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Multicenter Study
. 2025 May-Jun;42(3):475-480.
doi: 10.1111/pde.15802. Epub 2024 Dec 9.

Phenotypic Spectrum of GNA11 R183C Mosaicism

Donglin Zhang  1 , Luis Fernando Sánchez-Espino  2   3 , Marta Ivars  4 , Elena Pope  5 , Amy J Nopper  6 , Lisa M Arkin  1 , Megha M Tollefson  7 , Cinzia E Lavarino  8 , Maya Muldowney  1 , Nagore Gené Olaciregui  8 , Sonia Paco  8 , Beth A Drolet  1 , Eulàlia Baselga  4
Affiliations
Multicenter Study

Phenotypic Spectrum of GNA11 R183C Mosaicism

Donglin Zhang et al. Pediatr Dermatol. 2025 May-Jun.

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.

Keywords: genetic diseases; mechanisms; vascular malformation.

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Conflict of interest statement

Beth A Drolet is the Co‐founder and Board of Director at Arkayli Biopharma. Lisa M Arkin has no conflicts relevant to this study but is PI for research studies funded by Eli Lilly and Amgen, and receives consulting fees from Merck, Sanofi/Regeneron, and Nobel Pharma. DZ, LFSE, MI, EP, AJN, MMT, CEL, MM, NGO, SP, and EB have no conflicts to disclose.

Figures

FIGURE 1
FIGURE 1
Poorly demarcated, reticulated pink to red patches of the trunk.
FIGURE 2
FIGURE 2
Uniform overgrowth with increased length and circumference of the left leg affected by CM harboring the GNA11 R183C variant.
FIGURE 3
FIGURE 3
Nevus anemicus at the border of a large capillary malformation of the trunk.
See this image and copyright information in PMC

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