Marfan syndrome is a genetic disorder that affects the body’s connective tissue. Diagnosing Marfan syndrome can be complex, often relying on a set of clinical criteria known as the Ghent Nosology. The revised Ghent Nosology, updated in 2010, provides a framework for clinicians to accurately diagnose this condition. This article will delve into the specifics of the 2010 Revised Ghent Nosology, outlining the key rules used for Marfan’s diagnosis.
The 2010 Revised Ghent Nosology Criteria
The 2010 revision of the Ghent Nosology refines the diagnostic criteria for Marfan syndrome, placing a greater emphasis on aortic root dilatation and genetic testing. The criteria are categorized based on the presence or absence of a family history of Marfan syndrome.
Diagnostic Rules in the Absence of Family History
When there is no known family history of Marfan syndrome, diagnosis relies on specific combinations of clinical findings. Here are the rules:
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Aortic Root Dilatation and Ectopia Lentis: If an individual presents with aortic root dilatation, indicated by a Z-score of 2 or more (adjusted for age and body size), and ectopia lentis (dislocation of the eye lens), a diagnosis of Marfan syndrome is definitive. This rule highlights the significance of these two major criteria when they occur together in the absence of family history, unless features suggest other related syndromes like Shprintzen-Goldberg, Loeys-Dietz, or vascular Ehlers Danlos syndrome.
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Aortic Root Dilatation and FBN1 Mutation: The presence of aortic root dilatation (Z-score ≥ 2) or aortic dissection, coupled with the identification of a confirmed pathogenic mutation in the FBN1 gene, is also sufficient for a Marfan syndrome diagnosis. This criterion emphasizes the role of genetic testing in confirming the diagnosis, even if ectopia lentis is not present.
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Aortic Root Dilatation and Systemic Score: In cases where aortic root dilatation (Z-score ≥ 2) or dissection is present, but ectopia lentis is absent and FBN1 genetic testing is inconclusive or negative, a systemic score of 7 points or more, based on a defined scoring system assessing various systemic features of Marfan syndrome, can confirm the diagnosis. It is crucial to exclude similar conditions and consider alternative genetic testing for related syndromes in these cases.
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Ectopia Lentis and FBN1 Mutation Associated with Aortic Root Dilatation: If ectopia lentis is present without aortic root dilatation or dissection, identifying an FBN1 mutation that is known to be associated with aortic disease is necessary to diagnose Marfan syndrome. This rule underscores that while ectopia lentis is a major criterion, in the absence of aortic involvement, genetic confirmation linking the mutation to aortic risk is required for diagnosis.
Diagnostic Rules in the Presence of Family History
When an individual has a family history of Marfan syndrome, the diagnostic threshold is adjusted, recognizing the increased likelihood of inheriting the condition.
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Ectopia Lentis and Family History: The presence of ectopia lentis in an individual with a family history of Marfan syndrome (diagnosed according to the criteria mentioned above) is sufficient to diagnose Marfan syndrome. Family history lowers the threshold for diagnosis when a major criterion like ectopia lentis is present.
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Systemic Score and Family History: A systemic score of 7 points or greater in an individual with a family history of Marfan syndrome is also diagnostic. Similar to the previous point, family history makes a significant systemic feature score sufficient for diagnosis. Exclusion of other related syndromes and consideration of alternative genetic testing remain important.
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Aortic Root Dilatation and Family History: Aortic root dilatation, with a Z-score of 2 or more in individuals over 20 years old, or a Z-score of 3 or more in individuals under 20 years old, combined with a family history of Marfan syndrome, is diagnostic. This age-adjusted criterion for aortic root dilatation reflects the varying normal ranges at different ages and emphasizes the importance of family history in diagnosis. Again, excluding similar syndromes and considering further genetic testing is recommended.
Conclusion
The 2010 Revised Ghent Nosology provides a structured and updated approach to Marfan’s diagnosis. By considering aortic root involvement, ectopia lentis, FBN1 mutations, systemic scores, and family history, clinicians can more accurately and effectively diagnose Marfan syndrome. Understanding these criteria is crucial for both healthcare professionals and individuals and families affected by or at risk of Marfan syndrome. This framework ensures that diagnosis is thorough and considers the complexities of this genetic condition.
