1456
Multisystem connective tissue disorder of autosomal dominant inheritance.
Marfan syndrome (MFS) is an autosomal dominant disorder which affects 1 in 5–10,000 people.
Exhibits complete penetrance and variable expression with age dependency.
One-fourth of affected individuals are from new mutations and have no family history.
Hallmark features in cardiovascular, ocular and skeletal systems.
The phenotype becomes more apparent with increasing age in most affected families.
Gene for syndrome localized to chromosome 15q21.
FBN1 gene encodes the micrfibrillar protein fibrillin 1.
MFS arises from a mutation in the FBN1 gene, which encodes for the glycoprotein fibrillin-1, a major constituent of extracellular microfibrils which form connective tissues.
The glycoprotein fibrillin-1, a major constituent of extracellular microfibrils which form connective tissues.
Over 1,000 different mutations in FBN1 have been found to result in abnormal function of fibrillin, which consequently relates to connective tissues elongating progressively and weakening.
Because these fibers are found in tissues throughout the body, mutations in this gene can have a widespread effect on certain systems, including the skeletal, cardiovascular, and nervous system, as well as the eyes and lungs.
97% of patients with Marfan syndrome have FB1 mutations.
Severe neonatal syndrome associated with a cluster of mutations in the middle portion of FBN1.
Over 1,000 different mutations in FBN1 have been found to result in abnormal function of fibrillin, which consequently relates to connective tissues elongating progressively and weakening.
Because these fibers are found in tissues throughout the body, mutations in this gene can have a widespread effect on certain systems, including the skeletal, cardiovascular, and nervous system, as well as the eyes and lungs.
A subset of patients have heterozygous mutations in the gene encoding tissue growth factor-beta receptor 2 (TGFBR2) on chromosome 3p24.2-25.
Occurs worldwide with no gender predilection.
Tall stature and dolochostenomelia (long-bone overgrowth) account for the higher incidence among basketball and volleyball players.
Without medical intervention, prognosis of Marfan syndrome can range from moderate to life-threatening, with 90% of known causes of death in diagnosed patients relating to cardiovascular complications and congestive cardiac failure.
Other characteristics of MFS include an increased arm span and decreased upper to lower body ratio.
Strabismus frequent and if not corrected can lead to amblyopia.
Highly myopic patients benefit from glasses or contact lenses and are risk for retinal detachment because the globe is elongated.
Patients should avoid activities that involve blows to the head and eye.
About two-thirds of patients have ectopic lentis which is managed by drugs to constrict the pupil and glasses risk contact lenses to correct phakia and aphakia.
Lens extraction and insertion of a lens prosthesis is another mode of management
Cataracts and glaucoma are common problems in such patients
High incidence of aortic root aneurysm associated with life threatening aortic dissection.
Patients need regular follow up to monitor aortic size to determine the timing of aortic root replacement.
There are two major criteria for diagnosis of MS: aortic root dilation and the presence of ectopic lentis.
Patients have increased length of the upper torso and extremities ref2242ed to as as leptosomic features and is part of the minor criteria for diagnosis.
Minor criteria include: laxity of the tendons of the hands and wrists, anterior chest deformities including pectis carinatum, and pectus excavatum, hind foot deformities, spontaneous pneumothorax, Lumbosacral dural ecstasia, protusio acetabuli, scoliosis or thoracolumbar kyphosis, reduced elbow extension, facial features, skin striae, myopia, and mitral valve prolapse.
About three-fourths of patients have mitral valve prolapse.
Mitral valve prolapse can be complicated by mitral regurgitation.
Mitral valve abnormalities may warrant valvular repair or replacement.
Arrhythmias might be primary or secondary to valvular disease and can lead to sudden death.
Before use of aortic root replacement life expectancy was about two-thirds that of unaffected people.
Without medical intervention, prognosis of Marfan syndrome can range from moderate to life-threatening.
90% of known causes of death in diagnosed patients relating to cardiovascular complications and congestive cardiac failure.
Other characteristics of MFS include an increased arm span and decreased upper to lower body ratio.
Now a near normal life expectancy is expected.