Marfan syndrome (MFS) is an autosomal dominant disorder characterized by deformities in the skeletal, cardiovascular, and ocular systems. MFS is caused by a defect in the fibrillin-1 gene (FBN1), located on chromosome 15 at 15q21. Discovery: Marfan syndrome was first described in 1896 by Antoine Marfan, a French pediatrician. Worldwide, it is estimated to affect 2-3 in 10,000 people, although this number has been disputed. This figure probably underestimates the true incidence because the disease cannot always be diagnosed with certainty. Marfan syndrome patients have an increased height and disproportionately large arm spans. Many patients also display arachnodactyly (long digits) and/or anterior chest deformities resulting from overgrown ribs. Joint laxity and teeth crowding are also very common symptoms. Other characteristics can include scoliosis, flat feet, and craniofacial irregularities.
[...] Silverman DI, Burton KJ, Gray Bosner MS, Kouchoukos NT, Roman MJ, Boxer Devereux RB, Tsipouras (1995) Life expectancy in the Marfan syndrome. Am. J. Cardiol. 75: 157-160. Capotorti Gaddini de Benedetti Rizzo (1959) Contribution to the study of the heredity of Marfan's syndrome: description of a family tree of 4 generations with marriage between consanguineous parents. Acta Genet. Med. Gemellol. 455-482. Hayward Keston Brock DJH, Dietz HC: (1992) Fibrillin (FBN1) mutations in Marfan syndrome. (Letter) Hum. Mutat. 79. Karttunen Raghunath Lonnqvist Peltonen (1994) A compound- heterozygous Marfan patient: two defective fibrillin alleles result in a lethal phenotype. [...]
[...] Genetic Factors Pedigrees of Marfan syndrome were studied as early as 1959 to how family inheritance.4 Also, in 1988, Burgio et al. discovered a girl with mosaic Marfan syndrome localized to the left side of her body. They believed that it must be the result of an early stage somatic mutation, causing the syndrome in only the cells that come from the mutated cell.19 In 1992, Hayward5 suggested that there are many FBN1 mutations that can cause Marfan syndrome. Many families with Marfan syndrome have unique mutations. [...]
[...] Also, the fact that many Marfan syndrome patients often have less than 50% mutant fibrillin supported the dominant-negative framework.1 However, now it is suggested that fibrillin-1 malfunctions through haploinsufficiency.17 In other words, disease phenotype arises when the amount of normal fibrillin-1 protein falls below a certain threshold. Related Disorders Most disease alleles of fibrillin-1 cause some variant of Marfan syndrome. However some alleles cause different disorders. It is possible that some of these could be classified as different kinds of Marfan syndrome because they are very similar. [...]
[...] However it is also possible to correct the defects of Marfan syndrome by medicine or surgery so that normal activity is possible or life expectancy is longer. Many aortic abnormalities are now repaired by surgery. The Bentall operation (replacing the aorta grafted blood vessels) is suggested for all patients with an aortic diameter of more than 5.5 cm. The first medical therapy developed was beta-adrenergic blockade. This medical intervention has been suggested since the 1970's and is more effective today because of longer acting beta-selective agents. [...]
[...] Dietz HC, Cutting GR, Pyeritz RE, Maslen CL, Sakai LY, Corson GM, Puffenberger, EG, Hamosh Nanthakumar EJ, Curristin SM, Stetten Meyers DA, Francomano CA: (1991) Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 352: 337-339. Aoyama Francke Gasner Furthmayr (1995) Fibrillin abnormalities and prognosis in Marfan syndrome and related disorders. Am. J. Med. Genet. 58: 169-176. Beighton de Paepe Danks Finidori Gedde-Dahl Goodman Hall JG, Hollister DW, Horton McKusick VA, Opitz JM, Pope FM, Pyeritz RE, Rimoin DL, Sillence Spranger JW, Thompson Tsipouras Viljoen Winship Young (1988) International nosology of heritable disorders of connective tissue. [...]
APA Style reference
For your bibliographyOnline reading
with our online readerContent validated
by our reading committee
