Marfan syndrome, a genetic disorder affecting connective tissues, has been found to be more prevalent than previously recognized. Recent research indicates that one in 416 individuals possess predicted pathogenic variants in the FBN1 gene associated with the syndrome, highlighting the need for greater awareness among healthcare providers.
The study, published on March 18, 2025, utilized genetic data from the Genome Aggregation Database (gnomAD), enabling a comprehensive analysis of the frequency of Marfan syndrome in various populations. Existing literature suggested that the condition affected approximately one in 3000 to 5000 people; however, findings from this research point to a significantly higher occurrence.
Marfan syndrome is caused by pathogenic variants in the FBN1 gene, which encodes a vital component of connective tissue. Symptoms include tall stature, elongated limbs and digits, cardiovascular complications, and lens abnormalities. The study identified that predicted pathogenic variants were most common in East Asian individuals, recorded at one in 243, and least common among the Ashkenazi Jewish population, at one in 5185.
Using rigorous computational assessments, the researchers determined that the population frequency of predicted pathogenic variants in Marfan syndrome is around one in 416 individuals overall, or one in 356 in control samples. In contrast, null variants associated with aortic aneurysms were less common, occurring in only one in 8624 individuals.
In this study, the researchers emphasized the importance of correctly diagnosing Marfan syndrome due to its potentially fatal cardiac complications, including aortic dissection and rupture. Early diagnosis through genetic testing is critical, yet the variability in symptoms among individuals makes identification challenging.
The research was spearheaded by a team that included authors Choi, Huang, and Savige, who expressed the hope that their findings would enhance clinicians' awareness of Marfan syndrome and the risks involved, particularly in emergency departments and cardiac clinics.
Marfan syndrome is characterized by its autosomal dominant inheritance, meaning it can be passed down through families. The variable expression of symptoms means that some individuals may present with milder features or none at all, complicating the clinical picture.
For this analysis, the researchers utilized FBN1 genetic variants from gnomAD, including both missense and structural variants, to better understand the disease's frequency across diverse populations. The findings indicated that individuals of East Asian descent were significantly more likely to carry these variants, suggesting a need for targeted awareness and screening efforts within specific populations.
With the identification of approximately 1157 variants related to Marfan syndrome in the study data set, the research team provided necessary validation of their findings by comparing them with existing data from ClinVar and LOVD databases. They stressed that while their model provides valuable insight, the actual occurrence of Marfan syndrome may be underestimated due to individuals who lack identifiable pathologic mutations.
The implications of accurately determining the population frequency of Marfan syndrome extend beyond mere statistics. Increased awareness among healthcare providers can lead to early diagnosis and timely intervention, potentially reducing the severe cardiovascular risks associated with the condition.
Overall, the research underscores a critical need for continued emphasis on Marfan syndrome within medical training and practice, as untreated individuals remain susceptible to life-threatening complications. As a result, enhanced education and awareness can ultimately lead to improved patient outcomes and quality of life.
The findings compel a reassessment of how common Marfan syndrome truly is and pose fundamental questions about genetic variability and inheritance patterns in the human population.