Pub Date : 2024-01-08DOI: 10.1097/jova.0000000000000079
Bryan A. Sisk, Christine Bereitschaft, Jessica Goldberg, Anna M. Kerr
To characterize the experiences of patients with vascular malformations (VMs) when seeking care for acute or emergent health needs. Semistructured qualitative interviews and survey study. National recruitment through patient advocacy groups and multidisciplinary vascular anomaly clinics. Adult patients and parents of children with self-reported VM. We interviewed 25 young adult patients and 34 parents. We received survey responses from 138 adult patients and 73 parents who answered all items of interest (analytic cohort = 211). Interview participants described negative experiences with emergency care related to 4 themes: (1) delayed or inadequate care, (2) lack of competent, knowledgeable clinicians, (3) lack of collegial collaboration, and (4) insufficient trust of clinicians in parent’s or patient’s knowledge. Patients and parents reported an average of 1.7 and 2.6 VM-related health problems requiring emergent management in the prior year, respectively. In multivariable logistic regression, having at least one acute or emergent problem in the prior year was associated with household income ≥$100 000 (odds ratio = 0.34, 95% confidence interval, 0.17–0.70), but not gender, race, and ethnicity, age, having a VM specialist, or primary care doctor’s knowledge of VMs. Many patients with VMs require emergent or acute care for complications of their VM. Patients with lower household incomes are more likely to experience these emergent events. Negative experiences often focused on nonsupportive clinician behaviors. Future studies should develop tools to empower patient self-advocacy and provide high-yield information to nonspecialist clinicians.
{"title":"Emergency Care for Pediatric and Adult Patients Affected by Complex Vascular Malformations","authors":"Bryan A. Sisk, Christine Bereitschaft, Jessica Goldberg, Anna M. Kerr","doi":"10.1097/jova.0000000000000079","DOIUrl":"https://doi.org/10.1097/jova.0000000000000079","url":null,"abstract":"\u0000 \u0000 To characterize the experiences of patients with vascular malformations (VMs) when seeking care for acute or emergent health needs.\u0000 \u0000 \u0000 \u0000 Semistructured qualitative interviews and survey study.\u0000 \u0000 \u0000 \u0000 National recruitment through patient advocacy groups and multidisciplinary vascular anomaly clinics.\u0000 \u0000 \u0000 \u0000 Adult patients and parents of children with self-reported VM.\u0000 \u0000 \u0000 \u0000 We interviewed 25 young adult patients and 34 parents. We received survey responses from 138 adult patients and 73 parents who answered all items of interest (analytic cohort = 211). Interview participants described negative experiences with emergency care related to 4 themes: (1) delayed or inadequate care, (2) lack of competent, knowledgeable clinicians, (3) lack of collegial collaboration, and (4) insufficient trust of clinicians in parent’s or patient’s knowledge. Patients and parents reported an average of 1.7 and 2.6 VM-related health problems requiring emergent management in the prior year, respectively. In multivariable logistic regression, having at least one acute or emergent problem in the prior year was associated with household income ≥$100 000 (odds ratio = 0.34, 95% confidence interval, 0.17–0.70), but not gender, race, and ethnicity, age, having a VM specialist, or primary care doctor’s knowledge of VMs.\u0000 \u0000 \u0000 \u0000 Many patients with VMs require emergent or acute care for complications of their VM. Patients with lower household incomes are more likely to experience these emergent events. Negative experiences often focused on nonsupportive clinician behaviors. Future studies should develop tools to empower patient self-advocacy and provide high-yield information to nonspecialist clinicians.\u0000","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"26 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139445945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-08DOI: 10.1097/jova.0000000000000077
{"title":"Erratum to Parkes Weber Syndrome: Contribution of the Genotype to the Diagnosis","authors":"","doi":"10.1097/jova.0000000000000077","DOIUrl":"https://doi.org/10.1097/jova.0000000000000077","url":null,"abstract":"","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"38 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139446223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-05DOI: 10.1097/jova.0000000000000073
Michal Ad, A. Greene
Primary lymphedema most commonly affects the lower extremities, is progressive, and is not curable. The condition is associated with mutations in approximately 30 genes. Patients usually present with edema during infancy or adolescence. Four of 364 (1%) patients with primary lymphedema in our database were diagnosed by prenatal imaging. Three children did not exhibit lymphedema after birth, 2 had a VEGFC mutation, and 2 exhibited normal lymphatic function by lymphoscintigraphy. Lymphedema identified prenatally is associated with a VEGFC mutation and can resolve postnatally.
{"title":"Prenatal Lymphedema: A Genotype-Phenotype Analysis","authors":"Michal Ad, A. Greene","doi":"10.1097/jova.0000000000000073","DOIUrl":"https://doi.org/10.1097/jova.0000000000000073","url":null,"abstract":"Primary lymphedema most commonly affects the lower extremities, is progressive, and is not curable. The condition is associated with mutations in approximately 30 genes. Patients usually present with edema during infancy or adolescence. Four of 364 (1%) patients with primary lymphedema in our database were diagnosed by prenatal imaging. Three children did not exhibit lymphedema after birth, 2 had a VEGFC mutation, and 2 exhibited normal lymphatic function by lymphoscintigraphy. Lymphedema identified prenatally is associated with a VEGFC mutation and can resolve postnatally.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139383991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-22DOI: 10.1097/jova.0000000000000071
Lana Bricknell, Christopher M. Richmond, Romi Das Gupta, Diane Payton, Yun Phua, Roy M. Kimble
Eccrine angiomatous hamartoma (EAH) is a rare vascular anomaly with mixed eccrine and vascular components, typically identified in children. While benign, EAH can cause significant morbidity and be difficult to treat. The aims of this case series were to identify all patients with EAH that have been seen at the Queensland Children’s Hospital and describe their phenotypic and somatic genotypic details, in an effort to contribute to the limiting understanding and literature surrounding this condition. Individuals with EAH were retrospectively identified through engagement in a multidisciplinary vascular anomaly clinic in a tertiary Australian children’s hospital. All individuals had a previous histological diagnosis of EAH. High-read-depth sequencing of a panel of 27 genes known to be associated with vascular anomalies was undertaken on affected tissue. Samples were rereviewed by a senior pathologist and geneticist for this study. Five cases of EAH were identified. All were associated with 1 of 3 somatic PIK3CA variants (c.1633G>A;p.Glu545Lys, c.1624G>A;p.Glu542Lys, and c.3140A>G;p.Histo1047Arg) in low allele fractions. These variants have previously been reported in a range of tumors and vascular anomalies, including PIK3CA-related overgrowth spectrum, but not in EAH. Occurrence of somatic PIK3CA variants in EAH provides evidence for a novel gene-disease association and is plausibly the cause of EAH in some individuals. This finding expands the phenotypic spectrum of PIK3CA, contributes to understanding of the pathophysiology of this rare condition, and may avail molecularly targeted therapy in the future.
{"title":"Somatic PIK3CA Variants Are Associated With Eccrine Angiomatous Hamartomas","authors":"Lana Bricknell, Christopher M. Richmond, Romi Das Gupta, Diane Payton, Yun Phua, Roy M. Kimble","doi":"10.1097/jova.0000000000000071","DOIUrl":"https://doi.org/10.1097/jova.0000000000000071","url":null,"abstract":"Eccrine angiomatous hamartoma (EAH) is a rare vascular anomaly with mixed eccrine and vascular components, typically identified in children. While benign, EAH can cause significant morbidity and be difficult to treat. The aims of this case series were to identify all patients with EAH that have been seen at the Queensland Children’s Hospital and describe their phenotypic and somatic genotypic details, in an effort to contribute to the limiting understanding and literature surrounding this condition. Individuals with EAH were retrospectively identified through engagement in a multidisciplinary vascular anomaly clinic in a tertiary Australian children’s hospital. All individuals had a previous histological diagnosis of EAH. High-read-depth sequencing of a panel of 27 genes known to be associated with vascular anomalies was undertaken on affected tissue. Samples were rereviewed by a senior pathologist and geneticist for this study. Five cases of EAH were identified. All were associated with 1 of 3 somatic PIK3CA variants (c.1633G>A;p.Glu545Lys, c.1624G>A;p.Glu542Lys, and c.3140A>G;p.Histo1047Arg) in low allele fractions. These variants have previously been reported in a range of tumors and vascular anomalies, including PIK3CA-related overgrowth spectrum, but not in EAH. Occurrence of somatic PIK3CA variants in EAH provides evidence for a novel gene-disease association and is plausibly the cause of EAH in some individuals. This finding expands the phenotypic spectrum of PIK3CA, contributes to understanding of the pathophysiology of this rare condition, and may avail molecularly targeted therapy in the future.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"265 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139250090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-15DOI: 10.1097/jova.0000000000000070
Anna L. McCarter, M. Dellinger
Gorham-Stout disease (GSD) is a rare lymphatic anomaly that can be caused by somatic activating mutations in KRAS. This discovery has led investigators to suggest that MEK inhibitors could be a novel treatment for GSD. However, the effect of MEK inhibitors on bone disease in animal models of GSD has not been investigated. We recently reported that Osx-tTA;TetO-Vegfc mice exhibit a phenotype that resembles GSD. Osx-tTA;TetO-Vegfc mice overexpress vascular endothelial growth factor-C (VEGF-C) in bone, which stimulates the development of lymphatic vessels in bone and the gradual loss of cortical bone. The objective of this study was to characterize the effect of trametinib, an FDA-approved MEK1/2 inhibitor, on lymphangiogenesis and osteolysis in Osx-tTA;TetO-Vegfc mice. Immunoblotting was performed to assess the effect of trametinib on VEGF-C-induced phosphorylation of ERK1/2, AKT, and S6 in primary human lymphatic endothelial cells. Prevention and intervention experiments were performed to determine the effect of trametinib on lymphangiogenesis and osteolysis in Osx-tTA;TetO-Vegfc mice. We found that trametinib blocked VEGF-C-induced phosphorylation of ERK1/2 in primary human lymphatic endothelial cells. We also found that trametinib prevented VEGF-C-induced lymphatic invasion of bone and cortical bone loss in Osx-tTA;TetO-Vegfc mice. Additionally, trametinib slowed the progression of disease in Osx-tTA;TetO-Vegfc mice with established disease. However, it did not reverse disease in Osx-tTA;TetO-Vegfc mice. Our results show trametinib impacts bone disease in Osx-tTA;TetO-Vegfc mice. These findings further support the testing of MEK inhibitors in patients with GSD and other RAS pathway-driven complex lymphatic anomalies with bone involvement.
{"title":"Trametinib Inhibits Lymphatic Vessel Invasion of Bone in a Mouse Model of Gorham-Stout Disease","authors":"Anna L. McCarter, M. Dellinger","doi":"10.1097/jova.0000000000000070","DOIUrl":"https://doi.org/10.1097/jova.0000000000000070","url":null,"abstract":"Gorham-Stout disease (GSD) is a rare lymphatic anomaly that can be caused by somatic activating mutations in KRAS. This discovery has led investigators to suggest that MEK inhibitors could be a novel treatment for GSD. However, the effect of MEK inhibitors on bone disease in animal models of GSD has not been investigated. We recently reported that Osx-tTA;TetO-Vegfc mice exhibit a phenotype that resembles GSD. Osx-tTA;TetO-Vegfc mice overexpress vascular endothelial growth factor-C (VEGF-C) in bone, which stimulates the development of lymphatic vessels in bone and the gradual loss of cortical bone. The objective of this study was to characterize the effect of trametinib, an FDA-approved MEK1/2 inhibitor, on lymphangiogenesis and osteolysis in Osx-tTA;TetO-Vegfc mice. Immunoblotting was performed to assess the effect of trametinib on VEGF-C-induced phosphorylation of ERK1/2, AKT, and S6 in primary human lymphatic endothelial cells. Prevention and intervention experiments were performed to determine the effect of trametinib on lymphangiogenesis and osteolysis in Osx-tTA;TetO-Vegfc mice. We found that trametinib blocked VEGF-C-induced phosphorylation of ERK1/2 in primary human lymphatic endothelial cells. We also found that trametinib prevented VEGF-C-induced lymphatic invasion of bone and cortical bone loss in Osx-tTA;TetO-Vegfc mice. Additionally, trametinib slowed the progression of disease in Osx-tTA;TetO-Vegfc mice with established disease. However, it did not reverse disease in Osx-tTA;TetO-Vegfc mice. Our results show trametinib impacts bone disease in Osx-tTA;TetO-Vegfc mice. These findings further support the testing of MEK inhibitors in patients with GSD and other RAS pathway-driven complex lymphatic anomalies with bone involvement.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"44 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139273498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-15DOI: 10.1097/jova.0000000000000072
Ricardo Rodriguez Colon, Courtney Cripps, Francine Blei, Sheel Sharma
The literature on surgical management of vascular anomalies has primarily focused on the head and neck area, while studies of anomalies on the extremities have typically included larger and more dramatic clinical presentations. In this article, we aim to present our experience with surgical management of smaller symptomatic anomalies of the extremities. We performed a retrospective review of a single surgeon’s experience at a large academic center on patients from January 2013 to March 2022. We collected data on patient demographics, past medical and surgical history, operative dictations, clinic notes, and postoperative follow-up. Included patients were required to have confirmed vascular anomalies based on final pathology reports. A total of 47 patients underwent a total of 50 procedures, with 2 patients experiencing recurrence requiring repeat operative management. Our cohort had average age (standard deviation) of 27.16 (18.67). Sixteen patients had prior history of vascular anomalies upon presentation to our institution. The majority of lesions were located in a digit of the hand, the arm, or the foot. On surgical excision, the average size (range) of the excised lesions was 3.54 cm (0.5–15.0 cm) by 2.22 cm (0.3–8.0 cm). Four required coverage with local flaps, 3 with full-thickness skin graft (FTSG) and 2 with microvascular free flap. The 2 most common pathologic diagnoses were arteriovenous malformation and hemangioma, each with 14 patients. Overall complication rate was 2%, with 1 patient experiencing wound dehiscence requiring FTSG. Follow-up ranged from 0.1 months to 46.9 months with an average of 3.86 months. In the appropriately selected patient, surgical excision of symptomatic vascular anomalies of the extremities can be successfully performed with a low complication rate. Most lesions can be appropriately treated with direct excision and direct closure, although some may require FTSG, local flap, or microvascular free flap.
{"title":"Surgical Treatment of Vascular Anomalies in the Extremities: A Single Surgeon Experience","authors":"Ricardo Rodriguez Colon, Courtney Cripps, Francine Blei, Sheel Sharma","doi":"10.1097/jova.0000000000000072","DOIUrl":"https://doi.org/10.1097/jova.0000000000000072","url":null,"abstract":"The literature on surgical management of vascular anomalies has primarily focused on the head and neck area, while studies of anomalies on the extremities have typically included larger and more dramatic clinical presentations. In this article, we aim to present our experience with surgical management of smaller symptomatic anomalies of the extremities. We performed a retrospective review of a single surgeon’s experience at a large academic center on patients from January 2013 to March 2022. We collected data on patient demographics, past medical and surgical history, operative dictations, clinic notes, and postoperative follow-up. Included patients were required to have confirmed vascular anomalies based on final pathology reports. A total of 47 patients underwent a total of 50 procedures, with 2 patients experiencing recurrence requiring repeat operative management. Our cohort had average age (standard deviation) of 27.16 (18.67). Sixteen patients had prior history of vascular anomalies upon presentation to our institution. The majority of lesions were located in a digit of the hand, the arm, or the foot. On surgical excision, the average size (range) of the excised lesions was 3.54 cm (0.5–15.0 cm) by 2.22 cm (0.3–8.0 cm). Four required coverage with local flaps, 3 with full-thickness skin graft (FTSG) and 2 with microvascular free flap. The 2 most common pathologic diagnoses were arteriovenous malformation and hemangioma, each with 14 patients. Overall complication rate was 2%, with 1 patient experiencing wound dehiscence requiring FTSG. Follow-up ranged from 0.1 months to 46.9 months with an average of 3.86 months. In the appropriately selected patient, surgical excision of symptomatic vascular anomalies of the extremities can be successfully performed with a low complication rate. Most lesions can be appropriately treated with direct excision and direct closure, although some may require FTSG, local flap, or microvascular free flap.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"59 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139272255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-13DOI: 10.1097/jova.0000000000000074
Sheryl Tulin-Silver, Gabriela Asch-Ortiz, D. Tsze
The management of pain is one of the primary concerns when administering sclerotherapy in children with vascular malformations. However, there is currently no standard of care and limited data regarding the effective treatment of pain associated with sclerotherapy. In this case report, we describe the successful management of pain using music therapy in a child undergoing bedside sclerotherapy for a lymphatic malformation. This report is novel in that it demonstrates the effectiveness of music therapy as an individualized integrative approach for providing pain management to children undergoing bedside sclerotherapy.
{"title":"Music Therapy for Pediatric Pain Management During Bedside Sclerotherapy","authors":"Sheryl Tulin-Silver, Gabriela Asch-Ortiz, D. Tsze","doi":"10.1097/jova.0000000000000074","DOIUrl":"https://doi.org/10.1097/jova.0000000000000074","url":null,"abstract":"The management of pain is one of the primary concerns when administering sclerotherapy in children with vascular malformations. However, there is currently no standard of care and limited data regarding the effective treatment of pain associated with sclerotherapy. In this case report, we describe the successful management of pain using music therapy in a child undergoing bedside sclerotherapy for a lymphatic malformation. This report is novel in that it demonstrates the effectiveness of music therapy as an individualized integrative approach for providing pain management to children undergoing bedside sclerotherapy.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"65 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139278603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-13DOI: 10.1097/jova.0000000000000076
T. A. Andreoti, A. Tuleja, Y. Döring, Massimo Maiolo, André Schaller, Erik Vassella, C. Zweier, L. Boon, M. Vikkula, Jochen Rössler, S. Bernhard, Iris Baumgartner
Parkes Weber syndrome (PWS) is a rare disorder that combines overgrowth, capillary malformations, and arteriovenous malformations (AVM)/arteriovenous fistulas, for which underlying activating mutations in the ras/mitogen-activated protein kinase/extracellular-signal-regulated kinase signaling pathway have been described. The clinical overlap with Klippel-Trenauny syndrome, associated with mutations in PIK3CA, is significant. This case series aimed to elaborate on the phenotypic description of PWS, to underline its clinical overlap with Klippel-Trenauny syndrome and nonsyndromic AVM, and to evaluate the contribution of genotypic characterization to the diagnosis. All patients diagnosed with PWS upon enrollment in the Bernese VAScular COngenital Malformations (VASCOM) cohort were included. The diagnostic criteria of PWS were retrospectively reviewed. A next-generation sequencing (NGS) gene panel (TSO500, Illumina) was used on tissue biopsy samples. Overall, 10/559 patients of the VAScular COngenital Malformations cohort were initially diagnosed with PWS. Three patients were reclassified as nonsyndromic AVM (Kristen Rat Sarcoma Viral oncogene homolog [KRAS], KRAS+tumor protein p53, and protein tyrosine phosphatase non-receptor type 11). Finally, 7 patients fulfilled all clinical diagnostic criteria of PWS. Genetic testing was available in 5 PWS patients. Only 1 patient had the classic RASA1 mutation; another patient had mutations in G protein subunit alpha q (GNAQ) and phosphatase and tensin homolog. In a third case, a PIK3CA mutation was detected. In 2 patients, no mutations were identified. Overgrowth syndromes with vascular malformations are rare and their clinical overlap hampers the classification of individual phenotypes under specific syndrome labels, sometimes even despite genetic testing. To provide optimal patient care, an accurate phenotypic description combined with the identification of molecular targets for precision medicine may be more meaningful than the syndrome classification itself.
{"title":"Parkes Weber Syndrome: Contribution of the Genotype to the Diagnosis","authors":"T. A. Andreoti, A. Tuleja, Y. Döring, Massimo Maiolo, André Schaller, Erik Vassella, C. Zweier, L. Boon, M. Vikkula, Jochen Rössler, S. Bernhard, Iris Baumgartner","doi":"10.1097/jova.0000000000000076","DOIUrl":"https://doi.org/10.1097/jova.0000000000000076","url":null,"abstract":"Parkes Weber syndrome (PWS) is a rare disorder that combines overgrowth, capillary malformations, and arteriovenous malformations (AVM)/arteriovenous fistulas, for which underlying activating mutations in the ras/mitogen-activated protein kinase/extracellular-signal-regulated kinase signaling pathway have been described. The clinical overlap with Klippel-Trenauny syndrome, associated with mutations in PIK3CA, is significant. This case series aimed to elaborate on the phenotypic description of PWS, to underline its clinical overlap with Klippel-Trenauny syndrome and nonsyndromic AVM, and to evaluate the contribution of genotypic characterization to the diagnosis. All patients diagnosed with PWS upon enrollment in the Bernese VAScular COngenital Malformations (VASCOM) cohort were included. The diagnostic criteria of PWS were retrospectively reviewed. A next-generation sequencing (NGS) gene panel (TSO500, Illumina) was used on tissue biopsy samples. Overall, 10/559 patients of the VAScular COngenital Malformations cohort were initially diagnosed with PWS. Three patients were reclassified as nonsyndromic AVM (Kristen Rat Sarcoma Viral oncogene homolog [KRAS], KRAS+tumor protein p53, and protein tyrosine phosphatase non-receptor type 11). Finally, 7 patients fulfilled all clinical diagnostic criteria of PWS. Genetic testing was available in 5 PWS patients. Only 1 patient had the classic RASA1 mutation; another patient had mutations in G protein subunit alpha q (GNAQ) and phosphatase and tensin homolog. In a third case, a PIK3CA mutation was detected. In 2 patients, no mutations were identified. Overgrowth syndromes with vascular malformations are rare and their clinical overlap hampers the classification of individual phenotypes under specific syndrome labels, sometimes even despite genetic testing. To provide optimal patient care, an accurate phenotypic description combined with the identification of molecular targets for precision medicine may be more meaningful than the syndrome classification itself.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"232 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139278847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-08DOI: 10.1097/jova.0000000000000075
Sean S. Evans, Steven L. Goudy, Ching Siong Tey, R. Swerdlin, C. M. Hawkins
To determine baseline quality of life characteristics in patients with low-flow head and neck vascular malformations. Retrospective review of prospectively collected data. Tertiary Pediatric Hospital. Patients with low-flow head and neck vascular malformations (age 0–18 years) evaluated through our vascular anomalies clinic from 2016 to 2019 were reviewed. Patients with completed PedsQL surveys using parent-proxy reports for children 2–7 years old and both patient and parent-proxy data for patients ≥8 years old were included. In total 94 consecutive patients were included, with a mean age of 9.2 ± 4.7 years. Diagnoses included lymphatic malformations (n = 50), venous malformations (n = 41), and combined venolymphatic malformations (n = 3). Total parental quality of life scores were lower than their children’s (84.23 vs 87.45; P = .037), with lower emotional scores as age at presentation increased (d = −0.60; P < .01). Lower parental scores were also noted across multiple domains for submandibular/sublingual, oropharyngeal, hypopharyngeal, and orbital involvement. (g = −0.68 to −1.10; P < .05). Increasing subsite number involvement affected parents and children similarly (−0.30 vs −0.35; P ≤ .02). Higher physical function scores were noted in venous versus lymphatic malformations (d =−1.07; P = .01). The child-reported school function scores were lower in African-American versus Caucasian children (P = .04). Prior treatment was associated with lower parental scores (d = 0.59; P = .04). The parent and patient’s quality of life is reduced across multiple domains for low-flow head and neck vascular malformations based on age, lesion location and type, disease burden, race, and prior treatment.
确定低流量头颈部血管畸形患者的基线生活质量特征。 对前瞻性收集的数据进行回顾性分析。 三级儿科医院。 对2016年至2019年期间在本院血管畸形门诊接受评估的低流量头颈部血管畸形患者（0-18岁）进行回顾性研究。2-7岁儿童使用家长代理报告完成PedsQL调查，≥8岁患者使用患者和家长代理数据完成PedsQL调查。 共纳入了 94 名连续患者，平均年龄为（9.2 ± 4.7）岁。诊断包括淋巴畸形（50 例）、静脉畸形（41 例）和合并静脉淋巴畸形（3 例）。父母的生活质量总分低于子女（84.23 vs 87.45；P = .037），随着发病年龄的增加，父母的情绪得分也降低（d = -0.60；P < .01）。在下颌下/舌下、口咽、咽下和眼眶受累的多个领域中，家长的得分也较低。(g = -0.68 to -1.10; P < .05)。受累亚部位数量的增加对父母和儿童的影响相似（-0.30 vs -0.35；P ≤ .02）。静脉畸形与淋巴畸形相比，身体功能得分更高（d =-1.07; P = .01）。非裔美国儿童与高加索儿童相比，儿童报告的学校功能得分较低（P = .04）。曾接受过治疗的家长得分较低（d = 0.59；P = .04）。 根据年龄、病变位置和类型、疾病负担、种族和之前的治疗情况，低流量头颈部血管畸形的家长和患者在多个领域的生活质量都有所下降。
{"title":"Baseline Quality of Life in Low-Flow Head and Neck Vascular Malformations in Children","authors":"Sean S. Evans, Steven L. Goudy, Ching Siong Tey, R. Swerdlin, C. M. Hawkins","doi":"10.1097/jova.0000000000000075","DOIUrl":"https://doi.org/10.1097/jova.0000000000000075","url":null,"abstract":"To determine baseline quality of life characteristics in patients with low-flow head and neck vascular malformations. Retrospective review of prospectively collected data. Tertiary Pediatric Hospital. Patients with low-flow head and neck vascular malformations (age 0–18 years) evaluated through our vascular anomalies clinic from 2016 to 2019 were reviewed. Patients with completed PedsQL surveys using parent-proxy reports for children 2–7 years old and both patient and parent-proxy data for patients ≥8 years old were included. In total 94 consecutive patients were included, with a mean age of 9.2 ± 4.7 years. Diagnoses included lymphatic malformations (n = 50), venous malformations (n = 41), and combined venolymphatic malformations (n = 3). Total parental quality of life scores were lower than their children’s (84.23 vs 87.45; P = .037), with lower emotional scores as age at presentation increased (d = −0.60; P < .01). Lower parental scores were also noted across multiple domains for submandibular/sublingual, oropharyngeal, hypopharyngeal, and orbital involvement. (g = −0.68 to −1.10; P < .05). Increasing subsite number involvement affected parents and children similarly (−0.30 vs −0.35; P ≤ .02). Higher physical function scores were noted in venous versus lymphatic malformations (d =−1.07; P = .01). The child-reported school function scores were lower in African-American versus Caucasian children (P = .04). Prior treatment was associated with lower parental scores (d = 0.59; P = .04). The parent and patient’s quality of life is reduced across multiple domains for low-flow head and neck vascular malformations based on age, lesion location and type, disease burden, race, and prior treatment.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139282749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1097/JOVA.0000000000000069
Averill Clapp, Carrie J Shawber, June K Wu
Background: Slow-flow vascular malformations include venous, lymphatic, and lymphaticovenous malformations. Recent studies have linked genetic variants hyperactivating either the PI3K/AKT/mTOR and/or RAS/RAF/MAPK signaling pathways with slow-flow vascular malformation development, leading to the use of pharmacotherapies such as sirolimus and alpelisib. It is important that clinicians understand basic and translational research advances in slow-flow vascular malformations.
Methods: A literature review of basic science publications in slow-flow vascular malformations was performed on Pubmed, using search terms "venous malformation," "lymphatic malformation," "lymphaticovenous malformation," "genetic variant," "genetic mutation," "endothelial cells," and "animal model." Relevant publications were reviewed and summarized.
Results: The study of patient tissues and the use of primary pathogenic endothelial cells from vascular malformations shed light on their pathological behaviors, such as endothelial cell hyperproliferation and disruptions in vessel architecture. The use of xenograft and transgenic animal models confirmed the pathogenicity of genetic variants and allowed for preclinical testing of potential therapies. These discoveries underscore the importance of basic and translational research in understanding the pathophysiology of vascular malformations, which will allow for the development of improved biologically targeted treatments.
Conclusion: Despite basic and translation advances, a cure for slow-flow vascular malformations remains elusive. Many questions remain unanswered, including how genotype variants result in phenotypes, and genotype-phenotype heterogeneity. Continued research into venous and lymphatic malformation pathobiology is critical in understanding the mechanisms by which genetic variants contribute to vascular malformation phenotypic features.
{"title":"Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions.","authors":"Averill Clapp, Carrie J Shawber, June K Wu","doi":"10.1097/JOVA.0000000000000069","DOIUrl":"https://doi.org/10.1097/JOVA.0000000000000069","url":null,"abstract":"<p><strong>Background: </strong>Slow-flow vascular malformations include venous, lymphatic, and lymphaticovenous malformations. Recent studies have linked genetic variants hyperactivating either the PI3K/AKT/mTOR and/or RAS/RAF/MAPK signaling pathways with slow-flow vascular malformation development, leading to the use of pharmacotherapies such as sirolimus and alpelisib. It is important that clinicians understand basic and translational research advances in slow-flow vascular malformations.</p><p><strong>Methods: </strong>A literature review of basic science publications in slow-flow vascular malformations was performed on Pubmed, using search terms \"venous malformation,\" \"lymphatic malformation,\" \"lymphaticovenous malformation,\" \"genetic variant,\" \"genetic mutation,\" \"endothelial cells,\" and \"animal model.\" Relevant publications were reviewed and summarized.</p><p><strong>Results: </strong>The study of patient tissues and the use of primary pathogenic endothelial cells from vascular malformations shed light on their pathological behaviors, such as endothelial cell hyperproliferation and disruptions in vessel architecture. The use of xenograft and transgenic animal models confirmed the pathogenicity of genetic variants and allowed for preclinical testing of potential therapies. These discoveries underscore the importance of basic and translational research in understanding the pathophysiology of vascular malformations, which will allow for the development of improved biologically targeted treatments.</p><p><strong>Conclusion: </strong>Despite basic and translation advances, a cure for slow-flow vascular malformations remains elusive. Many questions remain unanswered, including how genotype variants result in phenotypes, and genotype-phenotype heterogeneity. Continued research into venous and lymphatic malformation pathobiology is critical in understanding the mechanisms by which genetic variants contribute to vascular malformation phenotypic features.</p>","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"4 3","pages":"e069"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9d/56/jv9-4-e069.PMC10473035.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10158198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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