Neurofibromatosis Type 2

Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder (incidence 1:33 000-40 000) characterized by formation of central nervous system tumors, due to mutation in the NF2 gene on chromosome 22q12. Vestibular schwannomas are the hallmark lesion, affecting 95% of individuals and typically occur bilaterally. Schwannomas commonly occur on other nerves intracranially and in the spinal compartment, along with meningiomas, ependymomas, and gliomas. Although histologically benign, tumors are associated with significant morbidity due to multiple problems including hearing and vision loss, gait abnormalities, paralysis, pain, and seizures. Risk of early mortality from brainstem compression and other complications is significant. Severity of disease is higher when NF2 presents during childhood. Children have a more variable presentation, which can be associated with significant delays in recognition of the condition. Careful examination of the skin and eyes can identify important clinical signs of NF2 during childhood, allowing timely initiation of disease-specific surveillance and treatment. Monitoring for complications comprises clinical evaluation, along with functional testing including audiology and serial neuroimaging, which together inform decisions regarding treatment. Evidence for disease-specific medical treatment options is increasing, nevertheless most patients will benefit from multimodal treatment including surgery during their lifetime. Patient enrolment in international natural history and treatment trials offers the best opportunity to accelerate our understanding of the complications and optimal treatment of NF2, with a view to improving outcomes for all affected individuals.

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Radiation-induced rhabdomyosarcoma of the brainstem in a patient with neurofibromatosis Type 2

Journal of Neurosurgery ◽

10.3171/2009.6.jns09105 ◽

2010 ◽

Vol 112 (1) ◽

pp. 81-87 ◽

Cited By ~ 29

Author(s):

Matthew L. Carlson ◽

Dusica Babovic-Vuksanovic ◽

Ludwine Messiaen ◽

Bernd W. Scheithauer ◽

Brian A. Neff ◽

...

Keyword(s):

Tumor Suppressor ◽

Stereotactic Radiosurgery ◽

Tumor Suppressor Gene ◽

Neurofibromatosis Type ◽

Suppressor Gene ◽

Neurofibromatosis Type 2 ◽

Benign Tumors ◽

Autosomal Dominant Disorder ◽

Peripheral Nerve Sheath Tumors

Neurofibromatosis Type 2 (NF2) is a rare autosomal dominant disorder characterized by the development of benign tumors of the peripheral nervous system and the CNS, including schwannomas, meningiomas, and ependymomas. The gene responsible for the development of NF2 acts as a tumor suppressor gene. Stereotactic radiotherapy (SRT) or single-fraction stereotactic radiosurgery has been increasingly used in the past decades to treat benign tumors in patients with NF2. These radiotherapy methods are less invasive and can be potentially used to treat multiple tumors in a single session. The risk of inducing malignancy is unclear. Few reports exist of malignant peripheral nerve sheath tumors, meningiomas, or ependymomas occurring after SRT or stereotactic radiosurgery in patients with NF2. The authors present the first documented case of rhabdomyosarcoma following SRT for multiple NF2-associated schwannomas. Compared with patients with sporadic tumors, NF2 patients having a germline tumor suppressor gene defect may be more prone to secondary malignancies after treatment involving radiation therapy.

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Gamma Knife radiosurgery for meningiomas in patients with neurofibromatosis Type 2

Journal of Neurosurgery ◽

10.3171/2014.10.jns132593 ◽

2015 ◽

Vol 122 (3) ◽

pp. 536-542 ◽

Cited By ~ 12

Author(s):

Ann Liu ◽

Elizabeth N. Kuhn ◽

John T. Lucas ◽

Adrian W. Laxton ◽

Stephen B. Tatter ◽

...

Keyword(s):

Treatment Failure ◽

Malignant Transformation ◽

Gamma Knife ◽

Gamma Knife Radiosurgery ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

Benign Tumors ◽

Distant Failure

OBJECT Neurofibromatosis Type 2 (NF2) is a rare autosomal dominant disorder predisposing patients to meningiomatosis. The role of stereotactic radiosurgery (SRS) is poorly defined in NF2, and although the procedure has excellent control rates in the non-NF2 population, its utility has been questioned because radiation has been hypothesized to predispose patients to malignant transformation of benign tumors. To the authors' knowledge, this is the first study to examine the use of SRS specifically for meningiomas in patients with NF2. METHODS The authors searched a tumor registry for all patients with NF2 who had undergone Gamma Knife radiosurgery (GKRS) for meningioma in the period from January 1, 1999, to September 19, 2013, at a single tertiary care cancer center. Medical records were retrospectively reviewed for patient and tumor characteristics and outcomes. Results Among the 12 patients who met the search criteria, 125 meningiomas were identified, 87 (70%) of which were symptomatic or progressive and thus treated with GKRS. The median age at the first GKRS was 31 years (interquartile range [IQR] 27–37 years). Five patients (42%) had multiple treatments with a median of 27 months (IQR 14–50 months) until the subsequent GKRS. The median follow-up in surviving patients was 43 months (IQR 34–110 months). The 5-year local tumor control and distant treatment failure rates were 92% and 77%, respectively. Toxicities occurred in 25% of the GKRS treatments, although the majority were Grade 1 or 2. At the last follow-up, 4 patients (33%) had died a neurological death at a median age of 39 years (IQR 37–46 years), and their cases accounted for 45% of all tumors, 55% of all treated tumors, and 58% of all GKRSs. Univariate analysis revealed several predictive variables for distant failure, including male sex (HR 0.28, 95% CI 0.086–0.92, p = 0.036), age at distant failure (HR 0.92, 95% CI 0.90–0.95, p < 0.0001), and prior number of GKRS treatments (HR 1.2, 95% CI 1.1–1.4, p = 0.0049). Local failure, maximum size of the treated tumor, delivered tumor margin dose, and WHO grade were not significant. On multivariate analysis, age at distant failure (HR 0.91, 95% CI 0.88–0.95, p < 0.0001) and prior number of GKRSs (HR 1.3, 95% CI 1.1–1.5, p = 0.004) remained significant. No malignant transformation events among treated tumors were observed. CONCLUSIONS Radiosurgery represents a feasible modality with minimal toxicity for NF2-associated meningiomas. Increasing patient age was associated with a decreased rate of distant failure, whereas an increasing number of prior GKRS treatments predicted distant failure. Further studies are necessary to determine the long-term patterns of treatment failure in these patients.

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New Developments in Neurofibromatosis Type 2 and Vestibular Schwannoma

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa153 ◽

2020 ◽

Author(s):

Yin Ren ◽

Divya A Chari ◽

Sasa Vasilijic ◽

D Bradley Welling ◽

Konstantina M Stankovic

Keyword(s):

Treatment Options ◽

Neurofibromatosis Type ◽

Suppressor Gene ◽

Severe Form ◽

Neurofibromatosis Type 2 ◽

Future Research ◽

Autosomal Dominant Disorder ◽

Management Options ◽

Stereotactic Radiation

Abstract Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder characterized by the development of multiple nervous system tumors due to mutation in the NF2 tumor suppressor gene. The hallmark feature of the NF2 syndrome is the development of bilateral vestibular schwannomas (VS). Although there is nearly 100% penetrance by 60 years of age, some patients suffer from a severe form of the disease and develop multiple tumors at an early age, while others are asymptomatic until later in life. Management options for VS include surgery, stereotactic radiation, and observation with serial imaging; however, currently there are no FDA-approved pharmacotherapies for NF2 or VS. Recent advancements in the molecular biology underlying NF2 have led to a better understanding of the etiology and pathogenesis of VS. These novel signaling pathways may be used to identify targeted therapies for these tumors. This review discusses the clinical features and treatment options for sporadic- and NF2-associated VS, the diagnostic and screening criteria, completed and ongoing clinical trials, quality of life metrics, and opportunities for future research.

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Neurofibromatosis Type 2: A Pandora’s Box of Variable Presentations

Indian Journal of Neurosurgery ◽

10.1055/s-0041-1722832 ◽

2021 ◽

Author(s):

Ashok Gandhi ◽

Swarup Sohan Gandhi ◽

Surendra Jain ◽

Shashikant Jain ◽

Paresh Sukhani

Keyword(s):

Nervous System ◽

Incidental Finding ◽

Significant Proportion ◽

Young Patients ◽

Neurofibromatosis Type ◽

Suppressor Gene ◽

Neurofibromatosis Type 2 ◽

Spinal Tumors ◽

Benign Tumors

Abstract Introduction Neurofibromatosis type 2 (NF2) also known as MISME syndrome stands for multiple inherited schwannomas, meningiomas, and ependymomas in the peripheral and central nervous system. It is a rare disorder of autosomal dominant inheritance due to mutations of a tumor-suppressor gene on the chromosome 22q12. Clinically, it is characterized by multiple benign tumors arising in both the central and peripheral nervous system, particularly from the bilateral vestibular nerve, in more than 90% of the patients, with more than two thirds of them developing spinal tumors. Materials and Methods Here, we studied the variable presentations of cases of NF2, and thorough evaluation of patients was done by contrast MRI of brain and spine. Also, evaluation of ocular manifestations and cutaneous features was done in cases of NF2, and a follow-up was done for a period of 18 months with monitoring of cranial and spinal lesions. Conclusion We studied the various presentations of NF2 and found that a significant proportion of the patients presented with nonvestibular tumors as the initial presentation, with bilateral cerebellopontine angle lesions being an incidental finding; also, the age of presentation in half of the patients was less than 30 years, and so we can conclude that in young patients with spinal tumors or multiple meningiomas, a thorough evaluation regarding family history and various features of NF2 should be done, so that early identification of the disease could be done and patients can be benefitted from timely interventions.

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