A 21-year-old male presents to medicine OPD with complain of vague chest pain on and off lasting for 5 minutes for past 2 months. He is recently finding difficulty in vasion as well. On examination, patient was tall stature with thin and long extremities. lamp examination of eye revealed upward dislocation of lens in left eye. He also cardiac involvement in form of aortic regurgitation. Patient was suspected to have Marfan syndrome and was worked up.
Q.1. What is the molecular defect in Marfan syndrome?
Q.2. What are the systems commonly involved in Marfan syndrome?
Q.3. Emphasize the role of fibrillin glycoprotein.
Ans 1. Marfan syndrome (MFS) is due to mutation of gene (FBNI) which encodes the connective tissue protein fibrillin 1. It is an autosomal dominant condition with a reported incidence of 1 in 3000 to 5000 individuals making it one of the most common inherited disorders.
Ans.2. Following systems are commonly involved in Marfan syndrome:
Upward subluxation of lens associated with cataract, thin tall extremities will long slender fingers, high-arched palates are characteristic finding. Thumb sign is positive when on making the fist, thumb protrudes out. Wrist sign is positive when on holding the wrist with other hand, thumb overlaps the fingers.
Chest deformity is also associated in form of pectus carinatum. Cardiovascular involvement is also seen and patient may have aortic regurgitation and mitral valve prolapse.
Ans 3. Fibrillin 1 is a glycoprotein which is an important component of extracellular matrix of connective tissue. These glycoproteins interact with other component in extracellular matrix and play very important role in making elastic and nonelastic fibers in extracellular matrix, thus have important role in tissue development, repair and homeostasis.
In addition to their structural role these fibrillins also play an important role in growth factor signaling and immune response.