Thrombosis risk factors in PIK3CA-related overgrowth spectrum and Proteus syndrome.
PIK3CA-related overgrowth spectrum (PROS)
Proteus syndrome
deep vein thrombosis (DVT)
pulmonary embolism (PE)
thrombosis
Journal
American journal of medical genetics. Part C, Seminars in medical genetics
ISSN: 1552-4876
Titre abrégé: Am J Med Genet C Semin Med Genet
Pays: United States
ID NLM: 101235745
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
15
04
2019
revised:
27
07
2019
accepted:
30
07
2019
pubmed:
7
9
2019
medline:
6
5
2020
entrez:
7
9
2019
Statut:
ppublish
Résumé
Increased risk of thromboembolism has been recognized in individuals with mosaic overgrowth disorders, Proteus syndrome (PS) and PIK3CA-related overgrowth spectrum (PROS), including Klippel-Trenaunay syndrome and CLOVES syndrome. PS and PROS have distinct, yet overlapping clinical findings and are caused by somatic pathogenic variants in the PI3K/AKT gene signaling pathway. PS is caused by a single somatic activating AKT1 c.49G > A p.E17K variant while PROS can be caused one of multiple variants in PIK3CA. The role of prothrombotic factors, endothelial cell adhesion molecules, and vascular malformations in both PS and PROS have not been previously investigated. A pilot study of prospective clinical and laboratory evaluations with the purposes of identifying potential risk factors for thrombosis was conducted. Doppler ultrasounds and magnetic resonance angiogram/ venography (MRA/MRV) scans identified vascular malformations in PS and PROS that were not appreciated on physical examination. Abnormal D-dimers (0.60-2.0 mcg/ml) occurred in half of individuals, many having vascular malformations, but no thromboses. Soluble vascular endothelial markers, including thrombomodulin, soluble vascular adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), E-selectin, and P-selectin were significantly higher in PS and PROS compared to controls. However, no single attribute was identified that explained the risk of thrombosis. Predisposition to thrombosis is likely multifactorial with risk factors including chronic stasis within vascular malformations, stasis from impaired mobility (e.g., following surgery), decreased anticoagulant proteins, and effects of AKT1 and PIK3CA variants on vascular endothelium. Based on our findings, we propose clinical recommendations for surveillance of thrombosis in PS and PROS.
Identifiants
pubmed: 31490637
doi: 10.1002/ajmg.c.31735
pmc: PMC8513083
mid: NIHMS1643848
doi:
Substances chimiques
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
571-581Subventions
Organisme : Intramural NIH HHS
ID : ZIA HG200388
Pays : United States
Organisme : NHGRI NIH HHS
ID : HG200388
Pays : United States
Informations de copyright
Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
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