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Marfan syndrome

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106-451: 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 and abnormally curved spines . The most serious complications involve the heart and aorta , with an increased risk of mitral valve prolapse and aortic aneurysm . The lungs, eyes, bones, and

212-419: 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 pediatrician Antoine Marfan , who first described it in 1896. More than 30 signs and symptoms are variably associated with Marfan syndrome. The most prominent of these affect

318-540: A hominid was in the fossil species Paranthropus robustus , with over a third of individuals displaying amelogenesis imperfecta . EDAR ( EDAR hypohidrotic ectodermal dysplasia ) Myopia Myopia , also known as near-sightedness and short-sightedness , is an eye disease where light from distant objects 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 headaches and eye strain . Severe myopia

424-445: A child affected by the disorder. Examples of this type of disorder are albinism , medium-chain acyl-CoA dehydrogenase deficiency , cystic fibrosis , sickle cell disease , Tay–Sachs disease , Niemann–Pick disease , spinal muscular atrophy , and Roberts syndrome . Certain other phenotypes, such as wet versus dry earwax , are also determined in an autosomal recessive fashion. Some autosomal recessive disorders are common because, in

530-422: A combination of thin wrists and long fingers. 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": There is no cure for Marfan syndrome, but life expectancy has increased significantly over the last few decades and

636-435: A condition in which an individual has a greater difficulty seeing in low-illumination areas, even though there are no symptoms in bright light, such as daylight. Under rare conditions, edema of the ciliary body can cause an anterior displacement of the lens, inducing a myopia shift in refractive error. A diagnosis of myopia is typically made by an eye care professional , usually an optometrist or ophthalmologist . This

742-577: A female in terms of disease severity. The chance of passing on an X-linked dominant disorder differs between men and women. The sons of a man with an X-linked dominant disorder will all be unaffected (since they receive their father's Y chromosome), but his daughters will all inherit the condition. A woman with an X-linked dominant disorder has a 50% chance of having an affected foetus with each pregnancy, although in cases such as incontinentia pigmenti, only female offspring are generally viable. X-linked recessive conditions are also caused by mutations in genes on

848-447: A gene into the potentially trillions of cells that carry the defective copy. Finding an answer to this has been a roadblock between understanding the genetic disorder and correcting the genetic disorder. Around 1 in 50 people are affected by a known single-gene disorder, while around 1 in 263 are affected by a chromosomal disorder . Around 65% of people have some kind of health problem as a result of congenital genetic mutations. Due to

954-418: A genetic disorder rests on the inheritance of genetic material. With an in depth family history , it is possible to anticipate possible disorders in children which direct medical professionals to specific tests depending on the disorder and allow parents the chance to prepare for potential lifestyle changes, anticipate the possibility of stillbirth , or contemplate termination . Prenatal diagnosis can detect

1060-507: 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. 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

1166-619: A hereditary disease is an acquired disease . Most cancers , although they involve genetic mutations to a small proportion of cells in the body, are acquired diseases. Some cancer syndromes , however, such as BRCA mutations , are hereditary genetic disorders. A single-gene disorder (or monogenic disorder ) is the result of a single mutated gene. Single-gene disorders can be passed on to subsequent generations in several ways. Genomic imprinting and uniparental disomy , however, may affect inheritance patterns. The divisions between recessive and dominant types are not "hard and fast", although

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1272-544: A high risk for early glaucoma and early cataracts . The most serious signs and symptoms associated with Marfan syndrome involve the cardiovascular system : undue fatigue , shortness of breath , heart palpitations , 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

1378-459: 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. During pregnancy, even in the absence of preconception cardiovascular abnormality, women with Marfan syndrome are at significant risk of aortic dissection, which

1484-636: A known single-gene disorder, while around 1 in 263 are affected by a chromosomal disorder . Around 65% of people have some kind of health problem as a result of congenital genetic mutations. Due to the significantly large number of genetic disorders, approximately 1 in 21 people are affected by a genetic disorder classified as " rare " (usually defined as affecting less than 1 in 2,000 people). Most genetic disorders are rare in themselves. Genetic disorders are present before birth, and some genetic disorders produce birth defects , but birth defects can also be developmental rather than hereditary . The opposite of

1590-432: 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

1696-450: 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 ) plays an important role in MFS. Fibrillin-1 directly binds

1802-558: A number of design drawbacks: small numbers , lack of adequate control group, and failure to mask examiners from knowledge of treatments used. The best approach is to combine multiple prevention and control methods. Among myopia specialists, mydriatic eyedrops are the most favored approach, applied by almost 75% in North America and more than 80% in Australia. Some studies have indicated that having children spend time outdoors reduces

1908-787: A person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent. The chance a child will inherit the mutated gene is 50%. Autosomal dominant conditions sometimes have reduced penetrance , which means although only one mutated copy is needed, not all individuals who inherit that mutation go on to develop the disease. Examples of this type of disorder are Huntington's disease , neurofibromatosis type 1 , neurofibromatosis type 2 , Marfan syndrome , hereditary nonpolyposis colorectal cancer , hereditary multiple exostoses (a highly penetrant autosomal dominant disorder), tuberous sclerosis , Von Willebrand disease , and acute intermittent porphyria . Birth defects are also called congenital anomalies. Two copies of

2014-431: 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

2120-414: A single genetic cause, either in a gene or chromosome . The mutation responsible can occur spontaneously before embryonic development (a de novo mutation), or it can be inherited from two parents who are carriers of a faulty gene ( autosomal recessive inheritance) or from a parent with the disorder ( autosomal dominant inheritance). When the genetic disorder is inherited from one or both parents, it

2226-440: A supportive material to withstand intraocular pressure and prevent further progression of the posterior staphyloma. The strain is reduced, although damage from the pathological process cannot be reversed. By stopping the progression of the disease, vision may be maintained or improved. The use of orthoK can also slow down axial lens elongation. The National Institutes of Health says there is no known way of preventing myopia, and

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2332-520: 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. Marfan syndrome affects males and females equally, and

2438-465: Is Leber's hereditary optic neuropathy . It is important to stress that the vast majority of mitochondrial diseases (particularly when symptoms develop in early life) are actually caused by a nuclear gene defect, as the mitochondria are mostly developed by non-mitochondrial DNA. These diseases most often follow autosomal recessive inheritance. Genetic disorders may also be complex, multifactorial, or polygenic, meaning they are likely associated with

2544-440: Is a refractive error, the physical cause of myopia is comparable to any optical system that is out of focus. Borish and Duke-Elder classified myopia by these physical causes: As with any optical system experiencing a defocus aberration , the effect can be exaggerated or masked by changing the aperture size . In the case of the eye, a large pupil emphasizes refractive error and a small pupil masks it. This phenomenon can cause

2650-473: 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 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 ,

2756-405: Is also a strong environmental component to many of them (e.g., blood pressure ). Other such cases include: A chromosomal disorder is a missing, extra, or irregular portion of chromosomal DNA. It can be from an atypical number of chromosomes or a structural abnormality in one or more chromosomes. An example of these disorders is Trisomy 21 (the most common form of Down syndrome ), in which there

2862-461: Is also classified as a hereditary disease . Some disorders are caused by a mutation on the X chromosome and have X-linked inheritance. Very few disorders are inherited on the Y chromosome or mitochondrial DNA (due to their size). There are well over 6,000 known genetic disorders, and new genetic disorders are constantly being described in medical literature. More than 600 genetic disorders are treatable. Around 1 in 50 people are affected by

2968-423: Is also considered a recessive condition, but heterozygous carriers have increased resistance to malaria in early childhood, which could be described as a related dominant condition. When a couple where one partner or both are affected or carriers of a single-gene disorder wish to have a child, they can do so through in vitro fertilization, which enables preimplantation genetic diagnosis to occur to check whether

3074-412: Is an extra copy of chromosome 21 in all cells. Due to the wide range of genetic disorders that are known, diagnosis is widely varied and dependent of the disorder. Most genetic disorders are diagnosed pre-birth , at birth , or during early childhood however some, such as Huntington's disease , can escape detection until the patient begins exhibiting symptoms well into adulthood. The basic aspects of

3180-630: Is associated with an increased risk of macular degeneration , retinal detachment , cataracts , and glaucoma . Myopia results from the length of the eyeball growing too long or less commonly the lens being too strong. It is a type of refractive error . Diagnosis is by the use of cycloplegics during eye examination. Tentative evidence indicates that the risk of myopia can be decreased by having young children spend more time outside. This decrease in risk may be related to natural light exposure. Myopia can be corrected with eyeglasses , contact lenses , or by refractive surgery . Eyeglasses are

3286-474: Is associated with variable expressivity ; complete penetrance has been definitively documented. Marfan syndrome is caused by mutations in the FBN1 gene on chromosome 15 , which encodes fibrillin 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

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3392-429: Is based on family history and a combination of major and minor indicators of the disorder, rare in the general population, that occur in one individual – for example: four skeletal signs with one or more signs in another body system such as ocular and cardiovascular in one individual. The following conditions may result from MFS, but may also occur in people without any known underlying disorder. In 2010,

3498-557: Is believed to be a combination of genetic and environmental factors. Risk factors include doing work that involves focusing on close objects, greater time spent indoors, urbanization, and a family history of the condition. It is also associated with a high socioeconomic class and higher level of education. A 2012 review could not find strong evidence for any single cause, although many theories have been discredited. Twin studies indicate that at least some genetic factors are involved. Myopia has been increasing rapidly throughout

3604-469: Is by refracting the eye with the use of cycloplegics such as atropine with responses recorded when accommodation is relaxed. Diagnosis of progressive myopia requires regular eye examination using the same method. Myopia can be classified into two major types; anatomical and clinical. The types of myopia based on anatomical features are axial, curvature, index and displacement of refractive element. Congenital , simple and pathological myopia are

3710-402: 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, ligaments and the ciliary zonules of the eye; consequently, these areas are among the worst affected. A transgenic mouse has been created carrying a single copy of a mutant fibrillin-1,

3816-417: Is increased. Care should be taken to attempt repair of damaged heart valves rather than replacement. 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

3922-401: 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 . Each parent with

4028-478: 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 arrhythmias , minimizing

4134-480: Is often fatal even when rapidly treated. Women with Marfan syndrome, then, should receive a thorough assessment prior to conception, and echocardiography 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 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

4240-451: 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 , thoracic lordosis , abnormal indentation ( pectus excavatum ) or protrusion ( pectus carinatum ) of

4346-421: Is only possible through the circumvention of infertility by medical intervention. This type of inheritance, also known as maternal inheritance, is the rarest and applies to the 13 genes encoded by mitochondrial DNA . Because only egg cells contribute mitochondria to the developing embryo, only mothers (who are affected) can pass on mitochondrial DNA conditions to their children. An example of this type of disorder

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4452-416: Is opposed to the more traditional phenotype-first approach, and may identify causal factors that have previously been obscured by clinical heterogeneity , penetrance , and expressivity. On a pedigree, polygenic diseases do tend to "run in families", but the inheritance does not fit simple patterns as with Mendelian diseases. This does not mean that the genes cannot eventually be located and studied. There

4558-707: Is part of the candidate genes that cause myopia. Instead of a simple one-gene locus controlling the onset of myopia, a complex interaction of many mutated proteins acting in concert may be the cause. Instead of myopia being caused by a defect in a structural protein, defects in the control of these structural proteins might be the actual cause of myopia. A collaboration of all myopia studies worldwide identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. The new loci include candidate genes with functions in neurotransmission, ion transport, retinoic acid metabolism, extracellular matrix remodeling and eye development. The carriers of

4664-405: Is slightly higher than boys. Rates have increased since the 1950s. Uncorrected myopia is one of the most common causes of vision impairment globally along with cataracts , macular degeneration , and vitamin A deficiency . A myopic individual can see clearly out to a certain distance (the far point of the eye), but objects placed beyond this distance appear blurred . If the extent of

4770-459: Is that a lack of normal visual stimuli causes improper development of the eyeball. Under this hypothesis, "normal" refers to the environmental stimuli that the eyeball evolved to. Modern humans who spend most of their time indoors, in dimly or fluorescently lit buildings may be at risk of development of myopia. People, and children especially, who spend more time doing physical exercise and outdoor play have lower rates of myopia, suggesting

4876-407: 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

4982-752: The Bates method . Scientific reviews have concluded that there was "no clear scientific evidence" that eye exercises are effective in treating myopia and as such they "cannot be advocated". Global refractive errors have been estimated to affect 800 million to 2.3 billion. The incidence of myopia within sampled population often varies with age, country, sex, race , ethnicity , occupation, environment, and other factors. Variability in testing and data collection methods makes comparisons of prevalence and progression difficult. The prevalence of myopia has been reported as high as 70–90% in some Asian countries, 30–40% in Europe and

5088-413: 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 make 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

5194-462: The duochrome test . The near work hypothesis, also referred to as the "use-abuse theory" states that spending time involved in near work strains the intraocular and extraocular muscles. Some studies support the hypothesis, while other studies do not. While an association is present, it is not clearly causal. Myopia is also more common in children with diabetes , childhood arthritis , uveitis , and systemic lupus erythematosus . Because myopia

5300-444: The heart rate , and lowering the person's blood pressure . The American Heart Association made the following recommendations for people with Marfan syndrome with no or mild aortic dilation: Management often includes the use of beta blockers such as propranolol or if not tolerated calcium channel blockers or ACE inhibitors . Beta blockers are used to reduce the stress exerted on the aorta and to decrease aortic dilation. If

5406-428: The lens can be detected clinically in about 60% of people with Marfan syndrome by the use of a slit-lamp 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 . Those with MFS are also at

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5512-530: The pleural space between the chest wall and a lung. The lung becomes partially compressed or collapsed. This can cause pain, shortness of breath, cyanosis , and, if not treated, death. 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 , bronchiectasis , bullae , apical fibrosis and congenital malformations such as middle lobe hypoplasia. Dural ectasia ,

5618-438: The sternum , abnormal joint flexibility , a high-arched palate with crowded teeth and an overbite, flat feet , hammer toes , stooped shoulders, and unexplained stretch marks on the skin. It can also cause pain in the joints, bones, and muscles. Some people with Marfan have speech disorders resulting from symptomatic high palates and small jaws. Early osteoarthritis may occur. Other signs include limited range of motion in

5724-481: 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: In the presence of a family history of MFS (as defined above): The thumb sign (Steinberg's sign) is elicited by asking the person to flex the thumb as far as possible and then close the fingers over it. A positive thumb sign

5830-412: The Ghent criteria, family history and genetic testing (DNA analysis). 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

5936-874: The United States, and 10–20% in Africa. Myopia is about twice as common in Jewish people than in people of non-Jewish ethnicity. Myopia is less common in African people and associated diaspora. In Americans between the ages of 12 and 54, myopia has been found to affect African Americans less than Caucasians. A new 2024 study published in the British Journal of Ophthalmology reveals that over one-third of children worldwide were nearsighted in 2023, with this figure projected to rise to nearly 40% by 2050. The prevalence of myopia among children and adolescents has increased significantly over

6042-399: The X chromosome. Males are much more frequently affected than females, because they only have the one X chromosome necessary for the condition to present. The chance of passing on the disorder differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected (since they receive their father's Y chromosome), but his daughters will be carriers of one copy of

6148-443: The Y chromosome. These conditions may only be transmitted from the heterogametic sex (e.g. male humans) to offspring of the same sex. More simply, this means that Y-linked disorders in humans can only be passed from men to their sons; females can never be affected because they do not possess Y-allosomes. Y-linked disorders are exceedingly rare but the most well-known examples typically cause infertility. Reproduction in such conditions

6254-448: The active time of a genetic disorder, patients mostly rely on maintaining or slowing the degradation of quality of life and maintain patient autonomy . This includes physical therapy and pain management . The treatment of genetic disorders is an ongoing battle, with over 1,800 gene therapy clinical trials having been completed, are ongoing, or have been approved worldwide. Despite this, most treatment options revolve around treating

6360-411: The amount of myopia. While PRK is a relatively safe procedure for up to 6 dioptres of myopia, the recovery phase post-surgery is usually painful. In a LASIK pre-procedure, a corneal flap is cut into the cornea and lifted to allow the excimer laser beam access to the exposed corneal tissue. After that, the excimer laser ablates the tissue according to the required correction. When the flap again covers

6466-455: 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

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6572-448: The clinical types of myopia. Various forms of myopia have been described by their clinical appearance: The degree of myopia is described in terms of the power of the ideal correction , which is measured in diopters : Myopia is sometimes classified by the age at onset: Various methods have been employed in an attempt to decrease the progression of myopia, although studies show mixed results. Many myopia treatment studies have

6678-461: The condition has a 50% risk of passing the genetic defect 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 mutations ; such spontaneous mutations occur in about one in 20,000 births. Marfan syndrome is also an example of dominant negative mutation and haploinsufficiency . It

6784-441: The cornea, the change in curvature generated by the laser ablation proceeds to the corneal surface. Though LASIK is usually painless and involves a short rehabilitation period post-surgery, it can potentially result in flap complications and loss of corneal stability (post-LASIK keratectasia ). Instead of modifying the corneal surface, as in laser vision correction (LVC), this procedure involves implanting an additional lens inside

6890-451: The cornea. Myopia is the most common eye problem and is estimated to affect 1.5 billion people (22% of the world population). Rates vary significantly in different areas of the world. Rates among adults are between 15% and 49%. Among children, it affects 1% of rural Nepalese, 4% of South Africans, 12% of people in the US, and 37% in some large Chinese cities. In China the proportion of girls

6996-414: The currently identified variants account for only a small fraction of myopia cases, suggesting the existence of a large number of yet unidentified low-frequency or small-effect variants, which underlie the majority of myopia cases. Environmental factors which increase the risk of myopia include insufficient light exposure, low physical activity, near work, and increased years of education. One hypothesis

7102-408: The developed world, suggesting environmental factors are involved. A single-author literature review in 2021 proposed that myopia is the result of corrective lenses interfering with emmetropization . A risk for myopia may be inherited from one's parents. Genetic linkage studies have identified 18 possible loci on 15 different chromosomes that are associated with myopia, but none of these loci

7208-432: 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 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

7314-440: The divisions between autosomal and X-linked types are (since the latter types are distinguished purely based on the chromosomal location of the gene). For example, the common form of dwarfism , achondroplasia , is typically considered a dominant disorder, but children with two genes for achondroplasia have a severe and usually lethal skeletal disorder, one that achondroplasics could be considered carriers for. Sickle cell anemia

7420-482: The earliest nationally representative estimates for myopia prevalence in the U.S., and found the prevalence in persons aged 12–54 was 25%. Using the same method, in 1999–2004, myopia prevalence was estimated to have climbed to 42%. A study of 2,523 children in grades 1 to 8 (age, 5–17 years) found nearly one in 10 (9%) have at least −0.75 diopters of myopia. In this study, 13% had at least +1.25 D hyperopia (farsightedness), and 28% had at least 1.00-D difference between

7526-421: The effects of multiple genes in combination with lifestyles and environmental factors. Multifactorial disorders include heart disease and diabetes . Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person's risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat because

7632-426: The embryo has the genetic disorder. Most congenital metabolic disorders known as inborn errors of metabolism result from single-gene defects. Many such single-gene defects can decrease the fitness of affected people and are therefore present in the population in lower frequencies compared to what would be expected based on simple probabilistic calculations. Only one mutated copy of the gene will be necessary for

7738-444: The evidence is speculative, questionable, or refuted. Ankyrin : Long QT syndrome 4 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 chromosome abnormality . Although polygenic disorders are the most common, the term is mostly used when discussing disorders with

7844-575: 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 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 (MPL), also referred to as Marfan lipodystrophy syndrome (MFLS),

7950-1023: The eye (i.e., in addition to the already existing natural lens). While it usually results in good control of the refractive change, it can induce potential serious long-term complications such as glaucoma, cataract and endothelial decompensation. Orthokeratology or simply Ortho-K is a temporary corneal reshaping process using rigid gas permeable (RGP) contact lenses. Overnight wearing of specially designed contact lenses will temporarily reshape cornea, so patients may see clearly without any lenses in daytime. Orthokeratology can correct myopia up to –6D. Several studies shown that Ortho-K can reduce myopia progression also. Risk factors of using Ortho-K lenses include microbial keratitis, corneal edema, etc. Other contact lens related complications like corneal aberration, photophobia, pain, irritation, redness etc. are usually temporary conditions, which may be eliminated by proper usage of lenses. The Intrastromal corneal ring segment (ICRS), commonly used in keratoconus treatment now,

8056-408: The gene must be mutated for a person to be affected by an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene and are referred to as genetic carriers . Each parent with a defective gene normally do not have symptoms. Two unaffected people who each carry one copy of the mutated gene have a 25% risk with each pregnancy of having

8162-456: The high-risk genes have a tenfold increased risk of myopia. Aberrant genetic recombination and gene splicing in the OPNLW1 and OPNMW1 genes that code for two retinal cone photopigment proteins can produce high myopia by interfering with refractive development of the eye. Human population studies suggest that contribution of genetic factors accounts for 60–90% of variance in refraction. However,

8268-445: The hips due to the femoral head protruding into abnormally deep hip sockets . 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

8374-413: The incidence of myopia. A 2017 study investigated the leading causal theory of association between greenspace exposure and spectacles use as a proxy for myopia, finding a 28% reduction in the likelihood of spectacles use per interquartile range increase in time spent in greenspace. In Taiwan, government policies that require schools to send all children outdoors for a minimum amount of time have driven down

8480-623: The increased magnitude and complexity of the visual stimuli encountered during these types of activities decrease myopic progression. There is preliminary evidence that the protective effect of outdoor activities on the development of myopia is due, at least in part, to the effect of long hours of exposure to daylight on the production and the release of retinal dopamine . Myopia can be induced with minus spherical lenses, and overminus in prescription lenses can induce myopia progression. Overminus during refraction can be avoided through various techniques and tests, such as fogging, plus to blur, and

8586-617: 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 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 management for several days in

8692-472: The lens moves with the cornea, keeping the optic axis in line with the visual axis and because the vertex distance has been reduced to zero. Refractive surgery includes procedures which alter the corneal curvature of some structure of the eye or which add additional refractive means inside the eye. Photorefractive keratectomy (PRK) involves ablation of corneal tissue from the corneal surface using an excimer laser . The amount of tissue ablation corresponds to

8798-469: The method for "myopia control". In some studies, bifocal and progressive lenses have not shown differences in altering the progression of myopia compared to placebo. In 2019, contact lenses to prevent the worsening of nearsightedness in children were approved for use in the United States. This "MiSight" type claims to work by focusing peripheral light in front of the retina. Anti-muscarinic topical medications in children under 18 years of age may slow

8904-407: 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 , aortic regurgitation ). However, the major sign that would lead a doctor to consider an underlying condition is a dilated aorta or an aortic aneurysm . Sometimes, no heart problems are apparent until

9010-643: The mutated gene. A woman who is a carrier of an X-linked recessive disorder (X X ) has a 50% chance of having sons who are affected and a 50% chance of having daughters who are carriers of one copy of the mutated gene. X-linked recessive conditions include the serious diseases hemophilia A , Duchenne muscular dystrophy , and Lesch–Nyhan syndrome , as well as common and less serious conditions such as male pattern baldness and red–green color blindness . X-linked recessive conditions can sometimes manifest in females due to skewed X-inactivation or monosomy X ( Turner syndrome ). Y-linked disorders are caused by mutations on

9116-792: The mutation shows no ethnic or geographical bias. Estimates indicate about 1 in 5,000 to 10,000 individuals have Marfan syndrome. 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. The gene linked to the disease was first identified by Francesco Ramirez at the Mount Sinai Medical Center in New York City in 1991. Notable people who have or had Marfan syndrome include: Other historical figures and celebrities have appeared on lists of people with Marfan syndrome, but from case to case

9222-496: The myopia is great enough, even standard reading distances can be affected. Upon routine examination of the eyes, the vast majority of myopic eyes appear structurally identical to nonmyopic eyes. Onset is often in school children, with worsening between the ages of 8 and 15. Myopic individuals have larger pupils than far-sighted ( hypermetropic ) and emmetropic individuals, likely due to requiring less accommodation (which results in pupil constriction). The underlying cause

9328-612: The past 30 years, rising from 24% in 1990 to almost 36% in 2023. Researchers noted a sharp spike in cases following the COVID-19 pandemic and highlighted regional differences in myopia rates. In some parts of Asia , myopia is very common. Myopia is common in the United States , with research suggesting this condition has increased dramatically in recent decades. In 1971–1972, the National Health and Nutrition Examination Survey provided

9434-1003: The past, carrying one of the faulty genes led to a slight protection against an infectious disease or toxin such as tuberculosis or malaria . Such disorders include cystic fibrosis, sickle cell disease, phenylketonuria and thalassaemia . X-linked dominant disorders are caused by mutations in genes on the X chromosome . Only a few disorders have this inheritance pattern, with a prime example being X-linked hypophosphatemic rickets . Males and females are both affected in these disorders, with males typically being more severely affected than females. Some X-linked dominant conditions, such as Rett syndrome , incontinentia pigmenti type 2, and Aicardi syndrome , are usually fatal in males either in utero or shortly after birth, and are therefore predominantly seen in females. Exceptions to this finding are extremely rare cases in which boys with Klinefelter syndrome (44+xxy) also inherit an X-linked dominant condition and exhibit symptoms more similar to those of

9540-606: The presence of characteristic abnormalities in fetal development through ultrasound , or detect the presence of characteristic substances via invasive procedures which involve inserting probes or needles into the uterus such as in amniocentesis . Not all genetic disorders directly result in death; however, there are no known cures for genetic disorders. Many genetic disorders affect stages of development, such as Down syndrome , while others result in purely physical symptoms such as muscular dystrophy . Other disorders, such as Huntington's disease , show no signs until adulthood. During

9646-422: The prevalence of myopia in children. The use of reading glasses when doing close work may improve vision by reducing or eliminating the need to accommodate. Altering the use of eyeglasses between full-time, part-time, and not at all does not appear to alter myopia progression. The American Optometric Association's Clinical Practice Guidelines found evidence of effectiveness of bifocal lenses and recommends it as

9752-529: 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 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

9858-423: The significantly large number of genetic disorders, approximately 1 in 21 people are affected by a genetic disorder classified as " rare " (usually defined as affecting less than 1 in 2,000 people). Most genetic disorders are rare in themselves. There are well over 6,000 known genetic disorders, and new genetic disorders are constantly being described in medical literature. The earliest known genetic condition in

9964-409: The simplest and safest method of correction. Contact lenses can provide a relatively wider corrected field of vision , but are associated with an increased risk of infection. Refractive surgeries like LASIK and PRK permanently change the shape of the cornea . Other procedures include implantable collamer lens (ICL) inside the anterior chamber in front of the natural eye lens. ICL doesn't affect

10070-431: The skeletal, cardiovascular, and ocular systems, but all fibrous connective tissue throughout the body can be affected. Most of the readily visible signs are associated with the skeletal system . 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,

10176-401: The specific factors that cause most of these disorders have not yet been identified. Studies that aim to identify the cause of complex disorders can use several methodological approaches to determine genotype – phenotype associations. One method, the genotype-first approach , starts by identifying genetic variants within patients and then determining the associated clinical manifestations. This

10282-442: The symptoms of the disorders in an attempt to improve patient quality of life . Gene therapy refers to a form of treatment where a healthy gene is introduced to a patient. This should alleviate the defect caused by a faulty gene or slow the progression of the disease. A major obstacle has been the delivery of genes to the appropriate cell, tissue, and organ affected by the disorder. Researchers have investigated how they can introduce

10388-437: The two principal meridians (cycloplegic autorefraction) of astigmatism . For myopia, Asians had the highest prevalence (19%), followed by Hispanics (13%). Caucasian children had the lowest prevalence of myopia (4%), which was not significantly different from African Americans (7%). A recent review found 25% of Americans aged 40 or over have at least −1.00 diopters of myopia and 5% have at least −5.00 diopters. In Australia ,

10494-521: The use of glasses or contact lenses does not affect its progression, unless the glasses or contact lenses are too strong of a prescription. There is no universally accepted method of preventing myopia and proposed methods need additional study to determine their effectiveness. Optical correction using glasses or contact lenses is the most common treatment; other approaches include orthokeratology , and refractive surgery . Medications (mostly atropine ) and vision therapy can be effective in addressing

10600-682: The various forms of pseudomyopia . Corrective lenses bend the light entering the eye in a way that places a focused image accurately onto the retina. The power of any lens system can be expressed in diopters , the reciprocal of its focal length in meters. Corrective lenses for myopia have negative powers because a divergent lens is required to move the far point of focus out to the distance. More severe myopia needs lens powers further from zero (more negative). However, strong eyeglass prescriptions create distortions such as prismatic movement and chromatic aberration . Strongly myopic wearers of contact lenses do not experience these distortions because

10706-400: 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

10812-442: The weakening of the connective tissue of the dural sac encasing the spinal cord , can result in a loss of quality of life . 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 headaches – symptoms which usually diminish when lying flat. On X-ray , however, dural ectasia

10918-418: The worsening of myopia. These treatments include pirenzepine gel , cyclopentolate eye drops , and atropine eye drops . While these treatments were shown to be effective in slowing the progression of myopia and reducing eyeball elongation associated with the condition, side effects included light sensitivity and near blur. Scleral reinforcement surgery is aimed to cover the thinning posterior pole with

11024-410: 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

11130-461: 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. 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

11236-471: Was originally designed to correct mild to moderate myopia. The thickness is directly related to flattening and the diameter of the ring is proportionally inverse to the flattening of cornea. So, if diameter is smaller or thickness is greater, resulting myopia correction will be greater. A number of alternative therapies have been claimed to improve myopia, including vision therapy , "behavioural optometry", various eye exercises and relaxation techniques, and

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