Visualizing Genetics: An Investigation of Dermoscopy as a Tool for Genetic Variant Prediction in Capillary Malformations

可视化遗传学:皮肤镜作为毛细血管畸形遗传变异预测工具的研究

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Abstract

BACKGROUND/OBJECTIVES: Capillary malformations (CMs) are congenital malformations of capillaries typically visible as blanchable, pink to brown patches on the skin and/or mucosa. The genetic cause of CMs guides diagnosis, treatment, and recurrence counseling. However, identification may be limited by the availability of samples, the type of tests, and insurance coverage. We hypothesize that there are distinct dermoscopic features associated with specific genotypes of congenital CMs. METHODS: A single-center, retrospective cohort study of 22 patients with CMs affecting the skin, a polarized dermoscopic photo of the lesion, and a single nucleotide variant in the EPHB4, GNA11/GNAQ, PIK3CA/PIK3R1, or RASA1 genes was performed. Three reviewers analyzed dermoscopic photos for the presence of apparent vessels, branching, lacunae, geometric shape formation, zones of dropout, follicle-sparing, vessel and background color, and length and width of vessels when discernable. Features were categorized by genotype. RESULTS: EPHB4-CMs have visible lengthwise and widthwise cross sections of vessels that exhibit branching. RASA1-CMs generally present with merely a red/pink/brown hue without visible vessels. GNA11 or GNAQ-CMs generally present with pink coloration and generally only with visible widthwise cross sections of vessels without branching. Geometric PIK3CA-CMs exhibit distinct purple lacunae that indicate a lymphatic component, but the reticulated PIK3CA-CMs otherwise demonstrate a varied presentation. CONCLUSION: Our research identified distinct genotype-phenotype correlations for CMs by dermoscopy. Dermoscopy can narrow the differential diagnosis, guide genetic testing, and aid in the interpretation of variants of uncertain significance (VUS). This study demonstrates that dermoscopy holds promise in aiding genetic diagnosis and ultimately medical management.

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