Marfan’s syndrome and related aortopathies

1. Marfan’s syndrome and related aortopathies Shehla Mohammed

2. 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)

3. 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 (ectopialentis and retinal detachment) • Mutations in Fibrillin 1 gene (FBN1) • Variable clinical expression • Several conditions with overlapping clinical manifestations MULTIPLE GENES INVOVED

4. Number of labs currently provide testing * FBN1 * TGFBR1 * TGFBR2 * TAAD Testing criteria available for all except FBN1 Current provision of testing

5. Clinical Geneticists Cardiologists with specialist interest Clinical Scientists Genetics Counsellors Patient support group PHG foundation External expert : Prof Bart Loeys UKGTN –RCP WORKSHOP

6. 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

7. 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

9. REVISED GHENT CRITERIA (Loeys 2010) Calculation of the Systemic Score Loeys BL et al. The revised Ghent nosology for the Marfan syndrome Journal of Medical Genetics 2010; 47: 476-485

10. 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)

11. Consultant Cardiologists (Adult, Paediatric) Clinical Geneticist Referrals

12. For suspected Marfan Syndrome ± Echo / MRI Clinical assessment using revised Ghent criteria (2010) Systemic score of ≥ 7 Aortic root dilation/ dissection EctopiaLentis FH of MFS OR OR OR 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.

13. 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

14. Acknowledgements • All workshop participants • UKGTN project team • Gurdeep Sagoo • Mark Kroese • Robin and Diane RUST