Marfan syndrome and differential diagnosis [42 genes]

Marfan disease is a systemic connective tissue disorder caused by mutations in the FBN1 gene, characterized by a high degree of phenotypic variability. Cardinal manifestations affect the ocular, skeletal, and cardiovascular systems.

• Ocular manifestations: myopia, ectopia lentis, retinal detachment, glaucoma and early cataracts.
• Skeletal manifestations: bone overgrowth and joint laxity, including disproportionately long limbs, pectus excavatum or carinatum, and scoliosis.
• Cardiovascular manifestations: proximal dilation of the aorta (predisposes to aortic dissection), mitral valve prolapse, tricuspid valve prolapse, and proximal enlargement of the pulmonary artery. They are, therefore, also predisposed to left ventricular dysfunction.

Marfan syndrome: 1 / 5,000 newborns (ORPHA:558).

Based on exome sequencing, this service is the most cost-efficient way to cover the study of the FBN1 gene and all genes involved in the differential diagnosis through a single test. A genetic diagnosis allows for personalized monitoring and management of the patient, including the adoption of primary prevention measures for the most severe cardiovascular complications.

The benefits derived from a genetic diagnosis in this context can range from family genetic counseling, typical of genetic studies in general, to the primary prevention of comorbidities of vital importance in patients with Marfan syndrome.

Service is indicated when, in the presence of aortic root dilation, ectopia lentis, or a characteristic systemic phenotype, Marfan syndrome is suspected.

In patients who meet clinical criteria for Marfan disease, the probability of finding a molecular cause after sequencing of single nucleotide variants and copy number variations is 98%. An exome approach will allow obtaining a performance very close to said value, taking into account the limitations of the technique.