PROTEUS SYNDROME

Proteus syndrome is an exceedingly rare disorder, perhaps the least common of all overgrowth syndromes but one of the most distinctive because of its segmental nature and unrelenting progression. Proteus syndrome occurs sporadically and was the first of the segmental overgrowth syndromes found to be caused by somatic mosaicism. The discovery of an activating mutation in AKT1 by Les Biesecker and colleagues at the National Institutes of Health provided the initial molecular proof for somatic mosaicism in Proteus syndrome. Overgrowth in Proteus syndrome can involve nearly any tissue or part of the body. Presumably a germline mutation that would affect all tissues of the body would be lethal. Overgrowth of a tissue or a body part is the distinctive manifestation of Proteus syndrome but in most cases will be accompanied by other cutaneous, skeletal, vascular, or soft tissue findings. Although the possibility of an increased risk for developing neoplastic disease is a concern in any overgrowth disorder, this has not been demonstrated in Proteus syndrome.