Wound-Healing Problems Associated with Combined Vascular Malformations in Klippel–Trenaunay Syndrome

Ishikawa, Kosuke; Yamamoto, Yuhei; Funayama, Emi; Furukawa, Hiroshi; Sasaki, Satoshi

doi:10.1089/wound.2018.0835

Cited by 8 publications

(2 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Figure 1 shows clinical photographs and magnetic resonance imaging (MRI) of all patients with detected PIK3CA variants. Patient 1 [ 21 ], patients 3 and 4 [ 22 ], and patient 9 [ 23 ] were previously reported without genetic analyses.…”

Section: Resultsmentioning

confidence: 99%

Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel–Trenaunay syndrome in an Asian population

Sasaki,

Ishikawa,

Hatanaka

et al. 2023

Orphanet J Rare Dis

Self Cite

View full text Add to dashboard Cite

Background Klippel–Trenaunay syndrome (KTS) is a rare slow-flow combined vascular malformation with limb hypertrophy. KTS is thought to lie on the PIK3CA-related overgrowth spectrum, but reports are limited. PIK3CA encodes p110α, a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) that plays an essential role in the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. We aimed to demonstrate the clinical utility of targeted next-generation sequencing (NGS) in identifying PIK3CA mosaicism in archival formalin-fixed paraffin-embedded (FFPE) tissues from patients with KTS. Results Participants were 9 female and 5 male patients with KTS diagnosed as capillaro-venous malformation (CVM) or capillaro-lymphatico-venous malformation (CLVM). Median age at resection was 14 years (range, 5–57 years). Median archival period before DNA extraction from FFPE tissues was 5.4 years (range, 3–7 years). NGS-based sequencing of PIK3CA achieved an amplicon mean coverage of 119,000x. PIK3CA missense mutations were found in 12 of 14 patients (85.7%; 6/8 CVM and 6/6 CLVM), with 8 patients showing the hotspot variants E542K, E545K, H1047R, and H1047L. The non-hotspot PIK3CA variants C420R, Q546K, and Q546R were identified in 4 patients. Overall, the mean variant allele frequency for identified PIK3CA variants was 6.9% (range, 1.6–17.4%). All patients with geographic capillary malformation, histopathological lymphatic malformation or macrodactyly of the foot had PIK3CA variants. No genotype–phenotype association between hotspot and non-hotspot PIK3CA variants was found. Histologically, the vessels and adipose tissues of the lesions showed phosphorylation of the proteins in the PI3K/AKT/mTOR signaling pathway, including p-AKT, p-mTOR, and p-4EBP1. Conclusions The PI3K/AKT/mTOR pathway in mesenchymal tissues was activated in patients with KTS. Amplicon-based targeted NGS could identify low-level mosaicism from low-input DNA extracted from FFPE tissues, potentially providing a diagnostic option for personalized medicine with inhibitors of the PI3K/AKT/mTOR signaling pathway.

show abstract

Section: Resultsmentioning

confidence: 99%

Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel–Trenaunay syndrome in an Asian population

Sasaki,

Ishikawa,

Hatanaka

et al. 2023

Orphanet J Rare Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Because venous damage can occur, the possibility of blood loss during surgery must be considered. Blood transfusions must be taken into account19 .Baraldini et al reported 29 pediatric patients withKTS underwent combination open surgery with semiinvasive intervention. The mean age was 10.3 years.…”

mentioning

confidence: 99%

Klippel Trenaunay Syndrome: A Brief Overview

Permatananda

Putra

2021

Bioscmed

View full text Add to dashboard Cite

Klippel-Trenaunay syndrome is a rare congenital vascular disease. The pathogenesis of this syndrome is unclear, but it is thought that most cases are the result of somatic mutations that affect genes that play a role in vasculogenesis and angiogenesis. Some patients come with a triad of capillary malformation (hemangioma or port-wine stain), venous varicosities and bony or soft tissue hypertrophy. Clinical presentation of this syndrome can lead to significant morbidities and mortalities due to severe bleeding and emboli. Although the number of cases is low, a doctor must be able to distinguish Klippel-Trenaunay Syndrome from other rare vascular disorders. Parkes Weber syndrome is usually similar to Klippel-Trenaunay syndrome, except in the arterial malformations associated with capillary malformations and soft tissue to skeletal or bone hypertrophy. The diagnosis of Klippel-Trenaunay Syndrome is carried out clinically and is quite difficult to do even with experienced doctors because there is no precise pathognomonic test. There are several options in relation to the management of Klippel-Trenaunay Syndrome and non-invasive procedure is considered to be the most important of therapy modalities. Early diagnoses, progression monitoring, and proper intervention should be carried out for better prognosis and preventing complication.

show abstract

Klippel-Trénaunay Syndrome (Klippel-Trénaunay-Weber Syndrome)

Panteliadis

2022

Neurocutaneous Disorders

View full text Add to dashboard Cite

Wound-Healing Problems Associated with Combined Vascular Malformations in Klippel–Trenaunay Syndrome

Cited by 8 publications

References 85 publications

Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel–Trenaunay syndrome in an Asian population

Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel–Trenaunay syndrome in an Asian population

Klippel Trenaunay Syndrome: A Brief Overview

Klippel-Trénaunay Syndrome (Klippel-Trénaunay-Weber Syndrome)

Contact Info

Product

Resources

About