Examples of this close relation are Noonan and Lentigines-Electrocardiographic conduction defects-Ocular hypertelorism-Pulmonary stenosis-Abnormalities of the genitalia-Retarded growth-Deafness (LEOPARD) syndromes (both can be caused by Protein Tyrosine Phosphatase Non-Receptor Type 11 gene (PTPN11) pathogenic variation), or the Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha gene (PIK3CA) pathogenic variation related Cowden and Klippel-Trenaunay-Weber syndromes. The gene discussed is PIK3CA; the disease is angioosteohypertrophic syndrome.