 |issue=13 |pages=e266–369 |year=2010 |month=April |pmid=20233780 |doi=10.1161/CIR.0b013e3181d4739e |url=}}</ref>==
===Aortic Imaging in Genetic Syndromes (DO NOT EDIT)<ref name="pmid20233780">{{cite journal |author=Hiratzka LF, Bakris GL, Beckman JA, ''et al.'' |title=2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine |journal=[[Circulation]] |volume=121 |issue=13 |pages=e266–369 |year=2010 |month=April |pmid=20233780 |doi=10.1161/CIR.0b013e3181d4739e |url=}}</ref>===
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Patients with [[Loeys-Dietz syndrome]] or a confirmed genetic [[mutation]] known to predispose to [[aortic aneurysm]]s and [[aortic dissection]]s ([[TGFBR1]], [[TGFBR2]], [[FBN1]], [[ACTA2]], or [[MYH11]]) should undergo complete aortic imaging at initial diagnosis and 6 months thereafter to establish if enlargement is occurring<ref name="pmid18695204">{{cite journal |author=Pearson GD, Devereux R, Loeys B, ''et al.'' |title=Report of the National Heart, Lung, and Blood Institute and National Marfan Foundation Working Group on research in Marfan syndrome and related disorders |journal=Circulation |volume=118 |issue=7 |pages=785–91 |year=2008 |month=August |pmid=18695204 |pmc=2909440 |doi=10.1161/CIRCULATIONAHA.108.783753 |url=}}</ref><ref name="pmid2766531">{{cite journal |author=Svensson LG, Crawford ES, Coselli JS, Safi HJ, Hess KR |title=Impact of cardiovascular operation on survival in the Marfan patient |journal=Circulation |volume=80 |issue=3 Pt 1 |pages=I233–42 |year=1989 |month=September |pmid=2766531 |doi= |url=}}</ref><ref name="pmid17307461">{{cite journal |author=Svensson LG, Blackstone EH, Feng J, ''et al.'' |title=Are Marfan syndrome and marfanoid patients distinguishable on long-term follow-up? |journal=Ann. Thorac. Surg. |volume=83 |issue=3 |pages=1067–74 |year=2007 |month=March |pmid=17307461 |doi=10.1016/j.athoracsur.2006.10.062 |url=}}</ref><ref name="pmid16444274">{{cite journal |author=Zhu L, Vranckx R, Khau Van Kien P, ''et al.'' |title=Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus |journal=Nat. Genet. |volume=38 |issue=3 |pages=343–9 |year=2006 |month=March |pmid=16444274 |doi=10.1038/ng1721 |url=}}</ref>. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Patients with [[Loeys-Dietz syndrome]] should have yearly [[magnetic resonance imaging]] from the cerebrovascular circulation to the pelvis<ref name="pmid17330129">{{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=Nat Clin Pract Cardiovasc Med |volume=4 |issue=3 |pages=167–71 |year=2007 |month=March |pmid=17330129 |pmc=2561071 |doi=10.1038/ncpcardio0797 |url=}}</ref><ref name="pmid16928994">{{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 |month=August |pmid=16928994 |doi=10.1056/NEJMoa055695 |url=}}</ref><ref name="pmid17257922">{{cite journal |author=Williams JA, Loeys BL, Nwakanma LU, ''et al.'' |title=Early surgical experience with Loeys-Dietz: a new syndrome of aggressive thoracic aortic aneurysm disease |journal=Ann. Thorac. Surg. |volume=83 |issue=2 |pages=S757–63; discussion S785–90 |year=2007 |month=February |pmid=17257922 |doi=10.1016/j.athoracsur.2006.10.091 |url=}}</ref>. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
===Genetic Syndromes of Familial Thoracic Aortic Aneurysms and Dissections (DO NOT EDIT) <ref name="pmid20233780">{{cite journal| author=Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE et al.| title=2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. | journal=Circulation | year= 2010 | volume= 121 | issue= 13 | pages= e266-369 | pmid=20233780 | doi=10.1161/CIR.0b013e3181d4739e | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20233780  }} </ref>===
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' If the [[mutant gene]] ([[FBN1]], [[TGFBR1]], [[TGFBR2]], [[COL3A1]], [[ACTA2]], [[MYH11]]) associated with [[aortic aneurysm]] and/or [[aortic dissection|dissection]] is identified in a patient, first-degree relatives should undergo counseling and testing. Then, only the relatives with the genetic mutation should undergo aortic imaging. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Sequencing of the [[ACTA2]] gene is reasonable in patients with a family history of thoracic aortic aneurysms and/or dissections to determine if ACTA2 mutations are responsible for the inherited predisposition<ref name="pmid16027248">{{cite journal |author=Pannu H, Fadulu VT, Chang J, ''et al.'' |title=Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections |journal=Circulation |volume=112 |issue=4 |pages=513–20 |year=2005 |month=July |pmid=16027248 |doi=10.1161/CIRCULATIONAHA.105.537340 |url=}}</ref><ref name="pmid17994018">{{cite journal |author=Guo DC, Pannu H, Tran-Fadulu V, ''et al.'' |title=Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections |journal=Nat. Genet. |volume=39 |issue=12 |pages=1488–93 |year=2007 |month=December |pmid=17994018 |doi=10.1038/ng.2007.6 |url=}}</ref><ref name="pmid16444274">{{cite journal |author=Zhu L, Vranckx R, Khau Van Kien P, ''et al.'' |title=Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus |journal=Nat. Genet. |volume=38 |issue=3 |pages=343–9 |year=2006 |month=March |pmid=16444274 |doi=10.1038/ng1721 |url=}}</ref><ref name="pmid16928994">{{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 |month=August |pmid=16928994 |doi=10.1056/NEJMoa055695 |url=}}</ref><ref name="pmid18781618">{{cite journal |author=Stheneur C, Collod-Béroud G, Faivre L, ''et al.'' |title=Identification of 23 TGFBR2 and 6 TGFBR1 gene mutations and genotype-phenotype investigations in 457 patients with Marfan syndrome type I and II, Loeys-Dietz syndrome and related disorders |journal=Hum. Mutat. |volume=29 |issue=11 |pages=E284–95 |year=2008 |month=November |pmid=18781618 |doi=10.1002/humu.20871 |url=}}</ref><ref name="pmid19409525">{{cite journal |author=Guo DC, Papke CL, Tran-Fadulu V, ''et al.'' |title=Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease |journal=Am. J. Hum. Genet. |volume=84 |issue=5 |pages=617–27 |year=2009 |month=May |pmid=19409525 |pmc=2680995 |doi=10.1016/j.ajhg.2009.04.007 |url=}}</ref>. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Sequencing of other genes known to cause familial thoracic aortic aneurysms and/or dissection ([[TGFBR1]], [[TGFBR2]], [[MYH11]]) may be considered in patients with a family history and clinical features associated with mutations in these genes. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
'''Treatment Guideline:'''
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' It is reasonable to consider surgical repair of the aorta in all adult patients with [[Loeys-Dietz syndrome]] or a confirmed [[TGFBR1]] or [[TGFBR2]] mutation and an aortic diameter of 4.2 cm or greater by transesophageal echocardiogram (internal diameter) or 4.4 to 4.6 cm or greater by computed tomographic imaging and/or magnetic resonance imaging (external diameter)<ref name="pmid16928994">{{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 |month=August |pmid=16928994 |doi=10.1056/NEJMoa055695 |url=}}</ref>. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence:C]])''<nowiki>"</nowiki>
|}


==References==
==References==
{{reflist|2}}
{{reflist|2}}
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.
 


[[Category:Cardiology]]
[[Category:Cardiology]]

Latest revision as of 17:43, 5 November 2012

Loeys-Dietz syndrome
OMIM 609192
DiseasesDB 34032

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]

Synonyms and keywords: Furlong's syndrome

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). It is characterized by numerous site of aneurysms in the aorta (outpouchings in the weakened areas) in children [1][2][3]. These aneurysms are more prone to rupture at a smaller diameter, putting the children at risk for major internal bleeding or dying if they are not detected and treated in a timely manner.

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

  • LDS type I - Presence of craniofacial involvement
  • LDS type II - Absence of craniofacial involvement

Pathophysiology

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
  • 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

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.

Physical Examination

Skin

  • Translucency of the skin with velvety texture

Bones and Joints

Heart

Neurological examination

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 Loeys-Dietz patients.

2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guideline Recommendations: Evaluation and Management of Acute Thoracic Aortic Disease (DO NOT EDIT)[4]

Aortic Imaging in Genetic Syndromes (DO NOT EDIT)[4]

Class I
"1. Patients with Loeys-Dietz syndrome or a confirmed genetic mutation known to predispose to aortic aneurysms and aortic dissections (TGFBR1, TGFBR2, FBN1, ACTA2, or MYH11) should undergo complete aortic imaging at initial diagnosis and 6 months thereafter to establish if enlargement is occurring[5][6][7][8]. (Level of Evidence: C)"
"2. Patients with Loeys-Dietz syndrome should have yearly magnetic resonance imaging from the cerebrovascular circulation to the pelvis[9][10][11]. (Level of Evidence: B)"

Genetic Syndromes of Familial Thoracic Aortic Aneurysms and Dissections (DO NOT EDIT) [4]

Class I
"1. If the mutant gene (FBN1, TGFBR1, TGFBR2, COL3A1, ACTA2, MYH11) associated with aortic aneurysm and/or dissection is identified in a patient, first-degree relatives should undergo counseling and testing. Then, only the relatives with the genetic mutation should undergo aortic imaging. (Level of Evidence: C)"
Class IIa
"1. Sequencing of the ACTA2 gene is reasonable in patients with a family history of thoracic aortic aneurysms and/or dissections to determine if ACTA2 mutations are responsible for the inherited predisposition[12][13][8][10][14][15]. (Level of Evidence: B)"
Class IIb
"1. Sequencing of other genes known to cause familial thoracic aortic aneurysms and/or dissection (TGFBR1, TGFBR2, MYH11) may be considered in patients with a family history and clinical features associated with mutations in these genes. (Level of Evidence: B)"

Treatment Guideline:

Class IIa
"1. It is reasonable to consider surgical repair of the aorta in all adult patients with Loeys-Dietz syndrome or a confirmed TGFBR1 or TGFBR2 mutation and an aortic diameter of 4.2 cm or greater by transesophageal echocardiogram (internal diameter) or 4.4 to 4.6 cm or greater by computed tomographic imaging and/or magnetic resonance imaging (external diameter)[10]. (Level of Evidence:C)"

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.
  4. ↑ 4.0 4.1 4.2 Hiratzka LF, Bakris GL, Beckman JA; et al. (2010). "2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine". Circulation. 121 (13): e266–369. doi:10.1161/CIR.0b013e3181d4739e. PMID 20233780. Unknown parameter |month= ignored (help)
  5. ↑ Pearson GD, Devereux R, Loeys B; et al. (2008). "Report of the National Heart, Lung, and Blood Institute and National Marfan Foundation Working Group on research in Marfan syndrome and related disorders". Circulation. 118 (7): 785–91. doi:10.1161/CIRCULATIONAHA.108.783753. PMC 2909440. PMID 18695204. Unknown parameter |month= ignored (help)
  6. ↑ Svensson LG, Crawford ES, Coselli JS, Safi HJ, Hess KR (1989). "Impact of cardiovascular operation on survival in the Marfan patient". Circulation. 80 (3 Pt 1): I233–42. PMID 2766531. Unknown parameter |month= ignored (help)
  7. ↑ Svensson LG, Blackstone EH, Feng J; et al. (2007). "Are Marfan syndrome and marfanoid patients distinguishable on long-term follow-up?". Ann. Thorac. Surg. 83 (3): 1067–74. doi:10.1016/j.athoracsur.2006.10.062. PMID 17307461. Unknown parameter |month= ignored (help)
  8. ↑ 8.0 8.1 Zhu L, Vranckx R, Khau Van Kien P; et al. (2006). "Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus". Nat. Genet. 38 (3): 343–9. doi:10.1038/ng1721. PMID 16444274. Unknown parameter |month= ignored (help)
  9. ↑ LeMaire SA, Pannu H, Tran-Fadulu V, Carter SA, Coselli JS, Milewicz DM (2007). "Severe aortic and arterial aneurysms associated with a TGFBR2 mutation". Nat Clin Pract Cardiovasc Med. 4 (3): 167–71. doi:10.1038/ncpcardio0797. PMC 2561071. PMID 17330129. Unknown parameter |month= ignored (help)
  10. ↑ 10.0 10.1 10.2 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. Unknown parameter |month= ignored (help)
  11. ↑ Williams JA, Loeys BL, Nwakanma LU; et al. (2007). "Early surgical experience with Loeys-Dietz: a new syndrome of aggressive thoracic aortic aneurysm disease". Ann. Thorac. Surg. 83 (2): S757–63, discussion S785–90. doi:10.1016/j.athoracsur.2006.10.091. PMID 17257922. Unknown parameter |month= ignored (help)
  12. ↑ Pannu H, Fadulu VT, Chang J; et al. (2005). "Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections". Circulation. 112 (4): 513–20. doi:10.1161/CIRCULATIONAHA.105.537340. PMID 16027248. Unknown parameter |month= ignored (help)
  13. ↑ Guo DC, Pannu H, Tran-Fadulu V; et al. (2007). "Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections". Nat. Genet. 39 (12): 1488–93. doi:10.1038/ng.2007.6. PMID 17994018. Unknown parameter |month= ignored (help)
  14. ↑ Stheneur C, Collod-Béroud G, Faivre L; et al. (2008). "Identification of 23 TGFBR2 and 6 TGFBR1 gene mutations and genotype-phenotype investigations in 457 patients with Marfan syndrome type I and II, Loeys-Dietz syndrome and related disorders". Hum. Mutat. 29 (11): E284–95. doi:10.1002/humu.20871. PMID 18781618. Unknown parameter |month= ignored (help)
  15. ↑ Guo DC, Papke CL, Tran-Fadulu V; et al. (2009). "Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease". Am. J. Hum. Genet. 84 (5): 617–27. doi:10.1016/j.ajhg.2009.04.007. PMC 2680995. PMID 19409525. Unknown parameter |month= ignored (help)

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