Pleiotropy of Marfan Syndrome Summary

Marfan syndrome is a connective tissue disease that is inherited and is characterized by pleiotropic manifestations exemplified in many organs such as the eyes, aorta, heart, skeleton, lung, and the pores and skin. Marfan syndrome is connected closely with the fibrillin gene which is placed on chromosome 15. On the other hand, there exists a cross-linkage between fibrillin gene and chromosome 5 which leads to the congenital contractural arachnodactyly: identifiably, this shares some physical points as the Marfan syndrome. Pleiotropy is the process whereby a single gene controls or influences multiple phenotypic features that are possibly unrelated. A growth factor called transforming growth factor beta (TGF B) has a primal effect in manifesting symptoms of Marfan syndrome; this is due to the fact that mutation in the fibrillin-1 gene causes the bioavailability of TGF B to be in excess, thus affecting the different types of connective tissues in the human body. On an average basis, patients suffering from Marfan syndrome have a reduced life expectancy by one-third (Pyeritz, 2005).

The heart is one of the phenotypes that are affected by pleiotropy of Marfan syndrome because of the vulnerability of the cardiovascular system to complications that are caused by the dilation of the ascending main artery (aorta) (Glesby and Pyeritz 1989). This is the reason why patients suffering from Marfan syndrome have a reduced life expectancy. Dissection of the aortic root can occur but due to the presence of connective tissues in the aortic root, the mutation only affects it. Different types of defects in elastin which lead to fragmentation of the elastic tissue have been suspected in the aorta’s tunica media. The heart is the central organ that keeps a human being alive and is capable of many functions that no other organ can perform. Among the functions of the heart is ensuring a continuous supply of substances throughout the body for the sustenance of homeostatic functioning of the body. When the functioning of the heart is interfered with, then the person is most likely not to live long unless the issue is curbed. The phenotypic variability including the clinical features of Marfan syndrome has been broadly discussed. Mutations of FBN1 gene which cause Marfan syndrome lead to a reduction in the fibrillin-1 amount produced by the cell, and, therefore, the bioavailability of TGF B factor increases. The diagnosis of this disease that is dominantly inherited is entirely based on family history and this has been problematic due to the extreme variability of expression clinically (Gott et al. 1986). The family history helps in identifying the phenotypic relationship between the parent genes and the offsprings’ genes which later helps in identifying the grossness of inherited disease (Hollister, Godfrey, Sakai, and Pyeritz, 1990).

The skeleton is also another phenotype that is affected by the pleiotropy of Marfan syndrome (Magid, Pyeritz, and Fishman 1990). The drastic effects that are experienced with the infestation of this pleiotropic autosomal dominant connective tissue disorder on the skeletal system are reduction of upper to lower segment ratio or arm span to height ratio greater than 1.05, pectus carinatum and pectus excavatum that requires surgery, spondylolisthesis, and wrist and thumb signs. FBN2 gene mutation is mostly linked to congenital contractural arachnodactyly. Missense mutations in FBN1 gene lead to vulnerability of the skeleton to Marfan syndrome. Congenital joint contracture which mostly affects the elbow occurs with moderate frequency in Marfan syndrome. The wrist sign is mostly dependent on the overlapping of the thumb of the terminal phalanx dominantly of the fifth digit in cases when one is grasping the contralateral wrist.

Consequently, another prominent manifestation of the pleiotropic autosomal dominant connective tissue disorder is the eye. The ocular system has a major criterion with regards to pleiotropy of Marfan syndrome being the ectopia lentis. Pupillary dilation and slit-lamp dislocations which can either be bilateral or unilateral need to be closely examined as they are some of the extreme effects that are related to the Marfan syndrome pleiotropy in the ocular system. Fluttering of the iris, commonly referred to as iridodonesis has been noted to be generally secondary to the major criterion of Marfan syndrome in the ocular system (ectopia lentis); this means, therefore, that iridodonesis is not separately counted as Marfan syndrome’s sign. Abnormal flattening of the cornea also needs to be examined as the degree to which this occurs is correlated positively with the presence of the major criterion of Marfan syndrome in the ocular system. Nuclear cataracts’ early development and open angle glaucoma have been considered typically as signs of Marfan syndrome. The axial length of the globe also increases with Marfan syndrome which later causes myopia and this augments retinal detachment (De Paepe et al 1996). Gene mutations of FBN1 gene that cause ectopia lentis change single amino acids located in the fibrillin-1 protein.

Ultimately, the dominant connective tissue disorder also affects the dura which is defined by neural canal enlargement anywhere along the spinal column. Several abnormalities in the signaling path way of TGF B which augments Marfan phenotype causes a decrease in the orderly incorporation of fibrillin directly into the connective tissue matrix. The major criterion involved in this phenotype is the lumbosacral dural ectasia by CT or MRI (Pyeritz et al 1988). Deletion mutations of the FBN1 gene will lead to the dura being affected as a phenotype of Marfan syndrome. The spinal column, therefore, remains vulnerable to being so much affected as a result of the neural canal enlargement along it. The neural canal enlargement occurs nearly always in the lower lumbar and sacral regions. Additionally, the thinning of the pedicles’ cortex vertebrae laminae and the neural foraminae widening are the other definitions of dural ectasia.

The skin and integument also comprise of the phenotypes that are affected by pleiotropy of Marfan syndrome (Grahame and Pyeritz 1995). Stretch marks (striae atrophicae) are preferentially localized on the shoulders, the lower or mid back, and the thighs; these are mostly seen in Marfan syndrome and also in MASS phenotype (Pyeritz 2008). The stretch marks have no association with marked changes in weight, pregnancy, or repetitive stress. According to Hollister et al (1990), the interference of the microfibrillar system is the lead reason why the skin is affected by the pleiotropy of the skin and the integument; this is due to dislocation of the fibrillin-1 gene encoded by FBN1 on chromosome 15 at band q21.1 (Dietz 1995; Ramirez and Perreira 1999). Fragmentation of the elastic tissue as a result of the numerous defects of elastin occurs in the skin in many patients that are vulnerable to Marfan syndrome.

The pulmonary system is another phenotype affected by the pleiotropy of Marfan syndrome (Streeten, Murphy, and Pyeritz 1987).In connection to this; the chest cavity is always at risk of attacks because of apical blebs which are ascertained by chest radiography and spontaneous pneumothorax (Hall et al 1984). Different types of defects in elastin which lead to fragmentation of the elastic tissue have been suspected in the arteries. Chest problems have a close link to affecting the cardiovascular system with regards to Marfan syndrome pleiotropy. Ultimately, a mutant FBN1 gene weakens the pulmonary system by disrupting fibrillin-1 multimerization and thereby preventing microfibril formation.


Marfan syndrome is a distinctively inheritable connective tissue disorder whose patients require much attention and care. Scientists are still looking into ways in which the menace can be done away with due to the fact that the affected families always have less of options with regards to their survival expectations. The dynamic scientific evolution has optimistically shown that there are better ways of getting rid of this disease from the human race. The study of genetics has also provided a basis for understanding on the tissues and organs that are most vulnerable to being affected as a result of Marfan syndrome and therefore it is important to prioritize in this study to make this a success. A mechanism that works against the phenotypic heterogeneity of Marfan syndrome is the only solution that can help reduce the augmenting risk of prevalence of the dominant connective-tissue disease; such will most likely include the reduced interaction between gene on chromosome 15 and fibrillin 1. Cases of misdiagnosis need also to be curbed to reduce the prevalence of Marfan syndrome.


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