Materiały źródłowe

• #1 Klippel–Trénaunay syndrome

  https://dermnetnz.org/topics/klippel-trenaunay-syndrome

  While the exact cause of KlippelTrnaunay syndrome is not clear, several genes and pathways have been identified in its pathogenesis. Notably, PIK3CA gene mutations have been detected in some cases of KlippelTrnaunay syndrome. PIK3CA encodes for a subunit of the phosphoinositide 3-kinase enzyme, which is involved in cell proliferation and migration. Gain-of-function mutations can lead to tissue hypertrophy in the bone, soft tissue, and blood vessels […] The angiogenic gene VG5Q has also been implicated in KlippelTrnaunay syndrome.

• #2 Klippel–Trénaunay syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Klippel%E2%80%93Tr%C3%A9naunay_syndrome

  Klippel-Trenaunay syndrome, formerly Klippel-Trenaunay-Weber syndrome and sometimes angioosteohypertrophy syndrome and hemangiectatic hypertrophy, is a rare congenital medical condition in which blood vessels and/or lymph vessels fail to form properly. […] It belongs to the PIK3CA-related overgrowth spectrum of diseases which are caused by mutations in the PIK3CA gene. […] As of 2016, it belongs to the PIK3CA-related overgrowth spectrum of diseases, which are caused by mutations in the PIK3CA gene. Mutations in phosphatidylinositol-4-5-bisphosphate 3 kinase, catalytic subunit (=PIK3CA) gene leads to dysregulation of the MTOR pathway. Activation of protein kinase leads to uninhibited mTOR action resulting in cell proliferation.

• #3 Klippel-Trenaunay-Weber Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK558989/

  Recent studies have linked the etiology of Klippel Trenaunay syndrome to somatic mutations in the phosphatidylinositol-4-5-bisphosphate 3 kinase, catalytic subunit (PIK3CA) gene. This leads to the activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase and cell overgrowth by dysregulation of the mTORC2 pathway. […] Mutations occur in the embryological stage of development involving angiogenesis, reflecting findings seen in this condition. Now, KTS is grouped under the umbrella of similar overgrowth syndromes – PIK3CA-related overgrowth spectrum (PROS). […] Rapamycin is a relatively newer therapy that can halt the progression of vascular malformation and improve the quality of life in patients with KTS. This drug works by inhibiting the PI3K/AKT/mTOR pathway. Rapamycin-protein complex inhibits the action of mTOR1, leading to the arrest of cell growth, thereby preventing tissue overgrowth.

• #4 Klippel-Trenaunay syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/klippel-trenaunay-syndrome/

  Klippel-Trenaunay syndrome can be caused by mutations in the PIK3CA gene. This gene provides instructions for making the p110 alpha (p110α) protein, which is one piece (subunit) of an enzyme called phosphatidylinositol 3-kinase (PI3K). PI3K plays a role in chemical signaling that is important for many cell activities, including cell growth and division (proliferation), movement (migration) of cells, and cell survival. These functions make PI3K important for the development of tissues throughout the body. […] The PIK3CA gene mutations associated with Klippel-Trenaunay syndrome alter the p110α protein. The altered subunit makes PI3K abnormally active, which allows cells to grow and divide continuously. Increased cell proliferation leads to abnormal growth of the bones, soft tissues, and blood vessels.

• #5 Klippel-Trenaunay syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/klippel-trenaunay-syndrome/

  Klippel-Trenaunay syndrome can be caused by mutations in the PIK3CA gene. This gene provides instructions for making the p110 alpha (p110α) protein, which is one piece (subunit) of an enzyme called phosphatidylinositol 3-kinase (PI3K). PI3K plays a role in chemical signaling that is important for many cell activities, including cell growth and division (proliferation), movement (migration) of cells, and cell survival. These functions make PI3K important for the development of tissues throughout the body. […] The PIK3CA gene mutations associated with Klippel-Trenaunay syndrome alter the p110α protein. The altered subunit makes PI3K abnormally active, which allows cells to grow and divide continuously. Increased cell proliferation leads to abnormal growth of the bones, soft tissues, and blood vessels.

• #6 Klippel-Trenaunay-Weber Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK558989/

  Recent studies have linked the etiology of Klippel Trenaunay syndrome to somatic mutations in the phosphatidylinositol-4-5-bisphosphate 3 kinase, catalytic subunit (PIK3CA) gene. This leads to the activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase and cell overgrowth by dysregulation of the mTORC2 pathway. […] Mutations occur in the embryological stage of development involving angiogenesis, reflecting findings seen in this condition. Now, KTS is grouped under the umbrella of similar overgrowth syndromes – PIK3CA-related overgrowth spectrum (PROS). […] Rapamycin is a relatively newer therapy that can halt the progression of vascular malformation and improve the quality of life in patients with KTS. This drug works by inhibiting the PI3K/AKT/mTOR pathway. Rapamycin-protein complex inhibits the action of mTOR1, leading to the arrest of cell growth, thereby preventing tissue overgrowth.

• #7 Klippel-Trenaunay syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/klippel-trenaunay-syndrome/

  Klippel-Trenaunay syndrome can be caused by mutations in the PIK3CA gene. This gene provides instructions for making the p110 alpha (p110α) protein, which is one piece (subunit) of an enzyme called phosphatidylinositol 3-kinase (PI3K). PI3K plays a role in chemical signaling that is important for many cell activities, including cell growth and division (proliferation), movement (migration) of cells, and cell survival. These functions make PI3K important for the development of tissues throughout the body. […] The PIK3CA gene mutations associated with Klippel-Trenaunay syndrome alter the p110α protein. The altered subunit makes PI3K abnormally active, which allows cells to grow and divide continuously. Increased cell proliferation leads to abnormal growth of the bones, soft tissues, and blood vessels.

• #8 Klippel-Trenaunay-Weber Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK558989/

  Recent studies have linked the etiology of Klippel Trenaunay syndrome to somatic mutations in the phosphatidylinositol-4-5-bisphosphate 3 kinase, catalytic subunit (PIK3CA) gene. This leads to the activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase and cell overgrowth by dysregulation of the mTORC2 pathway. […] Mutations occur in the embryological stage of development involving angiogenesis, reflecting findings seen in this condition. Now, KTS is grouped under the umbrella of similar overgrowth syndromes – PIK3CA-related overgrowth spectrum (PROS). […] Rapamycin is a relatively newer therapy that can halt the progression of vascular malformation and improve the quality of life in patients with KTS. This drug works by inhibiting the PI3K/AKT/mTOR pathway. Rapamycin-protein complex inhibits the action of mTOR1, leading to the arrest of cell growth, thereby preventing tissue overgrowth.

• #9 Klippel-Trenaunay-Weber Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK558989/

  Recent studies have linked the etiology of Klippel Trenaunay syndrome to somatic mutations in the phosphatidylinositol-4-5-bisphosphate 3 kinase, catalytic subunit (PIK3CA) gene. This leads to the activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase and cell overgrowth by dysregulation of the mTORC2 pathway. […] Mutations occur in the embryological stage of development involving angiogenesis, reflecting findings seen in this condition. Now, KTS is grouped under the umbrella of similar overgrowth syndromes – PIK3CA-related overgrowth spectrum (PROS). […] Rapamycin is a relatively newer therapy that can halt the progression of vascular malformation and improve the quality of life in patients with KTS. This drug works by inhibiting the PI3K/AKT/mTOR pathway. Rapamycin-protein complex inhibits the action of mTOR1, leading to the arrest of cell growth, thereby preventing tissue overgrowth.

• #10 Klippel-Trenaunay syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/klippel-trenaunay-syndrome/

  Klippel-Trenaunay syndrome is one of several overgrowth syndromes, including megalencephaly-capillary malformation syndrome, that are caused by mutations in the PIK3CA gene. Together, these conditions are known as the PIK3CA-related overgrowth spectrum (PROS). […] Because not everyone with Klippel-Trenaunay syndrome has a mutation in the PIK3CA gene, it is possible that mutations in unidentified genes may also cause this condition.

• #11 Klippel-Trenaunay syndrome – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/klippel-trenaunay/symptoms-causes/syc-20374152

  Klippel-Trenaunay (klih-PEL tray-no-NAY) syndrome also called KTS is a rare disorder found at birth (congenital) involving problems in the development of certain blood vessels, soft tissues (such as skin and muscles), bones and sometimes the lymphatic system. […] KTS is a genetic disorder. It involves genetic changes (mutations), most commonly in the PIK3CA gene. This gene is responsible for the growth of cells and the development of tissues in the body. A change in this gene results in overgrowth of tissues. […] KTS is not usually inherited. The gene changes occur randomly during cell division in early development before birth.

• #12 Klippel-Trenaunay Syndrome (KTS): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17152-klippel-trenaunay-syndrome-kts

  Klippel-Trenaunay syndrome (KTS) is a rare congenital (present at birth) disorder. It changes the way your soft tissues, bones and blood vessels develop and causes a red port-wine stain birthmark on one limb. Many people with KTS also have abnormalities in their lymphatic system. This system helps maintain fluid balance in your body. […] KTS often happens because of a variation in the PIK3CA gene. The gene variation occurs sporadically (for no known reason). You dont inherit it from your parents. […] Some people have KTS without having the PIK3CA variation. Because of this, researchers think other gene variations could also cause KTS.

• #13 Klippel-Trenaunay-Weber Syndrome: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/945760-overview

  A case report of KTWS in a monozygotic twin with an unaffected twin advances the theory of a paradominant inheritance pattern. […] This theory suggests that KTWS is produced by a single gene defect lethal in individuals who are homozygous for this gene. Heterozygotes carry the gene but are unaffected. The disease manifests in individuals who demonstrate loss of heterozygosity from a somatic mutation during embryogenesis. In these individuals, only the skin region harboring this cell population demonstrates the KTWS mutation. […] The association between the angiogenic factor gene AGGF1 and KTS appears to be significant. […] Common AGGF1 variants may confer risk of KTWS. […] Kihiczak et al report that KTWS may result from a pathogenic gene for vascular and tissue overgrowth.

• #14 Klippel-Trenaunay Syndrome (KTS) – Vascular Birthmarks Foundation

  https://birthmark.org/birthmark/klippel-trenaunay-syndrome/

  Klippel-Trenaunay syndrome (KTS) is a rare disorder that is present at birth (congenital) and is characterized by a triad of cutaneous capillary malformation (port-wine stain), lymphatic anomalies, and abnormal veins in association with variable overgrowth of soft tissue and bone. KTS occurs most frequently in the lower limb and less commonly in the upper extremity and trunk. […] A mutation in the PIK3CA gene is considered the cause of KTS. This mutation occurs in primitive cells of blood and lymphatic vessels, fat, and bones, of the affected limb.

• #15 Klippel-Trenaunay-Weber Syndrome: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/945760-overview

  A case report of KTWS in a monozygotic twin with an unaffected twin advances the theory of a paradominant inheritance pattern. […] This theory suggests that KTWS is produced by a single gene defect lethal in individuals who are homozygous for this gene. Heterozygotes carry the gene but are unaffected. The disease manifests in individuals who demonstrate loss of heterozygosity from a somatic mutation during embryogenesis. In these individuals, only the skin region harboring this cell population demonstrates the KTWS mutation. […] The association between the angiogenic factor gene AGGF1 and KTS appears to be significant. […] Common AGGF1 variants may confer risk of KTWS. […] Kihiczak et al report that KTWS may result from a pathogenic gene for vascular and tissue overgrowth.

• #16 Klippel-Trenaunay syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/klippel-trenaunay-syndrome/

  Klippel-Trenaunay syndrome is one of several overgrowth syndromes, including megalencephaly-capillary malformation syndrome, that are caused by mutations in the PIK3CA gene. Together, these conditions are known as the PIK3CA-related overgrowth spectrum (PROS). […] Because not everyone with Klippel-Trenaunay syndrome has a mutation in the PIK3CA gene, it is possible that mutations in unidentified genes may also cause this condition.

• #17 Klippel-Trenaunay Syndrome (KTS): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17152-klippel-trenaunay-syndrome-kts

  Klippel-Trenaunay syndrome (KTS) is a rare congenital (present at birth) disorder. It changes the way your soft tissues, bones and blood vessels develop and causes a red port-wine stain birthmark on one limb. Many people with KTS also have abnormalities in their lymphatic system. This system helps maintain fluid balance in your body. […] KTS often happens because of a variation in the PIK3CA gene. The gene variation occurs sporadically (for no known reason). You dont inherit it from your parents. […] Some people have KTS without having the PIK3CA variation. Because of this, researchers think other gene variations could also cause KTS.

• #18 Klippel-Trenaunay-Weber Syndrome: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/945760-overview

  A case report of KTWS in a monozygotic twin with an unaffected twin advances the theory of a paradominant inheritance pattern. […] This theory suggests that KTWS is produced by a single gene defect lethal in individuals who are homozygous for this gene. Heterozygotes carry the gene but are unaffected. The disease manifests in individuals who demonstrate loss of heterozygosity from a somatic mutation during embryogenesis. In these individuals, only the skin region harboring this cell population demonstrates the KTWS mutation. […] The association between the angiogenic factor gene AGGF1 and KTS appears to be significant. […] Common AGGF1 variants may confer risk of KTWS. […] Kihiczak et al report that KTWS may result from a pathogenic gene for vascular and tissue overgrowth.

• #19 Klippel–Trénaunay syndrome

  https://dermnetnz.org/topics/klippel-trenaunay-syndrome

  While the exact cause of KlippelTrnaunay syndrome is not clear, several genes and pathways have been identified in its pathogenesis. Notably, PIK3CA gene mutations have been detected in some cases of KlippelTrnaunay syndrome. PIK3CA encodes for a subunit of the phosphoinositide 3-kinase enzyme, which is involved in cell proliferation and migration. Gain-of-function mutations can lead to tissue hypertrophy in the bone, soft tissue, and blood vessels […] The angiogenic gene VG5Q has also been implicated in KlippelTrnaunay syndrome.

• #20 Identification of an angiogenic factor that when mutated causes susceptibility to Klippel–Trenaunay syndrome | Nature

  https://www.nature.com/articles/nature02320

  Angiogenic factors are critical to the initiation of angiogenesis and maintenance of the vascular network. Here we use human genetics as an approach to identify an angiogenic factor, VG5Q, and further define two genetic defects of VG5Q in patients with the vascular disease Klippel-Trenaunay syndrome (KTS). […] VG5Q shows strong expression in blood vessels and is secreted as vessel formation is initiated. VG5Q can bind to endothelial cells and promote cell proliferation, suggesting that it may act in an autocrine fashion. […] These results define VG5Q as an angiogenic factor, establish VG5Q as a susceptibility gene for KTS, and show that increased angiogenesis is a molecular pathogenic mechanism of KTS.

• #21 Identification of an angiogenic factor that when mutated causes susceptibility to Klippel–Trenaunay syndrome | Nature

  https://www.nature.com/articles/nature02320

  Angiogenic factors are critical to the initiation of angiogenesis and maintenance of the vascular network. Here we use human genetics as an approach to identify an angiogenic factor, VG5Q, and further define two genetic defects of VG5Q in patients with the vascular disease Klippel-Trenaunay syndrome (KTS). […] VG5Q shows strong expression in blood vessels and is secreted as vessel formation is initiated. VG5Q can bind to endothelial cells and promote cell proliferation, suggesting that it may act in an autocrine fashion. […] These results define VG5Q as an angiogenic factor, establish VG5Q as a susceptibility gene for KTS, and show that increased angiogenesis is a molecular pathogenic mechanism of KTS.

• #22 Compva: Klippel-Trénaunay syndrome

  https://www.compva.com/science/klippel-trenaunay-syndrome

  Klippel-Trnaunay syndrome occurs sporadically (not familial). […] It is based on a genetic mosaic. In at least some patients, somatic (present only in affected tissues) gain-of-function mutations have been detected in the PIK3CA oncogene, which encodes the catalytic alpha subunit of phosphatidylinositol 3-kinase (PI3K). PI3K activation causes overactivation of the PI3K (phosphatidylinositol 3-kinase)/AKT/mTOR pathway (with the consequences of enhanced cell growth and anti-apoptosis). […] In addition, sequence variants of the gene AGGF1, which encodes an angiogenic factor, have been identified as a predisposing factor.

• #23 Klippel-Trenaunay-Weber Syndrome: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/945760-overview

  A case report of KTWS in a monozygotic twin with an unaffected twin advances the theory of a paradominant inheritance pattern. […] This theory suggests that KTWS is produced by a single gene defect lethal in individuals who are homozygous for this gene. Heterozygotes carry the gene but are unaffected. The disease manifests in individuals who demonstrate loss of heterozygosity from a somatic mutation during embryogenesis. In these individuals, only the skin region harboring this cell population demonstrates the KTWS mutation. […] The association between the angiogenic factor gene AGGF1 and KTS appears to be significant. […] Common AGGF1 variants may confer risk of KTWS. […] Kihiczak et al report that KTWS may result from a pathogenic gene for vascular and tissue overgrowth.

• #24 Klippel-Trenaunay-Weber Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK558989/

  Recent studies have linked the etiology of Klippel Trenaunay syndrome to somatic mutations in the phosphatidylinositol-4-5-bisphosphate 3 kinase, catalytic subunit (PIK3CA) gene. This leads to the activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase and cell overgrowth by dysregulation of the mTORC2 pathway. […] Mutations occur in the embryological stage of development involving angiogenesis, reflecting findings seen in this condition. Now, KTS is grouped under the umbrella of similar overgrowth syndromes – PIK3CA-related overgrowth spectrum (PROS). […] Rapamycin is a relatively newer therapy that can halt the progression of vascular malformation and improve the quality of life in patients with KTS. This drug works by inhibiting the PI3K/AKT/mTOR pathway. Rapamycin-protein complex inhibits the action of mTOR1, leading to the arrest of cell growth, thereby preventing tissue overgrowth.

• #25 Compva: Klippel-Trénaunay syndrome

  https://www.compva.com/science/klippel-trenaunay-syndrome

  Klippel-Trnaunay syndrome occurs sporadically (not familial). […] It is based on a genetic mosaic. In at least some patients, somatic (present only in affected tissues) gain-of-function mutations have been detected in the PIK3CA oncogene, which encodes the catalytic alpha subunit of phosphatidylinositol 3-kinase (PI3K). PI3K activation causes overactivation of the PI3K (phosphatidylinositol 3-kinase)/AKT/mTOR pathway (with the consequences of enhanced cell growth and anti-apoptosis). […] In addition, sequence variants of the gene AGGF1, which encodes an angiogenic factor, have been identified as a predisposing factor.

• #26 Klippel-Trenaunay-Weber Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK558989/

  Recent studies have linked the etiology of Klippel Trenaunay syndrome to somatic mutations in the phosphatidylinositol-4-5-bisphosphate 3 kinase, catalytic subunit (PIK3CA) gene. This leads to the activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase and cell overgrowth by dysregulation of the mTORC2 pathway. […] Mutations occur in the embryological stage of development involving angiogenesis, reflecting findings seen in this condition. Now, KTS is grouped under the umbrella of similar overgrowth syndromes – PIK3CA-related overgrowth spectrum (PROS). […] Rapamycin is a relatively newer therapy that can halt the progression of vascular malformation and improve the quality of life in patients with KTS. This drug works by inhibiting the PI3K/AKT/mTOR pathway. Rapamycin-protein complex inhibits the action of mTOR1, leading to the arrest of cell growth, thereby preventing tissue overgrowth.

• #27 RRH: Rural and Remote Health article: 5348 – Klippel–Trénaunay syndrome: a case report of a rare vascular disorder identified in a rural Canadian hospital

  https://www.rrh.org.au/journal/article/5348/

  Recent studies investigated additional inhibitors of the PI3K (phosphoinositide-3-kinase)-Akt-mTOR signaling pathway in KTS. […] The cutaneous capillary malformation in KTS manifests as a port-wine stain (nevus flammeus). […] For physicians in rural areas managing patients with KTS, identification is important in order to manage possible complications. […] Another possible complication of KTS is bleeding from abnormal vessels. […] The fact that the patient was diagnosed at an advanced age clearly demonstrates the need of early diagnostic tools in suspected patients to prevent or decelerate possible complications. […] In recent years, the hypernym PIK3CA-related overgrowth spectrum (PROS) was established to classify diseases linked to somatic PIK3CA mutations.

• #28

  https://journals.lww.com/md-journal/fulltext/2025/02210/klippel_trenaunay_syndrome_with_multiorgan.38.aspx

  The fundamental cause of complications in KTS lies in its extensive vascular malformations, so all treatments for KTS should be based on correcting vascular abnormalities. […] Studies have suggested that KTS syndrome may be associated with mutations in the PIK3CA gene, which are related to abnormal vascular formation and proliferation, leading to vascular abnormalities and tissue overgrowth in patients. […] PIK3CA inhibitors as targeted drugs for treating KTS have potential efficacy. […] Accurate diagnosis serves as the foundation of treatment.

• #29 Orphanet: Klippel-Trénaunay syndrome

  https://www.orpha.net/en/disease/detail/90308

  A rare congenital complex vascular malformation syndrome characterized by capillary malformations manifesting as wine stains and venous varicosities typically prominent along the lateral aspect of the lower extremities, associated with overgrowth of a limb (most commonly a leg, less frequently other regions of the body), involving bone and/or soft tissues. […] The syndrome is due to heterozygous post-zygotic mosaic variation in the PIK3CA gene, occurring in early embryogenesis. It has to be noted that not all KTS appear to result from PIK3CA mosaic variation. […] Diagnosis must be confirmed by identification of a PIK3CA mosaic variation on affected tissue (most often skin) without culture, using high-depth high-throughput sequencing. […] Treatment with alpelisib changes the prognosis when a PIK3CA variant was identified.

• #30 Identification of an angiogenic factor that when mutated causes susceptibility to Klippel–Trenaunay syndrome | Nature

  https://www.nature.com/articles/nature02320

  Angiogenic factors are critical to the initiation of angiogenesis and maintenance of the vascular network. Here we use human genetics as an approach to identify an angiogenic factor, VG5Q, and further define two genetic defects of VG5Q in patients with the vascular disease Klippel-Trenaunay syndrome (KTS). […] VG5Q shows strong expression in blood vessels and is secreted as vessel formation is initiated. VG5Q can bind to endothelial cells and promote cell proliferation, suggesting that it may act in an autocrine fashion. […] These results define VG5Q as an angiogenic factor, establish VG5Q as a susceptibility gene for KTS, and show that increased angiogenesis is a molecular pathogenic mechanism of KTS.

• #31 Klippel Trenaunay Syndrome, Inverse Klippel Trenaunay Syndrome: H

  https://www.longdom.org/open-access/klippel-trenaunay-syndrome-inverse-klippel-trenaunay-syndrome-hypertrophy-of-lower-limbs-and-atrophy-of-the-upper-limbs–7392.html

  Klippel Trenaunay Syndrome (KTS) is a rare, congenital malformation. Several theories have been postulated to describe its pathogenesis. However, the exact etiology is not known. […] The presumed pathogenetic pathway is that of mesodermal developmental derangement, leading to maintenance of microscopic arteriovenous communications in the limb bud, with consequent development of the naeuvs, superficial varices, and limb hypertrophy. […] Several hypotheses regarding cause and pathogenesis in KTS exist, but none explains the full characteristics of KTS. Hypotheses include an alteration in vascular remodeling, perhaps at the level of altered angiopoietin-2 antagonism. […] Servelles theory stated that there is a primary obstruction of the venous system resulting in venous hypertension and thus development of abnormal venous pathways and tissue overgrowth. […] Also, maintenance of microscopic arteriovenous communication in the limb bud vein had been proposed. […] Others suggested alteration of the balance between angiogenesis and vasculogenesis, a process that is controlled by numerous genes.

• #32 Identification of an angiogenic factor that when mutated causes susceptibility to Klippel–Trenaunay syndrome | Nature

  https://www.nature.com/articles/nature02320

  Angiogenic factors are critical to the initiation of angiogenesis and maintenance of the vascular network. Here we use human genetics as an approach to identify an angiogenic factor, VG5Q, and further define two genetic defects of VG5Q in patients with the vascular disease Klippel-Trenaunay syndrome (KTS). […] VG5Q shows strong expression in blood vessels and is secreted as vessel formation is initiated. VG5Q can bind to endothelial cells and promote cell proliferation, suggesting that it may act in an autocrine fashion. […] These results define VG5Q as an angiogenic factor, establish VG5Q as a susceptibility gene for KTS, and show that increased angiogenesis is a molecular pathogenic mechanism of KTS.

• #33 Identification of an angiogenic factor that when mutated causes susceptibility to Klippel–Trenaunay syndrome | Nature

  https://www.nature.com/articles/nature02320

  Angiogenic factors are critical to the initiation of angiogenesis and maintenance of the vascular network. Here we use human genetics as an approach to identify an angiogenic factor, VG5Q, and further define two genetic defects of VG5Q in patients with the vascular disease Klippel-Trenaunay syndrome (KTS). […] VG5Q shows strong expression in blood vessels and is secreted as vessel formation is initiated. VG5Q can bind to endothelial cells and promote cell proliferation, suggesting that it may act in an autocrine fashion. […] These results define VG5Q as an angiogenic factor, establish VG5Q as a susceptibility gene for KTS, and show that increased angiogenesis is a molecular pathogenic mechanism of KTS.

• #34 Klippel-Trenaunay-Weber Syndrome: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/945760-overview

  The exact cause of Klippel-Trenaunay-Weber syndrome (KTWS) remains to be elucidated, although several theories exist. Bliznak and Staple suggested intrauterine damage to the sympathetic ganglia or intermediolateral tract leading to dilated microscopic arteriovenous anastomoses as the cause. […] Servelle believes that deep vein abnormalities, with resultant obstruction of venous flow, lead to venous hypertension, the development of varices, and limb hypertrophy. […] Baskerville et al contend that a mesodermal defect during fetal development causes maintenance of microscopic arteriovenous communications. […] Finally, McGrory and Amadio believe that an underlying mixed mesodermal and ectodermal dysplasia is likely responsible for the development of KTWS. […] Most cases KTWS are sporadic, although a few cases in the literature report an autosomal dominant pattern of inheritance.

• #35 Klippel-Trenaunay-Weber Syndrome: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/945760-overview

  The exact cause of Klippel-Trenaunay-Weber syndrome (KTWS) remains to be elucidated, although several theories exist. Bliznak and Staple suggested intrauterine damage to the sympathetic ganglia or intermediolateral tract leading to dilated microscopic arteriovenous anastomoses as the cause. […] Servelle believes that deep vein abnormalities, with resultant obstruction of venous flow, lead to venous hypertension, the development of varices, and limb hypertrophy. […] Baskerville et al contend that a mesodermal defect during fetal development causes maintenance of microscopic arteriovenous communications. […] Finally, McGrory and Amadio believe that an underlying mixed mesodermal and ectodermal dysplasia is likely responsible for the development of KTWS. […] Most cases KTWS are sporadic, although a few cases in the literature report an autosomal dominant pattern of inheritance.

• #36 Klippel–Trenaunay Syndrome, Segmental/Focal Overgrowth Malformations: A Review

  https://www.mdpi.com/2227-9067/10/8/1421

  A new road has been opened for the etiological basis of this syndrome on the evidence that the more severe cases of KTS have been linked to mosaic-activating variants in the PIK3CA gene. […] It has been hypothesized that atresia or obstruction of the dep veins in the leg as a first event may lead to chronic venous hypertension with subsequent anomalous development of nevus, varices, and hypertrophy. […] The inclusion of the KTS within the PROS group may be useful to reach new advances in the etiopathogenetic factors of the KTS.

• #37 Klippel-Trenaunay-Weber Syndrome: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/945760-overview

  The exact cause of Klippel-Trenaunay-Weber syndrome (KTWS) remains to be elucidated, although several theories exist. Bliznak and Staple suggested intrauterine damage to the sympathetic ganglia or intermediolateral tract leading to dilated microscopic arteriovenous anastomoses as the cause. […] Servelle believes that deep vein abnormalities, with resultant obstruction of venous flow, lead to venous hypertension, the development of varices, and limb hypertrophy. […] Baskerville et al contend that a mesodermal defect during fetal development causes maintenance of microscopic arteriovenous communications. […] Finally, McGrory and Amadio believe that an underlying mixed mesodermal and ectodermal dysplasia is likely responsible for the development of KTWS. […] Most cases KTWS are sporadic, although a few cases in the literature report an autosomal dominant pattern of inheritance.

• #38 Klippel Trenaunay Syndrome, Inverse Klippel Trenaunay Syndrome: H

  https://www.longdom.org/open-access/klippel-trenaunay-syndrome-inverse-klippel-trenaunay-syndrome-hypertrophy-of-lower-limbs-and-atrophy-of-the-upper-limbs–7392.html

  Klippel Trenaunay Syndrome (KTS) is a rare, congenital malformation. Several theories have been postulated to describe its pathogenesis. However, the exact etiology is not known. […] The presumed pathogenetic pathway is that of mesodermal developmental derangement, leading to maintenance of microscopic arteriovenous communications in the limb bud, with consequent development of the naeuvs, superficial varices, and limb hypertrophy. […] Several hypotheses regarding cause and pathogenesis in KTS exist, but none explains the full characteristics of KTS. Hypotheses include an alteration in vascular remodeling, perhaps at the level of altered angiopoietin-2 antagonism. […] Servelles theory stated that there is a primary obstruction of the venous system resulting in venous hypertension and thus development of abnormal venous pathways and tissue overgrowth. […] Also, maintenance of microscopic arteriovenous communication in the limb bud vein had been proposed. […] Others suggested alteration of the balance between angiogenesis and vasculogenesis, a process that is controlled by numerous genes.

• #39 Klippel-Trenaunay-Weber Syndrome: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/945760-overview

  The exact cause of Klippel-Trenaunay-Weber syndrome (KTWS) remains to be elucidated, although several theories exist. Bliznak and Staple suggested intrauterine damage to the sympathetic ganglia or intermediolateral tract leading to dilated microscopic arteriovenous anastomoses as the cause. […] Servelle believes that deep vein abnormalities, with resultant obstruction of venous flow, lead to venous hypertension, the development of varices, and limb hypertrophy. […] Baskerville et al contend that a mesodermal defect during fetal development causes maintenance of microscopic arteriovenous communications. […] Finally, McGrory and Amadio believe that an underlying mixed mesodermal and ectodermal dysplasia is likely responsible for the development of KTWS. […] Most cases KTWS are sporadic, although a few cases in the literature report an autosomal dominant pattern of inheritance.

• #40 Gastrointestinal involvement in Klippel-Trénaunay syndrome: pathophysiology, evaluation, and management | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02857-5

  Klippel-Trnaunay syndrome is typically a complex combined capillary-lymphatic-venous malformation in lower limb. […] The underlying pathophysiology of gastrointestinal involvement in Klippel-Trnaunay syndrome has been underrecognized. […] Anorectosigmoid vascular malformations in KTS have distinct and more complicated pathophysiologies than anorectal vascular malformation. […] Gastrointestinal involvement is common in KTS patients, which can be a source of significant morbidity and even mortality. […] Gastrointestinal involvement is typically presented with edematous and thickened colorectum by the venous malformation (VM) network around and intra-wall. […] Anorectosigmoid VM has distinct pathophysiologies from anorectal VM. […] The latter involves the malformation and abnormal hemodynamics of two vein systems, IIV and IMV, can cause portal hypertension.

• #41 Gastrointestinal involvement in Klippel-Trénaunay syndrome: pathophysiology, evaluation, and management | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02857-5

  Klippel-Trnaunay syndrome is typically a complex combined capillary-lymphatic-venous malformation in lower limb. […] The underlying pathophysiology of gastrointestinal involvement in Klippel-Trnaunay syndrome has been underrecognized. […] Anorectosigmoid vascular malformations in KTS have distinct and more complicated pathophysiologies than anorectal vascular malformation. […] Gastrointestinal involvement is common in KTS patients, which can be a source of significant morbidity and even mortality. […] Gastrointestinal involvement is typically presented with edematous and thickened colorectum by the venous malformation (VM) network around and intra-wall. […] Anorectosigmoid VM has distinct pathophysiologies from anorectal VM. […] The latter involves the malformation and abnormal hemodynamics of two vein systems, IIV and IMV, can cause portal hypertension.

• #42 Gastrointestinal involvement in Klippel-Trénaunay syndrome: pathophysiology, evaluation, and management | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02857-5

  The IMV, a usually overlooked vein system in patients with portal hypertension should be re-looked in patients with anorectosigmoid VM. […] The rupture of submucosal phlebectasia leads to rectal bleeding from VM. […] The pathophysiologies of anorectal and anorectosigmoid VM in KTS. […] In KTS patients with pelvis involvement, the IIV-gluteal-marginal vein system is a valveless malformed reflux channel, which can cause bleeding from pelvic organs (anorectum and genitourinary tract). […] Recognizing the distinct pathophysiology is required to prevent pitfalls in the management. […] The pathophysiology regarding portal hypertension in KTS we discussed should be considered in future guidelines for vascular diseases of the liver.

• #43 RRH: Rural and Remote Health article: 5348 – Klippel–Trénaunay syndrome: a case report of a rare vascular disorder identified in a rural Canadian hospital

  https://www.rrh.org.au/journal/article/5348/

  Recent studies investigated additional inhibitors of the PI3K (phosphoinositide-3-kinase)-Akt-mTOR signaling pathway in KTS. […] The cutaneous capillary malformation in KTS manifests as a port-wine stain (nevus flammeus). […] For physicians in rural areas managing patients with KTS, identification is important in order to manage possible complications. […] Another possible complication of KTS is bleeding from abnormal vessels. […] The fact that the patient was diagnosed at an advanced age clearly demonstrates the need of early diagnostic tools in suspected patients to prevent or decelerate possible complications. […] In recent years, the hypernym PIK3CA-related overgrowth spectrum (PROS) was established to classify diseases linked to somatic PIK3CA mutations.

• #44 Gastrointestinal involvement in Klippel-Trénaunay syndrome: pathophysiology, evaluation, and management | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02857-5

  The IMV, a usually overlooked vein system in patients with portal hypertension should be re-looked in patients with anorectosigmoid VM. […] The rupture of submucosal phlebectasia leads to rectal bleeding from VM. […] The pathophysiologies of anorectal and anorectosigmoid VM in KTS. […] In KTS patients with pelvis involvement, the IIV-gluteal-marginal vein system is a valveless malformed reflux channel, which can cause bleeding from pelvic organs (anorectum and genitourinary tract). […] Recognizing the distinct pathophysiology is required to prevent pitfalls in the management. […] The pathophysiology regarding portal hypertension in KTS we discussed should be considered in future guidelines for vascular diseases of the liver.

• #45 Klippel-Trenaunay Syndrome Case | Applied Radiology

  https://appliedradiology.com/articles/klippel-trenaunay-syndrome-case

  When these vessels persist, they disrupt the physiological growth of normal venous anatomy and often dilate to large diameters, greatly increasing the risk of venous stasis. […] When severe, this can result in life-threatening complications, including large-volume bleeding, pulmonary emboli, and venous thromboses. […] Despite being a common in affected children, the prevalence of these marginal veins is conservatively measured at around 15% to 20%, likely due to the highly variable phenotype of KTS. […] Treatment for this syndrome has historically been surgical, which can be associated with significant complications. New minimally invasive techniques, including RFA, EVLT, and sclerotherapy, have expanded treatment options with fewer complications.

• #46 What is Klippel-Trenaunay syndrome

  https://sturge-weber.org/new-to-swf/understanding-kt.html

  Klippel-Trenaunay Syndrome (congenital dysplastic angiopathy) is a congenital vascular disorder of unknown cause. […] Symptoms associated with KT can include internal organ involvement, hematuria (blood in the urine) rectal bleeding, vaginal bleeding, and cellulitis (infection within the skin). […] Some patients can develop a very serious clotting abnormality called DIC (disseminated intravascular coagulation). […] It is important that children with KT be monitored for these types of growth abnormalities. […] Patients with KT may rarely require amputation when the limb is grossly enlarged. […] Internal organ involvement should be ruled out in any patient presenting with KT or Parkes-Weber Syndrome. […] Patients with KT have a tendency to heal more slowly in the affected limb and can suffer post-surgery complications.

• #47 A rare manifestation of Klippel-Trenaunay syndrome with bilateral chylothorax requiring surgical management—a case report – Mayer – Current Challenges in Thoracic Surgery

  https://ccts.amegroups.org/article/view/47253/html

  The condition can lead to significant morbidity and mortality, as leakage of lymph fluid from the thoracic duct or its tributaries into the thoracic cavity can lead to significant loss of essential proteins, immunoglobulins, fat, vitamins, electrolytes and water. […] Due to the pathogenesis of the disease symptomatic drainage alone is likely to fail, resulting in recurrence and chronicity. […] Definitive treatment has to be prompt and effective to prevent deterioration due to sustained malnutrition and immunodeficiency. […] The management of chylothorax in this patient posed a challenge to our normal practice. […] Our accumulated knowledge from managing the condition on the right hemithorax helped us apply a more effective strategy when the patient represented with contralateral pathology, allowing for an uncomplicated procedure and faster recovery. […] Considering the course of our case and taking KTS background information into account, we recommend considering contralateral prophylactic pleurodesis or concurrent bilateral pleurodesis in KTS patients with chylothorax.

• #48 A rare manifestation of Klippel-Trenaunay syndrome with bilateral chylothorax requiring surgical management—a case report – Mayer – Current Challenges in Thoracic Surgery

  https://ccts.amegroups.org/article/view/47253/html

  The condition can lead to significant morbidity and mortality, as leakage of lymph fluid from the thoracic duct or its tributaries into the thoracic cavity can lead to significant loss of essential proteins, immunoglobulins, fat, vitamins, electrolytes and water. […] Due to the pathogenesis of the disease symptomatic drainage alone is likely to fail, resulting in recurrence and chronicity. […] Definitive treatment has to be prompt and effective to prevent deterioration due to sustained malnutrition and immunodeficiency. […] The management of chylothorax in this patient posed a challenge to our normal practice. […] Our accumulated knowledge from managing the condition on the right hemithorax helped us apply a more effective strategy when the patient represented with contralateral pathology, allowing for an uncomplicated procedure and faster recovery. […] Considering the course of our case and taking KTS background information into account, we recommend considering contralateral prophylactic pleurodesis or concurrent bilateral pleurodesis in KTS patients with chylothorax.

• #49 Klippel-Trenaunay-Weber Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK558989/

  Recent studies have linked the etiology of Klippel Trenaunay syndrome to somatic mutations in the phosphatidylinositol-4-5-bisphosphate 3 kinase, catalytic subunit (PIK3CA) gene. This leads to the activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase and cell overgrowth by dysregulation of the mTORC2 pathway. […] Mutations occur in the embryological stage of development involving angiogenesis, reflecting findings seen in this condition. Now, KTS is grouped under the umbrella of similar overgrowth syndromes – PIK3CA-related overgrowth spectrum (PROS). […] Rapamycin is a relatively newer therapy that can halt the progression of vascular malformation and improve the quality of life in patients with KTS. This drug works by inhibiting the PI3K/AKT/mTOR pathway. Rapamycin-protein complex inhibits the action of mTOR1, leading to the arrest of cell growth, thereby preventing tissue overgrowth.

• #50

  https://journals.lww.com/md-journal/fulltext/2025/02210/klippel_trenaunay_syndrome_with_multiorgan.38.aspx

  The fundamental cause of complications in KTS lies in its extensive vascular malformations, so all treatments for KTS should be based on correcting vascular abnormalities. […] Studies have suggested that KTS syndrome may be associated with mutations in the PIK3CA gene, which are related to abnormal vascular formation and proliferation, leading to vascular abnormalities and tissue overgrowth in patients. […] PIK3CA inhibitors as targeted drugs for treating KTS have potential efficacy. […] Accurate diagnosis serves as the foundation of treatment.

• #51 Orphanet: Klippel-Trénaunay syndrome

  https://www.orpha.net/en/disease/detail/90308

  A rare congenital complex vascular malformation syndrome characterized by capillary malformations manifesting as wine stains and venous varicosities typically prominent along the lateral aspect of the lower extremities, associated with overgrowth of a limb (most commonly a leg, less frequently other regions of the body), involving bone and/or soft tissues. […] The syndrome is due to heterozygous post-zygotic mosaic variation in the PIK3CA gene, occurring in early embryogenesis. It has to be noted that not all KTS appear to result from PIK3CA mosaic variation. […] Diagnosis must be confirmed by identification of a PIK3CA mosaic variation on affected tissue (most often skin) without culture, using high-depth high-throughput sequencing. […] Treatment with alpelisib changes the prognosis when a PIK3CA variant was identified.

• #52 Klippel-Trénaunay Syndrome – Seattle Children’s

  https://www.seattlechildrens.org/conditions/klippel-trenaunay-syndrome-kts/

  Klippel-Trenaunay syndrome (KTS) is a rare disorder that is present at birth (congenital). […] Children with KTS have changes in the PIK3CA gene. KTS is 1 of the conditions on the PIK3CA-related overgrowth spectrum (PROS). […] We have created a way to test a patients tissue for genetic changes (variants or mutations) known to cause vascular anomalies. Genetic test results help inform your childs diagnosis and may help guide their treatment. […] Our physician-scientists have created a way to test patients tissue and body fluids for the genetic changes known to cause vascular anomaly syndromes. The test is called a gene panel. We can test DNA in tissue sent to us from doctors across the nation. No other childrens hospital has a gene panel certified for clinical use with vascular anomalies. This certification means doctors can make treatment decisions based on the results. […] A precise diagnosis may expand your childs treatment options to include drugs that target the biological pathway causing their condition. These drugs may be new targeted therapies or those already used to treat other diseases.

• #53 Klippel-Trenaunay Syndrome | Texas Children’s

  https://www.texaschildrens.org/content/conditions/klippel-trenaunay-syndrome

  Klippel-Trenaunay Syndrome (KTS) is a very rare condition in which blood vessels do not form properly. It can affect the capillary, venous, and lymphatic vessels. […] Management of KTS involves a multidisciplinary team. Treatment goals include reducing the symptoms and risks associated with KTS.

• #54

  https://journals.lww.com/md-journal/fulltext/2025/02210/klippel_trenaunay_syndrome_with_multiorgan.38.aspx

  The fundamental cause of complications in KTS lies in its extensive vascular malformations, so all treatments for KTS should be based on correcting vascular abnormalities. […] Studies have suggested that KTS syndrome may be associated with mutations in the PIK3CA gene, which are related to abnormal vascular formation and proliferation, leading to vascular abnormalities and tissue overgrowth in patients. […] PIK3CA inhibitors as targeted drugs for treating KTS have potential efficacy. […] Accurate diagnosis serves as the foundation of treatment.

• #55 Gastrointestinal involvement in Klippel-Trénaunay syndrome: pathophysiology, evaluation, and management | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02857-5

  The IMV, a usually overlooked vein system in patients with portal hypertension should be re-looked in patients with anorectosigmoid VM. […] The rupture of submucosal phlebectasia leads to rectal bleeding from VM. […] The pathophysiologies of anorectal and anorectosigmoid VM in KTS. […] In KTS patients with pelvis involvement, the IIV-gluteal-marginal vein system is a valveless malformed reflux channel, which can cause bleeding from pelvic organs (anorectum and genitourinary tract). […] Recognizing the distinct pathophysiology is required to prevent pitfalls in the management. […] The pathophysiology regarding portal hypertension in KTS we discussed should be considered in future guidelines for vascular diseases of the liver.

• #56

  https://journals.lww.com/md-journal/fulltext/2025/02210/klippel_trenaunay_syndrome_with_multiorgan.38.aspx

  The fundamental cause of complications in KTS lies in its extensive vascular malformations, so all treatments for KTS should be based on correcting vascular abnormalities. […] Studies have suggested that KTS syndrome may be associated with mutations in the PIK3CA gene, which are related to abnormal vascular formation and proliferation, leading to vascular abnormalities and tissue overgrowth in patients. […] PIK3CA inhibitors as targeted drugs for treating KTS have potential efficacy. […] Accurate diagnosis serves as the foundation of treatment.

• #57 Klippel-Trenaunay Syndrome Case | Applied Radiology

  https://appliedradiology.com/articles/klippel-trenaunay-syndrome-case

  When these vessels persist, they disrupt the physiological growth of normal venous anatomy and often dilate to large diameters, greatly increasing the risk of venous stasis. […] When severe, this can result in life-threatening complications, including large-volume bleeding, pulmonary emboli, and venous thromboses. […] Despite being a common in affected children, the prevalence of these marginal veins is conservatively measured at around 15% to 20%, likely due to the highly variable phenotype of KTS. […] Treatment for this syndrome has historically been surgical, which can be associated with significant complications. New minimally invasive techniques, including RFA, EVLT, and sclerotherapy, have expanded treatment options with fewer complications.

• #58 A rare manifestation of Klippel-Trenaunay syndrome with bilateral chylothorax requiring surgical management—a case report – Mayer – Current Challenges in Thoracic Surgery

  https://ccts.amegroups.org/article/view/47253/html

  Klippel-Trenaunay syndrome (KTS) is a rare congenital disorder with pathognomonic capillary-lymphatic-venous malformation (CLVM) of an extremity in association with soft-tissue and/or skeletal overgrowth. […] In our experience, surgical management of chylothorax in KTS should be minimally invasive. […] Thoracic duct ligation is not recommended, mainly due to overexpression of lymphatic collaterals, and because of theoretically possible reflux of chyle to the lower part of the body. […] Nutritional status plays an essential role in chylothorax treatment, we recommend intraoperative insertion of a central line for post-operative total parenteral nutrition as a standard and lastly, considering the course of our case, we further recommend contralateral prophylactic pleurodesis or concurrent bilateral pleurodesis in KTS patients with chylothorax.

• #59

  https://link.springer.com/article/10.1007/s00018-005-4523-7

  Vascular morphogenesis is a vital process for embryonic development, normal physiologic conditions (e.g. wound healing) and pathological processes (e.g. atherosclerosis, cancer). A susceptibility gene, VG5Q (formally named AGGF1), was cloned for Klippel-Trenaunay syndrome (KTS). AGGF1 encodes a potent angiogenic factor, and KTS-associated mutations enhance angiogenic activity of AGGF1, defining increased angiogenesis as one molecular mechanism for the pathogenesis of KTS. […] Future studies of vascular anomaly genes will provide insights into the molecular mechanisms for vascular morphogenesis, and may lead to the development of therapeutic strategies for treating these and other angiogenesis-related diseases, including coronary artery disease and cancer.

• #60 Klippel-Trenaunay Syndrome | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/klippel-trenaunay-syndrome

  Klippel-Trenaunay syndrome (KTS) is a rare congenital (present at birth) vascular anomaly that results in your child having a large number of abnormal blood vessels. […] No one knows the precise cause of KTS. Some doctors think it’s caused by a mutation that occurs before birth (but isn’t inherited) in the cells that form the lymphatic system, veins, and other tissues. […] KTS is caused by errors that occur when blood and lymphatic vessels are forming. The Vascular Anomalies Center conducts research that may lead to the development of new, more effective treatments and perhaps ultimately result in ways to prevent KTS. […] Our investigators are currently probing the genes and molecules that regulate the formation and growth of blood and lymphatic vessels. We hope that understanding the genes that control these molecular events will result in new therapies for vascular malformations.

• #61 Klippel–Trenaunay Syndrome, Segmental/Focal Overgrowth Malformations: A Review

  https://www.mdpi.com/2227-9067/10/8/1421

  A new road has been opened for the etiological basis of this syndrome on the evidence that the more severe cases of KTS have been linked to mosaic-activating variants in the PIK3CA gene. […] It has been hypothesized that atresia or obstruction of the dep veins in the leg as a first event may lead to chronic venous hypertension with subsequent anomalous development of nevus, varices, and hypertrophy. […] The inclusion of the KTS within the PROS group may be useful to reach new advances in the etiopathogenetic factors of the KTS.

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