marfan syndrome

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Marfan Syndrome:

Marfan Syndrome Prepared by / ahmed khamees alhamss Supervised by / dr . Basem ayesh


description Heritable disorder of the connective tissue . Not tied to any particular sex, race, or ethnic group 1 in 10000 incidence Caused by a mutation in the FBN1 gene that determines the structure of fibrillin Fibrillin1 is an extracellular matrix glycoprotein that polymerizes to form microfibrils in connective tissue and elastic fibers in multiple parts of the body such as bones , joints , eyes , blood vessels , and heart .

FBN-1 Gene:

FBN-1 Gene Located on chromosome 15 . Marfan syndrome is caused by over 100 different mutations on FBN1 Mutations scattered across the gene and each family has it’s unique mutation .

Defective Fibrillin 1 Protein:

Defective Fibrillin 1 Protein Amount of fibrillin 1 protein produced by cells is reduced . Structure and stability of protein is affected . Transport of fibrillin 1 protein out of the cell is impaired . Amount of fibrillin 1 reduced means decreased microfibril production . Less microfibril leads to more active TGF-beta , which leads to Marfan’s symptoms .

Basic Genetic Information:

Basic Genetic Information 25-35 % de novo mutations . Autosomal Dominant . Dominant negative Mutation – the altered gene product antagonizes the product of the normal gene (mutant fibrilin1 inhibits formation of normal microfibrils by normal one or stimulates proteolysis of EC microfibrils )

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The phenotype is consistent within a family although the severity of phenotype may vary considerably . So , intrafamiliar and interfamiliar variability suggest that environmental and epigenetic factors play a significant role in determining the phenotype . The disease show age dependent development of the manifestations .


Fibrillin-1 mutation causes several Marfanlike disorders such as : the mitral valve prolapse . aortic dilation . (MASS) phenotype ( myopia,mitral valve prolapse skin, and skeletal features ) . or isolated ectopia lentis .

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Clinical picture Skeleton A tall, slender body build. Long arms, legs, fingers, and toes ( arachnodactylyl ). A person’s arm span (the distance from the fingertips of one hand to the fingertips of the other with the arms stretched out from the sides) may be greater than his or her height. A receding lower jaw, causing an overbite. A protruding or sunken chest. A curved spine. Flat feet that are rotated inward

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Eyes Off-center or dislocated lenses . Retinal detachment . Skin Strech marks with Increased risk for abdominal hernias .

Heart and Blood vessels:

Heart and Blood vessels The major cause of death from this disease . Abnormally large mitral valve leaflets Mitral regurgitation Weakened middle layer of aortic wall so , aneurysm may form Tears in inner and middle aortic layers .

Dural ectasia :

Dural ectasia a hallmark of Marfan syndrome that is very rare in the general population. ( 65-92% )

Pulmonary findings :

Pulmonary findings Spontaneous pneumothorax (about 5% of patients) Apical blebs on chest radiography Sleep apnea . This may be due to looseness of the connective tissue in the airways.


diagnosis The diagnosis cannot be based on molecular analysis alone because molecular diagnosis is not practically availiable as allelic heterogeneity makes identification of the causative mutation in each family prohibitively labor-intensive and because of the lack of reliable genotype-phenotype correlation. Marfan syndrome is currently diagnosed using criteria based on an evaluation of the family history , molecular data , and 6 organ systems .

Berlin criteria:

Berlin criteria Marfan syndrome was diagnosed on the basis of involvement of : the skeletal system 2 other systems at least one major manifestation (ectopia lentis, aortic dilatation or dissection, or dural ectasia )

Ghent criteria:

Ghent criteria Revised in 1995 based on clinical observation of various organ systems and on the family history.

Testing and Diagnosis:

Testing and Diagnosis Genetic diagnosis For at risk individuals , in families segregating the disease by detecting the mutations when it happens to be known . Prenatal diagnosis available only in families in which the mutation is known .

Testing and Diagnosis:

Testing and Diagnosis Imaging tests Chest x-ray MRI

Treatment :

Treatment There is no cure for Marfan Syndrome but there are some treatments to help improve the quality of life . B blockers for heart manifestations . Prophylactic replacement of aortic root . Surgery for scoliosis . Lens replacement .

Life Expectancy:

Life Expectancy For woman, life expectancy has risen from 49 to 74 years . For men, life expectancy has risen from 41 to 70 years in the last 32 years . This life expectancy of Marfan patients is now about that of and average person, this has grown because there is currently better treatment for Marfan Syndrome .

Clinical case:

Clinical case J.L., a healthy 16-year-old high school basketball star . was referred to the genetics clinic for evaluation for Marfan syndrome . His father, a tall, thin man, had died during a morning jog . No other family member with history of sudden death and congenital abnormalities . J.l had an asthenic habitus with a high arched palate, mild pectus carinatum , arachnodactyly , arm span-height ratio of 1.1, diastolic murmur, and stretch marks on his shoulders and thighs . dilatation of the aortic root with aortic regurgitation . displacement of the lenses . the geneticist explained to J.L. and his mother that he had Marfan syndrome.

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