Genetic syndromes with vascular malformations – update on molecular background and diagnostics

Ustaszewski, Adam; Janowska-Głowacka, Joanna; Wołyńska, Katarzyna; Pietrzak, Anna; Badura‐Stronka, Magdalena

doi:10.5114/aoms.2020.93260

Cited by 17 publications

(11 citation statements)

References 189 publications

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“…An eloquent example is the genetic testing of RASA1 gene mutations, which helps to differentiate the diagnosis of patients with port-wine stain type CMs (PWS, KTWS and CM-AVMs) [ 4 , 16 , 18 ].…”

Section: Discussion and Future Therapeutic Perspectives Correlated Wi...mentioning

confidence: 99%

“…They are present at birth, but can also appear later in life. CM-AVMs are frequently associated with high-flow arteriovenous malformations (AVMs) or arteriovenous fistulas (AVFs) located in muscles, skin, and other tissues (intracranial, intraspinal), aneurysmal malformation of the vein of Galen or Parkers Weber syndrome (PWS) [ 16 , 17 , 18 ].…”

Section: Vascular Anomalies: Ras/raf/mapk/erk Signaling Pathways (Ras...mentioning

confidence: 99%

“…Mutations of the RASA1 gene (RASp21 protein activator 1; OMIM 139150) [ 6 ] (located on the chromosome 5q14.3) and transmitted in an autosomal dominant manner, are responsible for different forms of VMs (CMs, AVMs, AVFs), as single manifestations, or in complex combinations, as in the case of PWS [ 16 , 18 ]. Initially, two loci for inherited CMs were identified on chromosome 5 (5q14-21 and 5q13-22), and later, the RASA1 (RAS P21 Protein Activator 1) gene was identified as a candidate gene for atypical CMs with AVMs and AVFs, and sporadically, in PWS [ 16 , 18 ].…”

Section: Vascular Anomalies: Ras/raf/mapk/erk Signaling Pathways (Ras...mentioning

confidence: 99%

“…The spectrum of capillary malformation—arteriovenous malformation syndrome 1 (CM-AVM1) includes all cases of VMs associated with RASA1 mutations. Later, other studies reported the presence of RASA1 mutation in atypical CMs as well as cases with aneurysmal malformation of the vein of Galen (VOGM) and Hereditary hemorrhagic telangiectasia (HHT) [ 18 ].…”

Section: Vascular Anomalies: Ras/raf/mapk/erk Signaling Pathways (Ras...mentioning

confidence: 99%

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The Genetic Architecture of Vascular Anomalies: Current Data and Future Therapeutic Perspectives Correlated with Molecular Mechanisms

Butnariu

Gorduza

Florea

et al. 2022

IJMS

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Vascular anomalies (VAs) are morphogenesis defects of the vascular system (arteries, capillaries, veins, lymphatic vessels) singularly or in complex combinations, sometimes with a severe impact on the quality of life. The progress made in recent years with the identification of the key molecular pathways (PI3K/AKT/mTOR and RAS/BRAF/MAPK/ERK) and the gene mutations that lead to the appearance of VAs has allowed the deciphering of their complex genetic architecture. Understanding these mechanisms is critical both for the correct definition of the phenotype and classification of VAs, as well as for the initiation of an optimal therapy and the development of new targeted therapies. The purpose of this review is to present in synthesis the current data related to the genetic factors involved in the etiology of VAs, as well as the possible directions for future research. We analyzed the data from the literature related to VAs, using databases (Google Scholar, PubMed, MEDLINE, OMIM, MedGen, Orphanet) and ClinicalTrials.gov. The obtained results revealed that the phenotypic variability of VAs is correlated with genetic heterogeneity. The identification of new genetic factors and the molecular mechanisms in which they intervene, will allow the development of modern therapies that act targeted as a personalized therapy. We emphasize the importance of the geneticist in the diagnosis and treatment of VAs, as part of a multidisciplinary team involved in the management of VAs.

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Section: Discussion and Future Therapeutic Perspectives Correlated Wi...mentioning

confidence: 99%

Section: Vascular Anomalies: Ras/raf/mapk/erk Signaling Pathways (Ras...mentioning

confidence: 99%

Section: Vascular Anomalies: Ras/raf/mapk/erk Signaling Pathways (Ras...mentioning

confidence: 99%

Section: Vascular Anomalies: Ras/raf/mapk/erk Signaling Pathways (Ras...mentioning

confidence: 99%

See 2 more Smart Citations

The Genetic Architecture of Vascular Anomalies: Current Data and Future Therapeutic Perspectives Correlated with Molecular Mechanisms

Butnariu

Gorduza

Florea

et al. 2022

IJMS

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“…Судинні аномалії становлять гетерогенну групу захворювань, які поділяють на судинні пухлини (судинні невуси) та судинні мальформації на основі класифікації, розробленої Міжнародним товариством з вивчення судинних аномалій [5]. Відповідно, судинні новоутворення шкіри стандартно розділяють на доброякісні (переважно гемангіоми), локально агресивні/прикордонні (включаючи саркому Капоші) і злоякісні (ангіосаркома), тоді як судинні мальформації розподіляються на прості (капілярні, венозні, артеріальні та лімфатичні мальформації), комбіновані (артеріовенозні та капілярно-венозно-лімфатичні мальформації), ураження великих судин (артерії, вени та лімфа) та синдромні форми (найчастішесиндром Кліппеля-Треноне (КТС) та синдром Мафуччі) [18]. Однак окремою групою є гломувенозні мальформації (ГВМ)гамартоматозні ураження, що характеризуються наявністю гломусних клітин у гладких м'язах судин [3].…”

Section: вступunclassified

Glomus Venous malformation of the skin of the left ankle-foot joint: a clinical case and review of the literature

Vernygorodskyi¹,

Kostiuk²,

Kostiukov³

2022

Rep. of Vinnytsia Nation. Med. Univ.

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Annotation. The work presents a clinical and histological description of a case of glomuvenous malformation and a review of modern data on the diagnosis and treatment of this disease. A case of diagnosis of glomuvenous malformation on the foot of the right lower limb in a 46-year-old man was analysed. The case was characterized by an uncertain dermatological status with the need to exclude malignant neoplasia of the skin. Considering doubts about the benign nature of the skin lesion, the patient was recommended to undergo a therapeutic and diagnostic biopsy. After a medical-diagnostic biopsy, histological sections showed skin with moderate hyperparakeratosis of the epidermis and a clearly delineated, non-encapsulated formation in the dermis. The tumour is represented by numerous vascular channels of the venous type of small and medium caliber, some of which have an enlarged lumen and a thickened wall, filled with erythrocytes. Clusters, chains, and fields of monomorphic glomus cells with weakly expressed eosinophilic cytoplasm and rounded nuclei with finely dispersed chromatin are located perivascularly, without atypia. Mitotic figures are absent. The intercellular stroma is sclerosed with focal oedema. Considering the results obtained by us and the data of modern studies, we can state the ambiguity of views on the diagnosis of glomuvenous malformation with the need for more aggressive diagnostic and therapeutic tactics in adults. The development of an algorithm for the management of adult patients with glomuvenous malformation of the skin is a prospect for further research.

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High‐depth next‐generation sequencing panel testing in the evaluation of arteriovenous malformations

Hernandez

King

Evenson

et al. 2023

American J of Med Genetics Pt A

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Arteriovenous malformations (AVMs) are vascular lesions in which an overgrowth of blood vessels of varying sizes develops with one or more direct connections between the arterial and venous circulation. We performed a retrospective review of a cohort of 54 patients with AVMs referred to our clinical genomic laboratory for high‐depth next‐generation sequencing (NGS) panel of Disorders of Somatic Mosaicism (DoSM). Thirty‐seven of 54 patients were female (68.5%). Among the 54 cases, 37 (68.5%) cases had pathogenic and/or likely pathogenic (P/LP) variants identified, two cases (3.7%) had variants of uncertain clinical significance, and the remaining 15 cases (27.8%) had negative results. MAP2K1 variants were found in 12 cases, followed by eight cases with KRAS variants and seven with TEK variants, and the remainder being identified in several other genes on the panel. Among the 37 positive cases, 32 cases had somatic alterations only; the remaining five cases had at least one germline P/LP variant, including four cases with PTEN and one with RASA1. Of note, two cases had the unexpected co‐existence of two P/LP variants. In summary, this study illustrated the molecular diagnostic yield (68.5%) of this cohort of patients with a clinical indication of AVMs by our high‐depth DoSM NGS panel.

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Genetic syndromes with vascular malformations – update on molecular background and diagnostics

Cited by 17 publications

References 189 publications

The Genetic Architecture of Vascular Anomalies: Current Data and Future Therapeutic Perspectives Correlated with Molecular Mechanisms

The Genetic Architecture of Vascular Anomalies: Current Data and Future Therapeutic Perspectives Correlated with Molecular Mechanisms

Glomus Venous malformation of the skin of the left ankle-foot joint: a clinical case and review of the literature

High‐depth next‐generation sequencing panel testing in the evaluation of arteriovenous malformations

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