LS is mainly caused by growth hormone receptor (GHR) gene mutations and monogenic defects of post-receptor components in the GH signal transduction pathway, such as signal transducer and activator of transcription 5B (STAT5B), IGFALS, IGF1, IGF-1R and pregnancy-associated plasma protease A2 (PAPPA2) (5–13). This evidence concerns the gene PAPPA2 and Leigh syndrome.