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Abstract: SA-PO526

Late-Onset Schwannomatosis in Two Unrelated Patients With Peripheral Neuropathy and Focal Segmental Glomerulosclerosis due to INF2 Mutations

Session Information

  • Genetic Diseases: Diagnosis
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic


  • Tran, Linh Nguyen Truc, Kansai Ika Daigaku Fuzoku Hirakata Byoin, Hirakata, Osaka, Japan
  • Tran Thuy, Huong Quynh, Kansai Ika Daigaku Fuzoku Hirakata Byoin, Hirakata, Osaka, Japan
  • Sato, Yoshinori, Showa Daigaku Fujigaoka Byoin, Yokohama, Kanagawa, Japan
  • Tsukaguchi, Hiroyasu, Kansai Ika Daigaku Fuzoku Hirakata Byoin, Hirakata, Osaka, Japan

INF2, a member of actin assembly factor formin, is implicated in fundamental biological processes, including maintenance of cell shape, polarity, and migration. Mutations in the extreme N-terminus of INF2 cause peripheral neuropathy of Charcot-Marie-Tooth (CMT) type, in addition to focal segmental glomerulosclerosis (FSGS). These two disorders are likely ascribed to progressive degeneration through actin dysregulation in podocytes and Schwann cells. Here we report two unrelated patients with CMT and FSGS due to INF2 mutations manifested schwannomatosis in later clinical course.

Case Description

Case 1 A 12-year female has a heterozygous INF2 p.G73D variant and had difficulty in walking since childhood, first noticed proteinuria. She showed steppage gait with asymmetric atrophy and weakness in the lower limb muscles and hearing disability. Pes cavus deformity was surgically corrected at age 11. At age 14, she developed nephrotic syndrome diagnosed as FSGS. The renal disease was resistant to steroids and progressed into ESRD at age 16. At around age 30, she noticed multiple subcutaneous nodules. A spinal MRI revealed schwannomatosis in the caudal nerves.
Case 2 A 10-year boy has a heterozygous INF2 p.V108D variant, first noticed walking disability, developed nephrotic syndrome with FSGS at age 14 and progression to ESRD at age 17. Since age around 20, he noticed subcutaneous nodules in his neck, spine, pelvic cavity, and left lower extremity. Biopsy of peroneal nerve revealed degeneration in large myelinated fibers with onion bulb formation. A spine MRI revealed schwannomatosis in the caudal nerves. Histology of biopsied cervical tumors at age 29 revealed schwannomas with a biphasic pattern of mixed hypercellular (Antoni A) and hypocellular (Antoni B) components.


This report first demonstrated, to our knowledge, multi-focal schwanomatosis development of peripheral neurons in later course of two CMT/FSGS cases with the INF2 mutations. Our observations shed a light on previously underrecognized, proliferative natures of INF2 mutations, thereby broadening a phenotypic spectrum of CMT/FSGS mutation that typically leads to cell degeneration. Further study is necessary to clarify the cellular mechanisms by which the CMT/FSGS type INF2 mutations could accelerate the proliferation in Schwann cells.