Parkes Weber Syndrome: Contribution of the Genotype to the Diagnosis

Themis-Areti A, Andreoti; Tuleja, Aleksandra; Döring, Yvonne; Maiolo, Massimo; Schaller, André; Vassella, Erik; Zweier, Christiane; Boon, Laurence M; Vikkula, Miikka; Rössler, Jochen; Bernhard, Sarah M.; Baumgartner, Iris (2023). Parkes Weber Syndrome: Contribution of the Genotype to the Diagnosis. Journal of vascular anomalies, 4(4), e076. Wolters Kluwer Health 10.1097/JOVA.0000000000000076

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Objectives:
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.

Methods:
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.

Results:
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.

Conclusion:
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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Human Genetics
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Angiology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hämatologie / Onkologie (Pädiatrie)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hämatologie / Onkologie (Pädiatrie)

Graduate School:

Graduate School for Health Sciences (GHS)

UniBE Contributor:

Tuleja, Aleksandra Beata, Döring, Yvonne, Maiolo, Massimo Vincenzo, Schaller, André, Vassella, Erik, Zweier, Christiane Gertrud, Rössler, Jochen Karl, Bernhard, Sarah Maike, Baumgartner, Iris

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2690-2702

Publisher:

Wolters Kluwer Health

Language:

English

Submitter:

Felix Loeper

Date Deposited:

23 Nov 2023 15:56

Last Modified:

03 Jun 2024 14:31

Publisher DOI:

10.1097/JOVA.0000000000000076

BORIS DOI:

10.48350/189304

URI:

https://boris.unibe.ch/id/eprint/189304

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