2010 Revised 2010 Revised Diagnostic CriteriaDiagnostic Criteria

ObjectivesObjectives

Review the new diagnostic Review the new diagnostic criteria for Marfan syndrome and criteria for Marfan syndrome and related disordersrelated disorders

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 Reinforce your job role as a contact support personcontact support person

BackgroundBackground

Heritable disorders of connective Heritable disorders of connective tissue include a wide range of tissue include a wide range of disorders with overlapping disorders with overlapping featuresfeatures

Accurate diagnosis is essential Accurate diagnosis is essential for proper medical management for proper medical management and requires careful clinical and requires careful clinical evaluation to identify associated evaluation to identify associated featuresfeatures

Purpose of Diagnostic Purpose of Diagnostic CriteriaCriteria

PATIENTS

PHYSICIANS & COUNSELORS

RESEARCHERS

Avoid undue patient burden

Improve proper patient management

Inform research

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 identified in over 95% of patients fulfilling mutations identified in over 95% of patients fulfilling Ghent criteriaGhent 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 The label “MFS” may cause a psychological burden and depression because of physical restrictionsdepression because of physical restrictions

Some diagnostic features have not been validated such as Some diagnostic features have not been validated such as stretch marksstretch marks

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

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 individual opinion based on extensive patient

care care practical experience with the use of the practical experience with the use of the

current criteria current criteria

Guiding principles: Guiding principles: maximal use of evidence-based decision maximal use of evidence-based decision

making 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

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 specific features of Marfan syndrome a numeric value so syndrome a numeric value so they are weighted properly in they are weighted properly in the evaluation process.the evaluation process.

New Features of the New Features of the 2010 Revised Diagnostic 2010 Revised Diagnostic

CriteriaCriteria 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 family history and those without a family historya family history

2010 Revised Diagnostic 2010 Revised Diagnostic CriteriaCriteria

Criteria for Marfan syndrome diagnosis Criteria for Marfan syndrome diagnosis in patients with no family historyin patients 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 Ao (Z ≥ 2) AND systemic features (≥ 7 points)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 Ao = aortic diameter above indicated Z-score or aortic root dissectionaortic root dissection

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

2010 Revised Diagnostic 2010 Revised Diagnostic CriteriaCriteria

Criteria for Marfan syndrome Criteria for Marfan syndrome diagnosis in patients with a positive diagnosis in patients with a positive family historyfamily 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)

Special considerations for Special considerations for children (<20 yrs):children (<20 yrs):

If insufficient systemic features (<7) and/or If insufficient systemic features (<7) and/or borderline aortic root measurements (Z < 3) borderline aortic root measurements (Z < 3) are present (without are present (without FBN1FBN1 mutation) mutation)

-> use -> use “non-specific connective tissue disorder”“non-specific connective tissue disorder” until follow-up echo evaluation shows aortic until follow-up echo evaluation shows aortic root dilation (Z≥3). root dilation (Z≥3).

If an If an FBN1FBN1 mutation is identified in sporadic or mutation is identified in sporadic or familial cases but aortic root measurements familial cases but aortic root measurements are still below Z=3, are still below Z=3,

-> use the term -> use the term “potential MFS”“potential MFS” until the aorta until the aorta reaches threshold. reaches threshold.

Emphasis on the Emphasis on the DifferentialDifferentialDiagnosisDiagnosis

Diagnosis of MFS must be made in Diagnosis of MFS must be made in the absence of features suggestive the absence of features suggestive of alternative diagnosis such as of alternative diagnosis such as Loeys Dietz Syndrome, Familial Loeys Dietz Syndrome, Familial Aortic Aneurysm etc.Aortic Aneurysm etc.

Consideration of genetic testing Consideration of genetic testing for TGFBR1/2, COL3A1, and other for TGFBR1/2, COL3A1, and other genes as they are identified over genes as they are identified over timetime

Differential Differential Diagnosis/Related Diagnosis/Related

DisordersDisorders Ectopia lentis syndromeEctopia lentis syndrome

– Dislocated lenses with or without systemic Dislocated lenses with or without systemic features AND with an features AND with an FBN1 FBN1 not associated with Ao not associated with Ao or no or no FBN1FBN1

MASS (myopia, MVP, borderline aortic MASS (myopia, MVP, borderline aortic root dilation, striae, skeletal findings)root dilation, striae, skeletal findings)– Ao (Z < 2) AND systemic features ≥ 5 (with at Ao (Z < 2) AND systemic features ≥ 5 (with at

least one skeletal feature) without ectopia lentisleast one skeletal feature) without ectopia lentis

Mitral valve prolapse syndromeMitral valve prolapse syndrome– MVP AND Ao (Z < 2) AND systemic features < 5 MVP AND Ao (Z < 2) AND systemic features < 5

without ectopia lentiswithout ectopia lentis

ConclusionsConclusions Accurate diagnosis of patients with Accurate diagnosis of patients with

connective tissue disorders is critical to connective tissue disorders is critical to guide medical management and provide guide medical management and provide families with appropriate risk assessmentfamilies with appropriate risk assessment

The revised Ghent criteria provides a The revised Ghent criteria provides a comprehensive approach to the evaluation comprehensive approach to the evaluation and management of patients with Marfan and management of patients with Marfan syndrome and related disorderssyndrome and 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

Your Role as Support Your Role as Support ContactContact

ListenListen Provide SupportProvide Support Key points Key points

– Clinical evaluation is necessaryClinical evaluation is necessary– Monitoring of the aorta frequently is Monitoring of the aorta frequently is

crucialcrucial