Proteus syndrome with sciatic nerve fibrolipomatous hamartoma: an uncommon finding in a rare disease: report of two cases with literature review

Proteus syndrome is an extremely rare condition, characterized by progressive asymmetric overgrowth of multiple body tissues. Here we present two cases of Proteus syndrome demonstrating typical clinical and radiological features of Proteus syndrome, in addition to an uncommon fibrolipomatous hamartoma of the sciatic nerve. The first case is a five-year-old girl who presented with seizures. The patient showed facial dysmorphic features, left head enlargement, kyphoscoliosis, asymmetric overgrowth of the right lower limb, right foot drop, and cribriform connective tissue nevi on the right palm and the right sole. Radiological examinations demonstrated left calvarial hyperostosis, dysplasia of the left cerebral hemisphere, dysregulation of the subcutaneous adipose fat of the body, kyphoscoliosis, and lipoma of the filum terminale. CT of both thighs showed asymmetric soft tissue overgrowth of the right thigh, associated with diffuse enlargement and fatty infiltration of the right sciatic nerve starting from the upper thigh, down to its bifurcation into the tibial and common peroneal nerves. The second case is an eighteen-year-old girl who presented with left conductive deafness. The patient showed facial dysmorphic features, right head enlargement, asymmetric overgrowth of the right upper limb, kyphoscoliosis, left foot drop, and cribriform connective tissue nevi on the nose and the left foot. Radiological examinations demonstrated right calvarial hyperostosis, left external auditory canal hyperostosis and stenosis, and kyphoscoliosis. CT and MRI of both thighs showed diffuse enlargement of the left sciatic nerve starting from the upper thigh down to the mid-thigh and showing inter fascicular adipose tissue proliferation, giving the typical features of nerve lipomatosis.

Case Report: Five-Year Experience of AKT Inhibition with Miransertib (MK-7075) in an Individual with Proteus Syndrome

Proteus syndrome is a rare overgrowth disorder caused by postzygotic activating variants in AKT1. Individuals may develop a range of skin, bone, and soft tissue overgrowth leading to functional impairment and disfigurement. Therapy for this disorder is limited to supportive care and surgical intervention. Inhibitors of AKT, originally designed as cancer therapeutics, are a rational, targeted pharmacologic strategy to mitigate the devastating morbidity of Proteus syndrome. We present the five-year follow up of an 18-year-old male with Proteus syndrome treated with miransertib (MK-7075), an oral pan-AKT inhibitor. At completion of a planned 48-week phase 1 pharmacodynamic study, the individual derived sufficient benefit that the study was amended to permit continued use and assess the long-term safety of miransertib. The treatment has been well tolerated with mild treatment-attributed side effects including headache, transient hyperglycemia, and transient elevations of aspartate aminotransferase, alanine aminotransferase, and bilirubin. He has experienced sustained improvement of pain and slowed growth of bilateral plantar cerebriform connective tissue nevi. This case report supplements the data from our prior study extending those findings out to five years. It shows that at the doses used, miransertib has a favorable safety profile and durable benefit of improving symptoms of pain and slowing progression of overgrowth in Proteus syndrome in a single individual. While an uncontrolled single report cannot prove safety or efficacy, these data lend support to the encouraging preliminary data of our prior phase 1 pharmacodynamic study.

Proteus Syndrome: A Rare Case in An Adult Ward

Proteus syndrome is an extremely rare disorder that manifests as an asymmetric, disproportionate overgrowth of any connective tissue, such as bone, fat or epidermal nevi, in a mosaic or patchy pattern. It has an estimated prevalence of less than 1/1,000,000 live births. The diagnosis can be difficult because the phenotypes of the patients are variable. Many individuals develop cutaneous capillary malformation and prominent varicosities (large and complex vascular malformations). Thus, Proteus syndrome patients are at risk of developing deep vein thrombosis and pulmonary embolism. The authors present the case of a patient with Proteus syndrome who was admitted because of pulmonary thromboembolism and presented hypertrophy of the left arm and left hemithorax.