P 295. Everolimus Trial for a Patient with Bannayan–Riley–Ruvalcaba’s Syndrome and Progressive Lipomatosis

Background: Bannayan–Riley–Ruvalcaba’s syndrome (BRRS; OMIM#153480) is a rare entity with the typical symptoms of macrocephaly, lipoma, developmental delay, and pigmented macules of the glans penis in affected male individuals. BRRS is associated with germline mutations of the PTEN gene and belongs to the PTEN hamartoma tumor syndrome. The protein produced from the PTEN gene is a tumor suppressor which plays a significant role in signaling pathways (PTEN/PI3K/AKT/mTOR) important for regulation of cellular proliferation, migration, and apoptosis. Patients with BRRS commonly develop tumors and lipomatosis with infiltrative growth.

Case Report: We present a case of a male patient with macrocephaly since birth, progressive lipoma of the back since toddler, muscular hypotonia, mild ataxia of the trunk, penile freckling, and mild developmental delay. Progressive epidural lipomatosis since the age of 5 years (from the sacrum to the seventh cervical vertebrae) with compression of the dural sac, shift of the spinal cord, extension through the neuroforamina, fatty degeneration of the bone marrow, as well as extensive lipomatosis in the retroperitoneal space and autochthonous back muscles. He developed progressive scoliosis since the age of 11 years. At the age of 17 years, dorsally instrumented spondylodesis is planned due to a Cobb angle of 56 degrees. Clinical diagnosis of BRRS was confirmed by detection of a point mutation in the PTEN gene.

Question/Objective: Whether treatment with the mTOR inhibitor, everolimus can stop further progression or even result in a reduction of the lipomatosis and prevent impending complications as paraparesis, bladder, and rectal paralysis.

Methods: Individual medical trial with everolimus (target drug level of 8 µg/L). Interim result with spinal magnetic resonance imaging (MRI) before and after 5 months of therapy.

Results: After 5 months of uncomplicated therapy, the MRI showed a mild but measurable reduction of the nodular lipomatosis of the back muscles. There was no visible decline of the epidural lipomatosis.

Conclusion Epidural lipomatosis is a rare complication of BRRS. In case of impossible surgical decompression and impending serious complications, a therapeutic attempt with everolimus seems justified. We could show a reduction of the nodular intramuscular lipomatosis in the short time frame. It remains to be seen whether long-term therapy will result in a sustained effect concerning reduction of the epidural and retroperitoneal lipomatosis too.