Document Type

Article

Publication Date

5-2025

Identifier

DOI: 10.1111/pde.15802; PMCID: PMC12118530

Abstract

BACKGROUND: Many vascular anomalies harbor postzygotic somatic variants in GNAQ and GNA11; however, the phenotype of specific G-protein variants has not been well described. We report the clinical characteristics of 17 patients with a GNA11 R183C variant.

METHODS: This case series is derived from a multinational cohort of vascular anomaly patients whose pathogenic mutations were identified using high-depth next generation sequencing. Data include vascular anomaly features, imaging reports, and extracutaneous manifestations of the GNA11 R183C variant.

RESULTS: We identified 17 subjects (median age 18 years [range 6-67]) with somatic GNA11 R183C variant. All patients had vascular lesions of the skin that presented as pink-to-red in children and deeper red in adults. Most lesions were large, poorly demarcated, and reticulated patches that were often bilaterally distributed. Nevus anemicus was observed in 53% (N = 9) and dermal melanocytosis in 13.3% (N = 2) of individuals. 82% (N = 14) of patients had limb growth discrepancies, and 1 patient had marked thoracic hypoplasia. 47% (N = 8) of patients had facial involvement, and 41% (N = 7) had forehead involvement. One patient experienced seizures due to right hemispheric leptomeningeal angiomatosis consistent with Sturge-Weber syndrome. Other findings included glaucoma (29%, N = 5) and psychomotor delay (29%, N = 5).

CONCLUSION: These findings contribute to our understanding of the clinical spectrum of GNA11 R183C capillary malformations (CMs); patients characteristically present with extensive, bilateral, poorly demarcated, pink-to-red CMs associated with nevus anemicus. Glaucoma and growth discrepancies (overgrowth or undergrowth) are common. Leptomeningeal angiomatosis and developmental delay can occur, appearing potentially less prevalent and severe than GNAQ-associated disease.

Journal Title

Pediatric dermatology

Volume

42

Issue

3

First Page

475

Last Page

480

MeSH Keywords

Humans; Child; Male; Female; Mosaicism; Phenotype; Adolescent; Adult; Young Adult; Middle Aged; Aged; GTP-Binding Protein alpha Subunits; Vascular Malformations; Mutation; GTP-Binding Protein alpha Subunits, Gq-G11

PubMed ID

39654261

Keywords

genetic diseases; mechanisms; vascular malformation

Comments

Grants and funding

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Publisher's Link: https://onlinelibrary.wiley.com/doi/10.1111/pde.15802

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