Marfan syndrome
Encyclopedia
Marfan syndrome is a genetic disorder
of the connective tissue
. People with Marfan's tend to be unusually tall, with long limb
s and long, thin fingers.
It is inherited as a dominant trait. It is carried by a gene called FBN1
, which encodes a connective protein called fibrillin
-1. People have a pair of FBN1 genes. Because it is dominant, people who have inherited one affected FBN1 gene from either parent will have Marfan's.
Marfan syndrome has a range of expressions, from mild to severe. The most serious complications are defects of the heart valves and aorta
. It may also affect the lung
s, eyes, the dural
sac surrounding the spinal cord
, skeleton and the hard palate
.
In addition to being a connective protein that forms the structural support for tissues outside the cell, the normal fibrillin-1 protein binds to another protein, transforming growth factor beta (TGF-β). TGF-β has deleterious effects on vascular smooth muscle development and the integrity of the extracellular matrix. Researchers now believe that secondary to mutated fibrillin there is excessive TGF-β at the lungs, heart valves, and aorta, and this weakens the tissues and causes the features of Marfan syndrome. Since angiotensin II receptor blockers (ARBs) also reduce TGF-β, they have tested this by giving ARBs (losartan
, etc.) to a small sample of young, severely affected Marfan syndrome patients. In some patients, the growth of the aorta was indeed reduced.
Marfan syndrome is named after Antoine Marfan
, the French pediatrician who first described the condition in 1896. The gene linked to the disease was first identified by Francesco Ramirez in 1991.
). This condition of elongated limbs is known as dolichostenomelia
. An individual's arms may be disproportionately long, with thin, weak wrists. In addition to affecting height and limb proportions, Marfan syndrome can produce other skeletal anomalies. Abnormal curvature of the spine
(scoliosis
) is not uncommon. Abnormal indentation (pectus excavatum
) or protrusion (pectus carinatum
) of the sternum. Other signs include abnormal joint flexibility, a high palate
, malocclusions, flat feet
, hammer toe
s, stooped shoulders, unexplained stretch marks
on the skin. It can also cause pain in the joints, bones and muscles in some patients. Some people with Marfan have speech disorder
s resulting from symptomatic high palates and small jaws. Early osteoarthritis
may occur.
and astigmatism
are common, but farsightedness can also result. Subluxation
(dislocation) of the crystalline lens
in one or both eyes (ectopia lentis
) (in 80% of patients) also occurs and may be detected by an ophthalmologist or optometrist using a slit-lamp
biomicroscope. In Marfan's the dislocation is typically superotemporal whereas in the similar condition homocystinuria
, the dislocation is inferonasal. Sometimes eye problems appear only after the weakening of connective tissue has caused detachment of the retina
. Early onset glaucoma
can be another related problem.
, or Angina pectoris with pain radiating to the back, shoulder, or arm. Cold arms, hands and feet can also be linked to Marfan's syndrome because of inadequate circulation. A heart murmur
, abnormal reading on an ECG
, or symptoms of angina can indicate further investigation. The signs of regurgitation from prolapse
of the mitral or aortic valves
(which control the flow of blood through the heart) result from cystic medial degeneration of the valves, which is commonly associated with Marfan's syndrome (see mitral valve prolapse
, aortic regurgitation). However, the major sign that would lead a doctor to consider an underlying condition is a dilated aorta
or an aortic aneurysm
. Sometimes, no heart problems are apparent until the weakening of the connective tissue (cystic medial degeneration) in the ascending aorta
causes an aortic aneurysm
or aortic dissection
, a surgical emergency. An aortic dissection is most often fatal and presents with pain radiating down the back, giving a tearing sensation.
Because of the underlying connective tissue abnormalities that cause Marfan syndrome, there is an increased incidence of dehiscence
of prosthetic mitral valve. Care should be taken to attempt repair of damaged heart valves rather than replacement.
During pregnancy, even in the absence of preconceived cardiovascular abnormality, women with Marfan syndrome are at significant risk of aortic dissection
, which is often fatal even when rapidly treated. For this reason, women with Marfan syndrome should receive a thorough assessment prior to conception, and echocardiography
should be performed every six to ten weeks during pregnancy, to assess the aortic root diameter. For most women, safe vaginal delivery is possible.
for spontaneous pneumothorax
. In spontaneous unilateral pneumothorax, air escapes from a lung and occupies the pleural space between the chest wall and a lung. The lung becomes partially compressed or collapsed. This can cause pain, shortness of breath, cyanosis
, and, if not treated, death. Marfan syndrome has also been associated with sleep apnea
and idiopathic
obstructive lung disease.
, the weakening of the connective tissue of the dural sac, the membrane that encases the spinal cord
. Dural ectasia can be present for a long time without producing any noticeable symptoms. Symptoms that can occur are lower back pain
, leg pain, abdominal pain
, other neurological symptoms in the lower extremities, or headache
s. Such symptoms usually diminish when the individual lies flat on his or her back. These types of symptoms might lead a doctor to order an X-ray
of the lower spine
. Dural ectasia is usually not visible on an X-ray in the early phases. A worsening of symptoms and the lack of finding any other cause should eventually lead a doctor to order an upright MRI of the lower spine. Dural ectasia that has progressed to the point of causing these symptoms would appear in an upright MRI image as a dilated pouch that is wearing away at the lumbar vertebrae
. Other spinal issues associated with Marfan include degenerative disk disease and spinal cysts. Marfan syndrome is also associated with dysautonomia
.
on chromosome 15
, which encodes
a glycoprotein
called fibrillin
-1, a component of the extracellular matrix. The Fibrillin 1 protein is essential for the proper formation of the extracellular matrix including the biogenesis and maintenance of elastic fibers
. The extracellular matrix is critical for both the structural integrity of connective tissue but also serves as a reservoir for growth factors. Elastin
fibers are found throughout the body but are particularly abundant in the aorta
, ligament
s and the ciliary zonule
s of the eye; consequently, these areas are among the worst affected.
A transgenic
mouse has been created carrying a single copy of a mutant fibrillin 1, a mutation similar to that found in the human fibrillin 1 gene that is known to cause Marfan syndrome. This mouse strain recapitulates many of the features of the human disease and promises to provide insights into the pathogenesis
of the disease. Reducing the level of normal fibrillin-1 causes a Marfan-related disease in mice.
Transforming growth factor
beta (TGFβ
) plays an important role in Marfan syndrome. Fibrillin-1 directly binds a latent form of TGFβ keeping it sequestered and unable to exert its biological activity. The simplest model of Marfan syndrome suggests that reduced levels of fibrillin-1 allow TGFβ levels to rise due to inadequate sequestration. Although it is not proven how elevated TGFβ levels are responsible for the specific pathology seen with the disease, an inflammatory reaction releasing proteases that slowly degrade the elastin fibers and other components of the extracellular matrix is known to occur. The importance of the TGFβ pathway was confirmed with the discovery of a similar syndrome Loeys-Dietz syndrome
involving the TGFβR2 gene on chromosome 3
, a receptor protein of TGFβ. Marfan syndrome has often been confused with Loeys-Dietz syndrome
, because of the considerable clinical overlap between the two pathologies.
has increased significantly over the last few decades, and clinical trials are underway for a promising new treatment. At present (2011), the syndrome is treated by simply addressing each issue as it arises and, in particular, preventive medication even for young children to slow progression of aortic dilation if such exists.
Marfan's syndrome is passed on to offspring dominantly. This means that a child with one parent a bearer of the gene have a 50% probability of getting the syndrome. However, as the gene causing Marfan's syndrome is known, there in principle are arduous genetic techniques of circumventing this. In 1996 the first preimplantation genetic testing therapy for Marfan's was conducted,http://www.ncbi.nlm.nih.gov/pubmed/9239687 in essence PGT means conducting a genetic testing on early stage IVF embryo cells and discarding those embryos affected by the Marfan mutation.
Regular checkups by a cardiologist are needed to monitor the health of the heart valves and the aorta. The goal of treatment is to slow the progression of aortic dilation and damage to heart valves by eliminating arrythmias, minimizing the heart rate
, and minimizing blood pressure
. Beta blocker
s have been used to control arrythmias and slow the heart rate
. Other medications might be needed to further minimize blood pressure without slowing the heart rate, such as ACE inhibitors and angiotensin II receptor antagonist
s, also known as angiontensin receptor blockers (ARBs). If the dilation of the aorta progresses to a significant diameter aneurysm
, causes a dissection or a rupture, or leads to failure of the aortic or other valve, then surgery (possibly a composite aortic valve graft [CAVG] or valve-sparing procedure) becomes necessary. Although aortic graft surgery (or any vascular surgery) is a serious undertaking it is generally successful if undertaken on an elective basis. Surgery in the setting of acute aortic dissection or rupture is considerably more problematic. Elective aortic valve/graft surgery is usually considered when aortic root diameter reaches 50 millimeters (2.0 inches), but each case needs to be specifically evaluated by a qualified cardiologist. New valve-sparing surgical techniques are becoming more common. As Marfan patients live longer, other vascular repairs are becoming more common, e.g., repairs of descending thoractic aortic aneurysms and aneurysms of vessels other than the aorta.
The skeletal and ocular manifestations of Marfan syndrome can also be serious, although not life-threatening. These symptoms are usually treated in the typical manner for the appropriate condition, such as with various kinds of pain medication or muscle relaxant
s. It is also common for patients to receive treatment from a physiotherapist, using TENS therapy
, ultrasound
and skeletal adjustment. This can also affect height, arm length, and life span. A physiotherapist can also help improve function and prevent injuries in individuals with Marfan's. The Nuss procedure
is now being offered to people with Marfan syndrome to correct 'sunken chest' or (pectus excavatum
). Because Marfan may cause spinal abnormalities that are asymptomatic, any spinal surgery contemplated on a Marfan patient should only follow detailed imaging and careful surgical planning, regardless of the indication for surgery.
Treatment of a spontaneous pneumothorax
is dependent on the volume of air in the pleural space and the natural progression of the individual's condition. A small pneumothorax might resolve without active treatment in one to two weeks. Recurrent pneumothoraces might require chest surgery. Moderately sized pneumothoraces might need chest drain
management for several days in a hospital. Large pneumothoraces are likely to be medical emergencies requiring emergency decompression.
Research in laboratory mice has suggested that the angiotensin II receptor antagonist
losartan
, which appears to block TGF-beta activity, can slow or halt the formation of aortic aneurysms in Marfan syndrome. A large clinical trial
sponsored by the National Institutes of Health
comparing the effects of losartan and atenolol on the aortas of Marfan patients was scheduled to begin in early 2007, coordinated by Johns Hopkins.
. It is associated with variable expressivity
; incomplete penetrance has not been definitively documented.
, the French pediatrician who first described the condition in 1896 after noticing striking features in a 5-year-old girl. The gene linked to the disease was first identified by Francesco Ramirez at the Mount Sinai Medical Center
in New York City
in 1991.
, an Olympic silver medalist in Women's Volleyball (1984) who died suddenly at a match from an aortic dissection; Jonathan Larson
, the author and composer of Rent
, who died from an aortic dissection the day before the off-Broadway opening of Rent; and Vincent Schiavelli
, an actor and spokesperson for the National Marfan Foundation.
Musicians and composers Niccolò Paganini
, Sergei Rachmaninoff
, and Robert Johnson are thought to have had the disease. Bradford Cox of the indie rock band Deerhunter has openly discussed having Marfan syndrome and its effects on his self-perception and confidence. Abraham Lincoln
was once thought to have had Marfan syndrome, but geneticists believe it unlikely, although he had some of the normal characteristic features. According to a 2007 theory, it is more likely that Lincoln had a different disorder, multiple endocrine neoplasia type 2B
, that caused skeletal features almost identical to Marfan syndrome.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
of the connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
. People with Marfan's tend to be unusually tall, with long limb
Limb (anatomy)
A limb is a jointed, or prehensile , appendage of the human or other animal body....
s and long, thin fingers.
It is inherited as a dominant trait. It is carried by a gene called FBN1
FBN1
Fibrillin-1 is a protein that in humans is encoded by the FBN1 gene.This gene encodes a member of the fibrillin family. The encoded protein is a large, extracellular matrix glycoprotein that serve as a structural component of 10-12 nm calcium-binding microfibrils...
, which encodes a connective protein called fibrillin
Fibrillin
Fibrillin is a glycoprotein, which is essential for the formation of elastic fibers found in connective tissue.Fibrillin is secreted into the extracellular matrix by fibroblasts and becomes incorporated into the insoluble microfibrils, which appear to provide a scaffoldfor deposition of elastin.It...
-1. People have a pair of FBN1 genes. Because it is dominant, people who have inherited one affected FBN1 gene from either parent will have Marfan's.
Marfan syndrome has a range of expressions, from mild to severe. The most serious complications are defects of the heart valves and aorta
Aorta
The aorta is the largest artery in the body, originating from the left ventricle of the heart and extending down to the abdomen, where it branches off into two smaller arteries...
. It may also affect the lung
Human lung
The human lungs are the organs of respiration in humans. Humans have two lungs, with the left being divided into two lobes and the right into three lobes. Together, the lungs contain approximately of airways and 300 to 500 million alveoli, having a total surface area of about in...
s, eyes, the dural
Dura mater
The dura mater , or dura, is the outermost of the three layers of the meninges surrounding the brain and spinal cord. It is derived from Mesoderm. The other two meningeal layers are the pia mater and the arachnoid mater. The dura surrounds the brain and the spinal cord and is responsible for...
sac surrounding the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
, skeleton and the hard palate
Hard palate
The hard palate is a thin horizontal bony plate of the skull, located in the roof of the mouth. It spans the arch formed by the upper teeth.It is formed by the palatine process of the maxilla and horizontal plate of palatine bone....
.
In addition to being a connective protein that forms the structural support for tissues outside the cell, the normal fibrillin-1 protein binds to another protein, transforming growth factor beta (TGF-β). TGF-β has deleterious effects on vascular smooth muscle development and the integrity of the extracellular matrix. Researchers now believe that secondary to mutated fibrillin there is excessive TGF-β at the lungs, heart valves, and aorta, and this weakens the tissues and causes the features of Marfan syndrome. Since angiotensin II receptor blockers (ARBs) also reduce TGF-β, they have tested this by giving ARBs (losartan
Losartan
Losartan is an angiotensin II receptor antagonist drug used mainly to treat high blood pressure . Losartan was the first angiotensin II receptor antagonist to be marketed. Losartan potassium is marketed by Merck & Co. Inc. under the trade name Cozaar...
, etc.) to a small sample of young, severely affected Marfan syndrome patients. In some patients, the growth of the aorta was indeed reduced.
Marfan syndrome is named after Antoine Marfan
Antoine Marfan
Antoine Bernard-Jean Marfan was a French pediatrician. He was born in Castelnaudary to Antoine Prosper Marfan and Adélaïde Thuries....
, the French pediatrician who first described the condition in 1896. The gene linked to the disease was first identified by Francesco Ramirez in 1991.
Signs and symptoms
The constellation of long limbs, dislocated lenses and the aortic root dilation are generally sufficient to make the diagnosis of Marfan syndrome with reasonable confidence. There are more than 30 other clinical features that are variably associated with the syndrome, most involving the skeleton, skin, and joints. There may be considerable clinical variability within families that carry the identical mutation.Skeletal system
Most of the readily visible signs are associated with the skeletal system. Many individuals with Marfan syndrome grow to above average height. Some have long slender limbs with long fingers and toes (arachnodactylyArachnodactyly
Arachnodactyly or achromachia, is a condition in which the fingers are abnormally long and slender in comparison to the palm of the hand...
). This condition of elongated limbs is known as dolichostenomelia
Dolichostenomelia
Dolichostenomelia is a human condition or habitus in which the limbs are unusually long. The name is derived from Ancient Greek...
. An individual's arms may be disproportionately long, with thin, weak wrists. In addition to affecting height and limb proportions, Marfan syndrome can produce other skeletal anomalies. Abnormal curvature of the spine
Vertebral column
In human anatomy, the vertebral column is a column usually consisting of 24 articulating vertebrae, and 9 fused vertebrae in the sacrum and the coccyx. It is situated in the dorsal aspect of the torso, separated by intervertebral discs...
(scoliosis
Scoliosis
Scoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
) is not uncommon. Abnormal indentation (pectus excavatum
Pectus excavatum
Pectus excavatum is the most common congenital deformity of the anterior wall of the chest, in which several ribs and the sternum grow abnormally. This produces a caved-in or sunken appearance of the chest...
) or protrusion (pectus carinatum
Pectus carinatum
Pectus carinatum, , also called pigeon chest, is a deformity of the chest characterized by a protrusion of the sternum and ribs. It is the opposite of pectus excavatum.-Causes:...
) of the sternum. Other signs include abnormal joint flexibility, a high palate
Palate
The palate is the roof of the mouth in humans and other mammals. It separates the oral cavity from the nasal cavity. A similar structure is found in crocodilians, but, in most other tetrapods, the oral and nasal cavities are not truly separate. The palate is divided into two parts, the anterior...
, malocclusions, flat feet
Flat feet
Flat feet is a formal reference to a medical condition in which the arch of the foot collapses, with the entire sole of the foot coming into complete or near-complete contact with the ground...
, hammer toe
Hammer toe
A hammer toe or contracted toe is a deformity of the proximal interphalangeal joint of the second, third, or fourth toe causing it to be permanently bent, resembling a hammer...
s, stooped shoulders, unexplained stretch marks
Stretch marks
Stretch marks or striae , as they are called in dermatology, are a form of scarring on the skin with an off-color hue. They are caused by tearing of the dermis, and over time can diminish but not disappear completely....
on the skin. It can also cause pain in the joints, bones and muscles in some patients. Some people with Marfan have speech disorder
Speech disorder
Speech disorders or speech impediments are a type of communication disorders where 'normal' speech is disrupted. This can mean stuttering, lisps, etc. Someone who is unable to speak due to a speech disorder is considered mute.-Classification:...
s resulting from symptomatic high palates and small jaws. Early osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
may occur.
Eyes
Marfan syndrome can also seriously affect the eyes and vision. NearsightednessMyopia
Myopia , "shortsightedness" ) is a refractive defect of the eye in which collimated light produces image focus in front of the retina under conditions of accommodation. In simpler terms, myopia is a condition of the eye where the light that comes in does not directly focus on the retina but in...
and astigmatism
Astigmatism (eye)
Astigmatism is an optical defect in which vision is blurred due to the inability of the optics of the eye to focus a point object into a sharp focused image on the retina. This may be due to an irregular or toric curvature of the cornea or lens. There are two types of astigmatism: regular and...
are common, but farsightedness can also result. Subluxation
Subluxation
A subluxation may have different meanings, depending on the medical specialty involved. It implies the presence of an incomplete or partial dislocation of a joint or organ. The World Health Organization defines both the medical subluxation and the chiropractic subluxation...
(dislocation) of the crystalline lens
Lens (anatomy)
The crystalline lens is a transparent, biconvex structure in the eye that, along with the cornea, helps to refract light to be focused on the retina. The lens, by changing shape, functions to change the focal distance of the eye so that it can focus on objects at various distances, thus allowing a...
in one or both eyes (ectopia lentis
Ectopia lentis
Ectopia lentis is a displacement or malposition of the eye's crystalline lens from its normal location. A partial dislocation of a lens is termed lens subluxation or subluxated lens; a complete dislocation of a lens is termed lens luxation or luxated lens.-Ectopia lentis in dogs and cats:Although...
) (in 80% of patients) also occurs and may be detected by an ophthalmologist or optometrist using a slit-lamp
Slit lamp
The slit lamp is an instrument consisting of a high-intensity light source that can be focused to shine a thin sheet of light into the eye. It is used in conjunction with a biomicroscope...
biomicroscope. In Marfan's the dislocation is typically superotemporal whereas in the similar condition homocystinuria
Homocystinuria
Homocystinuria, also known as cystathionine beta synthase deficiency or CBS deficiency, is an inherited disorder of the metabolism of the amino acid methionine, often involving cystathionine beta synthase...
, the dislocation is inferonasal. Sometimes eye problems appear only after the weakening of connective tissue has caused detachment of the retina
Retinal detachment
Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blindness. It is a medical emergency.The retina is a...
. Early onset glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
can be another related problem.
Cardiovascular system
The most serious signs and symptoms associated with Marfan syndrome involve the cardiovascular system. Undue fatigue, shortness of breath, heart palpitations, racing heartbeatsTachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
, or Angina pectoris with pain radiating to the back, shoulder, or arm. Cold arms, hands and feet can also be linked to Marfan's syndrome because of inadequate circulation. A heart murmur
Heart murmur
Murmurs are extra heart sounds that are produced as a result of turbulent blood flow that is sufficient to produce audible noise. Most murmurs can only be heard with the assistance of a stethoscope ....
, abnormal reading on an ECG
Electrocardiogram
Electrocardiography is a transthoracic interpretation of the electrical activity of the heart over a period of time, as detected by electrodes attached to the outer surface of the skin and recorded by a device external to the body...
, or symptoms of angina can indicate further investigation. The signs of regurgitation from prolapse
Prolapse
Prolapse literally means "to fall out of place", from the Latin prolabi meaning "to fall out". In medicine, prolapse is a condition where organs, such as the uterus, fall down or slip out of place. It is used for organs protruding through the vagina or the rectum or for the misalignment of the...
of the mitral or aortic valves
Heart valve
A heart valve normally allows blood flow in only one direction through the heart. The four valves commonly represented in a mammalian heart determine the pathway of blood flow through the heart...
(which control the flow of blood through the heart) result from cystic medial degeneration of the valves, which is commonly associated with Marfan's syndrome (see mitral valve prolapse
Mitral valve prolapse
Mitral valve prolapse is a valvular heart disease characterized by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. There are various types of MVP, broadly classified as classic and nonclassic. In its nonclassic form, MVP carries a low risk of...
, aortic regurgitation). However, the major sign that would lead a doctor to consider an underlying condition is a dilated aorta
Annuloaortic ectasia
Annuloaortic ectasia is a dilatation of the proximal ascending aorta and aortic annulus. It may cause aortic regurgitation, thoracic aortic dissection, aneurysm and rupture. It is often associated with Marfan syndrome. It can also be a complication due to tertiary syphilis...
or an aortic aneurysm
Aortic aneurysm
An aortic aneurysm is a general term for any swelling of the aorta to greater than 1.5 times normal, usually representing an underlying weakness in the wall of the aorta at that location...
. Sometimes, no heart problems are apparent until the weakening of the connective tissue (cystic medial degeneration) in the ascending aorta
Aorta
The aorta is the largest artery in the body, originating from the left ventricle of the heart and extending down to the abdomen, where it branches off into two smaller arteries...
causes an aortic aneurysm
Aortic aneurysm
An aortic aneurysm is a general term for any swelling of the aorta to greater than 1.5 times normal, usually representing an underlying weakness in the wall of the aorta at that location...
or aortic dissection
Aortic dissection
Aortic dissection occurs when a tear in the inner wall of the aorta causes blood to flow between the layers of the wall of the aorta and force the layers apart. The dissection typically extends anterograde, but can extend retrograde from the site of the intimal tear. Aortic dissection is a medical...
, a surgical emergency. An aortic dissection is most often fatal and presents with pain radiating down the back, giving a tearing sensation.
Because of the underlying connective tissue abnormalities that cause Marfan syndrome, there is an increased incidence of dehiscence
Dehiscence
Dehiscence can refer to:*Dehiscence is the spontaneous opening at maturity of a plant structure, such as a fruit, anther, or sporangium, to release its contents.*Wound dehiscence is a previously closed wound reopening....
of prosthetic mitral valve. Care should be taken to attempt repair of damaged heart valves rather than replacement.
During pregnancy, even in the absence of preconceived cardiovascular abnormality, women with Marfan syndrome are at significant risk of aortic dissection
Aortic dissection
Aortic dissection occurs when a tear in the inner wall of the aorta causes blood to flow between the layers of the wall of the aorta and force the layers apart. The dissection typically extends anterograde, but can extend retrograde from the site of the intimal tear. Aortic dissection is a medical...
, which is often fatal even when rapidly treated. For this reason, women with Marfan syndrome should receive a thorough assessment prior to conception, and echocardiography
Echocardiography
An echocardiogram, often referred to in the medical community as a cardiac ECHO or simply an ECHO, is a sonogram of the heart . Also known as a cardiac ultrasound, it uses standard ultrasound techniques to image two-dimensional slices of the heart...
should be performed every six to ten weeks during pregnancy, to assess the aortic root diameter. For most women, safe vaginal delivery is possible.
Lungs
Marfan syndrome is a risk factorRisk factor
In epidemiology, a risk factor is a variable associated with an increased risk of disease or infection. Sometimes, determinant is also used, being a variable associated with either increased or decreased risk.-Correlation vs causation:...
for spontaneous pneumothorax
Pneumothorax
Pneumothorax is a collection of air or gas in the pleural cavity of the chest between the lung and the chest wall. It may occur spontaneously in people without chronic lung conditions as well as in those with lung disease , and many pneumothoraces occur after physical trauma to the chest, blast...
. In spontaneous unilateral pneumothorax, air escapes from a lung and occupies the pleural space between the chest wall and a lung. The lung becomes partially compressed or collapsed. This can cause pain, shortness of breath, cyanosis
Cyanosis
Cyanosis is the appearance of a blue or purple coloration of the skin or mucous membranes due to the tissues near the skin surface being low on oxygen. The onset of cyanosis is 2.5 g/dL of deoxyhemoglobin. The bluish color is more readily apparent in those with high hemoglobin counts than it is...
, and, if not treated, death. Marfan syndrome has also been associated with sleep apnea
Sleep apnea
Sleep apnea is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur 5 to 30 times or more an hour. Similarly, each abnormally low...
and idiopathic
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
obstructive lung disease.
Central nervous system
Another condition that can reduce the quality of life for an individual, though not life-threatening, is dural ectasiaDural ectasia
Dural ectasia is a widening or ballooning of the dural sac surrounding the spinal cord usually at the lumbosacral level. It is one of the major manifestations of Marfan syndrome. It may cause low back pain, headaches and neurological signs such as weakness and loss of bowel and bladder function,...
, the weakening of the connective tissue of the dural sac, the membrane that encases the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
. Dural ectasia can be present for a long time without producing any noticeable symptoms. Symptoms that can occur are lower back pain
Back pain
Back pain is pain felt in the back that usually originates from the muscles, nerves, bones, joints or other structures in the spine.The pain can often be divided into neck pain, upper back pain, lower back pain or tailbone pain...
, leg pain, abdominal pain
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
, other neurological symptoms in the lower extremities, or headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
s. Such symptoms usually diminish when the individual lies flat on his or her back. These types of symptoms might lead a doctor to order an X-ray
X-ray
X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
of the lower spine
Lumbar
In tetrapod anatomy, lumbar is an adjective that means of or pertaining to the abdominal segment of the torso, between the diaphragm and the sacrum ...
. Dural ectasia is usually not visible on an X-ray in the early phases. A worsening of symptoms and the lack of finding any other cause should eventually lead a doctor to order an upright MRI of the lower spine. Dural ectasia that has progressed to the point of causing these symptoms would appear in an upright MRI image as a dilated pouch that is wearing away at the lumbar vertebrae
Lumbar vertebrae
The lumbar vertebrae are the largest segments of the movable part of the vertebral column, and are characterized by the absence of the foramen transversarium within the transverse process, and by the absence of facets on the sides of the body...
. Other spinal issues associated with Marfan include degenerative disk disease and spinal cysts. Marfan syndrome is also associated with dysautonomia
Dysautonomia
Dysautonomia is a broad term that describes any disease or malfunction of the autonomic nervous system. This includes postural orthostatic tachycardia syndrome , inappropriate sinus tachycardia , vasovagal syncope, mitral valve prolapse dysautonomia, pure autonomic failure, neurocardiogenic...
.
Pathogenesis
Marfan syndrome is caused by mutations in the FBN1 geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
on chromosome 15
Chromosome 15 (human)
right|frame|Human chromosome 15Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 106 million base pairs and represents between 3% and 3.5% of the total DNA in cells.Identifying genes on each chromosome is an...
, which encodes
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
a glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
called fibrillin
Fibrillin
Fibrillin is a glycoprotein, which is essential for the formation of elastic fibers found in connective tissue.Fibrillin is secreted into the extracellular matrix by fibroblasts and becomes incorporated into the insoluble microfibrils, which appear to provide a scaffoldfor deposition of elastin.It...
-1, a component of the extracellular matrix. The Fibrillin 1 protein is essential for the proper formation of the extracellular matrix including the biogenesis and maintenance of elastic fibers
Elastic fibers
Elastic fibres are bundles of proteins found in extracellular matrix of connective tissue and produced by fibroblasts and smooth muscle cells in arteries. These fibers can stretch up to 1.5 times their length, and snap back to their original length when relaxed...
. The extracellular matrix is critical for both the structural integrity of connective tissue but also serves as a reservoir for growth factors. Elastin
Elastin
Elastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of...
fibers are found throughout the body but are particularly abundant in the aorta
Aorta
The aorta is the largest artery in the body, originating from the left ventricle of the heart and extending down to the abdomen, where it branches off into two smaller arteries...
, ligament
Ligament
In anatomy, the term ligament is used to denote any of three types of structures. Most commonly, it refers to fibrous tissue that connects bones to other bones and is also known as articular ligament, articular larua, fibrous ligament, or true ligament.Ligament can also refer to:* Peritoneal...
s and the ciliary zonule
Zonule of Zinn
The zonule of Zinn is a ring of fibrous strands connecting the ciliary body with the crystalline lens of the eye....
s of the eye; consequently, these areas are among the worst affected.
A transgenic
Genetically modified organism
A genetically modified organism or genetically engineered organism is an organism whose genetic material has been altered using genetic engineering techniques. These techniques, generally known as recombinant DNA technology, use DNA molecules from different sources, which are combined into one...
mouse has been created carrying a single copy of a mutant fibrillin 1, a mutation similar to that found in the human fibrillin 1 gene that is known to cause Marfan syndrome. This mouse strain recapitulates many of the features of the human disease and promises to provide insights into the pathogenesis
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
of the disease. Reducing the level of normal fibrillin-1 causes a Marfan-related disease in mice.
Transforming growth factor
Transforming growth factor
Transforming growth factor is used to describe two classes of polypeptide growth factors, TGFα and TGFβ....
beta (TGFβ
TGF beta
Transforming growth factor beta is a protein that controls proliferation, cellular differentiation, and other functions in most cells. It plays a role in immunity, cancer, heart disease, diabetes, Marfan syndrome, and Loeys–Dietz syndrome....
) plays an important role in Marfan syndrome. Fibrillin-1 directly binds a latent form of TGFβ keeping it sequestered and unable to exert its biological activity. The simplest model of Marfan syndrome suggests that reduced levels of fibrillin-1 allow TGFβ levels to rise due to inadequate sequestration. Although it is not proven how elevated TGFβ levels are responsible for the specific pathology seen with the disease, an inflammatory reaction releasing proteases that slowly degrade the elastin fibers and other components of the extracellular matrix is known to occur. The importance of the TGFβ pathway was confirmed with the discovery of a similar syndrome Loeys-Dietz syndrome
Loeys-Dietz syndrome
Loeys-Dietz syndrome is a recently-discovered autosomal dominant genetic syndrome which has many features similar to Marfan syndrome, but which is caused by mutations in the genes encoding transforming growth factor beta receptor 1 or 2 .It was identified and characterized by American physician...
involving the TGFβR2 gene on chromosome 3
Chromosome 3 (human)
Chromosome 3 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 3 spans almost 200 million base pairs and represents about 6.5 percent of the total DNA in cells....
, a receptor protein of TGFβ. Marfan syndrome has often been confused with Loeys-Dietz syndrome
Loeys-Dietz syndrome
Loeys-Dietz syndrome is a recently-discovered autosomal dominant genetic syndrome which has many features similar to Marfan syndrome, but which is caused by mutations in the genes encoding transforming growth factor beta receptor 1 or 2 .It was identified and characterized by American physician...
, because of the considerable clinical overlap between the two pathologies.
Diagnosis
Diagnostic criteria of Marfan syndrome were agreed internationally in 1996. A diagnosis of Marfan syndrome is based on family history and a combination of major and minor indicators of the disorder, rare in the general population, that occur in one individual. For example: four skeletal signs with one or more signs in another body system such as ocular and cardiovascular in one individual. The following conditions may result from Marfan syndrome but may also occur in people without any known underlying disorder.Revised Ghent Nosology
According to the US National Marfan Foundation, in 2010 the Ghent Nosology was revised and new diagnostic criteria superseded the previous agreement made in 1996. There are seven new criteria that can lead to a diagnosis:- Aortic root dilatation (defined as a Z-Score of 2 or higher) and ectopia lentis (dislocated optic lens)
- Aortic root dilatation and a confirmed mutation in the Fibrilin-1 gene (FBN1)
- Aortic root dilatation and a systemic Score of 7 or higher (see systemic score below)
- Ectopia lentis and a FBN1 mutation known to cause an aortic aneurysm
- Ectopia lentis and a family history with someone meeting the above criteria
- Systemic score of 7 or greater and a family history of Marfan syndrome
- Aortic root dilatation (Z-Score of 2 or higher for 20 years old or older, 3 or higher for people under the age of 20) and a family history of Marfan syndrome
Differential diagnosis
Many disorders have the potential to produce the same type of body habitus (i.e. shape) as Marfan syndrome. Distinguishing among these "marfanoid" disorders can be facilitated by genetic testing, and by evaluating signs and symptoms other than body habitus. Among the disorders capable of producing a marfanoid body habitus are:- Congenital Contractural Arachnodactyly (CCA) or Beals SyndromeArachnodactylyArachnodactyly or achromachia, is a condition in which the fingers are abnormally long and slender in comparison to the palm of the hand...
- Ehlers–Danlos syndrome
- HomocystinuriaHomocystinuriaHomocystinuria, also known as cystathionine beta synthase deficiency or CBS deficiency, is an inherited disorder of the metabolism of the amino acid methionine, often involving cystathionine beta synthase...
- Loeys–Dietz syndrome
- MASS phenotypeMASS phenotypeMASS phenotype is a medical disorder similar to Marfan syndrome.MASS stands for: mitral valve prolapse, aortic root diameter at upper limits of normal for body size, stretch marks of the skin, and skeletal conditions similar to Marfan syndrome....
- Shprintzen–Goldberg syndrome
- Stickler syndromeStickler syndromeStickler syndrome is a group of genetic disorders affecting connective tissue, specifically collagen. It was first studied and characterized by Gunnar B. Stickler in 1965. Stickler syndrome is a subtype of collagenopathy, types II and XI...
- Multiple endocrine neoplasia, type 2BMultiple endocrine neoplasia type 2bMultiple endocrine neoplasia type 3 is a genetic disease that causes multiple tumors on the mouth, eyes, and endocrine glands...
Management
There is no cure for Marfan syndrome, but life expectancyLife expectancy
Life expectancy is the expected number of years of life remaining at a given age. It is denoted by ex, which means the average number of subsequent years of life for someone now aged x, according to a particular mortality experience...
has increased significantly over the last few decades, and clinical trials are underway for a promising new treatment. At present (2011), the syndrome is treated by simply addressing each issue as it arises and, in particular, preventive medication even for young children to slow progression of aortic dilation if such exists.
Marfan's syndrome is passed on to offspring dominantly. This means that a child with one parent a bearer of the gene have a 50% probability of getting the syndrome. However, as the gene causing Marfan's syndrome is known, there in principle are arduous genetic techniques of circumventing this. In 1996 the first preimplantation genetic testing therapy for Marfan's was conducted,http://www.ncbi.nlm.nih.gov/pubmed/9239687 in essence PGT means conducting a genetic testing on early stage IVF embryo cells and discarding those embryos affected by the Marfan mutation.
Regular checkups by a cardiologist are needed to monitor the health of the heart valves and the aorta. The goal of treatment is to slow the progression of aortic dilation and damage to heart valves by eliminating arrythmias, minimizing the heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
, and minimizing blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
. Beta blocker
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...
s have been used to control arrythmias and slow the heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
. Other medications might be needed to further minimize blood pressure without slowing the heart rate, such as ACE inhibitors and angiotensin II receptor antagonist
Angiotensin II receptor antagonist
Angiotensin II receptor antagonists, also known as angiotensin receptor blockers , AT1-receptor antagonists or sartans, are a group of pharmaceuticals which modulate the renin-angiotensin-aldosterone system...
s, also known as angiontensin receptor blockers (ARBs). If the dilation of the aorta progresses to a significant diameter aneurysm
Aneurysm
An aneurysm or aneurism is a localized, blood-filled balloon-like bulge in the wall of a blood vessel. Aneurysms can commonly occur in arteries at the base of the brain and an aortic aneurysm occurs in the main artery carrying blood from the left ventricle of the heart...
, causes a dissection or a rupture, or leads to failure of the aortic or other valve, then surgery (possibly a composite aortic valve graft [CAVG] or valve-sparing procedure) becomes necessary. Although aortic graft surgery (or any vascular surgery) is a serious undertaking it is generally successful if undertaken on an elective basis. Surgery in the setting of acute aortic dissection or rupture is considerably more problematic. Elective aortic valve/graft surgery is usually considered when aortic root diameter reaches 50 millimeters (2.0 inches), but each case needs to be specifically evaluated by a qualified cardiologist. New valve-sparing surgical techniques are becoming more common. As Marfan patients live longer, other vascular repairs are becoming more common, e.g., repairs of descending thoractic aortic aneurysms and aneurysms of vessels other than the aorta.
The skeletal and ocular manifestations of Marfan syndrome can also be serious, although not life-threatening. These symptoms are usually treated in the typical manner for the appropriate condition, such as with various kinds of pain medication or muscle relaxant
Muscle relaxant
A muscle relaxant is a drug which affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics...
s. It is also common for patients to receive treatment from a physiotherapist, using TENS therapy
Transcutaneous electrical nerve stimulation
Transcutaneous electrical nerve stimulation is the use of electric current produced by a device to stimulate the nerves for therapeutic purposes...
, ultrasound
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
and skeletal adjustment. This can also affect height, arm length, and life span. A physiotherapist can also help improve function and prevent injuries in individuals with Marfan's. The Nuss procedure
Nuss procedure
The Nuss procedure is a minimally-invasive procedure, invented by Dr. Donald Nuss for treating pectus excavatum. He developed it at Children's Hospital of The King's Daughters, in Norfolk, Virginia...
is now being offered to people with Marfan syndrome to correct 'sunken chest' or (pectus excavatum
Pectus excavatum
Pectus excavatum is the most common congenital deformity of the anterior wall of the chest, in which several ribs and the sternum grow abnormally. This produces a caved-in or sunken appearance of the chest...
). Because Marfan may cause spinal abnormalities that are asymptomatic, any spinal surgery contemplated on a Marfan patient should only follow detailed imaging and careful surgical planning, regardless of the indication for surgery.
Treatment of a spontaneous pneumothorax
Pneumothorax
Pneumothorax is a collection of air or gas in the pleural cavity of the chest between the lung and the chest wall. It may occur spontaneously in people without chronic lung conditions as well as in those with lung disease , and many pneumothoraces occur after physical trauma to the chest, blast...
is dependent on the volume of air in the pleural space and the natural progression of the individual's condition. A small pneumothorax might resolve without active treatment in one to two weeks. Recurrent pneumothoraces might require chest surgery. Moderately sized pneumothoraces might need chest drain
Chest tube
A chest tube is a flexible plastic tube that is inserted through the side of the chest into the pleural space. It is used to remove air or fluid , or pus from the intrathoracic space...
management for several days in a hospital. Large pneumothoraces are likely to be medical emergencies requiring emergency decompression.
Research in laboratory mice has suggested that the angiotensin II receptor antagonist
Angiotensin II receptor antagonist
Angiotensin II receptor antagonists, also known as angiotensin receptor blockers , AT1-receptor antagonists or sartans, are a group of pharmaceuticals which modulate the renin-angiotensin-aldosterone system...
losartan
Losartan
Losartan is an angiotensin II receptor antagonist drug used mainly to treat high blood pressure . Losartan was the first angiotensin II receptor antagonist to be marketed. Losartan potassium is marketed by Merck & Co. Inc. under the trade name Cozaar...
, which appears to block TGF-beta activity, can slow or halt the formation of aortic aneurysms in Marfan syndrome. A large clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
sponsored by the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
comparing the effects of losartan and atenolol on the aortas of Marfan patients was scheduled to begin in early 2007, coordinated by Johns Hopkins.
Epidemiology
Marfan syndrome affects males and females equally, and the mutation shows no ethnic or geographical bias. Estimates indicate that approximately 1 in 3,000 to 5,000 individuals have Marfan syndrome. Each parent with the condition has a 50% risk of passing the genetic defect on to any child due to its autosomal dominant nature. Most individuals with Marfan syndrome have another affected family member - approximately 15–30% of all cases are due to de novo genetic mutations—such spontaneous mutations occur in about 1 in 20,000 births. Marfan syndrome is also an example of dominant negative mutation and haploinsufficiencyHaploinsufficiency
Haploinsufficiency occurs when a diploid organism only has a single functional copy of a gene and the single functional copy of the gene does not produce enough of a gene product to bring about a wild-type condition, leading to an abnormal or diseased state...
. It is associated with variable expressivity
Expressivity
Expressivity is a term used in genetics to refer to variations in a phenotype among individuals carrying a particular genotype. The term can be used to characterize qualitatively or quantitatively the extent of phenotypic variation given a particular genotype. The term is analogous to the...
; incomplete penetrance has not been definitively documented.
History
Marfan syndrome is named after Antoine MarfanAntoine Marfan
Antoine Bernard-Jean Marfan was a French pediatrician. He was born in Castelnaudary to Antoine Prosper Marfan and Adélaïde Thuries....
, the French pediatrician who first described the condition in 1896 after noticing striking features in a 5-year-old girl. The gene linked to the disease was first identified by Francesco Ramirez at the Mount Sinai Medical Center
Mount Sinai Hospital, New York
Mount Sinai Hospital, founded in 1852, is one of the oldest and largest teaching hospitals in the United States. In 2011-2012, Mount Sinai Hospital was ranked as one of America's best hospitals by U.S...
in New York City
New York City
New York is the most populous city in the United States and the center of the New York Metropolitan Area, one of the most populous metropolitan areas in the world. New York exerts a significant impact upon global commerce, finance, media, art, fashion, research, technology, education, and...
in 1991.
Society and culture
Contributors to public perception of Marfan syndrome include Flo HymanFlo Hyman
Flora Jean Hyman was an American volleyball player and Olympic silver medalist. She died during a volleyball match in Japan, as a result of Marfan syndrome.-Early Life and Education:...
, an Olympic silver medalist in Women's Volleyball (1984) who died suddenly at a match from an aortic dissection; Jonathan Larson
Jonathan Larson
Jonathan Larson was an American composer and playwright noted for the serious social issues of multiculturalism, addiction, and homophobia explored in his work. Typical examples of his use of these themes are found in his works, Rent and tick, tick... BOOM!...
, the author and composer of Rent
Rent (musical)
Rent is a rock musical with music and lyrics by Jonathan Larson based on Giacomo Puccini's opera La bohème...
, who died from an aortic dissection the day before the off-Broadway opening of Rent; and Vincent Schiavelli
Vincent Schiavelli
Vincent Andrew Schiavelli was an American character actor noted for his work on stage, screen, and television often described as "the man with the sad eyes." He was notable for his numerous and often critically acclaimed cameo appearances.-Early life:Schiavelli was born in Brooklyn, New York, to a...
, an actor and spokesperson for the National Marfan Foundation.
Musicians and composers Niccolò Paganini
Niccolò Paganini
Niccolò Paganini was an Italian violinist, violist, guitarist, and composer. He was one of the most celebrated violin virtuosi of his time, and left his mark as one of the pillars of modern violin technique...
, Sergei Rachmaninoff
Sergei Rachmaninoff
Sergei Vasilievich Rachmaninoff was a Russian composer, pianist, and conductor. Rachmaninoff is widely considered one of the finest pianists of his day and, as a composer, one of the last great representatives of Romanticism in Russian classical music...
, and Robert Johnson are thought to have had the disease. Bradford Cox of the indie rock band Deerhunter has openly discussed having Marfan syndrome and its effects on his self-perception and confidence. Abraham Lincoln
Abraham Lincoln
Abraham Lincoln was the 16th President of the United States, serving from March 1861 until his assassination in April 1865. He successfully led his country through a great constitutional, military and moral crisis – the American Civil War – preserving the Union, while ending slavery, and...
was once thought to have had Marfan syndrome, but geneticists believe it unlikely, although he had some of the normal characteristic features. According to a 2007 theory, it is more likely that Lincoln had a different disorder, multiple endocrine neoplasia type 2B
Multiple endocrine neoplasia type 2b
Multiple endocrine neoplasia type 3 is a genetic disease that causes multiple tumors on the mouth, eyes, and endocrine glands...
, that caused skeletal features almost identical to Marfan syndrome.