FBN1

About FBN1

FBN1 on chromosome 15q21.1 encodes fibrillin 1, a large extracellular matrix glycoprotein that assembles into microfibrils, which provide a scaffold for elastic fibers and are found in the aorta, ligaments, skin, and the ciliary zonules that hold the lens of the eye. Fibrillin microfibrils also bind and regulate the availability of TGF beta. Pathogenic FBN1 variants cause Marfan syndrome, an autosomal dominant connective tissue disorder with a prevalence on the order of 1 in 5,000 people. Features include tall stature, long limbs with an arm span exceeding height, long fingers called arachnodactyly, chest wall deformity, scoliosis, joint hypermobility, dislocation of the lens typically upward, and, most importantly, dilation of the aortic root that can lead to aortic dissection. The condition is named after the French pediatrician Antoine Marfan, who described it in 1896, and FBN1 was identified as the cause in 1991. Diagnosis uses the revised Ghent criteria. Aortic dissection was historically the main cause of premature death, and management with medications such as beta blockers and angiotensin receptor blockers, regular imaging of the aorta, and preventive aortic surgery has greatly improved life expectancy. About a quarter of cases result from new variants. Other FBN1 variants cause acromicric and geleophysic dysplasias with short stature, the opposite end of the growth spectrum. Marfan syndrome must be distinguished from Loeys Dietz syndrome, vascular Ehlers Danlos syndrome, and homocystinuria.