The Diagnostic Criteria for Marfan Syndrome
The Ghent Nosology is a diagnostic system for Marfan syndrome and related connective tissue disorders. First established in 1996 and later revised in 2010, this system focuses on classifying the clinical features of Marfan syndrome and establishing criteria for diagnosis based on major and minor features across different organ systems, as well as genetic testing.
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The Ghent Nosology takes into account both clinical features and genetic testing results to establish a diagnosis of Marfan syndrome.
What is Marfan Syndrome?
Marfan Syndrome is a rare, inherited connective tissue disorder that affects multiple organ systems, leading to a variety of symptoms and potential complications. It is primarily caused by mutations in the FBN1 gene, which encodes fibrillin-1, a protein crucial for the elasticity and strength of connective tissues. As a result, people with Marfan syndrome tend to have overly flexible joints, elongated limbs, and abnormalities in the heart, blood vessels, and eyes.
Read more: What is Marfan Syndrome?
What is Ghent Nosology?
Ghent Nosology refers to a system used for diagnosing and classifying Marfan syndrome and related connective tissue disorders. It is an essential part of the clinical framework for identifying Marfan syndrome, a genetic disorder that affects connective tissue, leading to a variety of cardiovascular, skeletal, ocular, and pulmonary complications.
The Ghent Nosology has since become a key diagnostic tool for healthcare professionals dealing with Marfan syndrome and similar connective tissue disorders.
Read more: Symptoms of Marfan Syndrome
History and Background of Ghent Nosology
The term "Ghent Nosology" originated from the city of Ghent, Belgium, where an international group of experts, led by Dr. Peter De Paepe, convened to establish a more precise set of diagnostic criteria for Marfan syndrome. Prior to the Ghent Nosology, various diagnostic systems existed, but there were discrepancies in diagnosis, particularly with individuals who presented with overlapping features of Marfan syndrome and other connective tissue disorders.
In 1996, the Ghent Nosology was introduced as a comprehensive classification system to provide more consistent diagnostic criteria, primarily focusing on the major features of the syndrome. This new system was designed to minimize misdiagnosis by incorporating more objective measures, such as genetic testing and clinical findings, to assess the severity and presence of Marfan syndrome symptoms.
Note: Diagnostic Tools like Ghent Nosology Criteria are only to be used by medical professionals. These tools are not meant for self-diagnosis.(alert-warning)
Ghent Nosology Criteria (Revised 2010 Version)
The 2010 Ghent Nosology criteria provide a comprehensive and standardized approach to diagnosing Marfan Syndrome (MFS). These criteria focus on high-risk and defining features of the syndrome, emphasizing aortic root aneurysm/dilatation, ectopia lentis, and genetic confirmation through FBN1 mutation testing. They also incorporate a systemic score to evaluate other physical manifestations of the condition.
The framework accounts for whether there is a family history of Marfan syndrome or not, guiding the diagnostic process accordingly.
A. Key Diagnostic Components of 2010 Ghent Nosology
1. Aortic Root Aneurysm/Dilatation
➛ Defined as a Z-score ≥ 2.0 at the sinuses of Valsalva (adjusted for age and body size).
➛ A central feature in the diagnostic process due to its life-threatening nature.
2. Ectopia Lentis
➛ Dislocation of the eye lens (complete or partial), observed during ophthalmologic evaluation.
3. FBN1 Gene Mutation
➛ A confirmed pathogenic mutation in the FBN1 gene associated with Marfan syndrome.
4. Systemic Score
➛ A quantitative measure of physical features across multiple organ systems.
➛ A score ≥ 7 supports the diagnosis when combined with other findings.
5. Family History
➛ A confirmed diagnosis of Marfan syndrome in a first-degree relative.
B. Systemic Score of 2010 Ghent Nosology
The systemic score evaluates the following physical manifestations, with corresponding points assigned:
➧ Wrist and Thumb Sign (combined presence of both signs): 3 points
➧ Pectus Carinatum (pigeon chest): 2 points
➧ Pectus Excavatum (funnel chest) or Chest Asymmetry: 1 point
➧ Hindfoot Deformity (severe flatfoot with valgus deformity): 2 points
➧ Pes Planus (flat feet, no valgus deformity): 1 point
➧ Spontaneous Pneumothorax: 2 points
➧ Dural Ectasia (widening of the spinal dura): 2 points
➧ Protrusio Acetabuli (hip joint displacement): 2 points
➧ Reduced Upper-to-Lower Segment Ratio or Increased Arm Span-to-Height Ratio (> 1.05): 1 point
➧ Scoliosis or Thoracolumbar Kyphosis: 1 point
➧ Reduced Elbow Extension (<170°): 1 point
➧ Craniofacial Features (dolichocephaly, down-slanting palpebral fissures, malar hypoplasia): 1 point (combined)
➧ Myopia (>3 diopters): 1 point
➧ Skin Striae (stretch marks not linked to weight change or pregnancy): 1 point
➧ Mitral Valve Prolapse: 1 point
A systemic score of ≥ 7 indicates significant physical manifestations supporting a diagnosis of Marfan syndrome.
C. Diagnostic Pathways
1. No Family History of Marfan Syndrome
For individuals without a family history, diagnosis requires:
➹ Aortic Root Aneurysm/Dilatation (Z-score ≥ 2.0) AND Ectopia Lentis; OR
➹ Aortic Root Aneurysm/Dilatation (Z-score ≥ 2.0) AND FBN1 Mutation; OR
➹ Aortic Root Aneurysm/Dilatation (Z-score ≥ 2.0) AND a Systemic Score ≥ 7; OR
➹ Ectopia Lentis AND a confirmed FBN1 Mutation known to cause Marfan syndrome.
2. Family History of Marfan Syndrome
For individuals with a confirmed first-degree relative diagnosed with Marfan syndrome, diagnosis requires:
➹ Ectopia Lentis; OR
➹ Aortic Root Aneurysm/Dilatation (Z-score ≥ 2.0); OR
➹ A Systemic Score ≥ 7.
Key Principles of the 2010 Ghent Nosology
1. Cardiovascular Focus: Aortic root aneurysm/dilatation is a critical diagnostic feature due to its life-threatening implications.
2. Role of FBN1 Mutation Testing: Genetic testing for FBN1 mutations provides clarity in ambiguous cases and strengthens diagnostic certainty.
3. Elimination of "Major" and "Minor" Criteria: The systemic score replaces the previous dichotomy of "major" and "minor" criteria, providing a more objective and quantitative assessment.
4. Exclusion of Non-Specific Features: Features commonly seen in other connective tissue disorders are downplayed unless supported by other Marfan-specific findings.
5. Differentiation from Related Disorders: The revised criteria help distinguish Marfan syndrome from related conditions such as Loeys-Dietz syndrome and Ehlers-Danlos syndrome.
Summary
The Ghent Nosology scoring system helps to standardize the diagnostic criteria for Marfan syndrome, ensuring that patients are evaluated consistently and accurately. It is important to note that the diagnosis of Marfan syndrome should be made by a healthcare provider with expertise in managing this condition, as it can be difficult to distinguish from other connective tissue disorders.
