A limited form of proteus syndrome with bilateral plantar cerebriform collagenomas and varicose veins secondary to a mosaic AKT1 mutation.

IMPORTANCE

Proteus syndrome is an extremely rare disorder of mosaic postnatal overgrowth affecting multiple tissues including bone, soft tissue, and skin. It typically manifests in early childhood with asymmetric and progressive skeletal overgrowth that leads to severe distortion of the skeleton and disability. The genetic basis has recently been identified as a somatic activating mutation in the AKT1 gene, which encodes an enzyme mediating cell proliferation and apoptosis.

OBSERVATIONS: We present a 33-year-old man who developed plantar cerebriform collagenomas on the soles of both feet and varicose veins in early childhood, in the absence of any skeletal or other connective tissue abnormality. Although the patient did not meet the diagnostic criteria for Proteus syndrome, he was found to have the c.49G>A, p.Glu17Lys AKT1 mutation in lesional skin but not in his blood.

CONCLUSIONS AND RELEVANCE: To our knowledge, this is the mildest molecularly confirmed case of Proteus syndrome, occurring in the absence of the characteristic skeletal overgrowth. These findings extend the spectrum of Proteus syndrome pathological characteristics and suggest that somatic mutations late in development and restricted in distribution cause subtle clinical presentations that do not meet the published clinical criteria.