Classification and external resources
Marfan syndrome is an autosomal dominant genetic disorder of the connective tissue characterized by disproportionately long limbs, long thin fingers, a typically tall stature, and a predisposition to cardiovascular abnormalities, specifically those affecting the heart valves and aorta. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings Q00-Q89 - Congenital malformations and deformations (Q00-Q07 Nervous system ( Anencephaly and similar malformations The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Connective tissue is one of the four types of tissue in traditional classifications (the others being epithelial, Muscle, and Nervous tissue) A limb (from the Old English lim) is a jointed or Prehensile (as Octopus tentacles or new world Monkey tails Appendage of the In Anatomy, the heart valves are Valves in the Heart that maintain the unidirectional flow of blood by opening and closing depending on the difference The disorder may also affect numerous other structures and organs — including the lungs, eyes, dural sac surrounding the spinal cord, and hard palate. lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive The spinal cord is a long thin tubular bundle of Nerves that is an extension of the Central nervous system from the brain and is enclosed in and protected The hard palate is a thin horizontal bony plate of the Skull, located in the roof of the mouth It is named after Antoine Marfan, the French pediatrician who first described the condition in 1896 after noticing striking features in a 5 year old girl. Antoine Bernard-Jean Marfan ( June 23 1858 – 1942 was a French Pediatrician. This article is about the country For a topic outline on this subject see List of basic France topics. Pediatrics (also spelled paediatrics) is the branch of Medicine that deals with the medical care of Infants Children and Adolescents Year 1896 ( MDCCCXCVI) was a Leap year starting on Wednesday (link will display the full calendar of the Gregorian Calendar (or a Leap year 
Marfan syndrome affects males and females equally, and the mutation shows no geographical bias. Estimates indicate that approximately 60 000 (1 in 5000, or 0. 02% of the population) to 200 000 Americans have Marfan syndrome. Each parent with the condition has a 50% chance of passing it on to a child due to its autosomal dominant nature. Most individuals with Marfan syndrome have another affected family member, but approximately 15-30% of all cases are due to de novo genetic mutations — such spontaneous mutations occur in about 1 in 20 000 births. In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism Marfan syndrome is also an example of dominant negative mutation and haploinsufficiency. 1946 Nobel Prize winner Hermann J Muller (1890-1967 coined the terms amorph hypomorph hypermorph antimorph and neomorph to classify mutations based on their behaviour Haploinsufficiency occurs when a Diploid organism only has a single functional copy of a gene (with the other copy inactivated by Mutation) and the single  It is associated with variable expressivity. Incomplete penetrance has not been definitively documented. Penetrance is a term used in Genetics describing the proportion of individuals carrying a particular variation of a Gene (an Allele or genotype that also
Marfan syndrome is caused by mutations in the FBN1 gene on chromosome 15, which encodes a glycoprotein called fibrillin-1, a component of the extracellular matrix. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance A chromosome is an organized structure of DNA and Protein that is found in cells. Genetics (from Ancient Greek grc-Latn genetikos, “genitive” and that from grc-Latn genesis, “origin” a discipline of Biology, is Not to be confused with Peptidoglycan. Glycoproteins are proteins that contain Oligosaccharide chains ( Glycans) covalently attached Fibrillin is a Glycoprotein, which is essential for the formation of Elastic fibers found in Connective tissue. The Fibrillin 1 protein is essential for the proper formation of the extracellular matrix including the biogenesis and maintenance of elastic fibers. Elastic fibers (or yellow fibers) are bundles of Proteins ( Elastin) found in Connective tissue and produced by Fibroblasts and The extracellular matrix is critical for both the structural integrity of connective tissue but also serves as a reservoir for growth factors.  Elastin fibers are found throughout the body but are particularly abundant in the aorta, ligaments and the ciliary zonules of the eye, consequently these areas are among the worst affected. In Anatomy, the term ligament is used to denote three different types of structures Fibrous tissue that connects Bones to other bones The zonule of Zinn ( Zinn's membrane, ciliary zonule) is a ring of fibrous strands connecting the Ciliary body with the crystalline lens of the
A transgenic mouse has been created carrying a single copy of a mutant fibrillin 1, a mutation similar to that found in the human fibrillin 1 gene that is known to cause Marfan syndrome. This mouse strain recapitulates many of the features of the human disease and promises to provide insights into the pathogenesis of the disease. It has been found that simply reducing the level of normal fibrillin-1 causes a Marfan-related disease in mice. 
Transforming growth factor beta (TGFβ) plays an important role in Marfan syndrome. Transforming growth factor (sometimes referred to as Tumor growth factor, or TGF) is used to describe two classes of Polypeptide Growth factors Fibrillin-1 indirectly binds a latent form of TGFβ keeping it sequestered and unable to exert its biological activity. The simplest model of Marfan syndrome suggests that reduced levels of fibrillin-1 allow TGFb levels to rise due to inadequate sequestration. Although it is not proven how elevated TGFb levels would be responsible for the specific pathology seen with the disease, an inflammatory reaction releasing proteases that slowly degrade the elastin fibers and other components of the extracellular matrix is known to occur. The importance of the TGFb pathway was confirmed with the discovery of a similar syndrome Loeys-Dietz syndrome involving the TGFβR2 gene on chromosome 3, a receptor protein of TGFβ. Loeys-Dietz syndrome is a recently-discovered Autosomal dominant genetic Syndrome which has many features similar to Marfan syndrome, but which is A chromosome is an organized structure of DNA and Protein that is found in cells. In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling  Marfan syndrome has often been confused with Loeys-Dietz syndrome, because of the considerable clinical overlap between the two syndromes. Loeys-Dietz syndrome is a recently-discovered Autosomal dominant genetic Syndrome which has many features similar to Marfan syndrome, but which is 
Although there are no unique signs or symptoms of Marfan syndrome, the constellation of long limbs, dislocated lenses, and aortic root dilation is sufficient to make the diagnosis with confidence. There are more than thirty other clinical features that are variably associated with the syndrome most involving the skeleton, skin, and joints. There is a great deal of clinical variability even within families that carry the identical mutation.
The most readily visible signs are associated with the skeletal system. Many individuals with Marfan Syndrome grow to above average height. Some have long slender limbs with fingers and toes that are also abnormally long and slender (arachnodactyly). Arachnodactyly (" spider fingers " or achromachia, is a condition in which the fingers are abnormally long and slender in comparison to the palm This long, slender body habitus and long, slender limbs are known as dolichostenomelia. Dolichostenomelia is a Human Disease in which the limbs are unusually long An individual's arms may be disproportionately long, with thin, weak wrists. In addition to affecting height and limb proportions, Marfan syndrome can produce other skeletal signs. Abnormal curvature of the spine (scoliosis) is common, as is abnormal indentation (pectus excavatum) or protrusion (pectus carinatum) of the sternum. In Human anatomy, the vertebral column ( backbone or spine) is a column of 34 Vertebrae the Sacrum, Intervertebral Scoliosis is a medical condition in which a person's spine is curved from side to side and may also be rotated Pectus excavatum (a Latin term meaning hollowed chest) is the most common Congenital deformity of the anterior wall of the chest in which several Pectus carinatum, also called pigeon chest, is a deformity of the chest characterized by a protrusion of the Sternum and Ribs. The sternum (from Greek στέρνον sternon, "chest" or breastbone) is a long flat Bone located in the center of the thorax (chest Other signs include abnormal joint flexibility, a high palate, malocclusions, flat feet, stooped shoulders, unexplained stretch marks on the skin and thin wrists. The palate (ˈpælɨt is the roof of the Mouth in humans and Vertebrate animals " Striae " is also a general term referring to thin narrow grooves or channels or a thin line or band especially if several of them are parallel or close together Some people with Marfan have speech disorders resulting from symptomatic high palates and small jaws. Speech disorders or speech impediments, as they are also called are a type of Communication disorders where 'normal' speech is disrupted
Marfan syndrome can also seriously affect the eyes and vision. Nearsightedness and astigmatism are common, but farsightedness can also result. Myopia (from Greek: μυωπία myopia "near-sightedness" also called near- or short-sightedness, is a refractive defect Astigmatism is an optical defect whereby vision is blurred due to the inability of the optics of the eye to focus a point object into a sharp focused image on the retina Subluxation (dislocation) of the crystalline lens in one or both eyes (ectopia lentis) also occurs and may be detected by an ophthalmologist or optometrist using a slit-lamp biomicroscope. The lens is a transparent biconvex structure in the Eye that along with the Cornea, helps to Refract Light to be focused Ectopia lentis is a displacement or malposition of the Eye 's crystalline lens from its normal location Ophthalmology is the branch of Medicine which deals with the diseases and surgery of the visual pathways including the Eye, Brain Optometry is a health care profession concerned with Eyes and related structures as well as vision, Visual systems and vision information The slit lamp is an instrument consisting of a high-intensity Light source that can be focused to shine as a slit In Marfan's the dislocation is typically superotemporal whereas in the similar condition homocystinuria, the dislocation is inferonasal. Homocystinuria, also known as Cystathionine beta synthase deficiency, is an inherited disorder of the Metabolism of the Amino acid Methionine Sometimes eye problems appear only after the weakening of connective tissue has caused detachment of the retina. Retinal detachment is a disorder of the Eye in which the Retina peels away from its underlying layer of support tissue  Early onset glaucoma can be another complication. Glaucoma is a group of diseases of the Optic nerve involving loss of retinal ganglion cells in a characteristic pattern of optic neuropathy.
The most serious conditions associated with Marfan syndrome involve the cardiovascular system. Undue fatigue, shortness of breath, heart palpitations, racing heartbeats, or pain in the left chest, back, shoulder, or arm, can bring a person into the doctor's office. A palpitation (medical term ectopic heart beat) is an abnormal awareness of the beating of the Heart, whether it is too slow too fast irregular Angina pectoris, commonly known as angina, is severe Chest pain due to Ischemia (a lack of blood and hence Oxygen supply of the heart Cold arms, hands and feet can also be seriously linked to marfan syndrome because of a loss of blood circulation. A heart murmur heard on a stethoscope, an abnormal reading on an electrocardiogram, or symptoms of angina can lead a doctor to order an echocardiogram. Murmurs are abnormal Heart sounds that are produced as a result of turbulent blood flow which is sufficient to produce audible noise The stethoscope (from Greek στηθοσκόπιο, of στήθος stéthos - chest and σκοπή skopé - examination) is an acoustic Angina pectoris, commonly known as angina, is severe Chest pain due to Ischemia (a lack of blood and hence Oxygen supply of the heart An echocardiogram is a Sonography of the Heart. Also known as a cardiac ultrasound it uses standard ultrasound techniques to image two-dimensional slices of This can reveal signs of leakage or prolapse of the mitral or aortic valves that control the flow of blood through the heart. Prolapse literally means "To fall out of place" In Medicine, prolapse is a condition where organs such as the Uterus, fall down or slip out of place In Anatomy, the heart valves are Valves in the Heart that maintain the unidirectional flow of blood by opening and closing depending on the difference (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 ) However, the major sign that would lead a doctor to consider an underlying condition is a dilated aorta or an aortic aneurysm. Sometimes, no heart problems are apparent until the weakening of the connective tissue in the ascending aorta causes an aortic aneurysm or even aortic dissection.
Because of the underlying connective tissue abnormalities that cause Marfan syndrome, there is an increased incidence of dehiscence of prosthetic mitral valve.  Care should be taken to attempt repair of damaged heart valves rather than replacement.
During pregnancy, even in the absence of preconceived cardiovascular abnormality, women with Marfan syndrome are at significant risk of acute aortic dissection, which can be lethal if untreated. For this reason, women with Marfan syndrome should receive a thorough assessment prior to conception, and echocardiography should be performed every 6-10 weeks during pregnancy, to assess the aortic root diameter. An echocardiogram is a Sonography of the Heart. Also known as a cardiac ultrasound it uses standard ultrasound techniques to image two-dimensional slices of Most women however tolerate pregnancy well and safe vaginal delivery is possible. 
Marfan syndrome is a risk factor for spontaneous pneumothorax. A risk factor is a variable associated with an increased risk of Disease or Infection. In spontaneous unilateral pneumothorax, air escapes from a lung and occupies the pleural space between the chest wall and a lung. lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive The lung becomes partially compressed or collapsed. This can cause pain, shortness of breath, cyanosis, and, if not treated, death. Cyanosis is a blue coloration of the Skin and mucous membranes due to the presence of deoxygenated Hemoglobin in Blood vessels near the skin surface Marfan syndrome has also been associated with sleep apnea and idiopathic obstructive lung disease. Sleep apnea is a sleep disorder characterized by pauses in Breathing during Sleep. Idiopathic is an Adjective used primarily in Medicine meaning arising spontaneously or from an obscure or unknown cause.
Another condition that can reduce the quality of life for an individual, though not life-threatening, is dural ectasia, the weakening of the connective tissue of the dural sac, the membrane that encases the spinal cord. Dural ectasia is a widening or ballooning of the dural sac surrounding the Spinal cord usually at the lumbosacral level. The spinal cord is a long thin tubular bundle of Nerves that is an extension of the Central nervous system from the brain and is enclosed in and protected Dural ectasia can be present for a long time without producing any noticeable symptoms. Symptoms that can occur are lower back pain, leg pain, abdominal pain, other neurological symptoms in the lower extremities, or headaches. Back pain (also known " dorsalgia " is Pain felt in the back that usually originates from the Muscles Nerves Bones Abdominal pain can be one of the Symptoms associated with transient disorders or serious disease A headache ( cephalalgia in medical terminology is a condition of pain in the Head; sometimes Neck or upper back pain may also be interpreted Such symptoms usually diminish when the individual lies flat on his or her back. These types of symptoms might lead a doctor to order an X-ray of the lower spine. X-radiation (composed of X-rays) is a form of Electromagnetic radiation. In Anatomy, lumbar is an Adjective that means of or pertaining to the Abdominal segment of the Torso, between the diaphragm and Dural ectasia is usually not visible on an X-ray in the early phases. A worsening of symptoms and the lack of finding any other cause should eventually lead a doctor to order an upright MRI of the lower spine. Dural ectasia that has progressed to the point of causing these symptoms would appear in an upright MRI image as a dilated pouch that is wearing away at the lumbar vertebrae. The lumbar vertebrae are the largest segments of the movable part of the Vertebral column, and are characterized by the absence of the Foramen transversarium within  Other spinal issues associated with Marfan include degenerative disk disease and spinal cysts.
There is no cure for Marfan syndrome, but life expectancy has increased significantly over the last few decades, and clinical trials are underway for a promising new treatment.  The syndrome is treated by addressing each issue as it arises, and, in particular, considering prophylactic medication, even for young children, to slow progression of aortic dilation. Prophylaxis ( Greek "προφυλάσσω" to guard or prevent beforehand) is any medical or Public health procedure whose purpose
Regular checkups by a cardiologist are needed to monitor the health of the heart valves and the aorta. Cardiology (from Greek grc καρδίᾱ kardiā, "heart" and grc -λογία -logia) is the branch of Internal medicine The goal of treatment is to slow the progression of aortic dilation and damage to heart valves by eliminating arrythmias, minimizing the heart rate, and minimizing blood pressure. Dysrhythmia redirects here For the American band see Dysrhythmia (band. Measuring heart rate The Pulse rate (which in most people is identical to the heart rate can be measured at any point on the body where an Artery 's pulsation Blood pressure is also the title of a short story by Damon Runyan in Guys and Dolls and Other Stories Beta blockers have been used to control arrythmias and slow the heart rate. Beta blockers (sometimes written as β-blocker) are a class of drugs used for various indications but particularly for the management of Cardiac arrhythmias Dysrhythmia redirects here For the American band see Dysrhythmia (band. Measuring heart rate The Pulse rate (which in most people is identical to the heart rate can be measured at any point on the body where an Artery 's pulsation Other medications might be needed to further minimize blood pressure without slowing the heart rate, such as ACE inhibitors and angiotensin II receptor antagonists, also known as angiontensin receptor blockers (ARBs). Blood pressure is also the title of a short story by Damon Runyan in Guys and Dolls and Other Stories Measuring heart rate The Pulse rate (which in most people is identical to the heart rate can be measured at any point on the body where an Artery 's pulsation ACE inhibitors, or inhibitors of '''A'''ngiotensin-'''C'''onverting '''E'''nzyme, are a group of Pharmaceuticals that are used primarily in treatment of Hypertension Angiotensin II receptor antagonists, also known as angiotensin receptor blockers (ARBs AT1-receptor antagonists or sartans, are a group of If the dilation of the aorta progresses to a significant diameter aneurysm, causes a dissection or a rupture, or leads to failure of the aortic or other valve, then surgery (possibly a composite aortic valve graft [CAVG] or valve-sparing procedure) becomes necessary. An aneurysm (or aneurism) is a localized blood-filled dilation (balloon-like bulge of a blood vessel caused by disease or weakening of the vessel wall Although aortic graft surgery (or any vascular surgery) is a serious undertaking it is generally successful if undertaken on an elective basis.  Surgery in the setting of acute aortic dissection or rupture is considerably more problematic. Elective aortic valve/graft surgery is usually considered when aortic root diameter reaches 50 millimeters (2. 0 inches), but each case needs to be specifically evaluated by a qualified cardiologist. New valve-sparing surgical techniques are becoming more common.  As Marfan patients live longer, other vascular repairs are becoming more common, e. g. repairs of descending thoractic aortic aneurysms and aneurysms of vessels other than the aorta.
The skeletal and ocular manifestations of Marfan syndrome can also be serious, although not life-threatening. These symptoms are usually treated in the typical manner for the appropriate condition. This can also affect height, arm length, and life span. The Nuss procedure is now being offered to people with Marfan syndrome to correct 'sunken chest' or (pectus excavatum). The Nuss procedure is a Minimally-invasive procedure invented by Dr Pectus excavatum (a Latin term meaning hollowed chest) is the most common Congenital deformity of the anterior wall of the chest in which several  Because Marfan may cause spinal abnormalities that are asymptomatic, any spinal surgery contemplated on a Marfan patient should only follow detailed imaging and careful surgical planning, regardless of the indication for surgery.
Clinical trials have been conducted of the drug acetazolamide in the treatment of symptoms of dural ectasia. Acetazolamide, sold under the trade name Diamox, is a Carbonic anhydrase inhibitor that is used to treat Glaucoma, Epileptic seizures Benign Dural ectasia is a widening or ballooning of the dural sac surrounding the Spinal cord usually at the lumbosacral level. The treatment has demonstrated significant functional improvements in some sufferers.  Other medical treatments, as well as physical therapy, are also available.
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 1 to 2 weeks. Recurrent pneumothoraces might require chest surgery. Moderately sized pneumothoraces might need chest drain management for several days in a hospital. A chest tube ( chest drain or tube thoracostomy) is a flexible plastic tube that is inserted through the side of the chest into the pleural space. Large pneumothoraces are likely to be medical emergencies requiring emergency decompression.
Research in laboratory mice has suggested that the angiotensin II receptor antagonist losartan, which appears to block TGF-beta activity, can slow or halt the formation of aortic aneurysms in Marfan syndrome. A mouse (plural mice) is a small Animal that belongs to one Angiotensin II receptor antagonists, also known as angiotensin receptor blockers (ARBs AT1-receptor antagonists or sartans, are a group of Losartan ( rINN) (loʊˈsɑrtən is an Angiotensin II receptor antagonist drug used mainly to treat high blood pressure ( Hypertension)  A large clinical trial sponsored by the National Institutes of Health comparing the effects of losartan and atenolol on the aortas of Marfan patients is scheduled to begin in early 2007, coordinated by Johns Hopkins. In health care clinical trials are conducted to allow safety and Efficacy data to be collected for new drugs or devices "NIH" redirects here For other meanings of NIH see NIH (disambiguation. Atenolol is a β1 receptor specific antagonist a drug belonging to the group of β-blockers, a class of drugs used primarily in Cardiovascular diseases 
Genetic counseling and specialized clinics are available at many academic medical centers for affected persons and family members.
Below is a list of prominent figures known or believed to have had Marfan syndrome:
There are a number of historical persons believed to have suffered from Marfan's syndrome, but as proper Marfan diagnosis was not available before well into the 20th century most such claims can only be considered as speculation based on sparse medical records and pictures. Euell Theophilus Gibbons ( September 8, 1911 &ndash December 29, 1975) was an outdoorsman and proponent of natural diets, famous Flora ("Flo" Jean Hyman (July 31 1954 in Inglewood California – January 24 1986 in Japan) was an American Volleyball player and Robert Leroy Johnson (May 8 1911 – August 16 1938 is among the most famous of Delta blues musicians Vincent Andrew Schiavelli ( November 11 1948 – December 26 2005) was an American Actor noted for his work in Film WikipediaWikiProject Composers#Lead section --> Not to be confused with John Taverner Atlas Sound is the name of a musical solo project of Bradford James Cox, the lead singer of Atlanta five-piece Deerhunter. Deerhunter is an American five-piece group originated from Atlanta Georgia. Atlas Sound is the name of a musical solo project of Bradford James Cox, the lead singer of Atlanta five-piece Deerhunter. Joey Ramone ( May 19 1951 – April 15 2001) born as Jeffrey Ross Hyman, was a vocalist and Songwriter best The Ramones were an American rock band often regarded as the first Punk rock group Jonathan Larson ( February 4, 1960 – January 25, 1996) was an American Tony Award -winning Composer and Rent is a Rock musical, with music and lyrics by Jonathan Larson based on Giacomo Puccini 's Opera La Bohème Brent Collins ( 31 October 1941 - 6 January 1988) was an American Actor, best known for his role as Mr Arsenio Hall (born February 12 1955 in Cleveland Ohio) is an African-American Actor, Comedian, and former Talk show host
The following conditions may result from Marfan syndrome but may also occur in people without any known underlying disorder. A diagnosis of Marfan syndrome is based on family history and a combination of major and minor indicators of the disorder, rare in the general population, that occur in one individual. For example: four skeletal signs with one or more signs in another body system such as ocular and cardiovascular in one individual.
The following disorders have similar signs and symptoms of Marfan syndrome: