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 ...
heart
The heart is a muscular Organ (biology), 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 ca ...
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. Ther ...
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 aorti ...
. 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'', one of the genes that makes fibrillin, which results in abnormal connective tissue. It is an autosomal dominant 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.
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 blockers such as propranolol or atenolol or, if they are not tolerated, calcium channel blockers or ACE inhibitors. Surgery may be required to repair the aorta or replace a heart valve. 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 pediatricianAntoine Marfan, who first described it in 1896.
Signs and symptoms
More than 30 signs and symptoms 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 individuals 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 ty ...
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 ...
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 ...
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 (myopia), and blurred vision are common due to connective tissue defects in the eye. Farsightedness can also result particularly if the lens is highly subluxated. Subluxation (partial dislocation) of the lens 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 seg ...
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, exotropia, 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 aqueous humor, fluid withi ...
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 ...
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 di ...
,
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 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, 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 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. Ther ...
,
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 cons ...
). 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 aorti ...
. 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 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 is common. 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 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 and idiopathic obstructive lung disease. Pathologic changes in the lungs have been described such as cystic changes, emphysema,
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 severit ...
,
bronchiectasis
Bronchiectasis is a disease in which there is permanent enlargement of parts of the airways of the lung. Symptoms typically include a chronic cough with mucus production. Other symptoms include shortness of breath, coughing up blood, and chest ...
, bullae, apical fibrosis and congenital malformations such as middle lobe hypoplasia.
Nervous system
Dural ectasia, 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 sp ...
, 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 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. Other spinal issues associated with MFS include degenerative disc disease, spinal cysts, 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 disorde ...
on to any child due to its autosomal dominant 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, ...
s; such spontaneous mutations occur in about one in 20,000 births. Marfan syndrome is also an example of dominant negative mutation and haploinsufficiency. 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 b ...
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 ...
, which encodesfibrillin 1, 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 l ...
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 collec ...
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 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 of the disease. Reducing the level of normal fibrillin 1 causes a Marfan-related disease in mice.Transforming growth factor 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 s ...
) 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 involving the ''TGFβR2'' gene on chromosome 3, 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 (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
An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used t ...
(also referred to as Wiedemann–Rautenstrauch syndrome) in which the levels of white adipose tissue 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, 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 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
* GERD
* Bicuspid aortic valve
*
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 sympt ...
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 aqueous humor, fluid withi ...
* 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 ...
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. Ther ...
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 ty ...
In 2010, the Ghent nosology 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
# 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 = 2
** Protrusio acetabuli = 2
** pneumothorax = 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 ty ...
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)
** Skin striae ( stretch marks) = 1
** Myopia > 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. Ther ...
= 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 com ...
the thumb as far as possible and then close the fingers over it. A positive thumb sign is where the entire distal phalanx is visible beyond the ulnar 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 h ...
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. 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, 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 ...
.
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 deat ...
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.
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 ( ...
, 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) 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 relaxants. 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 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 aqueous humor, fluid withi ...
and cataracts.
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 substances ...
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 ...
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 ...
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 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 embryo cells and discarding those embryos affected by the Marfan mutation.
Prognosis
Prior to modern cardiovascular surgical techniques and medications such as losartan, and metoprolol, 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, 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. 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 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 ...
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 ...
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 sy ...
*
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 th ...
* John Tavener
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 D ...
(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.)
* Osama bin Laden (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, an ...
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 throu ...
(disputed speculative diagnosis—Lincoln's DNA has not been tested)
* Niccolò Paganini (speculative)
* Michael Phelps (disputed by Phelps)
* Sergei Rachmaninoff (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, twt-ꜥnḫ-jmn), Egyptological pronunciation Tutankhamen () (), sometimes referred to as King Tut, was an Egyptian pharaoh who was the last of his royal family to rule during the end of the Eighteenth Dynasty (ruled ...
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. Ther ...