Marfan

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Marfans syndrome and related aortopathies

• Shehla Mohammed

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Marfans 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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Marfans 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 testing
• appropriate, timely management
• accommodate testing for panel approach?
• Publish agreed pathways and TC
• phg foundation report

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RCP workshop key mesages

• 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?

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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 gt 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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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      
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Calculation of Systemic scoreRevised Ghent
Criteria ( 2010)

• Score gt 7 indicates systemic involvement
• Aortic root enlargement
• Z- score gt 2 gt 20yrs
• Z- score gt 3 lt 20 yrs
• Aortic size standardised to age and body size
  for accurate interpretation
• Z score gt 2.0 above 95th percentile
• gt 3.0 above 99th percentile
  

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Referrals

• Consultant Cardiologists (Adult, Paediatric)
• Clinical Geneticist

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For suspected Marfan Syndrome Echo / MRI
Clinical assessment using revised Ghent criteria
(2010)
Fulfils Criteria
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 Marfans 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