The Diagnostic Criteria for Marfan Syndrome
The diagnostic criteria for Marfan syndrome are based on a scoring system called the Ghent Nosology. This system was developed in 2010 by a group of international experts in the diagnosis and management of Marfan syndrome, and it provides a standardized method for evaluating patients and making a definitive diagnosis.
The Ghent Nosology takes into account both clinical features and genetic testing results to establish a diagnosis of Marfan syndrome.
Read more: Marfan Syndrome
The Ghent Nosology consists of two major sets of criteria: major criteria and minor criteria. The major criteria are considered sufficient for the diagnosis of Marfan syndrome, while the minor criteria are supportive features that contribute to the diagnosis.
Major Criteria
Major criteria are features that are strongly associated with Marfan syndrome.
Major criteria include:
1.) Aortic root dilatation - enlargement of the aorta at the level of the sinuses of Valsalva
2.) Ectopia lentis - displacement of the lens of the eye
3.) Systemic score - a calculated score based on the presence of certain clinical features such as skeletal abnormalities, skin features, and other organ system involvement
4.) FBN1 gene mutation - identification of a pathogenic mutation in the FBN1 gene, which is responsible for encoding fibrillin-1, a protein involved in the formation of connective tissue
Minor Criteria
Minor criteria are features that are less strongly associated with Marfan syndrome.
Minor criteria include:
1.) Pectus carinatum or excavatum - abnormal chest shape
2.) Joint hypermobility - increased range of motion in the joints
3.) High-arched palate - the roof of the mouth is arched higher than usual
4.) Mitral valve prolapse - an abnormal movement of the mitral valve in the heart
5.) Skin striae - stretch marks on the skin
Diagnosis Criteria for Marfan Syndrome
To establish a diagnosis of Marfan syndrome using the Ghent Nosology, a patient must meet specific criteria based on the presence of major or minor criteria, systemic score, and genetic testing results.
The systemic score is based on the presence or absence of certain features of Marfan syndrome, including skeletal, cardiovascular, ocular, and skin manifestations. Each feature is assigned a certain number of points based on its severity and clinical significance. The higher the systemic score, the more likely the patient has Marfan syndrome.
What is the Scoring System?
The scoring system aims to provide an objective measure of the likelihood of a patient having Marfan syndrome. Higher scores indicate a greater probability of Marfan syndrome, while lower scores suggest a lower likelihood.
To calculate the systemic score, a healthcare professional evaluates the patient's medical history, performs a physical examination, and may order additional tests such as imaging studies, echocardiograms, or genetic testing. The presence or absence of specific features, as well as their severity, are assessed and assigned the corresponding point values.
For example, skeletal features that may contribute to the systemic score include long limbs, abnormal joint flexibility, a high-arched palate, and a disproportionately tall stature. Cardiovascular features can include aortic root dilatation or dissection, mitral valve prolapse, and other heart abnormalities. Ocular features may involve lens dislocation, nearsightedness, or an enlarged cornea. Skin features could include stretch marks or soft, velvety skin.
After evaluating all relevant criteria and assigning points accordingly, the individual scores are summed to obtain the systemic score. A higher systemic score indicates a greater likelihood of Marfan syndrome, while a lower score suggests that the diagnostic criteria for the syndrome may not be met.
It is important to note that the systemic score alone does not provide a definitive diagnosis of Marfan syndrome. Genetic testing results are also considered as part of the diagnostic process. In some cases, a genetic mutation associated with Marfan syndrome, such as a mutation in the FBN1 gene, can confirm the diagnosis even if the systemic score is low.
Read more: Symptoms of Marfan Syndrome
How to Reach a Diagnosis?
To establish a diagnosis of Marfan syndrome using the Ghent Nosology, a patient must meet one of the following criteria: (Note: Either one of the two criteria can be used to diagnose Marfan Syndrome)
Criteria 1
🠞 Presence of a pathogenic FBN1 gene mutation, plus a major criterion or a systemic score greater than or equal to 7.
The FBN1 gene is responsible for encoding fibrillin-1, a protein involved in the formation of connective tissue. A pathogenic FBN1 gene mutation is a genetic mutation that is known to cause Marfan syndrome.
In this case, if a patient has a pathogenic FBN1 gene mutation, they must also meet at least one major criterion or have a systemic score greater than or equal to 7. This means that the patient has significant clinical features associated with Marfan syndrome, which may include aortic root dilatation, ectopia lentis, or other skeletal or organ system abnormalities.
Criteria 2
🠞 No identified FBN1 gene mutation, plus a major criterion and a minor criterion, OR a systemic score greater than or equal to 7 and a minor criterion.
In some cases, a patient may present with the clinical features of Marfan syndrome, but genetic testing may not identify a pathogenic mutation in the FBN1 gene.
Therefore, if a patient presents with one major criterion (e.g., aortic root dilatation) and one minor criterion (e.g., pectus carinatum), or a systemic score of 7 or greater and one minor criteria (e.g., high-arched palate), then the patient can be diagnosed with Marfan syndrome, even if a pathogenic FBN1 gene mutation is not identified.
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.
