Calcified Sclero-Choroidal Choristomas in Mosaic RASopathies

To evaluate the imaging and clinical features of unusual calcified lesions seen in the fundus of mosaic RASopathy patients. Single-center retrospective observational study. Ten eyes with calcified fundus lesions in 7 mosaic RASopathy patients. The lesions were evaluated with fundus photography, oral fundus fluorescein angiography, B-scan ultrasonography, Magnetic Resonance Imaging (MRI), and Computed Tomography (CT) scan where available. The imaging characteristics of calcified fundus lesions were assessed. We found seven patients with mosaic RASopathies, 5 males and 2 females (3 with Linear Sebaceous Nevus Syndrome, 3 with Oculoectodermal Syndrome, and 1 with Encephalocraniocutaneous Lipomatosis) with molecular confirmation in 5 cases, all 5 having KRAS-pathogenic variants. Calcified fundus lesions were identified in 10 eyes (bilateral in 3 patients), appearing as slightly elevated, creamy-yellow lesions around or adjacent to the optic nerve, extending supero-nasally; all but two of these lesions involved both the choroid and sclera, with two of them only involving the sclera at the time of examination. One case developed a choroidal neovascular membrane (CNV) necessitating intravitreal bevacizumab injections. All 7 patients had B-scan ultrasonography and the lesion appeared as a hyperechogenic area with an acoustic shadow posteriorly despite reduced gain. Five patients had MRI, and where fundus lesions were present, there was a focal defect in the sclero-choroidal layer. Four patients had a CT scan and all four showed calcifications affecting both the posteromedial sclero-choroid and adjacent medial rectus muscle. Two of these patients had normal eye movements, one had a unilateral fixed adducted eye and a vestigial fibrous medial rectus muscle seen in imaging and intraoperatively, and the fourth had marked exotropia with a right gaze deficit affecting both eyes. We propose that the lesions seen in this cohort are calcified sclero-choroidal choristomas (CaSCCs) and should be suspected in mosaic RASopathies when creamy-yellow lesions are seen in the fundus. If identified, the possibility of choroidal neovascularization should be considered during follow-up. In all cases where a CT scan was performed, a novel sign of sclero-muscular calcification involving the medial rectus muscle was seen.