Marfan Syndrome Essay Examples

!Marfan syndrome is an autosomal dominant disorder of connective tissue and mainly caused due to heterozygous mutations in fibrillin-1 encoding gene. This syndrome was described by Antoine Bernard-Jean Marfan in the year 1896. This disorder involves skeletal, ocular, cardiovascular systems, dura, lungs and integument. The manifestations observed are aortic aneurysm, dislocation of ocular lens, over growth of long bone. Most of the cases are due to FBN1 mutations. This syndrome affects 1 in 3000-5000 and one-fourth of the cases are sporadic. Diagnosis of this syndrome is often challenging since it is age-dependent and frequent in all types of populations, Marfan syndrome is inherited in Mendelian fashion and is lethal.
!!This syndrome is autosomal dominant disorder with high level of penetrance. Marfan syndrome is mainly caused due to fibrillin-19FBN-1) gene mutation on chromosome 15. Fibrillin-1 is a glycoprotein present in matrix of non elastic and elastic tissues. The elastic fibres are formed due to integration of fibrillin-1 monomers called as microfibrils. Homeostasis of extracellular matrix is maintained by cytokine TGF-β. TGF-β remains inactive in the extracellular medium. Once a physiological stimulus is received, the TGF-β molecules are released with the help of proteases whilst initiating signal transduction. Sequestration in matrix gets disturbed due to mutated or decreased forms of fibrillin-1.
Patients suffering with Marfan syndrome shows disorganization, fragmentation and related abnormalities in the medial layer of aorta. One of the important characteristic observed in patients is that the elastic lamina is replaced by glucosaminoglycans. The mutated allele produces defective fibrillin-1 which interferes with fibrillin polymerization and results in dominant negative effects such as structural abnormalities. Joint hyperlaxity, dural ectasia and lens luxation are the manifestations developed as a result of connective tissue weakness.
In cardiovascular system, prolapsed with regurgitation is observed. In people below age of 40 years, pulmonary artery is dilated due to peripheral stenosis. Mitral annulus is calcified in younger people. The annulus of abdominal aorta or descending thoracic is also observed.FBN1 testing in prenatal diagnosis is prevalent in case of known familial mutation. Detection of FBN1 mutation is difficult due to its complexity and size. FBN1 constitutes 65 exons in 200kb of DNA. The understanding of correlation established between phenotype and genotype is often poor till now. The substitution of cysteines in exons 26 -32 is responsible for this syndrome in early life. !!!The gene testing feasibility is always challenging because other factors in addition to FBN1 genotype is observed in MFS patients. This syndrome is caused by fibrillin-1 gene variants on 15th chromosome. Sequence variants were observed in TGF-β receptor factor 1 and 2 located on 3p22 and 9q22. 50% risk of recurrence is observed in patient’s children. Germline mosaicism is reported due to presence of gene variant (FBN1) in germ cells and FBN1 gene variants have high rate of penetrance. Complications arise due to incomplete penetrance of gene variants and their expressivity. Diagnosis of this syndrome is complicated as its age dependant and appearance of non specific symptoms. Due to these limitations, gene testing is used for medical screening and initiate ophthalmologic and cardiovascular surveillance.
Current gene testing may not be used because it won’t give a picture of all disease causing variants. As per Ghent’s criteria, the variants of causal gene can’t be detected in 30% of individuals. This syndrome testing can be performed by direct sequence analysis of introns-exon junctions and exons. Multiple ligation dependent probe amplification is used to detect duplications and multiexon deletions among patients with non detective FBN1 variant.
!!!!Patients with Marfan syndrome show aortic dilation, aortic aneurysms, aortic dissection, mitral valve prolapsed and aortic regurgitation. Aortic aneurysms and dilation is considered serious since aorta is enlarged and rupture or tear is imminent. Z score and aortic measurement are of greater importance when dealing with Marfan syndrome. Tear or rupture between aorta layers are observed leading to aortic dissection and lead to blood flow in between these layers. Aortic dissection is classified into two types namely dissection of ascending aorta and descending aorta. The dissection observed in ascending aorta is life threatening and immediate surgery is recommended. If descending aorta is observed, loss of blood flow occurs and aorta is severely dilated. If heart contracts, billowing was observed in the mitral valves. Irregular breathing and heartbeats are the main symptoms when patients suffer with mitral valve leakage. Aortic valve doesn’t get closed thus blood leaks into heart.
!!!!!Treatment considerations vary with different symptoms in case of Marfan syndrome. More than 50% of patients with this syndrome develop scoliosis. Back braces of 200 and 400 can be employed for children with scoliosis but this can’t straighten the curve. If the curve is more than 400, then surgery is an important action. Kyphosis occurs in lower spline and thoracic spline however the treatment remains same as scoliosis.
Regular tests should be undertaken to monitor cardiovascular condition. Beta blockers can be administered to reduce blood pressure resulting in decrement of heartbeat force. This drug also slows aortic dilation and decrease the incidence of aortic dissection. Because of more advantages, beta blockers are the drug of first choice. Angiotensin receptor blockers such as losartan can be employed to decrease aortic growth. Blood pressure and aortic stress can be controlled by Angiotensin converting enzyme inhibitors (ACE-i). ACE-i is the drug of choice if patient doesn’t respond to beta blockers.
If aorta attains certain size, a surgery is to be performed to repair ascending aorta. Once the heart pumps hard, a mitral valve surgery is imminent. Repair of abdominal aorta and descending thoracic is achieved by surgery. If patient suffers from lens dislocation, then implantation of artificial lens is recommended. Amblyopia is generally observed in case of patients with Marfan syndrome and it can be treated by stimulating lazy eye. It can be treated with atropine on the stronger eye to provoke the lazy eye. An opaque patch can be worn on the stronger eye for months to provoke the lazy eye. Pulmonary rehabilitation is a series of therapies and energy conservation techniques which can be practiced by the patients. In case of pneumothorax, a chest tube can be inserted and the air in the lungs is drained so as to facilitate the re-expansion of lungs. Pleurodesis can also be employed surgically which have positive effects on the patients rather than chemical treatment.
Some of the recommendations offered by emergency department are completion of emergency preparedness kit, bringing to the notice of emergency department. Exercise can bring well being at emotional and physical level for the patients suffering from Marfan
Syndrome. The important health measure to be considered in case of this syndrome is regular and gentle exercise and can bring the life expectancy to 70’s.
Marfan syndrome has no cure however treatment can be administered for each of the symptoms. There is a need of special training and enlightment to the physicians to deal patients with this syndrome.