Materiały źródłowe

• #1 Marfan syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/marfan-syndrome/

  Mutations in the FBN1 gene cause Marfan syndrome. The FBN1 gene provides instructions for making a protein called fibrillin-1. Fibrillin-1 attaches (binds) to other fibrillin-1 proteins and other molecules to form threadlike filaments called microfibrils. Microfibrils become part of the fibers that provide strength and flexibility to connective tissue. Additionally, microfibrils bind to molecules called growth factors and release them at various times to control the growth and repair of tissues and organs throughout the body. A mutation in the FBN1 gene can reduce the amount of functional fibrillin-1 that is available to form microfibrils, which leads to decreased microfibril formation. As a result, microfibrils cannot bind to growth factors, so excess growth factors are available and elasticity in many tissues is decreased, leading to overgrowth and instability of tissues in Marfan syndrome.

• #2 Marfan Syndrome (MFS): Practice Essentials, Pathophysiology and Etiology, Epidemiology

  https://emedicine.medscape.com/article/1258926-overview

  Marfan syndrome (MFS) is a spectrum of disorders caused by a heritable genetic defect of connective tissue that has an autosomal dominant mode of transmission. […] The defect itself has been isolated to the FBN1 gene on chromosome 15, which codes for the connective tissue protein fibrillin. […] Several point mutations have been identified in the fibrillin gene, most of which affect cysteine residues within the microfibril. […] Thus, these mutations are thought to cause defective fibrillin to be produced. […] Mutations in the FBN1 locus of the fibrillin gene on chromosome 15 have been linked to MFS and other distinct clinical entities with similar findings.

• #3 Marfan syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/marfan-syndrome/

  Mutations in the FBN1 gene cause Marfan syndrome. The FBN1 gene provides instructions for making a protein called fibrillin-1. Fibrillin-1 attaches (binds) to other fibrillin-1 proteins and other molecules to form threadlike filaments called microfibrils. Microfibrils become part of the fibers that provide strength and flexibility to connective tissue. Additionally, microfibrils bind to molecules called growth factors and release them at various times to control the growth and repair of tissues and organs throughout the body. A mutation in the FBN1 gene can reduce the amount of functional fibrillin-1 that is available to form microfibrils, which leads to decreased microfibril formation. As a result, microfibrils cannot bind to growth factors, so excess growth factors are available and elasticity in many tissues is decreased, leading to overgrowth and instability of tissues in Marfan syndrome.

• #4 Marfan syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/marfan-syndrome/

  Mutations in the FBN1 gene cause Marfan syndrome. The FBN1 gene provides instructions for making a protein called fibrillin-1. Fibrillin-1 attaches (binds) to other fibrillin-1 proteins and other molecules to form threadlike filaments called microfibrils. Microfibrils become part of the fibers that provide strength and flexibility to connective tissue. Additionally, microfibrils bind to molecules called growth factors and release them at various times to control the growth and repair of tissues and organs throughout the body. A mutation in the FBN1 gene can reduce the amount of functional fibrillin-1 that is available to form microfibrils, which leads to decreased microfibril formation. As a result, microfibrils cannot bind to growth factors, so excess growth factors are available and elasticity in many tissues is decreased, leading to overgrowth and instability of tissues in Marfan syndrome.

• #5 Marfan Syndrome – Marfan Foundation

  https://marfan.org/conditions/marfan-syndrome/

  Marfan syndrome is a genetic condition that affects the body’s connective tissue. Connective tissue holds all the body’s cells, organs and tissue together. It also plays an important role in helping the body grow and develop properly. […] About 3 out of 4 people with Marfan syndrome inherit it, meaning they get the genetic mutation from a parent who has it. But some people with Marfan syndrome are the first in their family to have it; when this happens it is called a spontaneous mutation. There is a 50 percent chance that a person with Marfan syndrome will pass along the genetic mutation each time they have a child. […] Marfan syndrome is caused by a defect (or mutation) in the gene that tells the body how to make fibrillin-1. This mutation results in an increase in a protein called transforming growth factor beta, or TGF-. The increase in TGF- causes problems in connective tissues throughout the body, which in turn creates the features and medical problems associated with Marfan syndrome and some related conditions.

• #6 Marfan Syndrome

  https://www.rwjbh.org/treatment-care/heart-and-vascular-care/diseases-conditions/marfan-syndrome/

  Marfan syndrome is caused by a defect (or mutation) in the gene that tells the body how to make fibrillin-1. This mutation results in an increase in a protein called transforming growth factor beta, or TGF-. […] Marfan syndrome is caused by a defect (or mutation) in the gene that tells the body how to make fibrillin-1. This mutation results in an increase in a protein called transforming growth factor beta, or TGF-.

• #7 The Molecular Genetics of Marfan Syndrome

  https://www.medsci.org/v18p2752.htm

  MFS and related disorders including LDS, SGS, MASS phenotype etc., display a significant overlap. […] Multiple genes contribute to MFS and related diseases, such as the FBN-encoding genes FBN1 and FBN2, and genes encoding signaling molecules of the TGF- pathway, such as TGFBR1/2, LTBPs and SKI. […] Mutations of FBN1 were observed in 90% of cases of MFS. […] The FBN1 gene is located on chromosome 15q21.1 and is comprised of 66 exons. […] A total of 3,077 mutations of FBN1 in patients with MFS have been reported to date, including 2,499 (73.09%) point mutations and 51 (1.66%) large rearrangements. […] Mutations of FBN1 occur across almost the entire gene, and there is no obvious aggregation area and periodicity. […] The repetitiveness of this mutation is ~12%. […] The classification of mutant types would influence the correlation of genotype-phenotype, assignment of the HI versus DN effects in MFS should base on the protein products and the effect of a specific mutation would be identified through experimental protein work.

• #8 Neonatal Marfan Syndrome | Signs of Marfan in a Newborn

  https://marfan.org/conditions/neonatal-marfan/

  Marfan syndrome is caused by mutations in the FBN1 gene on chromosome 15, which encodes the protein fibrillin-1. Mutations along the entire length of the gene can cause Marfan syndrome. Mutations that cause neonatal Marfan syndrome most often cluster in exons 23-32 of the gene. However, neonatal Marfan syndrome may also arise due to mutations outside this region. Similarly, mutations in exons 23-32 of the FBN1 gene may also lead to classical or even mild Marfan syndrome. […] It has been suggested that mutations in exons 25 and 26 are associated with shorter survival in children diagnosed with Marfan syndrome before the age of 1 year, but this is based on a limited and perhaps biased experience.

• #9 Marfan syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/marfan-syndrome/

  This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. […] At least 25 percent of Marfan syndrome cases result from a new mutation in the FBN1 gene. These cases occur in people with no history of the disorder in their family.

• #10 Marfan Syndrome Causes & Diagnosis | Northwestern Medicine

  https://www.nm.org/conditions-and-care-areas/heart-and-vascular/conditions-and-treatments/marfan-and-related-disorders/causes-and-diagnoses

  Marfan is an inherited disorder, passed down genetically from a parent. […] In most cases, Marfan syndrome is autosomal dominant, which means it occurs equally in men and women. […] The condition can be inherited from just one parent with Marfan syndrome. […] A patient with Marfan syndrome has a 50 percent possibility of passing on the gene that causes Marfan syndrome to an unborn child. […] Marfan syndrome is a variable expression genetic disorder meaning not everyone experiences the same symptoms or abnormalities to the same degree despite having the same defective gene. […] Marfan syndrome is a genetic disorder that affects the body’s connective tissue.

• #11 Marfan syndrome | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/marfan-syndrome?content_id=CON-20155270

  Marfan syndrome is caused by a defect in the gene that enables your body to produce a protein that helps give connective tissue its elasticity and strength. […] Most people with Marfan syndrome inherit the abnormal gene from a parent who has the disorder. Each child of an affected parent has a 50-50 chance of inheriting the defective gene. In about 25% of the people who have Marfan syndrome, the abnormal gene comes from neither parent. In these cases, a new mutation develops spontaneously.

• #12 What is Marfan Syndrome? Symptoms & Causes | NIAMS

  https://www.niams.nih.gov/health-topics/marfan-syndrome

  Marfan syndrome is a genetic disorder that changes the proteins that help make healthy connective tissue. This leads to problems with the development of connective tissue, which supports the bones, muscles, organs, and tissues in your body. Mutations (changes) to a specific gene cause Marfan syndrome, and most people inherit the disorder from their parents. […] A mutation or change in the fibrillin-1 (FBN1) gene causes Marfan syndrome. People with Marfan syndrome generally inherit one normal copy of the FBN1 gene from one parent and one abnormal copy of from the other parent. One abnormal copy of the FBN1 gene is sufficient to cause Marfan syndrome, meaning that an affected child would inherit the condition from an affected parent. […] About one-quarter of people with Marfan syndrome have a new change in the FBN1 gene, meaning that neither parent is affected and that they are the first person in their family to have the condition. This is a so-called dominant mode of inheritance. A person with a dominant mutation has a 50% chance (1 in 2) of passing on the disorder to each of his or her children.

• #13 Marfan Syndrome: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17209-marfan-syndrome

  Marfan syndrome (MFS) is a genetic condition that makes your connective tissue too loose and elastic. […] A genetic change (variant) causes Marfan syndrome. More specifically, there’s a change in the gene fibrillin-1 or FBN1 that gives your cells instructions to make fibrillin. Fibrillin is a protein that’s the main component of elastic fibers in your connective tissue. […] In most cases, you inherit Marfan syndrome from a biological parent. The syndrome has an autosomal dominant inheritance. This means you only need to receive the altered gene from one parent to inherit the condition. People with Marfan syndrome have a 50% chance of passing on the disorder to each of their children. […] In 25% of Marfan syndrome cases, a new gene change occurs due to an unknown cause.

• #14 Marfan Syndrome – Marfan Foundation

  https://marfan.org/conditions/marfan-syndrome/

  Marfan syndrome is a genetic condition that affects the body’s connective tissue. Connective tissue holds all the body’s cells, organs and tissue together. It also plays an important role in helping the body grow and develop properly. […] About 3 out of 4 people with Marfan syndrome inherit it, meaning they get the genetic mutation from a parent who has it. But some people with Marfan syndrome are the first in their family to have it; when this happens it is called a spontaneous mutation. There is a 50 percent chance that a person with Marfan syndrome will pass along the genetic mutation each time they have a child. […] Marfan syndrome is caused by a defect (or mutation) in the gene that tells the body how to make fibrillin-1. This mutation results in an increase in a protein called transforming growth factor beta, or TGF-. The increase in TGF- causes problems in connective tissues throughout the body, which in turn creates the features and medical problems associated with Marfan syndrome and some related conditions.

• #15 Marfan Syndrome in Children | Valley Children’s Healthcare

  https://www.valleychildrens.org/heart/conditions/marfan-syndrome-in-children

  Marfan syndrome is caused by an abnormal gene. The affected gene is FBN1. It helps make a protein in connective tissue called fibrillin-1. The abnormal gene happens as follows: […] In about 3 out of 4 cases, the gene is inherited from a parent who is affected. Each child of an affected parent has a 1 in 2 chance of having the disorder (autosomal dominant inheritance). […] In about 1 out of 4 cases, the abnormal gene is from a new mutation. It is not inherited from a parent. Researchers believe this happens more often when the father is older than 45. The child also has a 1 in 2 chance of passing on the gene to their children.

• #16 Marfan Syndrome in Adults | Saint Luke’s Health System

  https://www.saintlukeskc.org/health-library/marfan-syndrome-adults

  Marfan syndrome is caused by a change (mutation) in a gene. The gene is called FBN1. It helps make a protein in connective tissue called fibrillin-1. The mutation causes problems with this process. […] The gene mutation is either: […] In about 3 out of 4 cases, the gene is inherited from a parent who is affected. Each child of an affected parent has a 1 in 2 chance of having the disorder. This is called autosomal dominant inheritance. […] In about 1 out of 4 cases, the abnormal gene is from a new mutation. It’s not inherited from a parent. Researchers believe this happens more often when the father is older than 45. A person with Marfan has a 1 in 2 chance of passing on the gene.

• #17 Etiology and pathogenesis of the Marfan syndrome: current understanding – Pyeritz- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/16414/html

  Much has changed regarding Marfan syndrome (MFS) over the past few decades. Once described solely as a heritable disorder of connective tissue, MFS is now one of a number of conditions recognized to be a disorder of abnormal signalling in the TGF- pathway. […] Over several decades, a variety of components of the extracellular matrix were identified biochemically as being abnormal, including several forms of collagen, production of hyaluronic acid and defects in elastin. What was clear to most clinical investigators over the latter half of the twentieth century was that efforts at treatment would best be stimulated by pathogenesis rather than etiology. […] Fast forward to 1991 when a pediatric cardiology fellow, Hal Dietz, collaborated with me and other colleagues at Hopkins first, to precisely map the chromosomal locus of the Marfan gene, and second, to determine that the product of that gene (FBN1) was fibrillin-1, an intrinsic component of the extracellular microfibril, which, in turn, was present in all elastic fibers, was mutated. This finding also supported the notion of weak connective tissue.

• #18 Etiology and pathogenesis of the Marfan syndrome: current understanding – Pyeritz- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/16414/html

  However, a few years later, the Dietz lab capitalized on the fact that a fundamental function of fibrillin-1 was to bind the latent transforming growth factor- binding protein (LTGBP). As a result, control of the cellular activity of the growth factor was disrupted. Defective fibrillin-1 resulted in excessive activity of transforming growth factor- (TGF-), which led to a cascade through its canonical signaling pathway, resulting in increased activity of SMAD2/3. […] Losartan, an AT1 angiotensin receptor blocking drug, was shown to protect mouse models of MFS from developing aortic aneurysms. Not only did the aorta not dilate or dissect, but the histopathology appeared unaffected. Overexpression of TGF- was shown to result in several of the biochemical findings once thought to be primary, such as increased hyaluronan deposition and expression of matrix metalloproteinases. […] Further understanding of the pathogenesis of MFS, especially in the human, will undoubtedly lead to more effective medical treatments in the future.

• #19 The Molecular Genetics of Marfan Syndrome

  https://www.medsci.org/v18p2752.htm

  Abnormalities of the TGF- pathway signaling is another important pathological mechanism by which aneurysms develop in patients with MFS. […] The up- and down-regulation of TGF- pathway signaling are both related to MFS, canonical and non-canonical signaling exert antagonistic effects and co-adjust the mechanism of development of aneurysms in MFS.

• #20 Etiology and pathogenesis of the Marfan syndrome: current understanding – Pyeritz- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/16414/html

  However, a few years later, the Dietz lab capitalized on the fact that a fundamental function of fibrillin-1 was to bind the latent transforming growth factor- binding protein (LTGBP). As a result, control of the cellular activity of the growth factor was disrupted. Defective fibrillin-1 resulted in excessive activity of transforming growth factor- (TGF-), which led to a cascade through its canonical signaling pathway, resulting in increased activity of SMAD2/3. […] Losartan, an AT1 angiotensin receptor blocking drug, was shown to protect mouse models of MFS from developing aortic aneurysms. Not only did the aorta not dilate or dissect, but the histopathology appeared unaffected. Overexpression of TGF- was shown to result in several of the biochemical findings once thought to be primary, such as increased hyaluronan deposition and expression of matrix metalloproteinases. […] Further understanding of the pathogenesis of MFS, especially in the human, will undoubtedly lead to more effective medical treatments in the future.

• #21 Marfan Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK537339/

  In patients with atypical presentations reminiscent of MFS, a mutation in a gene encoding for transforming growth factor-beta receptor (TGFBR) may be the cause. […] MFS is, therefore, caused by vascular remodeling due to a combination of structural microfibril changes, excess TGF-beta, and overexpression of MMP-2 and MMP-9.

• #22 Genetics of Marfan Syndrome: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/946315-overview

  Studies have suggested that abnormalities in the transforming growth factor-beta (TGF)-signaling pathway may represent a common pathway for the development of the Marfan phenotype. […] Abnormalities in TGFR1 and TGFR2 were also reported to cause a new dominant syndrome similar to MFS1; it was associated with aortic aneurysm and congenital anomalies, including Loeys-Dietz syndrome (LDS). […] A study by Benarroch et al suggested that clinical variability in MFS may result from alternative splicing of FBN1. […] FBN1 mutations cause several Marfan-like disorders, such as the MASS (myopia, mitral valve prolapse, borderline and nonprogressive aortic enlargement, nonspecific skin and skeletal findings) phenotype and isolated ectopia lentis.

• #23 The Molecular Genetics of Marfan Syndrome

  https://www.medsci.org/v18p2752.htm

  MFS and related disorders including LDS, SGS, MASS phenotype etc., display a significant overlap. […] Multiple genes contribute to MFS and related diseases, such as the FBN-encoding genes FBN1 and FBN2, and genes encoding signaling molecules of the TGF- pathway, such as TGFBR1/2, LTBPs and SKI. […] Mutations of FBN1 were observed in 90% of cases of MFS. […] The FBN1 gene is located on chromosome 15q21.1 and is comprised of 66 exons. […] A total of 3,077 mutations of FBN1 in patients with MFS have been reported to date, including 2,499 (73.09%) point mutations and 51 (1.66%) large rearrangements. […] Mutations of FBN1 occur across almost the entire gene, and there is no obvious aggregation area and periodicity. […] The repetitiveness of this mutation is ~12%. […] The classification of mutant types would influence the correlation of genotype-phenotype, assignment of the HI versus DN effects in MFS should base on the protein products and the effect of a specific mutation would be identified through experimental protein work.

• #24 Marfan Syndrome

  https://learn.genetics.utah.edu/content/genetics/marfan/

  Even when Marfan Syndrome runs in a family, individual people can have different symptoms. Some of this variability is due to variation in other genes. For example, some genes code for proteins that influence the amount of fibrillin-1 protein a person makes. Other gene variations affect the risk for heart conditions that are part of Marfan syndrome.

• #25 Marfan Syndrome

  https://learn.genetics.utah.edu/content/genetics/marfan/

  Even when Marfan Syndrome runs in a family, individual people can have different symptoms. Some of this variability is due to variation in other genes. For example, some genes code for proteins that influence the amount of fibrillin-1 protein a person makes. Other gene variations affect the risk for heart conditions that are part of Marfan syndrome.

• #26 Genetics of Marfan Syndrome: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/946315-overview

  Studies have suggested that abnormalities in the transforming growth factor-beta (TGF)-signaling pathway may represent a common pathway for the development of the Marfan phenotype. […] Abnormalities in TGFR1 and TGFR2 were also reported to cause a new dominant syndrome similar to MFS1; it was associated with aortic aneurysm and congenital anomalies, including Loeys-Dietz syndrome (LDS). […] A study by Benarroch et al suggested that clinical variability in MFS may result from alternative splicing of FBN1. […] FBN1 mutations cause several Marfan-like disorders, such as the MASS (myopia, mitral valve prolapse, borderline and nonprogressive aortic enlargement, nonspecific skin and skeletal findings) phenotype and isolated ectopia lentis.

• #27 Genetics of Marfan Syndrome: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/946315-overview

  Studies have suggested that abnormalities in the transforming growth factor-beta (TGF)-signaling pathway may represent a common pathway for the development of the Marfan phenotype. […] Abnormalities in TGFR1 and TGFR2 were also reported to cause a new dominant syndrome similar to MFS1; it was associated with aortic aneurysm and congenital anomalies, including Loeys-Dietz syndrome (LDS). […] A study by Benarroch et al suggested that clinical variability in MFS may result from alternative splicing of FBN1. […] FBN1 mutations cause several Marfan-like disorders, such as the MASS (myopia, mitral valve prolapse, borderline and nonprogressive aortic enlargement, nonspecific skin and skeletal findings) phenotype and isolated ectopia lentis.

• #28

  https://www.nhs.uk/conditions/marfan-syndrome/

  Marfan syndrome is hereditary, which means it can be passed to a child from a parent who’s affected. […] In around 3 in 4 cases, Marfan syndrome is inherited from 1 parent. […] The syndrome is autosomal dominant, which means a child can inherit it even if only 1 parent has the syndrome. […] The gene defect leads to reduced production of a protein called fibrillin, resulting in parts of the body being able to stretch abnormally when placed under any kind of stress. […] The defective fibrillin gene also causes some bones to grow longer than they should. […] In the remaining 1 in 4 cases, neither parent has the syndrome. […] In these cases, the fibrillin gene changes (mutates) for the first time in the parent’s egg or sperm. […] The mutated gene can be passed on to the child, who will then go on to develop the syndrome.

• #29 Marfan Syndrome – Children’s Health Issues – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/children-s-health-issues/connective-tissue-disorders-in-children/marfan-syndrome

  Marfan syndrome is caused by mutations in the gene that codes for a protein called fibrillin. […] If the fibrillin gene is mutated, some fibers and other parts of connective tissue undergo changes that ultimately weaken the tissue. […] Weakened tissues stretch, distort, and can even tear. […] There is no cure for Marfan syndrome or any way to correct the abnormalities in the connective tissue.

• #30 Marfan Syndrome – Children’s Health Issues – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/children-s-health-issues/connective-tissue-disorders-in-children/marfan-syndrome

  Marfan syndrome is caused by mutations in the gene that codes for a protein called fibrillin. […] If the fibrillin gene is mutated, some fibers and other parts of connective tissue undergo changes that ultimately weaken the tissue. […] Weakened tissues stretch, distort, and can even tear. […] There is no cure for Marfan syndrome or any way to correct the abnormalities in the connective tissue.

• #31 Marfan Syndrome – Pediatrics – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/pediatrics/connective-tissue-disorders-in-children/marfan-syndrome

  Inheritance of Marfan syndrome is autosomal dominant. The basic molecular defect results from mutations in the gene encoding the glycoprotein fibrillin-1 (FBN1), which is the main component of microfibrils and helps anchor cells to the extracellular matrix. […] There are many different manifestations of the genetic mutation that causes Marfan syndrome; however, it is typically recognized by the constellation of long limbs, aortic root dilation, and dislocated lenses. […] Marfan syndrome results from an autosomal dominant mutation of the gene encoding the glycoprotein fibrillin-1, which is the main component of microfibrils, resulting in numerous possible deformities and defects. […] Manifestations vary widely, but the principal structural defects involve the cardiovascular, musculoskeletal, and ocular systems, causing a typical constellation of long limbs, aortic root dilation, and dislocated lenses.

• #32 Marfan Syndrome Causes, Symptoms, and Treatment

  https://www.upmc.com/services/heart-vascular/conditions/marfan-syndrome

  Marfan syndrome is caused by a genetic mutation that limits the body’s ability to make proteins that build connective tissue. […] Although about 25 percent of people develop Marfan syndrome for unknown reasons, it is most commonly passed from parent to child. […] Problems with the aorta such as aortic aneurysm or dissection are the most common cause of death in people with Marfan syndrome.

• #33 Marfan syndrome – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/marfan-syndrome/diagnosis-treatment/drc-20350787

  Genetic testing is often used to confirm the diagnosis of Marfan syndrome. If a Marfan mutation is found, family members can be tested to see if they are also affected. […] The classic abnormality is Marfan syndrome but other rare abnormalities have been defined such as Ehler-Danlos syndrome, Loeys-Dietz syndrome and a few others. […] The most common genetic aortic abnormality affecting the aortic root is bicuspid aortic valve disease.

• #34 Marfan syndrome – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/marfan-syndrome/diagnosis-treatment/drc-20350787

  Genetic testing is often used to confirm the diagnosis of Marfan syndrome. If a Marfan mutation is found, family members can be tested to see if they are also affected. […] The classic abnormality is Marfan syndrome but other rare abnormalities have been defined such as Ehler-Danlos syndrome, Loeys-Dietz syndrome and a few others. […] The most common genetic aortic abnormality affecting the aortic root is bicuspid aortic valve disease.

• #35 Marfan Syndrome – GenTAC Alliance

  https://www.gentacalliance.org/conditions/marfan-syndrome/

  Genetic testing may also provide helpful information. If someone has a family history of Marfan syndrome, genetic testing can help show which family members have Marfan syndrome and need additional care. […] Some of the outward features of Marfan syndrome can be found in other disorders related to Marfan syndrome, such as Loeys-Dietz syndrome or isolated thoracic aortic aneurysms. For this reason, genetic testing may be helpful when a diagnosis cannot be determined through an exam, family history, and imaging tests alone or when lens dislocation (ectopia lentis) is not present and features suggesting an alternative diagnosis are present. Knowing the precise diagnosis is critical to the follow up monitoring and treatment plan.

• #36 Marfan Syndrome – GenTAC Alliance

  https://www.gentacalliance.org/conditions/marfan-syndrome/

  Genetic testing may also provide helpful information. If someone has a family history of Marfan syndrome, genetic testing can help show which family members have Marfan syndrome and need additional care. […] Some of the outward features of Marfan syndrome can be found in other disorders related to Marfan syndrome, such as Loeys-Dietz syndrome or isolated thoracic aortic aneurysms. For this reason, genetic testing may be helpful when a diagnosis cannot be determined through an exam, family history, and imaging tests alone or when lens dislocation (ectopia lentis) is not present and features suggesting an alternative diagnosis are present. Knowing the precise diagnosis is critical to the follow up monitoring and treatment plan.

• #37 Etiology and pathogenesis of the Marfan syndrome: current understanding – Pyeritz- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/16414/html

  However, a few years later, the Dietz lab capitalized on the fact that a fundamental function of fibrillin-1 was to bind the latent transforming growth factor- binding protein (LTGBP). As a result, control of the cellular activity of the growth factor was disrupted. Defective fibrillin-1 resulted in excessive activity of transforming growth factor- (TGF-), which led to a cascade through its canonical signaling pathway, resulting in increased activity of SMAD2/3. […] Losartan, an AT1 angiotensin receptor blocking drug, was shown to protect mouse models of MFS from developing aortic aneurysms. Not only did the aorta not dilate or dissect, but the histopathology appeared unaffected. Overexpression of TGF- was shown to result in several of the biochemical findings once thought to be primary, such as increased hyaluronan deposition and expression of matrix metalloproteinases. […] Further understanding of the pathogenesis of MFS, especially in the human, will undoubtedly lead to more effective medical treatments in the future.

• #38 Treating kids with Marfan syndrome – UChicago Medicine

  https://www.uchicagomedicine.org/forefront/pediatrics-articles/2024/january/treating-kids-with-marfan-syndrome

  Early diagnosis offers an opportunity to intervene with medical therapies that can slow the progression of Marfans and other genetic causes of aortic aneurysm. […] Clinical trials have found that medical therapies may slow the rate of aortic dilation and may prevent aortic complications over time, potentially eliminating the need for surgery. […] Patients may be on medications such as beta blockers or angiotensin receptor blockers to slow aortic root dilation and prevent emergent dissections. […] The younger children are when they are diagnosed with Marfan syndrome, the greater the likelihood they will have profound heart failure. […] Although surgery prevents potentially lethal aortic rupture, patients need lifelong axial imaging to detect aneurysms on the rest of the vascular tree or pseudo aneurysms that can arise late following surgical intervention.

• #39 Treating kids with Marfan syndrome – UChicago Medicine

  https://www.uchicagomedicine.org/forefront/pediatrics-articles/2024/january/treating-kids-with-marfan-syndrome

  Early diagnosis offers an opportunity to intervene with medical therapies that can slow the progression of Marfans and other genetic causes of aortic aneurysm. […] Clinical trials have found that medical therapies may slow the rate of aortic dilation and may prevent aortic complications over time, potentially eliminating the need for surgery. […] Patients may be on medications such as beta blockers or angiotensin receptor blockers to slow aortic root dilation and prevent emergent dissections. […] The younger children are when they are diagnosed with Marfan syndrome, the greater the likelihood they will have profound heart failure. […] Although surgery prevents potentially lethal aortic rupture, patients need lifelong axial imaging to detect aneurysms on the rest of the vascular tree or pseudo aneurysms that can arise late following surgical intervention.

• #40 Etiology and pathogenesis of the Marfan syndrome: current understanding – Pyeritz- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/16414/html

  However, a few years later, the Dietz lab capitalized on the fact that a fundamental function of fibrillin-1 was to bind the latent transforming growth factor- binding protein (LTGBP). As a result, control of the cellular activity of the growth factor was disrupted. Defective fibrillin-1 resulted in excessive activity of transforming growth factor- (TGF-), which led to a cascade through its canonical signaling pathway, resulting in increased activity of SMAD2/3. […] Losartan, an AT1 angiotensin receptor blocking drug, was shown to protect mouse models of MFS from developing aortic aneurysms. Not only did the aorta not dilate or dissect, but the histopathology appeared unaffected. Overexpression of TGF- was shown to result in several of the biochemical findings once thought to be primary, such as increased hyaluronan deposition and expression of matrix metalloproteinases. […] Further understanding of the pathogenesis of MFS, especially in the human, will undoubtedly lead to more effective medical treatments in the future.

• #41 Genetics of Marfan Syndrome: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/946315-overview

  Marfan syndrome (MFS) is an inherited connective tissue disorder noteworthy for its worldwide distribution, relatively high prevalence, and clinical variability. This autosomal dominant syndrome has pleiotropic manifestations involving primarily the ocular, cardiovascular, and skeletal systems. […] Classic MFS (MFS type 1, MFS1) has been considered a condition caused by the deficiency of a structural extracellular matrix protein, fibrillin-1; however, studies of Marfan mouse models and Marfan-related conditions have expanded our current understanding to a pathogenic model that involves dysregulation of cytokine-transforming growth factor beta (TGF) signaling. […] The identification of mutations in TGFR2 in patients with MFS type 2 (MFS2 mapped at 3p24.2-p25) provided direct evidence of abnormal TGF signaling in the pathogenesis of MFS.

• #42 The Molecular Genetics of Marfan Syndrome

  https://www.medsci.org/v18p2752.htm

  Marfan syndrome (MFS) is a complex connective tissue disease that is primarily characterized by cardiovascular, ocular and skeletal systems disorders. […] It has been shown that molecular genetic factors serve critical roles in the pathogenesis of MFS. […] FBN1 is associated with MFS and the other genes such as FBN2, transforming growth factor beta (TGF-) receptors (TGFBR1 and TGFBR2), latent TGF–binding protein 2 (LTBP2) and SKI, amongst others also have their associated syndromes, however high overlap may exist between these syndromes and MFS. […] Abnormalities in the TGF- signaling pathway also contribute to the development of aneurysms in patients with MFS, although the detailed molecular mechanism remains unclear. […] The purpose of the present review is to provide an up-to-date understanding of MFS-related genes and relevant assessment technologies, with the aim of laying a foundation for the early diagnosis, consultation and treatment of MFS.

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