Bennett MF et al. (Bennett et al., 2022) reported a maternally inherited pathogenic germline variant (c.48delG) in NPRL3 gene in two brothers with FCD, and found a somatic variant (c.338C>T) in WNT2 gene in the brain-derived DNA from the elder brother at an allele fraction estimated at 0.3% by ddPCR, further confirming the 2-hit model in FCD caused by NPRL3. Therefore, the 2-hit model of germline and somatic mutations might cause the different clinical phenotypes and penetrance insufficiency in NPRL3 families. This evidence concerns the gene NPRL3 and fleck corneal dystrophy.