Clinical features and genetic analysis of a patient with type 2 neurofibromatosis manifested as oculomotor nerve palsy / 中华医学遗传学杂志

OBJECTIVE@#To report on a rare case of Neurofibromatosis type 2 (NF2) manifesting as oculomotor nerve palsy and explore its genetic basis.@*METHODS@#A patient with NF2 who had presented at Beijing Ditan Hospital Affiliated to Capital Medical University on July 10, 2021 was selected as the study subject. Cranial and spinal cord magnetic resonance imaging (MRI) was carried out on the patient and his parents. Peripheral blood samples were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing.@*RESULTS@#MRI revealed bilateral vestibular Schwannomas, bilateral cavernous sinus meningiomas, popliteal neurogenic tumors, and multiple subcutaneous nodules in the patient. DNA sequencing revealed that he has harbored a de novo nonsense variant of the NF2 gene, namely c.757A>T, which has replaced a codon (AAG) encoding lysine (K) at position 253 with a stop codon (TAG). This has resulted in removal of the Merlin protein encoded by the NF2 gene from position 253 onwards. The variant was not found in public databases. Bioinformatic analysis suggested that the corresponding amino acid is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting+PP3+PP4).@*CONCLUSION@#The heterozygous nonsense variant c.757A>T (p.K253*) of the NF2 gene probably underlay the disease in this patient with an early onset, atypical but severe phenotype.

Percepção auditiva e desenvolvimento de linguagem oral após cirurgia de implante auditivo de tronco encefálico: uma revisão de escopo / Auditory perception and oral language in brainstem auditory implant users: a scoping review

RESUMO Objetivo mapear as evidências atuais em relação à percepção auditiva da fala e desenvolvimento de linguagem oral em usuários de implante auditivo de tronco encefálico (auditory brainstem implant - ABI), para responder à seguinte questão norteadora: "O que se sabe sobre a habilidade de percepção auditiva da fala e de linguagem oral em indivíduos usuários de implante auditivo de tronco encefálico?" Estratégia de pesquisa a busca foi realizada nas bases de dados BVSalud, PubMed e SciELO e, para literatura cinzenta, utilizou-se a fonte de informação Google Acadêmico, por meio dos descritores: implante auditivo de tronco encefálico (auditory brainstem implantation), linguagem (language), audição (hearing) e percepção auditiva (auditory perception). Critérios de seleção foram incluídos estudos nos quais foram aplicados testes para avalição da percepção auditiva ou para verificar desenvolvimento de linguagem oral em crianças e/ou adultos usuários de ABI. Foram incluídos artigos publicados nos últimos cinco anos e excluídos estudos secundários. Resultados Foram encontrados 1767 artigos nas bases de dados e fonte de informação, dos quais, 27 foram incluídos na revisão. Observou-se que a maioria dos usuários de ABI torna-se capaz de perceber alguns sons ambientais, alguns tornam-se capazes de reconhecer vocábulos, porém, poucos atingem o reconhecimento de frases. Conclusão a maioria dos usuários de ABI não avança para a habilidade de reconhecimento auditivo em conjunto aberto e há unanimidade na recomendação de métodos de comunicação visual para esses indivíduos.

ABSTRACT Purpose This scope review aims to map current evidence in relation to auditory perception of speech and oral language development in users of Auditory Brainstem Implant - ABI, to answer the following guiding question: "what do we know about the ability of auditory perception of speech and oral language in auditory brainstem implants users?" Research strategy The search was performed in the BVSalud, PubMed and SciELO databases and for gray literature the source of information Google Academic, using the descriptors: auditory brainstem implantation , language, hearing and auditory perception. Selection criteria Studies were included in which tests were applied to assess auditory perception or to verify oral language development in children and/or adults using ABI. Articles published in the last five years were included and secondary studies were excluded. Results 1767 articles were found in the databases and source of information, of which 27 studies were included. It was observed that most users of ABI become able to perceive some environmental sounds, some become able to recognize words, but few reach the recognition of sentences. Conclusion Most ABI users do not advance towards the open set auditory recognition skill and there is unanimity in recommending visual communication methods for these individuals.

Epidemiological features of meningiomas: a single Brazilian center's experience with 993 cases / Características epidemiológicas de meningiomas: experiência de um centro único brasileiro com 993 casos

ABSTRACT Background: Meningiomas are the most frequent primary central nervous system (CNS) tumors. Their geographical and ethnic characteristics need to be known, in order to enable rational treatment. Objective: To investigate clinical and epidemiological aspects in a series of patients with meningiomas. Methods: Retrospective analysis on the demographic profile, location and histopathology of 993 patients with meningiomas (768 operated and 225 not operated). Results: Meningiomas represented 43.8% of the primary CNS tumors; 6.8% were multiple tumors (14.7% with neurofibromatosis 2) and 0.6% were radiation-induced tumors. The mean ages were 53.0 and 63.9 years for operated and non-operated patients and the female/male ratios were 3.2:1 and 6.3:1. Diagnosis was made later among females. The peak incidences were in the 6th and 7th decades respectively for operated and non-operated patients. The incidence was low at early ages and higher among patients aged 70+ years. The meningiomas were intracranial in 96.5% and most were WHO grade I (88.9%) and transitional. In the spinal canal (3.5%), they occurred mainly in the dorsal region (all grade I; mostly transitional). The racial distribution was 1.0% in Asian-Brazilians, 87% in Caucasians and 12% in African-Brazilians. 83.4% and 51.6% of the patients were estimated to be recurrence-free at 10 and 20 years, and the mortality rate was 3%. Conclusions: Most of the demographic data were similar to what has been observed in other western centers. Differences were higher incidence of meningiomas, female and older predominance in non-operated patients, predominance in Caucasian, and higher association with neurofibromatosis 2.

RESUMO Antecedentes: Meningiomas são os tumores mais frequentes do sistema nervoso central (SNC). Suas características étnicas e geográficas precisam ser conhecidas para o seu tratamento racional. Objetivo: Investigar aspectos clínicos e epidemiológicos de uma série de pacientes com meningiomas. Métodos: Análise retrospectiva demográfica de 993 pacientes com meningiomas (768 operados e 225 tratados conservadoramente) Resultados: Meningiomas constituíram 43.8% dos tumores primários do SNC. 0.8% deles eram múltiplos (14,7% com neurofibromatose 2) e 0,6% eram radioinduzidos. A idade média e o índice mulheres/homens foram respectivamente 53,0 e 63,9 anos e 3.2:1 e 6.3:1 para pacientes operados e não operados. O diagnóstico foi mais tardio em mulheres. Ocorreram picos de incidências na 6ª e na 7ª décadas respectivamente para pacientes operados e não operados. A incidência foi menor na infância e maior após 70 anos. Meningiomas predominaram no crânio (96.5%), a maioria grau I da OMS, subtipo transicional. Do total, 3.5% ocorreram no canal raquídeo, principalmente na região torácica, todos grau I, a maioria transicional. Em relação à distribuição racial, 1.0% dos meningiomas ocorreu em amarelos, 87% em brancos e 12% em negros. As taxas de sobrevida sem recorrência foram 83.4% e 51.6% em 10 e 20 anos e a mortalidade operatória foi 3%. Conclusões: A maioria dos dados demográficos observados foi similar aos de outros centros ocidentais. As diferenças observadas foram maior incidência, predominância em mulheres e idosos nos pacientes não operados e em caucasianos, e maior associação com neurofibromatose 2.

Síndrome de pseudo-Duane secundario a Schwannoma de nervio abducens: Reporte de caso y revisión / Pseudo-Duane syndrome secondary to abducens nerve schwannoma: Case report and review

Reporte de caso de síndrome de pseudo-Duane asociado a schwannoma de nervio abducens y neurofibromatosis tipo 2 (NF2). Este síndrome es raro, caracterizado por limitación en abducción, retracción ocular, disminución de hendidura palpebral en abducción y restricción del recto medial ipsilateral en test de ducción forzada. La NF2 es también una enfermedad infrecuente caracterizada por tumores de sistema nervioso central y periférico. Los schwannomas de nervio abducens son también poco frecuentes, y se presentan comúnmente con diplopia. Se revisan brevemente estas enfermedades. Es el primer caso reportado de pseudo-Duane secundario a schwannoma de nervio abducens y NF2 según nuestro conocimiento.

A pseudo-Duane syndrome case associated with abducens nerve schwannoma and neurofibromatosis type 2 (NF2) is presented. This syndrome is a rare disease characterised by abduction limitation, ocular retraction, narrowing of the palpebral fissure in abduction, and ipsilateral medial rectus restriction on forced duction test. NF2 is also an uncommon disease which is characterised by peripheral and central nervous system tumours. Abducens nerve schwannomas are also uncommon and presents usually as diplopia. A short review of these diseases is given. This is the first case of pseudo-Duane secondary to abducens nerve schwannoma, to our knowledge.

Neurofibromatosis tipo 2, entidad a tener presente durante la práctica clínica / Neurofibromatosis type 2, entity to have present during clinical practice

La neurofibromatosis tipo 2 es un trastorno poco frecuente, que pertenece al grupo de las neurofibromatosis, que se caracterizan por la mayor propensión al desarrollo de tumores. Se presenta con múltiples tumores no malignos del sistema nervioso, incluidos schwannomas, meningiomas, ependimomas y gliomas, siendo los schwannomas vestibulares bilaterales una característica clásica. La mayoría de los casos se diagnostican en la adultez, sin embargo, las características clínicas habitualmente están presentes durante muchos años antes del diagnóstico. Es importante un alto índice de sospecha y un adecuado examen cutáneo y neurológico, ya que es crítico para hacer un diagnóstico correcto y precoz, y así, realizar un tratamiento interdisciplinario adecuado, evitando posibles complicaciones como son la pérdida auditiva y el uso de ayudas técnicas.

Neurofibromatosis type 2 is a rare disorder, belonging to the group of neurofibromatosis, which are characterized by the propensity for tumor development. The usual presentation are multiple non-malignant tumors of the nervous system, including schwannomas, meningiomas, ependymomas, and gliomas, with bilateral vestibular schwannomas being a classic feature. Most cases are diagnosed in adulthood; however, the clinical features are usually present for many years before diagnosis. A high index of suspicion and an adequate skin and neurological examination are important, since it is critical to make a correct and early diagnosis, so an appropriate interdisciplinary treatment can be performed, avoiding possible complications such as hearing loss and use of technical aids.

Neurofibromatosis tipos 1 y 2 / Neurofibromatosis type 1 and 2

La neurofibromatosis (NF) comprende un grupo de enfermedades genéticas de herencia autosómica dominante, que se clasifican de la siguiente manera: neurofibromatosis tipo 1 (NF1), neurofibromatosis tipo 2 (NF2) y schwannomatosis (también conocida como neurofibromatosis tipo 3). Esta última es una enfermedad muy infrecuente, con una prevalencia aproximada de 1/126 000 personas, por lo que solo profundizaremos las dos primeras. La NF1, también conocida como la enfermedad de Von Recklinghausen, es la más frecuente de las tres y afecta principalmente la piel y el sistema nervioso periférico. Se caracteriza por la presencia de máculas "café con leche", pecas axilares o inguinales, nódulos de Lisch (hamartomas en el iris) y neurofibromas (tumores de la vaina de nervios periféricos). Otras manifestaciones menos frecuentes, aunque de mayor gravedad, incluyen gliomas del nervio óptico, meningiomas, neurofibromas malignos, escoliosis y displasia de la tibia. Su diagnóstico se suele realizar al nacimiento o durante los primeros años de vida, y se estima que un 50% de quienes la padecen presenta dificultades cognitivas. No hay datos concluyentes sobre la mortalidad en los pacientes con NF1, aunque se sabe que la expectativa de vida es menor que en la población general. La NF2 tiene una prevalencia considerablemente menor que la NF1 y su inicio es más tardío, afectando principalmente a adultos jóvenes. La presentación clínica típica se caracteriza por acúfenos, hipoacusia y ataxia en contexto de la presencia de schwannomas vestibulares bilaterales. Otros hallazgos menos frecuentes incluyen schwannomas de nervios periféricos, meningiomas, ependimomas o astrocitomas. La esperanza de vida es de unos 36 años, con una supervivencia media desde el momento del diagnóstico de 15 años. (AU)

Neurofibromatosis (NF) includes a group of genetic diseases with an autosomal-dominant inheritance pattern, and they are classified as follows: Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and Schwannomatosis (also known as neurofibromatosis type 3). This last one is a very rare disease, with an approximate prevalence of 1/126000, so we will only deepen in the first two. NF1, also known as von Recklinghausen disease, is the most frequent, and mainly affects the skin and peripheral nervous system. Its typical manifestations are the presence of café-au-lait macules, axillary or inguinal freckles, Lisch nodules (hamartomas in the iris) and neurofibromas (peripheral nerve sheath tumors). Less frequent manifestations, although more serious, include optic nerve gliomas, meningiomas, malignant neurofibromas, scoliosis and tibial dysplasia. The diagnosis is usually made at birth or during the first years of life, and approximately 50% of patients present cognitive difficulties. There is no conclusive data on mortality in patients with NF1, although it is known that life expectancy is lower than in general population. NF2 has a considerably lower prevalence than NF1, and its onset is later in life, mainly affecting young adults. Its typical clinical presentation is characterized by tinnitus, hearing loss and ataxia in the context in the presence of bilateral vestibular schwannomas. Less frequent findings include peripheral nerve schwannomas, meningiomas, ependymomas or astrocytomas. Life expectancy is about 36 years old, with a median survival from the moment of diagnosis of 15 years. (AU)

Expression of NF2 Modulates the Progression of BRAFV600E Mutated Thyroid Cancer Cells

BACKGROUND: We previously reported the frequent neurofibromatosis 2 (NF2) gene mutations in anaplastic thyroid cancers in association with the BRAF V600E mutation. We aimed to investigate the role of NF2 in thyroid cancer with BRAF mutation. METHODS: To identify the function of NF2 in thyroid cancers, we investigated the changes in cell proliferation, colon formation, migration and invasion of thyroid cancer cells (8505C, BHT101, and KTC-1) with BRAF V600E mutation after overexpression and knock-down of NF2. We also examined how cell proliferation changed when NF2 was mutagenized. Human NF2 expression in papillary thyroid carcinoma (PTC) was analyzed using the The Cancer Genome Atlas (TCGA) data. RESULTS: First, NF2 was overexpressed in 8505C and KTC-1 cells. Compared to control, NF2 overexpressed group of both thyroid cancer cells showed significant inhibition in cell proliferation and colony formation. These results were also confirmed by cell migration and invasion assay. After knock-down of NF2 in 8505C cells, there were no significant changes in cell proliferation and colony formation, compared with the control group. However, after mutagenized S288* and Q470* sites of NF2 gene, the cell proliferation increased compared to NF2 overexpression group. In the analysis of TCGA data, the mRNA expression of NF2 was significantly decreased in PTCs with lateral cervical lymph node (LN) metastasis compared with PTCs without LN metastasis. CONCLUSION: Our study suggests that NF2 might play a role as a tumor suppressor in thyroid cancer with BRAF mutation. More studies are needed to elucidate the mechanism how NF2 acts in thyroid cancer with BRAF mutation.

Concomitant Occurrence of Vestibular Schwannoma and Epidermoid Cyst in Neurofibromatosis: Case description and Review of the Literature

We report a case of a 16-year-old female patient harboring neurofibromatosis type 2 who presented with bilateral hearing impairment, which was on the left side, as well as facial paresis (House-Brackmann grade III) and ataxic gait. A magnetic resonance imaging (MRI) exam evidenced bilateral lesions in the cerebellopontine angles (CPAs) with extension into the internal acoustic meatus, and an additional lesion in the right CPA with radiological characteristics of an epidermoid cyst. The patient was submitted to microsurgical resection, confirming a collision of a vestibular schwannoma and an epidermoid cyst in the right CPA. In the present case report, we describe the first case reported in the literature with preoperative diagnostic work-up, intraoperative findings, postoperative course of the patient, as well as a detailed literature review of these specific coinciding pathologies, denoting the importance of further genomic studies regarding multiple central nervous system (CNS) lesions.

Relatamos o caso de uma paciente de 16 anos de idade com neurofibromatose tipo II com deficiência auditiva bilateral, pior no ouvido esquerdo, assim como paresia facial (HouseBrackmann grau III) e ataxia. Estudo de ressonância magnética comprovou lesão bilateral nos ângulos cerebelopontinos (ACPs) com extensão ao meato acústico interno, e uma lesão adicional no ACP direito com características radiológicas de um cisto epidermoide. A paciente foi submetida a ressecção microcirúrgica, confirmando a colisão de um schwannoma vestibular com um cisto epidermoide no ACP direito. No presente estudo, descrevemos o primeiro caso relatado na literatura com trabalho diagnóstico pré-operatório, resultados intraoperatórios, evolução da paciente no pós-operatório, assim como revisão detalhada da literatura específica sobre essas patologias, demonstrando a importância de mais estudos genômicos sobre as múltiplas lesões do sistema nervoso central (SNC).

Cervicomedullary Junction Ependymoma Associated with Neurofibromatosis Type II: Case Report and Literature Review

Neurofibromatosis type II (NF2) is a rare autosomal dominant inherited disease caused by a mutation in chromosome 22q12 and associated with multiple central nervous system tumors. In this paper, we describe a rare case of cervicomedullary junction ependymoma associated with NF2 in a 25-year-old man who underwent surgical treatment with total resection and had a good clinical outcome. We discussed the nuances of the surgical resection and the literature concerning this rare form of presentation of NF2.

Neurofibromatose tipo II (NF2) é uma doença autossômica dominante provocada por uma mutação no cromossomo 22q12, e que está relacionada ao surgimento de múltiplos tumores do sistema nervoso central. Neste artigo, é descrito um caso raro de um paciente com 25 anos de idade submetido ao tratamento cirúrgico de um ependimoma da junção cervicobulbar, com ressecção total "en bloc" e bom resultado clínico. Discutimos as nuances da ressecção cirúrgica, bem como a literatura sobre o tratamento destas lesões raras.

Genetic and clinical characteristics of Korean patients with neurofibromatosis type 2

PURPOSE: Neurofibromatosis type 2 (NF2) is characterized by multiple tumors, including vestibular schwannoma (VS) and others affecting cranial and peripheral nerves. NF2 is caused by mutation of the NF2 gene. The mutation spectrum of NF2 has not been characterized in Korean patients. In the current study, the clinical and genetic characteristics of Korean NF2 patients were analyzed. MATERIALS AND METHODS: Twenty-five unrelated Korean families were enrolled according to the Manchester criteria. Genetic analysis was performed by direct sequencing and multiplex ligation-dependent probe amplification methods using genomic DNA from peripheral lymphocytes or tumor tissues. RESULTS: All patients had bilateral/unilateral VS and/or other cranial and peripheral nerve tumors. Two patients were familial cases and the other 24 patients were sporadic. Germline NF2 mutations were detected in peripheral lymphocytes from both familial cases, but only in 26.1% of the 23 sporadic families. Somatic mutations were also found in tumor tissues from two of the sporadic families. These somatic mutations were not found in peripheral lymphocytes. A total of 10 different mutations including 2 novel mutations were found in 40.0% of studied families. Five mutations (50.0%) were located in exon 6 of NF2, the FERM domain coding region. CONCLUSION: Family history was an important factor in identifying germline NF2 mutations. Further study is required to investigate whether exon 6 is a mutation hotspot in Korean NF2 patients and its correlation to phenotypic severity.

Recurred Segmental Schwannomatosis Without Neurofibromatosis Type 2

Schwannomas are the most common type of benign peripheral nerve sheath tumors. They typically present as a solitary lesion, but multiple schwannomas rarely occur in patients with neurofibromatosis type 2 (NF2), or patients without the other hallmarks of NF2. The latter is termed schwannomatosis. They most commonly occur in the head and neck involving the brachial plexus and spinal nerves. Although rarely found in the extremities, when these masses occur peripherally, they most commonly affect the sciatic, ulnar, and tibial nerve. It is reported that 2.4% to 5% of all patients undergoing schwannoma excision present as schwannomatosis. One-third of patients with schwannomatosis show tumors limited to a single extremity or segment of the spine and it is referred to as segmental schwannomatosis. We report a case of recurred segmental schwannomatosis of the posterior tibial nerve without features of NF2 after schwannoma excision.

Hearing Restoration in Neurofibromatosis Type II Patients

Patients with neurofibromatosis type II will eventually succumb to bilateral deafness. For patients with hearing loss, modern medical science technology can provide efficient hearing restoration through a number of various methods. In this article, several hearing restoration methods for patients with neurofibromatosis type II are introduced.

Treatment research progress on the treatment of neurofibromatosis type 2-associated vestibular schwannoma / 临床耳鼻咽喉头颈外科杂志

Neurofibromatosis type 2 (NF2) is a dominantly inherited genetic condition. Bilateral vestibular schwannoma, which are benign tumors, composed of neoplastic Schwann cells that arise from the eighth cranial nerve, are the hallmark of NF2. Standard approaches for treatment of growing vestibular schwannoma include observation, surgical removal and radiation therapy. Molecular targeted therapies also present great prosperity in recent years. In this review, we summarize the latest progresses on the treatment of NF2-associated vestibular schwannoma.

Multiple Schwannomas of the Spine: Review of the Schwannomatosis or Congenital Neurilemmomatosis: A Case Report

Schwannomas are the most common benign nerve sheath tumors originating in Schwann cells. With special conditions like neurofibromatosis type 2 or entity called schwannomatosis, patients develop multiple schwannomas. But in clinical setting, distinguishing schwannomatosis from neurofibromatosis type 2 is challengeable. We describe 58-year-old male who presented with severe neuropathic pain, from schwannomatosis featuring multiple schwannomas of spine and trunk, and underwent surgical treatment. We demonstrate his radiologic and clinical findings, and discuss about important clinical features of this condition. To confirm schwannomatosis, we performed brain magnetic resonance imaging, and took his familial history. Staged surgery was done for pathological confirmation and relief of the pain. Schwannomatosis and neurofibromatosis type 2 are similar but different disease. There are diagnostic hallmarks of these conditions, including familial history, pathology, and brain imaging. Because of different prognosis, the two diseases must be distinguished, so diagnostic tests that are mentioned above should be performed in caution.

A Case of Cochlear Implantation in Neurofibromatosis Type II / 대한이비인후과학회지

Patients with neurofibromatosis type 2 (NF2) develop bilateral vestibular schwannomas that can cause binaural progressive hearing loss in most individuals. Auditory rehabilitation for bilateral profound sensorineural hearing loss in patients with NF2 poses a great therapeutic challenge. An auditory brainstem implantation may be an option after tumor excision, but its hearing results are still relatively unsatisfactory. A cochlear implantation (CI) may be another option in those cases where the cochlear nerve has been left intact after tumor excision or in those cases that have been kept stable after treating with Gamma-Knife. Here we report a case of undergoing CI after having been treated with Gamma-Knife in NF2 and showing improved open-set speech perception.

Spectral-domain Optical Coherence Tomography of Combined Hamartoma of the Retina and Retinal Pigment Epithelium in Neurofibromatosis

A 5-year-old girl was diagnosed with neurofibromatosis type 2 (NF-2) due to multiple neurofibromas, cafe-au-lait spots, and schwannomas of the brain. During ophthalmologic evaluation, a posterior subcapsular cataract and a gray-green colored subretinal lesion were found in right eye. Fluorescein angiography (FA) revealed a combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). At age 9, she underwent cataract surgery. At this time FA and spectral-domain optical coherence tomography (SD-OCT) were taken. The SD-OCT showed an elevated hyperreflective mass in the retina with prominent attenuation of the inner and outer retina, but minimal attenuation in the photoreceptor layers. The underlying retina appeared to be disorganized and thick (791 microm). This is the first case report of SD-OCT imaging of a CHRRPE associated with NF-2 in a pediatric patient. By using SD-OCT in this patient, we could obtain detailed tumor characteristics, and SD-OCT may be helpful in the diagnosis and management of CHRRPE.

Merlina y nuevos tratamientos de schwannomas vestibulares en pacientes con neurofibromatosis tipo 2 / Merlin and new treatments for vestibular schwannomas in patients with Neurofibromatosis type 2

Los schwannomas vestibulares son tumores benignos que habitualmente se presentan en forma esporádica y unilateral, pero pueden aparecer de manera bilateral en el contexto de una neurofibromatosis tipo 2 (NF2). En aquellos asociados a NF2 se han identificado mutaciones del gen NF2 que codifica para merlina, una proteína citoplasmática que se localiza primariamente en protrusiones celulares ricas en actina, y en sitios de contacto entre células y matriz extracelular. La evidencia sugiere que merlina ejerce un rol como proteína supresora de tumores ya que regula la cascada de activación de diversos tipos de receptores de factores de crecimiento celular De esta manera, el déficit de merlina provoca un patrón de proliferación celular aumentado, alteraciones del citoesqueleto, apoptosis disminuida, y un incremento de la adhesión a la matriz extracelular. Se han desarrollado terapias clínicas para la NF2 con anticuerpos monoclonales e inhibidores dirigidos contra distintas moléculas involucradas en las cascadas de señalización celular moduladas por merlina. En este artículo se revisan y discuten los mecanismos celulares dependientes de merlina y los diversos estudios clínicos y experimentales que se han probado en pacientes con NF2.

Vestibular schwannomas are benign tumors that may occur bilaterally in the context of neurofibromatosis type 2 (NF2). A mutation in the NF2 gene coding for merlin protein has been identified in those cases associated with NF2. Merlin is a cytoplasmic protein localized in actin rich cell protrusions, and near contact sites between cells and extracellular matrix. The evidence suggests that merlin plays a role as tumor suppressor protein, regulating the activation cascade of different types of receptors for cell growth factors. Thus, merlin deficiency causes a pattern of increased cell proliferation, cytoskeletal alterations, decreased apoptosis and increased cell adhesion to the extracellular matrix. Several clinical therapies have been developed for NF2 patients including monoclonal antibodies and inhibitors directed against different molecules involved in cell signaling cascades modulated by merlin. In this article we review and discuss cellular mechanisms dependent of merlin and some clinical and experimental studies that have been studied in patients with NF2.

Uncommon Ocular Manifestations of Neurofibromatosis: Case Report and Review

PURPOSE: To report and review several cases of uncommon ocular manifestations in neurofibromatosis patients. CASE SUMMARY: A 19-year-old woman diagnosed with type 2 neurofibromatosis visited our hospital with amblyopia of the right eye and mild visual disturbance of the left eye. Best corrected visual acuity was 20/250 in the right eye, 20/25 in the left eye and relative afferent pupillary defect in the right eye was observed. Fundus examination of both eyes showed papilledema. Magnetic resonance imaging showed schwannoma from the optic nerve to the optic chiasm. A 28-year-old woman diagnosed with type 2 neurofibromatosis visited our hospital with amblyopia of the right eye. Best corrected visual acuity was finger count in the right eye, 20/20 in the left eye and relative afferent pupillary defect in the right eye was observed. Fundus examination of the right eye showed a slightly elevated lesion at the macula, as well as dragged optic disc and retinal vessels to the macula. An 8-year-old girl diagnosed with type 1 neurofibromatosis visited our hospital with enophthalmos and strabismus of the left eye. On exophthalmometry, enophthalmos in the left eye was found; measurements were 15.0 mm in the right eye and 13.0 mm in the left eye. Three-dimensional computed tomography revealed sphenoidal hypoplasia and a left lateral orbital wall defect. CONCLUSIONS: The authors of the present study report on neurofibromatosis patients who had an uncommon ocular manifestation. Neurofibromatosis can represent various ocular manifestations but reports of compressive optic neuropathy, dragged disc syndrome and sphenoidal hypoplasia are rare.