Management Strategies of Neurofibromatosis Type 2 in Pediatric Patients : Challenges and Emerging Therapies

Abstract

Neurofibromatosis type 2 (NF2) is a rare genetic disorder caused by mutations in the NF2 tumor suppressor gene, characterized by bilateral vestibular schwannomas and other central and peripheral nervous system tumors. Pediatric patients often present with more aggressive disease, greater tumor burdens, and increased morbidity compared to adults. Management requires a multidisciplinary approach that balances tumor control with functional preservation. While surgery and radiosurgery remain key treatment options, they carry risks such as hearing loss and malignant transformation of existing tumors. Bevacizumab and emerging therapies like gene therapy show promising therapeutic effects but are limited by variability in efficacy. Comprehensive care, including psychosocial support, is essential to improve clinical outcomes and quality of life for children with NF2.

Keywords: Neoplasms; Neurofibromatosis 2; Pediatrics; Schwannoma; Therapeutics.

Fig. 1.

A 15-year-old female presented with multiple subcutaneous neurofibromas. A : Bilateral VSs were identified on MRI, and NF2 was diagnosed. B : Over the next 3 years, the VS increased in size, accompanied by a decline in hearing function. Fractionated GKRS (4 Gy×4) was performed on the left VS. C : The tumor remained stable for a period, but after 3 years, it began to regrow, resulting in the loss of left hearing function. D : The left VS was surgically resected in a subtotal fashion. E : Over the following 6 years, the left VS remained stable, but the right VS gradually increased in size. Fractionated GKRS (6 Gy×5) was performed on the right VS. F : Over the subsequent 6.5 years, five additional GKRSs were performed on multiple intracranial tumors, including the bilateral VSs. VS : vestibular schwannoma, MRI : magnetic resonance imaging, NF2 : neurofibromatosis type 2, GKRS : gamma knife radiosurgery.

Fig. 2.

A 6-year-old male first presented with left third nerve palsy. A : At the age of 12, bilateral VSs were identified on MRI, with normal hearing function. Genetic testing confirmed a diagnosis of NF2 (NM_000268.3:c.586C>T (p.Arg196Ter)). B and C : Over the next 4 years, the size of multiple cranial nerve tumors increased, including bilateral VSs and left cavernous sinus infiltrating tumors. Fractionated GKRS (5.5 Gy×4) was performed on the left VS and cavernous sinus tumors. D : For 2 years, the irradiated tumors remained stable. However, with increased tumor burden in untreated areas, bevacizumab treatment (5 to 7.5 mg/kg every 2 to 3 weeks) was initiated. E : After 1 year of bevacizumab treatment, there showed partial effects on other tumors, but no significant effect was observed on the right VS. Right hearing function declined as the size of the right VS increased. F : Fractionated GKRS (5.5 Gy×4) was performed on the right VS. G : One year later, the tumor size remained stable, and hearing function was similar to the prior evaluation. VS : vestibular schwannoma, MRI : magnetic resonance imaging, NF2 : neurofibromatosis type 2, GKRS : gamma knife radiosurgery.