Marfan’s syndrome and related aortopathies
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Transcript of Marfan’s syndrome and related aortopathies
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Marfan’s syndrome and
related aortopathies
Shehla Mohammed
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Marfan’s syndrome
• Common multisystem connective tissue disorder
• 1 in 5000
• Altered body proportions risk of aortic dissection and
rupture risk of eye problems (lens
dislocation and retinal detachment)
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Marfan’s syndrome and related aortopathies
• Common multisystem connective tissue disorder
• 1 in 5000
• Altered body proportions• risk of aortic dissection and rupture
• risk of eye problems (ectopia lentis and retinal detachment)
• Mutations in Fibrillin 1 gene (FBN1)
• Variable clinical expression
• Several conditions with overlapping clinical manifestations
MULTIPLE GENES INVOVED
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Current provision of testing
• Number of labs currently provide testing
* FBN1 * TGFBR1 * TGFBR2 * TAAD
•Testing criteria available for all except FBN1
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UKGTN –RCP WORKSHOP
• Clinical Geneticists• Cardiologists with specialist interest• Clinical Scientists• Genetics Counsellors• Patient support group• PHG foundation
• External expert : Prof Bart Loeys
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Aims of workshop – RCP Sept 2012
• Consensus TC for MFS revisions to draft testing criteria?
incorporate revised Ghent criteria (2010)
• Draw up combined clinical and testing pathways to:
facilitate and optimise targeted testingappropriate, timely managementaccommodate testing for panel approach?
• Publish agreed pathways and TC• phg foundation report
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• Aortic aneurysms a major health issue• Incidence of aortopathies 10.4/ 100,000• Early identification critical for prophylactic
surgery to improve health outcomes• Communication, role of GP, early referral• Bart Loeys:
“ Does identification of FBN1 mutation equate to a diagnosis of Marfans? “
RCP workshop : key mesages
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Criteria : Suspected diagnosis of Marfan syndrome REVISED GHENT CRITERIA (Loeys 2010)
Tick if this patient meets criteria
Dilated Aortic root AND Ectopia Lentis
OR: Dilated Aortic root AND Systemic score > 7 ( See Box for score)
AND Purpose for knowing mutation in this individual case must be one or more from list below… :
- affects aortic screening /clinical management
OR - allows prenatal testing
OR - enables cascade family testing
OR - avoids other investigation or seeking other clinical opinions for index case or relatives
OR - enables targeting clinical screening in relatives
OR - provides knowledge of genetic risk
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Feature Value
Wrist AND thumb sign 3
Wrist OR thumb sign 1
Pectus carinatum deformity 2
Pectus excavatum or chest asymmetry 1
Hindfoot deformity 2
Plain flat foot (pes planus) 1
Pneumothorax 2
Dural ectasia 2
Protrusio acetabulae 2
Reduced upper segment / lower segment AND increased arm span/height ratios 1
Scoliosis or thoracolumbar kyphosis 1
Reduced elbow extension 1
3 of 5 facial features 1
Skin striae 1
Myopia 1
Mitral valve prolapse 1
Loeys BL et al. The revised Ghent nosology for the Marfan syndrome Journal of Medical Genetics 2010; 47: 476-485
REVISED GHENT CRITERIA (Loeys 2010)Calculation of the Systemic Score
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• Score > 7 indicates systemic involvement• Aortic root enlargement:
Z- score > 2 : > 20yrs
Z- score > 3 : < 20 yrs• Aortic size standardised to age and body size for accurate interpretation
Z score > 2.0 above 95th percentile
> 3.0 above 99th percentile
Calculation of Systemic scoreRevised Ghent Criteria ( 2010)
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• Consultant Cardiologists (Adult, Paediatric)
• Clinical Geneticist
Referrals
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For suspected Marfan Syndrome ± Echo / MRI
Clinical assessment using revised Ghent criteria (2010)
Aortic root dilation/
dissection
Ectopia Lentis FH of MFS Systemic scoreof ≥ 7
OR OR OR
FulfilsCriteria
Fibrillin 1 testing
If negative, refer to specialist service for assessment
If positive, continue standard MFS care
Other aortopathies to be considered such as LDS, BAV,
AOS, TAAD etc.
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Recommendations
Consideration by UKGTN for approval and implementation :
Testing Criteria for Marfan’s syndrome Clinical Diagnostic pathway
Panel test for “aortopathies” : encouragement for an NHS lab to develop
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Acknowledgements• All workshop participants• UKGTN project team
• Gurdeep Sagoo• Mark Kroese
• Robin and Diane RUST