 Segmental overgrowth syndromes are very rare diseases with an extremely relevant genetic background. In some of them, only about 200 cases are known worldwide, such as for example the Proteus syndrome which presents with asymmetric and fast growth of extremities. Further overgrowth diseases are the SOLAMEN and the CLOVE syndrome with lipomatosis, vascular malformations and epidermal nevus as well as the Cowden syndrome with multiple hamartomas and the Bannayan-Riley-Ruvalcaba syndrome with lipomatosis and macrocephalus. The patients with overgrowth syndromes all show close clinical overlap. For several years, clinical criteria phenotype for diagnosis and discrimination of these syndromes have been defined. 