Some genes led to LVNC and caused complex and critical clinical disease syndromes, such as Rubinstein–Taybi syndrome (i.e., ABCC9 gene), Ehlers–Danlos syndrome (i.e., COL3A1 gene), Emery–Dreifuss muscular dystrophy (i.e., EMD gene), Danon disease (i.e., LAMP2 gene), intellectual disability syndrome (i.e., NONO gene), Sotos syndrome (i.e., NSD1 gene), LEOPARD syndrome (i.e., PTPN11 gene), Coffin-Lowry syndrome (i.e., RPS6KA3 gene), Cornelia de Lange syndrome (i.e., SMC1A gene), Barth syndrome (i.e., TAZ gene), and Holt–Oram syndrome (i.e., TBX5 gene). The gene discussed is RPS6KA3; the disease is Noonan syndrome with multiple lentigines.