Marfan’s syndrome
and
related aortopathies
Shehla Mohammed
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)
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
Current provision of testing
•
Number of labs currently provide testing
*
*
*
*
FBN1
TGFBR1
TGFBR2
TAAD
• Testing criteria available for all except FBN1
UKGTN –RCP WORKSHOP
•
•
•
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•
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Clinical Geneticists
Cardiologists with specialist interest
Clinical Scientists
Genetics Counsellors
Patient support group
PHG foundation
•
External expert : Prof Bart Loeys
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 testing
appropriate, timely management
accommodate testing for panel approach?
•
•
Publish agreed pathways and TC
phg foundation report
RCP workshop : key mesages
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•
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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? “
Criteria :
Suspected diagnosis of Marfan syndrome
REVISED GHENT CRITERIA (Loeys 2010)
OR:
AND
Dilated Aortic root
Ectopia Lentis
AND
Dilated Aortic root
Systemic score > 7
AND
( See Box for score)
Purpose for knowing mutation in this individual
case must be one or more from list below… :
- affects aortic screening /clinical management
OR
OR
- allows prenatal testing
- 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
Tick if this
patient meets
criteria
REVISED GHENT CRITERIA (Loeys 2010)
Calculation of the Systemic Score
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
Calculation of Systemic score
Revised Ghent Criteria ( 2010)
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•
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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
Referrals
•
Consultant Cardiologists (Adult, Paediatric)
•
Clinical Geneticist
For suspected Marfan Syndrome ± Echo / MRI
Clinical assessment using revised Ghent criteria (2010)
Aortic root
dilation/
dissection
OR
Ectopia Lentis
OR
FH of MFS
OR
Systemic score
of ≥ 7
Fulfils
Criteria
Fibrillin 1
testing
If negative, refer to specialist
service for assessment
Other aortopathies to be
considered such as LDS, BAV,
AOS, TAAD etc.
If positive, continue standard
MFS care
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
Acknowledgements
• All workshop participants
• UKGTN project team
• Gurdeep Sagoo
• Mark Kroese
• Robin and Diane RUST