Ras proteins play an important signal transduction role in conveying extracellular growth factor stimuli to the cell. Mosaic RASopathy refers to a group of rare genetic diseases that impact the Ras/MAPK signaling pathway and which can display a wide range of phenotypic presentations and severities. A case series investigation of 7 patients with mosaic RASopathy identified novel clinical features of the associated ocular lesions on fundus examination that appear to differentiate these masses from typical choroidal osteomas. If validated, these findings suggest that the presence of calcified sclero-choroidal choristomas could be useful in the diagnosis and prognostication of mosaic RASopathy.
Study Design
This was a single center, retrospective analysis of clinical and imaging records for 7 patients (10 eyes) diagnosed with mosaic RASopathy and scleral or choroidal choristomas. Multimodal imaging of the ocular lesions included the use of fundus photography, oral fundus fluorescein angiography, B-scan ultrasonography, magnetic resonance imaging (MRI), and computed tomography (CT).
Outcomes
Three patients had linear sebaceous nevus syndrome, 3 had oculoectodermal syndrome, and 1 had encephalocraniocutaneous lipomatosis. Five patients had molecular confirmation of mosaic RASopathy, all of whom had KRAS-pathogenic variants. Calcified fundus lesions were present in the sclera of all eyes and appeared as slightly elevated, yellow lesions extending superonasal from the optic disc; in 8 of 10 eyes, both the sclera and choroid were involved. One lesion was associated with choroidal neovascular membrane development. Of 4 patients imaged with CT scans, all had calcification of the adjacent medial rectus muscle, which was associated with extraocular motility deficits in 2 patients.
Limitations
The small sample size, single study center, and retrospective study design limit the ability to draw broad conclusions from these data. MRI and CT imaging were only available for a subset of patients, and the temporal association between medial rectus calcification and extraocular motility deficits could not be assessed.
Clinical Significance
Calcified sclero-choroidal choristomas should be considered in the differential diagnosis for elevated, amelanotic lesions extending superonasally from the optic disc. Calcification of such lesions can be confirmed with B-scan ultrasonography, and molecular investigation for mosaic RASopathies should be strongly considered in the presence of any suggestive dermatologic or ocular surface features. Patients with calcified sclero-choroidal choristomas should be monitored for choroidal neovascularization, and neuroimaging may reveal sclero-muscular calcification of the medial rectus muscle.
Financial Disclosures: Dr. Lauren Dalvin discloses financial relationships with Leonard and Mary Lou Hoeft Career Development Award Fund, National Cancer Institute, National Center for Advancing Translational Science (Grant Support).