Marfan syndrome (MFS) is a multi-systemic
genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
that affects the
connective tissue
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
.
Those with the condition tend to be tall and thin, with
long arms, legs,
fingers, and toes.
[ They also typically have exceptionally flexible joints and abnormally curved spines.][ The most serious complications involve the ]heart
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
and aorta
The aorta ( ) is the main and largest artery in the human body, originating from the left ventricle of the heart and extending down to the abdomen, where it splits into two smaller arteries (the common iliac arteries). The aorta distributes ...
, with an increased risk of mitral valve prolapse
Mitral valve prolapse (MVP) is a valvular heart disease characterized by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. It is the primary form of myxomatous degeneration of the valve. There ar ...
and aortic aneurysm
An aortic aneurysm is an enlargement (dilatation) of the aorta to greater than 1.5 times normal size. They usually cause no symptoms except when ruptured. Occasionally, there may be abdominal, back, or leg pain. The prevalence of abdominal aortic ...
.[ The lungs, eyes, bones, and the covering of the spinal cord are also commonly affected.][ The severity of the symptoms is variable.]
MFS is caused by a mutation in ''FBN1
Fibrillin-1 is a protein that in humans is encoded by the ''FBN1'' gene, located on chromosome 15. It is a large, extracellular matrix glycoprotein that serves as a structural component of 10-12 nm calcium-binding microfibrils. These microfibr ...
'', one of the genes that makes 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 ...
, which results in abnormal connective tissue. It is an autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
disorder.[ In about 75% of cases, it is inherited from a parent with the condition, while in about 25% it is a new mutation.][ Diagnosis is often based on the ]Ghent criteria
Marfan syndrome (MFS) is a multi-systemic genetic disorder that affects the connective tissue. Those with the condition tend to be tall and thin, with long arms, legs, fingers, and toes. They also typically have exceptionally flexible joints a ...
.
There is no known cure for MFS.[ Many of those with the disorder have a normal life expectancy with proper treatment.][ Management often includes the use of ]beta blocker
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage cardiac arrhythmia, abnormal heart rhythms, and to protect the heart from a second myocardial infarction, heart attack after a first heart ...
s such as propranolol
Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anx ...
or atenolol
Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of mi ...
or, if they are not tolerated, calcium channel blocker
Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...
s or ACE inhibitor
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...
s.[ Surgery may be required to repair the aorta or replace a ]heart valve
A heart valve is a one-way valve that allows blood to flow in one direction through the chambers of the heart. Four valves are usually present in a mammalian heart and together they determine the pathway of blood flow through the heart. A heart v ...
. Avoiding strenuous exercise is recommended for those with the condition.[
About 1 in 5,000 to 1 in 10,000 people have MFS.] Rates of the condition are similar in different regions of the world.[ It is named after French ]pediatrician
Pediatrics ( also spelled ''paediatrics'' or ''pædiatrics'') is the branch of medicine that involves the medical care of infants, children, adolescents, and young adults. In the United Kingdom, paediatrics covers many of their youth until the ...
Antoine Marfan
Antoine Bernard-Jean Marfan (; June 23, 1858 – February 11, 1942) was a French paediatrician.
He was born in Castelnaudary (département Aude, Languedoc-Roussillon) to Antoine Prosper Marfan and Adélaïde Thuries. He began his medical studies i ...
, who first described it in 1896.
Signs and symptoms
More than 30 signs and symptom
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...
s are variably associated with Marfan syndrome. The most prominent of these affect the skeletal, cardiovascular, and ocular systems, but all fibrous connective tissue throughout the body can be affected.
Skeletal system
Most of the readily visible signs are associated with the skeletal system
A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...
. Many people with Marfan syndrome grow to above-average height, and some have disproportionately long, slender limbs with thin, weak wrists and long fingers and toes.
The Steinberg sign, also known as the thumb sign, is one of the clinical examination tests for Marfan disease in the hands. It is a clinical test in which the tip of the thumb extends beyond the palm when the thumb is clasped in the clenched hand.
Besides affecting height and limb proportions, people with Marfan syndrome may have abnormal lateral curvature of the spine scoliosis
Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...
, thoracic lordosis
Lordosis is historically defined as an ''abnormal'' inward curvature of the lumbar spine. However, the terms ''lordosis'' and ''lordotic'' are also used to refer to the normal inward curvature of the lumbar and cervical regions of the human spi ...
, abnormal indentation (''pectus excavatum
Pectus excavatum is a structural deformity of the anterior thoracic wall in which the sternum and rib cage are shaped abnormally. This produces a caved-in or sunken appearance of the chest. It can either be present at birth or develop after pubert ...
'') or protrusion (''pectus carinatum
Pectus carinatum, also called pigeon chest, is a malformation of the chest characterized by a protrusion of the sternum and ribs. It is distinct from the related malformation pectus excavatum.
Signs and symptoms
People with pectus carinatum usua ...
'') of the sternum
The sternum or breastbone is a long flat bone located in the central part of the chest. It connects to the ribs via cartilage and forms the front of the rib cage, thus helping to protect the heart, lungs, and major blood vessels from injury. Sh ...
, abnormal joint flexibility, a high-arched palate
A high-arched palate (also termed high-vaulted palate) is where the palate is unusually high and narrow. It is usually a congenital developmental feature that results from the failure of the palatal shelves to fuse correctly in development, the sa ...
with crowded teeth and an overbite, flat feet
Flat feet (also called pes planus or fallen arches) is a postural deformity in which the arches of the foot collapse, with the entire sole of the foot coming into complete or near-complete contact with the ground. Sometimes children are born ...
, hammer toe
A hammer toe or contracted toe is a deformity of the muscles and ligaments of the proximal interphalangeal joint of the second, third, fourth, or fifth toe causing it to be bent, resembling a hammer. In the early stage a flexible hammertoe is m ...
s, stooped shoulders, and unexplained stretch marks
Stretch marks, also known as striae () or striae distensae, are a form of scarring on the skin with an off-color hue. Over time they may diminish, but will not disappear completely. Striae are caused by tearing of the dermis during periods of r ...
on the skin. It can also cause pain in the joints, bones, and muscles. Some people with Marfan have speech disorder
Speech disorders or speech impairments are a type of communication disorder in which normal speech is disrupted. This can mean stuttering, lisps, etc. Someone who is unable to speak due to a speech disorder is considered mute. Speech skills ar ...
s resulting from symptomatic high palates and small jaws. Early osteoarthritis
Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...
may occur. Other signs include limited range of motion in the hips due to the femoral head
The femoral head (femur head or head of the femur) is the highest part of the thigh bone (femur). It is supported by the femoral neck.
Structure
The head is globular and forms rather more than a hemisphere, is directed upward, medialward, and a l ...
protruding into abnormally deep hip sockets.
Eyes
In Marfan syndrome, the health of the eye can be affected in many ways, but the principal change is partial lens dislocation, where the lens is shifted out of its normal position. This occurs because of weakness in the ciliary zonules, the connective tissue strands which suspend the lens within the eye. The mutations responsible for Marfan syndrome weaken the zonules and cause them to stretch. The inferior zonules are most frequently stretched resulting in the lens shifting upwards and outwards, but it can shift in other directions as well. Nearsightedness
Near-sightedness, also known as myopia and short-sightedness, is an eye disease where light focuses in front of, instead of on, the retina. As a result, distant objects appear blurry while close objects appear normal. Other symptoms may include ...
(myopia), and blurred vision
Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details.
Temporary blurred vision may involve dry eyes, eye infections, alcohol poisoning, hypoglycemia, or low blood pressure. ...
are common due to connective tissue defects in the eye. Farsightedness can also result particularly if the lens is highly subluxated. Subluxation
A subluxation is an incomplete or partial dislocation of a joint or organ.
According to the World Health Organization (WHO), a subluxation is a "significant structural displacement", and is therefore always visible on static imaging studies, suc ...
(partial dislocation) of the lens
A lens is a transmissive optical device which focuses or disperses a light beam by means of refraction. A simple lens consists of a single piece of transparent material, while a compound lens consists of several simple lenses (''elements''), ...
can be detected clinically in about 60% of people with Marfan syndrome by the use of a slit-lamp
A 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. The lamp facilitates an examination of the anterior segm ...
biomicroscope. If the lens subluxation is subtle, then imaging with high-resolution ultrasound biomicroscopy might be used.
Other signs and symptoms affecting the eye include increased length along an axis of the globe, myopia, corneal flatness, strabismus
Strabismus is a vision disorder in which the eyes do not properly align with each other when looking at an object. The eye that is focused on an object can alternate. The condition may be present occasionally or constantly. If present during a ...
, exotropia
Exotropia is a form of strabismus where the eyes are deviated outward. It is the opposite of esotropia and usually involves more severe axis deviation than exophoria. People with exotropia often experience crossed diplopia. Intermittent exotropi ...
, and esotropia
Esotropia is a form of strabismus in which one or both eyes turns inward. The condition can be constantly present, or occur intermittently, and can give the affected individual a "cross-eyed" appearance. It is the opposite of exotropia and usual ...
. Those with MFS are also at a high risk for early glaucoma
Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...
and early cataract
A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...
s.
Cardiovascular system
The most serious signs and symptoms associated with Marfan syndrome involve the cardiovascular system
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
: undue fatigue
Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
, shortness of breath
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...
, heart palpitations
Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart.
Symptoms include a rapi ...
, racing heartbeats, or chest pain
Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with n ...
radiating to the back, shoulder, or arm. Cold arms, hands, and feet can also be linked to MFS because of inadequate circulation. A heart murmur
Heart murmurs are unique heart sounds produced when blood flows across a heart valve or blood vessel. This occurs when turbulent blood flow creates a sound loud enough to hear with a stethoscope. Turbulent blood flow is not smooth. The sound di ...
, abnormal reading on an ECG
Electrocardiography is the process of producing an electrocardiogram (ECG or EKG), a recording of the heart's electrical activity. It is an electrogram of the heart which is a graph of voltage versus time of the electrical activity of the hear ...
, or symptoms of angina
Angina, also known as angina pectoris, is chest pain or pressure, usually caused by ischemia, insufficient blood flow to the Cardiac muscle, heart muscle (myocardium). It is most commonly a symptom of coronary artery disease.
Angina is typical ...
can indicate further investigation. The signs of regurgitation from prolapse
In medicine, prolapse is a condition in which organs fall down or slip out of place. It is used for organs protruding through the vagina, rectum, or for the misalignment of the valves of the heart. A spinal disc herniation is also sometimes call ...
of the mitral or aortic valves (which control the flow of blood through the heart) result from cystic medial degeneration
Familial thoracic aortic aneurysm is an autosomal Dominance (genetics), dominant disorder of large arteries.
There is an association between familial thoracic aortic aneurysm and Marfan syndrome as well as other hereditary connective tissue disord ...
of the valves, which is commonly associated with MFS (see mitral valve prolapse
Mitral valve prolapse (MVP) is a valvular heart disease characterized by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. It is the primary form of myxomatous degeneration of the valve. There ar ...
, aortic regurgitation
Aortic regurgitation (AR), also known as aortic insufficiency (AI), is the leaking of the aortic valve of the heart that causes blood to flow in the reverse direction during ventricular diastole, from the aorta into the left ventricle. As a conseq ...
). However, the major sign that would lead a doctor to consider an underlying condition is a dilated aorta or an aortic aneurysm
An aortic aneurysm is an enlargement (dilatation) of the aorta to greater than 1.5 times normal size. They usually cause no symptoms except when ruptured. Occasionally, there may be abdominal, back, or leg pain. The prevalence of abdominal aortic ...
. 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
Aortic dissection (AD) occurs when an injury to the innermost layer of the aorta allows blood to flow between the layers of the aortic wall, forcing the layers apart. In most cases, this is associated with a sudden onset of severe chest or ...
, a surgical emergency. An aortic dissection is most often fatal and presents with pain radiating down the back, giving a tearing sensation.
Because underlying connective tissue abnormalities cause MFS, the incidence of dehiscence of prosthetic mitral valve is increased. Care should be taken to attempt repair of damaged heart valves rather than replacement.
Lungs
Individuals with Marfan Syndrome may be affected by various lung-related problems. One study found that only 37% of the patient sample studied (mean age 32±14 years; M 45%) had normal lung function. Spontaneous pneumothorax
A pneumothorax is an abnormal collection of air in the pleural space between the lung and the chest wall. Symptoms typically include sudden onset of sharp, one-sided chest pain and shortness of breath. In a minority of cases, a one-way valve ...
is common. In spontaneous unilateral pneumothorax, air escapes from a lung and occupies the pleural
The pleural cavity, pleural space, or interpleural space is the potential space between the pleurae of the pleural sac that surrounds each lung. A small amount of serous pleural fluid is maintained in the pleural cavity to enable lubrication bet ...
space between the chest wall and a lung. The lung becomes partially compressed or collapsed. This can cause pain, shortness of breath, cyanosis
Cyanosis is the change of body tissue color to a bluish-purple hue as a result of having decreased amounts of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Body tissues that show cyanosis are usually in locations ...
, and, if not treated, death. Other possible pulmonary manifestations of MFS include sleep apnea
Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many times ...
and idiopathic
An idiopathic disease is any disease with an unknown cause or mechanism of apparent wikt:spontaneous, spontaneous origin. From Ancient Greek, Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approxi ...
obstructive lung disease. Pathologic changes in the lungs have been described such as cyst
A cyst is a closed sac, having a distinct envelope and cell division, division compared with the nearby Biological tissue, tissue. Hence, it is a cluster of Cell (biology), cells that have grouped together to form a sac (like the manner in which ...
ic changes, emphysema
Emphysema, or pulmonary emphysema, is a lower respiratory tract disease, characterised by air-filled spaces ( pneumatoses) in the lungs, that can vary in size and may be very large. The spaces are caused by the breakdown of the walls of the alve ...
, pneumonia
Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...
, bronchiectasis
Bronchiectasis is a disease in which there is permanent enlargement of parts of the bronchi, airways of the lung. Symptoms typically include a chronic cough with sputum, mucus production. Other symptoms include shortness of breath, hemoptysis, co ...
, bullae, apical fibrosis
Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...
and congenital malformations such as middle lobe hypoplasia.
Nervous system
Dural ectasia
Dural ectasia is widening or ballooning of the dural sac surrounding the spinal cord. This usually occurs in the lumbosacral region, as this is where the cerebrospinal fluid pressure is greatest, but the spinal canal can be affected in any plane.
...
, the weakening of the connective tissue of the dural sac encasing the spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...
, can result in a loss of quality of life
Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...
. It 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 headachessymptoms which usually diminish when lying flat. On X-ray
An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nb ...
, however, dural ectasia is not often visible in the early stages. A worsening of symptoms might warrant an MRI
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
of the lower spine. Dural ectasia that has progressed to this stage would appear in an MRI as a dilated pouch wearing away at the lumbar vertebrae
The lumbar vertebrae are, in human anatomy, the five vertebrae between the rib cage and the pelvis. They are the largest segments of the vertebral column and are characterized by the absence of the foramen transversarium within the transverse p ...
. Other spinal issues associated with MFS include degenerative disc disease
Degenerative disc disease (DDD) is a medical condition typically brought on by the normal aging process in which there are anatomic changes and possibly a loss of function of one or more intervertebral discs of the spine. DDD can take place with ...
, spinal cyst
A cyst is a closed sac, having a distinct envelope and cell division, division compared with the nearby Biological tissue, tissue. Hence, it is a cluster of Cell (biology), cells that have grouped together to form a sac (like the manner in which ...
s, and dysfunction of the autonomic nervous system.
Genetics
Each parent with the condition has a 50% risk of passing the genetic defect
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
on to any child due to its autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
nature. Most individuals with MFS have another affected family member. About 75% of cases are inherited. On the other hand, about 15–30% of all cases are due to ''de novo'' genetic mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...
s; such spontaneous mutations occur in about one in 20,000 births. Marfan syndrome is also an example of dominant negative mutation
Hermann J. Muller (1890–1967), who was a 1946 Nobel Prize winner, coined the terms amorph, hypomorph, hypermorph, antimorph and neomorph to classify mutations based on their behaviour in various genetic situations, as well as gene interacti ...
and haploinsufficiency
Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type ...
. It is associated with variable expressivity; complete penetrance has been definitively documented.
Pathogenesis
Marfan syndrome is caused by mutations in the ''FBN1'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
on chromosome 15
Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 102 million base pairs (the building material of DNA) and represents between 3% and 3.5% of the total DNA ...
, which encodes fibrillin 1
Fibrillin-1 is a protein that in humans is encoded by the ''FBN1'' gene, located on chromosome 15. It is a large, extracellular matrix glycoprotein that serves as a structural component of 10-12 nm calcium-binding microfibrils. These microfibr ...
, a glycoprotein component of the extracellular matrix. Fibrillin-1 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. Elastic fibers are found throughout the body, but are particularly abundant in the aorta, ligament
A ligament is the fibrous connective tissue that connects bones to other bones. It is also known as ''articular ligament'', ''articular larua'', ''fibrous ligament'', or ''true ligament''. Other ligaments in the body include the:
* Peritoneal li ...
s and the ciliary zonule
The zonule of Zinn () (Zinn's membrane, ciliary zonule) (after Johann Gottfried Zinn) is a ring of fibrous strands forming a zonule (little band) that connects the ciliary body with the crystalline lens of the eye. These fibers are sometimes colle ...
s of the eye; consequently, these areas are among the worst affected. It can also be caused by a range of intravenous crystal treatments in those susceptible to the disorder.
A transgenic
A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
mouse has been created carrying a single copy of a mutant fibrillin-1, a mutation similar to that found in the human gene known to cause MFS. This mouse strain recapitulates many of the features of the human disease and promises to provide insights into the pathogenesis
Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
of the disease. Reducing the level of normal fibrillin 1 causes a Marfan-related disease in mice.
Transforming growth factor Transforming growth factor (, or TGF) is used to describe two classes of polypeptide growth factors, TGFα and TGFβ.
The name "Transforming Growth Factor" is somewhat arbitrary, since the two classes of TGFs are not structurally or genetically rel ...
beta (TGF-β
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...
) plays an important role in MFS. Fibrillin-1 directly binds a latent form of TGF-β, keeping it sequestered and unable to exert its biological activity. The simplest model suggests reduced levels of fibrillin-1 allow TGF-β levels to rise due to inadequate sequestration. Although how elevated TGF-β levels are responsible for the specific pathology seen with the disease is not proven, an inflammatory reaction releasing proteases that slowly degrade the elastic fibers and other components of the extracellular matrix is known to occur. The importance of the TGF-β pathway was confirmed with the discovery of the similar Loeys–Dietz syndrome
Loeys–Dietz syndrome (LDS) is an autosomal dominant genetic connective tissue disorder. It has features similar to Marfan syndrome and Ehlers–Danlos syndrome. The disorder is marked by aneurysms in the aorta, often in children, and the aorta ...
involving the ''TGFβR2'' gene on chromosome 3
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 (the building material of DNA) and represents about 6.5 percent of the total DNA in ...
, a receptor protein
In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a recept ...
of TGF-β. Marfan syndrome has often been confused with Loeys–Dietz syndrome, because of the considerable clinical overlap between the two pathologies.
Marfanoid–progeroid–lipodystrophy syndrome
Marfanoid–progeroid–lipodystrophy syndrome
Marfanoid–progeroid–lipodystrophy syndrome (MPL), also known as Marfan lipodystrophy syndrome (MFLS) or progeroid fibrillinopathy, is an extremely rare medical condition which manifests as a variety of symptoms including those usually associat ...
(MPL), also referred to as Marfan lipodystrophy syndrome (MFLS), is a variant of MFS in which Marfan symptoms are accompanied by features usually associated with neonatal progeroid syndrome (also referred to as Wiedemann–Rautenstrauch syndrome) in which the levels of white adipose tissue
White adipose tissue or white fat is one of the two types of adipose tissue found in mammals. The other kind is brown adipose tissue. White adipose tissue is composed of monolocular adipocytes.
In humans, the healthy amount of white adipose ti ...
are reduced. Since 2010, evidence has been accumulating that MPL is caused by mutations near the 3'-terminus of the ''FBN1'' gene. It has been shown that these people are also deficient in asprosin
Asprosin is a protein hormone produced by mammals in ( white adipose) tissues that stimulates the liver to release glucose into the blood stream. Asprosin is encoded by the gene ''FBN1'' as part of the protein profibrillin and is released from the ...
, a gluco-regulatory protein hormone which is the C-terminal cleavage product of profibrillin. The levels of asprosin seen in these people were lower than expected for a heterozygous genotype, consistent with a dominant negative
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
effect.
Diagnosis
Diagnostic criteria of MFS were agreed upon internationally in 1996. However, Marfan syndrome is often difficult to diagnose in children, as they typically do not show symptoms until reaching pubescence. A diagnosis 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 individualfor 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 MFS, but may also occur in people without any known underlying disorder.
* Aortic aneurysm or dilation
* Arachnodactyly
Arachnodactyly ("spider fingers") is a medical condition that is characterized by fingers and toes that are abnormally long and slender, in comparison to the palm of the hand and arch of the foot. In some cases, the thumbs of an individual with the ...
* GERD Gerd or GERD may refer to:
* Gerd (given name), a list of people with the given name or nickname
* Gerd (moon), a moon of Saturn
* Gerd Island, South Orkney Islands, Antarctica
* Gastroesophageal reflux disease, a chronic symptom of mucosal damage ...
* Bicuspid aortic valve
Bicuspid aortic valve (aka BAV) is a form of heart disease in which two of the leaflets of the aortic valve fuse during development in the womb resulting in a two-leaflet (bicuspid) valve instead of the normal three-leaflet (tricuspid) valve. BA ...
* Cysts
A cyst is a closed sac, having a distinct envelope and division compared with the nearby tissue. Hence, it is a cluster of cells that have grouped together to form a sac (like the manner in which water molecules group together to form a bubble) ...
* Cystic medial necrosis
Familial thoracic aortic aneurysm is an autosomal dominant disorder of large arteries.
There is an association between familial thoracic aortic aneurysm and Marfan syndrome as well as other hereditary connective tissue disorders.
Signs and symp ...
* Degenerative disk disease
Degenerative disc disease (DDD) is a medical condition typically brought on by the normal aging process in which there are anatomic changes and possibly a loss of function of one or more intervertebral discs of the spine. DDD can take place with ...
* Deviated septum
Nasal septum deviation is a physical disorder of the nose, involving a displacement of the nasal septum. Some displacement is common, affecting 80% of people, mostly without their knowledge.
Signs and symptoms
The nasal septum is the bone and ...
* Dural ectasia
Dural ectasia is widening or ballooning of the dural sac surrounding the spinal cord. This usually occurs in the lumbosacral region, as this is where the cerebrospinal fluid pressure is greatest, but the spinal canal can be affected in any plane.
...
* Early cataract
A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...
s
* Early glaucoma
Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...
* Early osteoarthritis
Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...
* 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 lu ...
* Emphysema
Emphysema, or pulmonary emphysema, is a lower respiratory tract disease, characterised by air-filled spaces ( pneumatoses) in the lungs, that can vary in size and may be very large. The spaces are caused by the breakdown of the walls of the alve ...
* Iris
Iris most often refers to:
*Iris (anatomy), part of the eye
*Iris (mythology), a Greek goddess
* ''Iris'' (plant), a genus of flowering plants
* Iris (color), an ambiguous color term
Iris or IRIS may also refer to:
Arts and media
Fictional ent ...
coloboma
A coloboma (from the Greek , meaning defect) is a hole in one of the structures of the eye, such as the iris, retina, choroid, or optic disc. The hole is present from birth and can be caused when a gap called the choroid fissure, which is pres ...
* Above-average height
* Heart palpitation
Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart.
Symptoms include a rapi ...
s
* Hernias
A hernia is the abnormal exit of tissue or an organ, such as the bowel, through the wall of the cavity in which it normally resides. Various types of hernias can occur, most commonly involving the abdomen, and specifically the groin. Groin herni ...
* High-arched palate
A high-arched palate (also termed high-vaulted palate) is where the palate is unusually high and narrow. It is usually a congenital developmental feature that results from the failure of the palatal shelves to fuse correctly in development, the sa ...
* Hypermobility of the joints
* Kyphosis
Kyphosis is an abnormally excessive convex curvature of the spine as it occurs in the thoracic and sacral regions. Abnormal inward concave ''lordotic'' curving of the cervical and lumbar regions of the spine is called lordosis. It can result fr ...
(hunched back)
* Leaky heart valve
A heart valve is a one-way valve that allows blood to flow in one direction through the chambers of the heart. Four valves are usually present in a mammalian heart and together they determine the pathway of blood flow through the heart. A heart v ...
* Malocclusion
In orthodontics, a malocclusion is a misalignment or incorrect relation between the teeth of the upper and lower dental arches when they approach each other as the jaws close. The English-language term dates from 1864; Edward Angle (1855-1930), ...
* Micrognathia
Micrognathism is a condition where the jaw is undersized. It is also sometimes called mandibular hypoplasia. It is common in infants, but is usually self-corrected during growth, due to the jaws' increasing in size. It may be a cause of abnorm ...
(small lower jaw)
* Mitral valve prolapse
Mitral valve prolapse (MVP) is a valvular heart disease characterized by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. It is the primary form of myxomatous degeneration of the valve. There ar ...
* Myopia
Near-sightedness, also known as myopia and short-sightedness, is an eye disease where light focuses in front of, instead of on, the retina. As a result, distant objects appear blurry while close objects appear normal. Other symptoms may include ...
(nearsightedness)
* Obstructive lung disease
Obstructive lung disease is a category of respiratory disease characterized by airway obstruction. Many obstructive diseases of the lung result from narrowing (obstruction) of the smaller bronchi and larger bronchioles, often because of excessive ...
* Osteopenia
Osteopenia, known as "low bone mass" or "low bone density", is a condition in which bone mineral density is low. Because their bones are weaker, people with osteopenia may have a higher risk of fractures, and some people may go on to develop osteop ...
(low bone density)
* Pectus carinatum
Pectus carinatum, also called pigeon chest, is a malformation of the chest characterized by a protrusion of the sternum and ribs. It is distinct from the related malformation pectus excavatum.
Signs and symptoms
People with pectus carinatum usua ...
or excavatum
* Pes planus (flat feet
Flat feet (also called pes planus or fallen arches) is a postural deformity in which the arches of the foot collapse, with the entire sole of the foot coming into complete or near-complete contact with the ground. Sometimes children are born ...
)
* Pneumothorax
A pneumothorax is an abnormal collection of air in the pleural space between the lung and the chest wall. Symptoms typically include sudden onset of sharp, one-sided chest pain and shortness of breath. In a minority of cases, a one-way valve ...
(collapsed lung)
* 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 blin ...
* Scoliosis
Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...
* Sleep apnea
Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many times ...
* Stretch marks
Stretch marks, also known as striae () or striae distensae, are a form of scarring on the skin with an off-color hue. Over time they may diminish, but will not disappear completely. Striae are caused by tearing of the dermis during periods of r ...
not from pregnancy or obesity
* Teeth crowded
* "Narrow, thin face"
* Temporomandibular joint dysfunction
Temporomandibular joint dysfunction (TMD, TMJD) is an umbrella term covering pain and dysfunction of the muscles of mastication (the muscles that move the jaw) and the temporomandibular joints (the joints which connect the mandible to the skul ...
(TMD)
Revised Ghent nosology
In 2010, the Ghent nosology
Nosology () is the branch of medical science that deals with the classification of diseases. Fully classifying a medical condition requires knowing its cause (and that there is only one cause), the effects it has on the body, the symptoms that ...
was revised, and new diagnostic criteria superseded the previous agreement made in 1996. The seven new criteria can lead to a diagnosis:
In the absence of a family history of MFS:
# Aortic root Z-score ≥ 2 AND ectopia lentis
# Aortic root Z-score ≥ 2 AND an FBN1 mutation
# Aortic root Z-score ≥ 2 AND a systemic score* > 7 points
# Ectopia lentis AND an FBN1 mutation with known aortic pathology
In the presence of a family history of MFS (as defined above):
# 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 lu ...
# Systemic score* ≥ 7
# Aortic root Z-score ≥ 2
* Points for systemic score:
** Wrist AND thumb sign = 3 (wrist OR thumb sign = 1)
** Pectus carinatum deformity = 2 (pectus excavatum or chest asymmetry = 1)
** Hindfoot deformity = 2 (plain pes planus = 1)
** Dural ectasia
Dural ectasia is widening or ballooning of the dural sac surrounding the spinal cord. This usually occurs in the lumbosacral region, as this is where the cerebrospinal fluid pressure is greatest, but the spinal canal can be affected in any plane.
...
= 2
** Protrusio acetabuli
''Protrusio acetabuli'' is an uncommon defect of the ''acetabulum'', the socket that receives the femoral head to make the hip joint. The hip bone of the pelvic bone/girdle is composed of three bones, the ilium (bone), ilium, the ischium and the p ...
= 2
** pneumothorax
A pneumothorax is an abnormal collection of air in the pleural space between the lung and the chest wall. Symptoms typically include sudden onset of sharp, one-sided chest pain and shortness of breath. In a minority of cases, a one-way valve ...
= 2
** Reduced upper segment/lower segment ratio AND increased arm/height AND no severe scoliosis = 1
** Scoliosis
Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...
or thoracolumbar kyphosis
Kyphosis is an abnormally excessive convex curvature of the spine as it occurs in the thoracic and sacral regions. Abnormal inward concave ''lordotic'' curving of the cervical and lumbar regions of the spine is called lordosis. It can result fr ...
= 1
** Reduced elbow extension = 1
** Facial features (3/5) = 1 (dolichocephaly
Dolichocephaly (derived from the Ancient Greek δολιχός 'long' and κεφαλή 'head') is a condition where the head is longer than would be expected, relative to its width. In humans, scaphocephaly is a form of dolichocephaly.
Dolichocep ...
, enophthalmos
Enophthalmos is a posterior displacement of the eyeball within the orbit. It is due to either enlargement of the bony orbit and/or reduction of the orbital content, this in relation to each other.
It should not be confused with its opposite, ex ...
, downslanting palpebral fissure
The palpebral fissure is the elliptic space between the medial and lateral canthi of the two open eyelids. In simple terms, it is the opening between the eyelids. In adult humans, this measures about 10 mm vertically and 30 mm horizontally.
Var ...
s, malar hypoplasia
Hypoplasia (from Ancient Greek ὑπo- ''hypo-'' 'under' + πλάσις ''plasis'' 'formation'; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.retrognathia
Retrognathia is a type of malocclusion which refers to an abnormal posterior positioning of the maxilla or mandible, particularly the mandible, relative to the facial skeleton and soft tissues.
A retrognathic mandible is commonly referred to as a ...
)
** Skin striae (stretch marks
Stretch marks, also known as striae () or striae distensae, are a form of scarring on the skin with an off-color hue. Over time they may diminish, but will not disappear completely. Striae are caused by tearing of the dermis during periods of r ...
) = 1
** Myopia
Near-sightedness, also known as myopia and short-sightedness, is an eye disease where light focuses in front of, instead of on, the retina. As a result, distant objects appear blurry while close objects appear normal. Other symptoms may include ...
> 3 diopters = 1
** Mitral valve prolapse
Mitral valve prolapse (MVP) is a valvular heart disease characterized by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. It is the primary form of myxomatous degeneration of the valve. There ar ...
= 1
The thumb sign (Steinberg's sign) is elicited by asking the person to flex
Flex or FLEX may refer to:
Computing
* Flex (language), developed by Alan Kay
* FLEX (operating system), a single-tasking operating system for the Motorola 6800
* FlexOS, an operating system developed by Digital Research
* FLEX (protocol), a comm ...
the thumb as far as possible and then close the fingers over it. A positive thumb sign is where the entire distal phalanx
The phalanx ( grc, φάλαγξ; plural phalanxes or phalanges, , ) was a rectangular mass military formation, usually composed entirely of heavy infantry armed with spears, pikes, sarissas, or similar pole weapons. The term is particularly use ...
is visible beyond the ulna
The ulna (''pl''. ulnae or ulnas) is a long bone found in the forearm that stretches from the elbow to the smallest finger, and when in anatomical position, is found on the medial side of the forearm. That is, the ulna is on the same side of t ...
r border of the hand, caused by a combination of hypermobility of the thumb as well as a thumb which is longer than usual.
The wrist sign (Walker-Murdoch sign) is elicited by asking the person to curl the thumb and fingers of one hand around the other wrist. A positive wrist sign is where the little finger and the thumb overlap, caused by a combination of thin wrists and long fingers.
Differential diagnosis
Many other disorders can produce the same type of body characteristics as Marfan syndrome. Genetic testing and evaluating other signs and symptoms can help to differentiate these. The following are some of the disorders that can manifest as "marfanoid":
* Congenital contractural arachnodactyly
Congenital contractural arachnodactyly (CCA), also known as Beals-Hecht syndrome, is a rare autosomal dominant congenital connective tissue disorder. As with Marfan syndrome, people with CCA typically have an arm span that is greater than their hei ...
, also known as Beals-Hecht syndrome
* Ehlers–Danlos syndrome
* Homocystinuria
Homocystinuria or HCU is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase. It is an inherited autosomal recessive trait, which means a child needs to inh ...
* Loeys–Dietz syndrome
Loeys–Dietz syndrome (LDS) is an autosomal dominant genetic connective tissue disorder. It has features similar to Marfan syndrome and Ehlers–Danlos syndrome. The disorder is marked by aneurysms in the aorta, often in children, and the aorta ...
* MASS phenotype
MASS syndrome is a medical disorder of the connective tissue 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 si ...
* Multiple endocrine neoplasia, type 2B
* Shprintzen–Goldberg syndrome
* Stickler syndrome
Stickler syndrome (hereditary progressive arthro-ophthalmodystrophy) is a group of rare genetic disorders affecting connective tissue, specifically collagen. Stickler syndrome is a subtype of collagenopathy, types II and XI. Stickler syndrome i ...
Management
There is no cure for Marfan syndrome, but life expectancy has increased significantly over the last few decades and is now similar to that of the average person.
Regular checkups are recommended to monitor the health of the heart valves and the aorta
The aorta ( ) is the main and largest artery in the human body, originating from the left ventricle of the heart and extending down to the abdomen, where it splits into two smaller arteries (the common iliac arteries). The aorta distributes ...
. Marfan syndrome is treated by addressing each issue as it arises and, in particular, preventive medication even for young children to slow progression of aortic dilation. The goal of this treatment strategy is to slow the progression of aortic dilation and prevent any damage to heart valves by eliminating heart arrythmias, minimizing the heart rate
Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and excr ...
, and lowering the person's blood pressure
Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
.
Physical activity
The American Heart Association
The American Heart Association (AHA) is a nonprofit organization in the United States that funds cardiovascular medical research, educates consumers on healthy living and fosters appropriate cardiac care in an effort to reduce disability and death ...
made the following recommendations for people with Marfan syndrome with no or mild aortic dilation:
* Probably permissible activities: bowling, golf, skating (but not ice hockey), snorkeling, brisk walking, treadmill, stationary biking, modest hiking, and tennis (doubles and singles).
* Intermediate risk: basketball (both full- and half-court), racquetball, squash, running (sprinting and jogging), skiing (downhill and cross-country), soccer, touch (flag) football, baseball, softball, biking, lap swimming, motorcycling, and horseback riding.
* High risk: bodybuilding, weightlifting (non-free and free weights), ice hockey, rock climbing, windsurfing, surfing, and scuba diving.
Medication
Management often includes the use of beta blocker
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage cardiac arrhythmia, abnormal heart rhythms, and to protect the heart from a second myocardial infarction, heart attack after a first heart ...
s such as propranolol
Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anx ...
or if not tolerated calcium channel blocker
Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...
s or ACE inhibitor
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...
s.[ Beta blockers are used to reduce the stress exerted on the aorta and to decrease aortic dilation.]
Surgery
If the dilation of the aorta progresses to a significant-diameter aneurysm
An aneurysm is an outward bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also be a nidus (s ...
, causes a dissection or a rupture, or leads to failure of the aortic or other valve, then surgery (possibly a composite aortic valve graft or valve-sparing aortic root replacement
Valve-sparing aortic root replacement (also known as the David procedure) is a cardiac surgery procedure which is used to treat Aortic aneurysms and to prevent Aortic dissection. It involves replacement of the aortic root without replacement of the ...
) 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 , but each case needs to be specifically evaluated by a qualified cardiologist. New valve-sparing surgical techniques are becoming more common. As people with Marfan syndrome live longer, other vascular repairs are becoming more common, e.g., repairs of descending thoracic 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 an appropriate manner for the condition, such as with pain medications or muscle relaxant
A muscle relaxant is a drug that 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 therapeu ...
s. Because Marfan syndrome may cause asymptomatic spinal abnormalities, any spinal surgery contemplated on a person Marfan should only follow detailed imaging and careful surgical planning, regardless of the indication for surgery. The ocular complications of MFS can often be treated with surgery. 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 lu ...
can be treated, as artificial lenses can be surgically implanted. In addition, surgery can address glaucoma
Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...
and cataract
A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...
s.
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
A chest tube (also chest drain, thoracic catheter, tube thoracostomy or intercostal drain) is a surgical drain that is inserted through the chest wall and into the pleural space or the mediastinum in order to remove clinically undesired substance ...
management for several days in a hospital. Large pneumothoraces are likely to be medical emergencies requiring emergency decompression.
As an alternative approach, custom-built supports for the aortic root are also being used. As of 2020 this procedure has been used in over 300 people with the first case occurring in 2004.
Pregnancy
During pregnancy, even in the absence of preconception cardiovascular abnormality, women with Marfan syndrome are at significant risk of aortic dissection, which is often fatal even when rapidly treated. Women with Marfan syndrome, then, should receive a thorough assessment prior to conception, and echocardiography
An echocardiography, echocardiogram, cardiac echo or simply an echo, is an ultrasound of the heart.
It is a type of medical imaging of the heart, using standard ultrasound or Doppler ultrasound.
Echocardiography has become routinely used in t ...
should be performed every six to 10 weeks during pregnancy, to assess the aortic root diameter. For most women, safe vaginal delivery is possible.
Prenatal testing
Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health of ...
can be performed in females with Marfan syndrome to determine if the condition has been inherited in their child. At 10 to 12 weeks of pregnancy, examining a piece of placental tissue through a test called chorionic villus sampling can be performed to make a diagnosis. Another prenatal test can be performed called amniocentesis
Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is ne ...
at 16 to 18 weeks of pregnancy.
Marfan syndrome is expressed dominantly. This means a child with one parent a bearer of the gene has a 50% probability of getting the syndrome. In 1996, the first preimplantation genetic testing (PGT) therapy for Marfan was conducted; in essence PGT means conducting a genetic test on early-stage IVF
In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating an individual's ovulatory process, removing an ovum or ova (egg or eggs) fr ...
embryo cells and discarding those embryos affected by the Marfan mutation.
Prognosis
Prior to modern cardiovascular surgical techniques and medications such as losartan
Losartan, sold under the brand name Cozaar among others, is a medication used to treat high blood pressure (hypertension). It is in the angiotensin II receptor antagonist, angiotensin receptor blocker (ARB) family of medication, and is consider ...
, and metoprolol
Metoprolol, sold under the brand name Lopressor, among others, is a selective β1 receptor blocker medication. It is used to treat high blood pressure, chest pain due to poor blood flow to the heart, and a number of conditions involving an a ...
, the prognosis of those with Marfan syndrome was not good: a range of untreatable cardiovascular issues was common. Lifespan was reduced by at least a third, and many died in their teens and twenties due to cardiovascular problems. Today, cardiovascular symptoms of Marfan syndrome are still the most significant issues in diagnosis and management of the disease, but adequate prophylactic monitoring and prophylactic therapy offers something approaching a normal lifespan, and more manifestations of the disease are being discovered as more patients live longer. Women with Marfan syndrome live longer than men.
Epidemiology
Marfan syndrome affects males and females equally, and the mutation shows no ethnic or geographical bias.[ Estimates indicate about 1 in 5,000 to 10,000 individuals have Marfan syndrome.][
]
History
Marfan syndrome is named after Antoine Marfan
Antoine Bernard-Jean Marfan (; June 23, 1858 – February 11, 1942) was a French paediatrician.
He was born in Castelnaudary (département Aude, Languedoc-Roussillon) to Antoine Prosper Marfan and Adélaïde Thuries. He began his medical studies i ...
, the French pediatrician who first described the condition in 1896 after noticing striking features in a five-year-old girl.[Johns Hopkins Comprehensive Marfan Center.](_blank)
Johns Hopkins Medicine. Retrieved on January 6, 2009. The gene linked to the disease was first identified by Francesco Ramirez at the Mount Sinai Medical Center
Mount Sinai Hospital, formerly at times known as Mount Sinai Medical Center, is a 319-bed major urban hospital in Chicago, Illinois, with its main campus located adjacent to Douglass Park at 15th Street and California Avenue on the city's West Si ...
in New York City
New York, often called New York City or NYC, is the List of United States cities by population, most populous city in the United States. With a 2020 population of 8,804,190 distributed over , New York City is also the L ...
in 1991.[Brown P (July 27, 1991)]
"Marfan syndrome linked to gene".
''New Scientist''. Retrieved on August 11, 2008.
Famous patients
Famous people who have had Marfan syndrome include:
* Isaiah Austin
Isaiah Charles Austin (born October 25, 1993) is an American former professional basketball player. He played two years of college basketball for Baylor University and was set to enter the NBA in 2014 until he was diagnosed with a mild form of M ...
* Javier Botet
Javier Botet López (born 30 July 1977) is a Spanish actor. Often cast in creature roles, he has portrayed Tristana Medeiros in the ''REC'' franchise (2007–2012), the title character in '' Mama'' (2013), Set in '' The Mummy'' (2017), and Sl ...
* Austin Carlile
Austin Robert Carlile (born September 27, 1987) is an American musician and baseball coach from Pensacola, Florida. He achieved prominence as formerly the lead vocalist of Attack Attack! and Of Mice & Men. After leaving Of Mice & Men, he bega ...
* Bradford Cox
Bradford James Cox (born May 15, 1982) is an American singer-songwriter and musician, best known as the lead singer and guitarist of the indie rock band Deerhunter. He also pursues a solo career under the moniker Atlas Sound.
Cox formed Deerh ...
* Euell Gibbons
Euell Theophilus Gibbons (September 8, 1911 – December 29, 1975) was an outdoorsman and early health food advocate, promoting eating wild foods during the 1960s.
Early career
Gibbons was born in Clarksville, Texas, on September 8, 1911, a ...
* Flo Hyman
Flora Jean "Flo" Hyman (July 31, 1954 – January 24, 1986) was an American athlete who played volleyball. She was an Olympic silver medalist and played professional volleyball in Japan.
Early life and education
Hyman was the second of eight chi ...
* Jonathan Jeanne
* Vincent Schiavelli
Vincent Andrew Schiavelli (; November 11, 1948 – December 26, 2005) was an American character actor noted for his work on stage, screen, and television. Described as an "instantly recognizable sad-faced actor", he was diagnosed with Marfan s ...
* Troye Sivan
Troye Sivan Mellet ( ; born 5 June 1995) is an Australian singer-songwriter, actor and YouTuber. After gaining popularity as a singer on YouTube and in Australian talent competitions, Sivan signed with EMI Australia in 2013 and released his thi ...
* John Tavener
Sir John Kenneth Tavener (28 January 1944 – 12 November 2013) was an English composer, known for his extensive output of choral religious works. Among his best known works are '' The Lamb'' (1982), '' The Protecting Veil'' (1988), and ''Song ...
In addition the following historical figures and celebrities often appear on lists of people with Marfan syndrome, but from case to case the evidence is speculative, questionable, or even refuted.
* Akhenaten
Akhenaten (pronounced ), also spelled Echnaton, Akhenaton, ( egy, ꜣḫ-n-jtn ''ʾŪḫə-nə-yātəy'', , meaning "Effective for the Aten"), was an ancient Egyptian pharaoh reigning or 1351–1334 BC, the tenth ruler of the Eighteenth Dy ...
(Artistic depictions show many physical characteristics of people with Marfan, such as elongated skull and larger pelvis with enlarged thighs and spindly calves. Most Egyptologists as of 2021 argue that Akhenaten's portrayals are not the results of a genetic or medical condition, but rather should be interpreted as stylized portrayals influenced by Atenism
Atenism, the Aten religion, the Amarna religion, or the "Amarna heresy" was a religion and the religious changes associated with the ancient Egyptian Eighteenth Dynasty pharaoh Akhenaten. The religion centered on the cult of the god Aten, depi ...
.)
* Osama bin Laden
Osama bin Mohammed bin Awad bin Laden (10 March 1957 – 2 May 2011) was a Saudi-born extremist militant who founded al-Qaeda and served as its leader from 1988 until Killing of Osama bin Laden, his death in 2011. Ideologically a Pan-Islamism ...
(Marfan rumors deemed "likely false" by journalists)
* Julius Caesar
Gaius Julius Caesar (; ; 12 July 100 BC – 15 March 44 BC), was a Roman general and statesman. A member of the First Triumvirate, Caesar led the Roman armies in the Gallic Wars before defeating his political rival Pompey in a civil war, and ...
(speculative)
* Robert Johnson
Robert Leroy Johnson (May 8, 1911August 16, 1938) was an American blues musician and songwriter. His landmark recordings in 1936 and 1937 display a combination of singing, guitar skills, and songwriting talent that has influenced later generati ...
(speculative)
* Jonathan Larson
Jonathan David Larson (February 4, 1960 – January 25, 1996) was an American composer, lyricist and playwright most famous for writing the musicals ''Rent'' and '' Tick, Tick... Boom!'', which explored the social issues of multiculturalism, ...
(speculative)
* Abraham Lincoln
Abraham Lincoln ( ; February 12, 1809 – April 15, 1865) was an American lawyer, politician, and statesman who served as the 16th president of the United States from 1861 until his assassination in 1865. Lincoln led the nation thro ...
(disputed speculative diagnosis—Lincoln's DNA has not been tested)
* Niccolò Paganini
Niccolò (or Nicolò) Paganini (; 27 October 178227 May 1840) was an Italian violinist and composer. He was the most celebrated violin virtuoso of his time, and left his mark as one of the pillars of modern violin technique. His 24 Caprices f ...
(speculative)
* Michael Phelps
Michael Fred Phelps II (born June 30, 1985) is an American former competitive swimmer. He is the most successful and most decorated Olympian of all time with a total of 28 medals. Phelps also holds the all-time records for Olympic gold me ...
(disputed by Phelps)
* Sergei Rachmaninoff
Sergei Vasilyevich Rachmaninoff; in Russian pre-revolutionary script. (28 March 1943) was a Russian composer, virtuoso pianist, and conductor. Rachmaninoff is widely considered one of the finest pianists of his day and, as a composer, one o ...
(disputed: "Rachmaninov did not clearly exhibit any of the other clinical characteristics typical of Marfan's. . . . Nor did he express any of the clinical effects of a Marfan-related syndrome")
* Tutankhamen
Tutankhamun (, egy, wikt:twt-ꜥnḫ-jmn, twt-ꜥnḫ-jmn), Egyptological pronunciation Tutankhamen () (), sometimes referred to as King Tut, was an ancient Egypt, Egyptian pharaoh who was the last of his royal family to rule during the end ...
(did not have Marfan Syndrome)
See also
* Ehlers–Danlos syndrome
* Kashin–Beck disease
Kashin–Beck disease (KBD) is a chronic condition, chronic, endemic (epidemiology), endemic type of osteochondropathy (disease of the bone) that is mainly distributed from northeastern to southwestern China, including 15 provinces of China, provi ...
* Loeys–Dietz syndrome
Loeys–Dietz syndrome (LDS) is an autosomal dominant genetic connective tissue disorder. It has features similar to Marfan syndrome and Ehlers–Danlos syndrome. The disorder is marked by aneurysms in the aorta, often in children, and the aorta ...
* Nail-Patella syndrome
* Mitral valve prolapse
Mitral valve prolapse (MVP) is a valvular heart disease characterized by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. It is the primary form of myxomatous degeneration of the valve. There ar ...
* Uner Tan syndrome
Uner Tan syndrome (UTS) is a syndrome that was discovered by the Turkish evolutionary biologist Üner Tan. People affected by UTS walk with a quadrupedal locomotion and often have severe learning disabilities. Tan postulated that this is an exampl ...
Bibliography
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References
External links
*
Orphanet's disease page on Marfan syndrome
{{Authority control
Rare genetic syndromes
Autosomal dominant disorders
Cytoskeletal defects
Collagen disease
Disorders of fascia
Abnormalities of dermal fibrous and elastic tissue
Systemic connective tissue disorders
Syndromes affecting the heart
Syndromes affecting the lung
Syndromes affecting the eye
Syndromes affecting the nervous system
Syndromes with musculoskeletal abnormalities
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