When DNA methylation changes and somatic mutations in formalin-fixed and paraffin-embedded tissues from 57 LS patients were investigated, targeted-NGS showed that somatic mutations in LS-adenomas frequently affect CTNNB1, SMAD4, KRAS, and TP53 genes, with a frequency from 15% up to 24% respectively. Here, SMAD4 is linked to Leigh syndrome.