This test is for individuals with a clinical diagnosis of Marfan syndrome. The Invitae Marfan Syndrome Test analyzes a single gene, FBN1, which has been definitively associated with this syndrome.
Individuals with clinical symptoms of Marfan syndrome may benefit from diagnostic genetic testing to better understand risks, confirm a diagnosis, or inform management. Asymptomatic individuals within a family with a known FBN1 pathogenic variant may also benefit, as testing may clarify their own personal risk of developing Marfan syndrome or other FBN1-related disorders and inform medical management.
The clinical features of Marfan syndrome can overlap with aortopathies, including thoracic aortic aneurysms and dissections and other connective tissue disorders. Marfan syndrome can also be ordered as part of a broader panel to test for aortopathy disorders. Depending on the individual’s clinical and family history, this broader panel may be appropriate. This broader panel can be ordered at no additional charge.
Marfan syndrome is a connective tissue disorder involving the cardiovascular, skeletal, pulmonary and ocular systems. Common features include tall stature, aortic aneurysm with risk of dissection, mitral valve prolapse, ectopia lentis, myopia, and retinal detachment. Other features may include scoliosis and chest wall deformities, pneumothorax, and dural ectasia. Marfan syndrome and other FBN1-related disorders demonstrate clinical variability, ranging from severe, multi-system features in the neonatal period to an isolated feature or mild symptoms at any age. A clinical diagnosis of Marfan syndrome relies on a combination of clinical features and family history or positive genetic test results.
Approximately 70%-93% of individuals with Marfan syndrome have an identifiable FBN1 pathogenic sequence variant or deletion/duplication. This test includes both full gene sequencing and deletion/duplication analysis of FBN1.
Marfan syndrome is inherited in an autosomal dominant pattern. However, approximately 25% of individuals with Marfan syndrome have a de novo pathogenic variant in FBN1.
Penetrance is high for individuals with a pathogenic variant in FBN1. Clinical variability occurs between individuals, even within the same family. The cardiovascular feature of progressive aortic aneurysm with risk of dissection is the most common cause of early mortality.
The prevalence of Marfan syndrome is approximately 1 in 5,000 to 1 in 10,000 individuals.
This test may be considered for individuals with:
For links to published management guidelines, please refer to our Management guidelines page.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|