Somatic TEK variant with intraarticular venous malformation and knee hemarthrosis treated with rapamycin.
TEK/TIE2
genetics
rapamycin
vascular malformation
venous malformation
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
09
03
2022
received:
04
01
2022
accepted:
14
03
2022
pubmed:
16
4
2022
medline:
14
6
2022
entrez:
15
4
2022
Statut:
ppublish
Résumé
Venous malformations (VMs) are the most common vascular anomalies and have been associated with somatic variants in TEK. Current treatment of VM joint component might be challenging due to the size or location of some lesions or ineffective with recurrence of malformed veins. Targeted molecular therapies after identification of genetic defects might be an alternative. We report a case with intraarticular bleeding due to VM with a TEK pathogenic somatic variant treated with rapamycin. A 26-year-old female patient was evaluated for right calf pain secondary to venous malformation of the right inferior limb with an intraarticular component in the right knee. Hemarthrosis and degenerative chondropathy of the knee were evidenced at MRA. Molecular diagnosis evidenced a pathogenic somatic TEK variant. Rapamycin was introduced to stop bleeding, with good tolerance and efficacy. The TEK receptor signals through the PI3K/AKT/mTOR pathway and TEK mutations have been linked to AKT activation. As rapamycin acts against angiogenesis and reduces phosphorylated-AKT levels, targeted molecular therapy should be discussed as first-line therapy in patients with proven molecular diagnosis and diffuse VM inaccessible to conventional treatment.
Sections du résumé
BACKGROUND
Venous malformations (VMs) are the most common vascular anomalies and have been associated with somatic variants in TEK. Current treatment of VM joint component might be challenging due to the size or location of some lesions or ineffective with recurrence of malformed veins. Targeted molecular therapies after identification of genetic defects might be an alternative.
METHODS
We report a case with intraarticular bleeding due to VM with a TEK pathogenic somatic variant treated with rapamycin.
RESULTS
A 26-year-old female patient was evaluated for right calf pain secondary to venous malformation of the right inferior limb with an intraarticular component in the right knee. Hemarthrosis and degenerative chondropathy of the knee were evidenced at MRA. Molecular diagnosis evidenced a pathogenic somatic TEK variant. Rapamycin was introduced to stop bleeding, with good tolerance and efficacy.
CONCLUSION
The TEK receptor signals through the PI3K/AKT/mTOR pathway and TEK mutations have been linked to AKT activation. As rapamycin acts against angiogenesis and reduces phosphorylated-AKT levels, targeted molecular therapy should be discussed as first-line therapy in patients with proven molecular diagnosis and diffuse VM inaccessible to conventional treatment.
Identifiants
pubmed: 35426265
doi: 10.1002/mgg3.1931
pmc: PMC9184663
doi:
Substances chimiques
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Sirolimus
W36ZG6FT64
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1931Informations de copyright
© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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Mol Genet Genomic Med. 2022 Jun;10(6):e1931
pubmed: 35426265