Proteus syndrome is a rare genetic disorder distinguished by an overgrowth of many different tissues in the body in a mosaic pattern. The skin, the musculoskeletal system, the central nervous system, and adipose tissues are affected the most, producing profound disfigurement and life-threatening complications. The diagnosis is made through a combination of clinical criteria and positive genetic studies for AKT1 gene mutations.
Although Proteus syndrome is rarely encountered in clinical practice, several distinct signs are recognized in the affected population. Tissue overgrowth is, by far, the most important feature of this disorder and the skeletal system seems to be most severely affected      . After an apparently normal birth, first signs usually appear in late infancy and early childhood (6-18 months of age), but a delayed presentation up to puberty has been encountered  . Skeletal changes affect the limbs in most cases in an evidently disproportionate, asymmetric, and often severe and rapidly progressing fashion (leg length discrepancy of up to 20 centimeters has been reported)  . The connective tissues and fat are also affected by this phenomenon, but atrophy of the adipose tissue can be simultaneously present in some patients   . Furthermore, studies have reported cases with overgrowth of different organs, including the thymus, the gastrointestinal tract, the spleen, and the liver  . Vascular malformations involving, the arterial, venous, and/or lymphatic vessels are very frequent and predispose to life-threatening thromboembolic events   . Apart from tissue overgrowth, the formation of cutaneous lesions, such as linear verrucous epidermal nevi and cerebriform connective tissue nevi (CCTN) are hallmarks of Proteus syndrome    . Other notable findings seen in Proteus syndrome are    :
Unfortunately, Proteus syndrome is severely debilitating during childhood and adolescence and up to 25% of patients are at risk of not surviving past the beginning of the third decade of life . For this reason, an early diagnosis is essential. To recognize Proteus syndrome, it is first necessary to establish prerequisite criteria - a mosaic pattern of lesions, the absence of a familial component, and a rapidly progressive course of symptoms   . During the clinical assessment, use of diagnostic criteria that have been revised in the previous decade should be sufficient to solidify clinical suspicion   .
The diagnosis is made when either Category A is fulfilled, when two signs from category B exist, or if three signs from category C are observed   . In addition to clinical findings, the revelation of specific mutations involving the AKT1 gene has allowed mutational analysis to be performed in this population ; thus genetic testing can be employed as a definitive diagnostic method   .