Challenge of Clinical Diagnosis and Treatment for Proteus Syndrome: A Case Report

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Proteus syndrome (PS) is an extremely rare complex disorder, and caused by PS associated somatic mosaic AKT1 gene mutation. PS is characterized by progressive asymmetric, disproportionate overgrowth of patient’s skin, soft tissue, and bone of the different body parts since infant period. There is diversity in both clinical appearances, and with or without PS associated pathogenic genetic mutation situation can be existed for each patient. That caused clinical challenges for both accurate diagnosis and proper early treatment. We report a case of 17 years-old girl she presented with significant craniofacial dysmorphism, including prominent craniosynostosis and generalized skull bone sclerotic hyperostosis changes, hearing impairment after age of 3 years-old, progressive asymmetric overgrowth of the left lower limb with leg length discrepancy in childhood. Focal lipomatous tumors grow over the abdomen, left thigh and spinal deformity developed around teenage years. Hypermenorrhea with adenomyosis and ovarian cystadenoma lesions after menarche 12 years-old. Patient was fulfilled positive clinical criteria > 17 points for clinical Proteus syndrome diagnosis, clinically strict met (mosaic distribution of lesions, sporadic occurrence, and progressive course) three general criteria for PS diagnosis. Although the whole exome sequencing test from affected thigh lipoma did not identify pathogenic/likely pathogenic variant AKT1, PTEN, PIK3CA gene. Whole genome sequencing test from affected cranial hyperostosis bone revealed MSH6 variant of uncertain significance (NM-000179.3: c.754T>G) gene mutation. The patient has received surgical treated at three different medical centers in Taiwan for craniofacial dysmorphism, hearing loss, leg length discrepancy, and hypermenorrhea problems respectively. All clinical symptoms and problems with postoperative have partial relieved and improvement. Further more complicated surgery was necessary for her. Clinically we are challenged both for early confirming PS clinical diagnosis, and make the differential diagnosis from other clinical mimic overgrowth spectrum disorder.