From the Guidelines
Yes, Marfan syndrome is inherited, specifically as an autosomal dominant genetic disorder, meaning a person only needs to inherit one copy of the defective gene from one parent to develop the condition. About 75% of people with Marfan syndrome inherit it from a parent who has the condition, while the remaining 25% develop it due to a new genetic mutation 1. The disorder affects the body's connective tissue and is caused by mutations in the FBN1 gene, which provides instructions for making a protein called fibrillin-1. This protein is essential for forming elastic fibers that provide strength and flexibility to connective tissues throughout the body. When someone has Marfan syndrome, each of their children has a 50% chance of inheriting the condition. The severity of symptoms can vary widely even within the same family due to variable expressivity of the gene.
Key aspects of Marfan syndrome include:
- It is an autosomal dominant disorder, which means only one copy of the mutated gene is needed to cause the condition 1.
- The FBN1 gene mutations lead to the production of abnormal fibrillin-1, affecting the formation of elastic fibers in connective tissue 1.
- Approximately 25% of cases are due to new mutations, not inherited from a parent 1.
- Early diagnosis and management are crucial to prevent or delay serious complications involving the heart, blood vessels, eyes, and skeletal system 1.
Given the most recent and highest quality evidence, the inheritance pattern of Marfan syndrome is well-established as autosomal dominant, with significant implications for genetic counseling and family planning 1. This understanding is critical for the management and potential prevention of complications associated with Marfan syndrome, emphasizing the importance of genetic testing and regular monitoring for individuals with a family history of the condition.
From the Research
Inheritance of Marfan's Syndrome
- Marfan's syndrome is an autosomal dominant condition, meaning that a single copy of the mutated gene is enough to cause the disorder 2, 3, 4, 5, 6.
- The syndrome is caused by pathogenetic variants in the FBN1 gene, which encodes fibrillin-1, a major structural component of the extracellular matrix 2, 4, 5.
- Up to 25% of individuals with Marfan's syndrome have de novo variants, meaning that the mutation occurs for the first time in the affected individual and is not inherited from either parent 2.
- The autosomal dominant pattern of inheritance means that each child of an affected parent has a 50% chance of inheriting the mutated gene and developing the syndrome 3, 4, 5, 6.
Genetic Transmission
- Marfan's syndrome is inherited as an autosomal dominant trait, with few cases reported to display an autosomal recessive transmission 4.
- The FBN1 gene is located on chromosome 15q21.1 and is made up of 66 exons 4.
- Mutations in the FBN1 gene can lead to a range of clinical manifestations, including cardiovascular, ocular, and skeletal abnormalities 2, 3, 4, 5.