Phenotypic Spectrum of GNA11 R183C Mosaicism

Area of Science:

• Genetics
• Dermatology
• Vascular Biology

Background:

• Postzygotic somatic variants in GNAQ and GNA11 are implicated in vascular anomalies.
• The specific clinical phenotypes associated with individual G-protein variants remain underexplored.

Purpose of the Study:

• To describe the clinical characteristics and extracutaneous manifestations of the GNA11 R183C variant in patients with vascular anomalies.

Main Methods:

• A multinational case series of 17 patients with vascular anomalies harboring the GNA11 R183C variant.
• High-depth next-generation sequencing was used for mutation identification.
• Data included detailed vascular anomaly features, imaging, and extracutaneous findings.

Main Results:

• Seventeen patients (median age 18 years) with somatic GNA11 R183C variant were identified.
• Characteristic findings include extensive, bilateral, poorly demarcated, pink-to-red capillary malformations (CMs), often with nevus anemicus (53%) and dermal melanocytosis (13.3%).
• Common extracutaneous manifestations include limb growth discrepancies (82%), glaucoma (29%), and psychomotor delay (29%). One patient had leptomeningeal angiomatosis consistent with Sturge-Weber syndrome.

Conclusions:

• The GNA11 R183C variant is associated with a distinct spectrum of capillary malformations (CMs), frequently presenting as extensive, bilateral lesions with nevus anemicus.
• Glaucoma and growth discrepancies are common comorbidities.
• While leptomeningeal angiomatosis and developmental delay can occur, they may be less prevalent or severe compared to GNAQ-associated diseases.