[15] Clinical symptoms of MFS such as aortic root dilation, pulmonary emphysema, atrioventricular valve changes and skeletal muscle myopathy are induced by altered TGF-β activation and signalling.
[16] Antagonism of TGF-β also further reduced MFS symptoms where it helped muscle regeneration, architecture and strength, pulmonary alveolar septation and mitral valve morphology.
[17] Fibrillin-1 is a large cysteine rich-glycoprotein approximately 350 kDa mainly composed of tandemly repeating domains of epidermal growth factor (EGF)-like modules.
There is no correlation between phenotype and genotype at a molecular level [17] The mutations of the FBN-1 gene at six chromosomal loci, TAAD1 at 5q13-14, FAA1 at 11q23-24, TAAD2 at 3p24-25, TAAD3 at 15q24-26, TAAD4 at 10q23-24 and MYH11 at 16p12-13 are known to be triggers of MFS.
[23] A nonsynonymous amino acid change affecting conserved cysteine of the CaB-EGF-like domain encoded by exon 13 of the FBN1 gene can cause MFS to develop.
[21] Elastin and the development of the ECM system integrated with surrounding VSMC are needed for higher vertebrates to function correctly.
[21] CYR61 induction also functions to support cell adhesion and regulate matrix remodelling and is fundamental in the formation of large vessels and their integrity.
[25] MFS is not an easily diagnosed pathology with a scoring system called the Ghent nosology table used, rather than a single molecule test.
[9] The remaining 20% of MFS cases occur from de novo mutations (new germline mutations not inherited from either parent) and results in the individual phenotypically displaying long and thin limbs and extremities, a curved spine usually resulting in thoracic scoliosis, hyperflexible joints, pectus excavatum (sunken chest), and retinal detachment.
[19] This manifestation is characterised histologically by straight, thin collagen bundles arranged in a parallel to the skin and the elastic fibres.
[18] In MFS affected adults, it is recommended they reduce emotional and physical stress and switch from high impact sports such as martial arts, football, basketball etc to isotonic, low impact exercise such as swimming, biking or jogging where the pulse rate lies approximately at <110 beats per minute.
[5] Fibrillin-1 is a 350-kDa, 2871-amino acid cystine-rich glycoprotein that is responsible for the amalgamation of elastin into the elastic fibres of the connective tissue in the extracellular matrix (ECM).
[27][28] The fragility of the connective tissue usually results in aortic aneurysms due to the wall having the inability to withstand intraluminal pressure.
[29] Mutations in Fibrillin-1 cause elevated levels of TGF-β in the EC space due to LLC being unable to attach to the microfibrils and latent forms not being produced.
[25] Clinical symptoms of MFS such as aortic root dilation, pulmonary emphysema, atrioventricular valve changes and skeletal muscle myopathy are induced by altered TGF-β activation and signalling.
[16] Antagonism of TGF-β also further reduced MFS symptoms where it helped muscle regeneration, architecture and strength, pulmonary alveolar septation and mitral valve morphology.
TGF-β in its complex and free-form can leach into the circulation due to the mutated ECM sequestration and increased LLC activation.
[16] Losartan can work independently or with β-blocker therapy to reduce rate of change in the aortic root diameter of MFS pathology.