Mosaic KRAS Variant as a Cause of Developmental Eye Anomalies in an Individual With EncephaloCranioCutaneous Lipomatosis

Mosaic RASopathies are a group of rare developmental disorders arising from post-zygotic variants in members of the RAS/MAPK signalling pathway and with a cancer predisposition. Their phenotypic manifestations are highly variable and depend on the extent and distribution of tissue involvement. Ocular features typically include epibulbar dermoids, although structural eye anomalies are also less commonly reported. We describe a girl with microphthalmia and coloboma whose extraocular features were suggestive of the mosaic RASopathy, EncephaloCranioCutaneous Lipomatosis (ECCL). Genetic analyses of affected tissues revealed a missense variant in the RAS pathway gene KRAS (p.[Ala146Pro]), located in a recurrent hotspot for mosaic RASopathies. The variant was absent in blood, confirming a tissue-restricted distribution. The identification of this mosaic KRAS variant genetically confirmed the clinical diagnosis of ECCL and prompted appropriate tumour surveillance. This case highlights mosaic RASopathies as a cause of developmental eye anomalies.