2010 revised diagnostic criteria nvn

An overview of the 2010 Revised Ghent Nosology for Marfan Syndrome. Created to train those knowledgable of the disorder of the changes in how the disorder is diagnosed, including systemic score, z-score calculation, genetic testing, differential diagnosis, etc.

1. 2010 Revised 2010 Revised
Diagnostic CriteriaDiagnostic Criteria

2. ObjectivesObjectives
Review the new diagnostic criteria Review the new diagnostic criteria
for Marfan syndrome and related for Marfan syndrome and related
disordersdisorders
Recognize and appreciate the Recognize and appreciate the
distinguishing characteristics of distinguishing characteristics of
select disorders with overlapping select disorders with overlapping
featuresfeatures
Reinforce your job role as a contact Reinforce your job role as a contact
support personsupport person

3. BackgroundBackground
Heritable disorders of connective Heritable disorders of connective
tissue include a wide range of tissue include a wide range of
disorders with overlapping featuresdisorders with overlapping features
Accurate diagnosis is essential for Accurate diagnosis is essential for
proper medical management and proper medical management and
requires careful clinical evaluation to requires careful clinical evaluation to
identify associated featuresidentify associated features

4. Purpose of Diagnostic CriteriaPurpose of Diagnostic Criteria
PATIENTS
PHYSICIANS &
COUNSELORS
RESEARCHERS
Avoid undue patient
burden
Improve proper patient
management
Inform
research

5. Pros/Cons of 1996 Diagnostic Pros/Cons of 1996 Diagnostic
CriteriaCriteria
Pros:Pros:
World-wide applicationWorld-wide application
Helpful in making the diagnosis of MFSHelpful in making the diagnosis of MFS
Proved to be both sensitive and specific with Proved to be both sensitive and specific with FBN1FBN1 mutations mutations
identified in over 95% of patients fulfilling Ghent criteriaidentified in over 95% of patients fulfilling Ghent criteria
Cons:Cons:
In the absence of aortic enlargement, the diagnosis can be In the absence of aortic enlargement, the diagnosis can be
stigmatizing, hampering career aspirations and restricting stigmatizing, hampering career aspirations and restricting
insurance opportunitiesinsurance opportunities
The label “MFS” may cause a psychological burden and depression The label “MFS” may cause a psychological burden and depression
because of physical restrictionsbecause of physical restrictions
Some diagnostic features have not been validated such as stretch Some diagnostic features have not been validated such as stretch
marksmarks
Others necessitate imaging that is not clinically indicated Others necessitate imaging that is not clinically indicated
e.g. dural ectasiae.g. dural ectasia
Difficult application in childrenDifficult application in children

6. Methods for Improving Methods for Improving
1996 Diagnostic Criteria1996 Diagnostic Criteria
Expert panel meeting relied on:Expert panel meeting relied on:
Large database of medical recordsLarge database of medical records
individual opinion based on extensive patient care individual opinion based on extensive patient care
practical experience with the use of the current practical experience with the use of the current
criteria criteria
Guiding principles: Guiding principles:
maximal use of evidence-based decision making maximal use of evidence-based decision making
consider patient-centric implicationsconsider patient-centric implications
focus on distinguishing MFS from its related focus on distinguishing MFS from its related
disordersdisorders
define purposeful featuresdefine purposeful features

7. 2010 Revised Diagnostic 2010 Revised Diagnostic
CriteriaCriteria
Emphasis on the key features of Emphasis on the key features of
Marfan syndromeMarfan syndrome
–Aortic root aneurysm/ aortic root Aortic root aneurysm/ aortic root
dissectiondissection
–Ectopia lentis (lens dislocation)Ectopia lentis (lens dislocation)
New systemic score assigns less New systemic score assigns less
specific features of Marfan syndrome specific features of Marfan syndrome
a numeric value so they are weighted a numeric value so they are weighted
properly in the evaluation process.properly in the evaluation process.

8. New Features of the New Features of the
2010 Revised Diagnostic Criteria2010 Revised Diagnostic Criteria
Highlights the identification of Highlights the identification of
additional features that would additional features that would
suggest an alternative diagnosissuggest an alternative diagnosis
Provides a more precise role for Provides a more precise role for
molecular testingmolecular testing
Defines criteria for those with a Defines criteria for those with a
family history and those without a family history and those without a
family historyfamily history

9. 2010 Revised Diagnostic Criteria2010 Revised Diagnostic Criteria
Criteria for Marfan syndrome diagnosis in Criteria for Marfan syndrome diagnosis in
patients with no family historypatients with no family history
- - Ao (Z ≥ 2) AND ectopia lentisAo (Z ≥ 2) AND ectopia lentis
- - Ao (Z ≥ 2) AND Ao (Z ≥ 2) AND FBN1 FBN1 mutationmutation
- - Ao (Z ≥ 2) AND systemic features (≥ 7 points)Ao (Z ≥ 2) AND systemic features (≥ 7 points)
- - Ectopia lentis AND Ectopia lentis AND FBN1 FBN1 associated with associated with
known aortic involvementknown aortic involvement
Ao = aortic diameter above indicated Z-score or aortic root Ao = aortic diameter above indicated Z-score or aortic root
dissectiondissection

10. Systemic FeaturesSystemic Features
Wrist AND thumb signWrist AND thumb sign 33
Wrist OR thumb sign Wrist OR thumb sign 11
Pectus carinatum (protruding)Pectus carinatum (protruding)22
Pectus excavatum or chest Pectus excavatum or chest 11
asymmetry (indented)asymmetry (indented)
Hindfoot deformity Hindfoot deformity 22
Plain pes planus (flat feet)Plain pes planus (flat feet) 11
Pneumothorax (lung)Pneumothorax (lung) 22
Dural ectasia (lower back)Dural ectasia (lower back) 22
Protrusio acetabuli (hip)Protrusio acetabuli (hip) 22
Reduced US/LS AND increased Reduced US/LS AND increased 11
arm/height AND no severe scoliosisarm/height AND no severe scoliosis
Scoliosis or thoracolumbar kyphosisScoliosis or thoracolumbar kyphosis11
Reduced elbow extension Reduced elbow extension 11
Facial features- (3/5):Facial features- (3/5): 11
dolichocephaly, dolichocephaly, enophthalmos, enophthalmos,
downslanting palpebral fissures, downslanting palpebral fissures,
malar hypoplasia, retrognathiamalar hypoplasia, retrognathia
Skin stretch marks Skin stretch marks 11
Myopia > 3 diopters Myopia > 3 diopters 11
Mitral valve prolapse Mitral valve prolapse 11
Maximum total: 20 ≥ 7 systemic Maximum total: 20 ≥ 7 systemic
involvementinvolvement

11. 2010 Revised Diagnostic Criteria2010 Revised Diagnostic Criteria
Criteria for Marfan syndrome diagnosis in Criteria for Marfan syndrome diagnosis in
patients with a positive family historypatients with a positive family history
–Ectopia lentis AND family history of MFSEctopia lentis AND family history of MFS
–Systemic features (≥ 7 points) AND family Systemic features (≥ 7 points) AND family
history of MFShistory of MFS
–Ao family history of MFSAo family history of MFS
(Z ≥ 2 above 20 years, ≥ 3 below 20 (Z ≥ 2 above 20 years, ≥ 3 below 20 years)years)

12. Special considerations for Special considerations for
children (<20 yrs):children (<20 yrs):
If insufficient systemic features (<7) and/or borderline If insufficient systemic features (<7) and/or borderline
aortic root measurements (Z < 3) are present aortic root measurements (Z < 3) are present
(without (without FBN1FBN1 mutation) mutation)
-> use -> use “non-specific connective tissue disorder”“non-specific connective tissue disorder” until until
follow-up echo evaluation shows aortic root dilation follow-up echo evaluation shows aortic root dilation
(Z≥3). (Z≥3).
If an If an FBN1FBN1 mutation is identified in sporadic or familial mutation is identified in sporadic or familial
cases but aortic root measurements are still below cases but aortic root measurements are still below
Z=3, Z=3,
-> use the term -> use the term “potential MFS”“potential MFS” until the aorta reaches until the aorta reaches
threshold. threshold.

13. Emphasis on the DifferentialEmphasis on the Differential
DiagnosisDiagnosis
Diagnosis of MFS must be made in Diagnosis of MFS must be made in
the absence of features suggestive of the absence of features suggestive of
alternative diagnosis such as Loeys alternative diagnosis such as Loeys
Dietz Syndrome, Familial Aortic Dietz Syndrome, Familial Aortic
Aneurysm etc.Aneurysm etc.
Consideration of genetic testing for Consideration of genetic testing for
TGFBR1/2, COL3A1, and other genes TGFBR1/2, COL3A1, and other genes
as they are identified over timeas they are identified over time

14. Differential Diagnosis/Related Differential Diagnosis/Related
DisordersDisorders
Ectopia lentis syndromeEctopia lentis syndrome
–Dislocated lenses with or without systemic features AND Dislocated lenses with or without systemic features AND
with an with an FBN1 FBN1 not associated with Ao or no not associated with Ao or no FBN1FBN1
MASS (myopia, MVP, borderline aortic root MASS (myopia, MVP, borderline aortic root
dilation, striae, skeletal findings)dilation, striae, skeletal findings)
–Ao (Z < 2) AND systemic features ≥ 5 (with at least one Ao (Z < 2) AND systemic features ≥ 5 (with at least one
skeletal feature) without ectopia lentisskeletal feature) without ectopia lentis
Mitral valve prolapse syndromeMitral valve prolapse syndrome
–MVP AND Ao (Z < 2) AND systemic features < 5 without MVP AND Ao (Z < 2) AND systemic features < 5 without
ectopia lentisectopia lentis

15. ConclusionsConclusions
Accurate diagnosis of patients with connective Accurate diagnosis of patients with connective
tissue disorders is critical to guide medical tissue disorders is critical to guide medical
management and provide families with management and provide families with
appropriate risk assessmentappropriate risk assessment
The revised Ghent criteria provides a The revised Ghent criteria provides a
comprehensive approach to the evaluation and comprehensive approach to the evaluation and
management of patients with Marfan syndrome management of patients with Marfan syndrome
and related disordersand related disorders
New information and new discoveries will New information and new discoveries will
continue to shape and refine these continue to shape and refine these
recommendationsrecommendations

16. Your Role as Support ContactYour Role as Support Contact
ListenListen
Provide SupportProvide Support
Key points Key points
–Clinical evaluation is necessaryClinical evaluation is necessary
–Monitoring of the aorta frequently is crucialMonitoring of the aorta frequently is crucial