From the Guidelines
Marfan syndrome (MFS) is an autosomal dominant disorder, meaning that a single copy of the mutated gene is enough to cause the condition, and each child of an affected parent has a 50% chance of inheriting the mutated gene.
Inheritance Risk
- The risk of inheriting MFS is 50% for each child of an affected parent 1.
- Approximately 25% of patients with MFS do not have a family history and represent new cases due to sporadic mutations 1.
- The FBN1 gene is responsible for MFS, and mutations in this gene can lead to the development of the condition 1.
Key Points
- MFS is a highly penetrant but variable expressivity disorder, meaning that almost all individuals with the mutated gene will develop some features of the condition, but the severity and extent of the features can vary widely 1.
- The diagnosis of MFS is based on a combination of clinical findings, family history, and genetic testing 1.
From the Research
Inheritance Risk of Marfan Syndrome
The inheritance risk of Marfan syndrome (MFS) is a crucial aspect of understanding the disorder. Key points to consider include:
- MFS is inherited in an autosomal dominant fashion, meaning a single copy of the mutated gene is sufficient to cause the condition 2, 3, 4.
- The disorder is classically caused by mutations in the gene coding for fibrillin-1, FBN1 2, 4.
- The estimated prevalence of MFS is one in 10,000 to 20,000 individuals 3.
Genetic Basis and Clinical Variability
Research has quantified the genetic basis of MFS clinical variability, including:
- Strong correlations between features within the same system (e.g., ophthalmology, skeletal, cardiovascular) suggesting common underlying determinants 5.
- Features belonging to different systems are largely uncorrelated 5.
- Most clinical features show strong familial aggregation and high heritability, indicating a significant contribution of inherited modifiers to variability 5.
Implications for Inheritance Risk
The autosomal dominant inheritance pattern of MFS implies that:
- Each child of an affected parent has a 50% chance of inheriting the mutated gene and developing the condition 2, 3, 4.
- The risk of inheritance is independent of the sex of the parent or child 2, 3, 4.
- Genetic testing and counseling can help identify individuals at risk and inform family planning decisions 2, 4.