Neurofibromatosis laríngea pediátrica: reporte de localización atípica / Pediatric neurofibromatosis of the larynx: report of atypical location

Los neurofibromas laríngeos (NFL) son tumores benignos poco frecuentes de localización principalmente supraglótica. Se manifiestan con síntomas obstructivos de la vía aérea. El tratamiento es la resección completa del tumor mediante abordaje endoscópico; se reserva la cirugía abierta para tumores de gran extensión. Se presenta el caso de un paciente pediátrico con localización atípica de NFL asociado a neurofibromatosis tipo 1 (NF1). Se realizó resección endoscópica del tumor y la anatomía patológica informó neurofibroma plexiforme. Es importante sospechar de esta patología en todo niño con estridor inspiratorio atípico progresivo. Se sugiere seguimiento a largo plazo por la alta probabilidad de recidiva.

Laryngeal neurofibromas (LNFs) are rare benign tumors mainly located in the supraglottis. LNFs occur with airway obstruction symptoms. The treatment is complete resection via an endoscopic technique; the open approach is reserved for large tumors. Here we describe the case of a pediatric patient with LNF of atypical location associated with neurofibromatosis type 1 (NF-1). The tumor was resected with an endoscopic technique, and the pathological study reported a plexiform neurofibroma. It is important to suspect this condition in any child with atypical, progressive inspiratory stridor. Long-term follow-up is recommended due to the high rate of recurrence

Neurofibromatosis tipo 1. Más allá de las manchas café con leche: ¿es necesario actualizar criterios? / Neurofibromatosis type 1. Beyond to café-au-lait spots: necessary update criteria?

Neurofibromatosis type 1 (NF1) is the most common neurocutaneous syndrome. Diagnosis is based on clinical findings that meets the criteria developed by the NIH in 1997, which remain highly sensitive and specific in adults, but not in children, in which the manifestations vary with age. In children under 2 years in the pretumoral stage with a negative family history, it would be useful to have additional clinical diagnostic criteria. Genetic testing is not widely available and although café-au-lait spots remain the cardinal and most frequent clinical sign, they cannot make the diagnosis of NF-1 on their own. (AU)

Neurofibromatosis segmentaria / Segmental neurofibromatosis

RESUMEN Presentamos un caso de neurofibromatosis segmentaria, en un paciente de sexo masculino de 60 años de edad. Los neurofibromas se localizaban en región cervical, los mismos eran asintomáticos, de 8 años de evolución.

ABSTRACT A case of segmental neurofibromatosis in a 60 years old male patient is presented along with a brief review of the literature. The patient had 8 years old neurofibromas, located in the cervical region; they were asymptomatic. No other alteration of type 1 neurofibromatosis was found.

Antiphospholipid syndrome and neurofibromatosis type I: a coincidence or new association? / Síndrome antifosfolípide e neurofibromatose tipo I: uma coincidência ou nova associação?

ABSTRACT - Numerous studies have reported on structural vascular anomalies and ischemia associated with neurofibromatosis type 1 that are thought to stem from dysfunction of neurofibromin, the neurofibromatosis type 1 protein. Documented cases of associated antiphospholipid syndrome fulfilling the accepted diagnostic criteria are exceptionally rare, with only three cases reported in the literature. Here, we report on a patient with neurofibromatosis type 1 and a history of spontaneous abortions presenting with sudden vision loss in the right eye and swelling of the optic nerve head. Fluorescein angiography indicated anterior ischemic optic neuropathy. Brain magnetic resonance imaging revealed findings consistent with left cavernous sinus meningioma. Serologic testing demonstrated persistently elevated anti-b2-glycoprotein antibodies. Her findings suggested antiphospholipid syndrome with concomitant clinical and laboratory evidence of antiphospholipid syndrome: frequent abortions, a vaso-occlusive episode, and persistently elevated antiphospholipid syndrome antibodies. To our knowledge, this case represents the first neuro-ophthalmic manifestation of antiphospholipid syndrome associated with neurofibromatosis type 1.

RESUMO - Inúmeros estudos têm relatado anomalias vasculares estruturais e isquemia associada com à neurofibromatose tipo 1 que, acredita-se, resultam da disfunção da neurofibromina, a proteína tipo 1 da neurofibromatose. Casos documentados de síndrome antifosfolípide associada que atendem aos critérios diagnósticos aceitos são excepcionalmente raros, com apenas três casos relatados na literatura. Aqui, relatamos um paciente com neurofibromatose tipo 1 e histórico de abortos espontâneos apresentando perda repentina de visão no olho direito e edema de cabeça do nervo óptico. A angiofluoresceínografia indicou neuropatia óptica isquêmica anterior. Ressonância magnética cerebral revelou achados compatíveis com meningioma do seio cavernoso esquerdo. O teste sorológico demonstrou anticorpos anti-b2 glicoproteína persistentemente elevados. Seus achados sugerem síndrome antifosfolípide com evidências clínicas e laboratoriais concomitantes de síndrome antifosfolipídica: abortos frequentes, episódio vaso-oclusivo e anticorpos antifosfolípides persistentemente elevados. Pelo nosso conhecimento, este caso pode representar a primeira manifestação neuro-oftálmica da síndrome antifosfolípide associada à neurofibromatose tipo 1.

Neurofibrome plexiforme orbito-palpebral dans la maladie de recklinghausen: à propos de 8 cas

Introduction : La localisation orbito-palpéral du neurofibrome plexiforme dans la maladie de Von Recklinghausen est rare. Nous en rapportons 8 cas. Patients et Méthode : Il s'agissait d'une étude rétrospective descriptive portant sur les dossiers de patients chez qui un diagnostic clinique et paraclinique de neurofibrome plexiforme palpébro-orbitaire était posé et pris en charge dans les services de Dermatologie-Vénérologie, d'Ophtalmologie et de Neurochirurgie du Centre Hospitalier Universitaire Yalgado Ouédraogo de 2005 à 2018. Résultats : Caracté-ristiques épidémiologiques : huit dossiers étaient colligés. Cinq patients étaient de sexe féminin et 3 de sexe masculin. Leur âge moyen était de 15,8 ans. Caractéristiques cliniques : Les atteintes cutanées de la maladie de Von Recklinghausen étaient des taches café au lait, des neurofibromes dermiques, le neurofibrome plexiforme orbito-palpébral unilatéral. L'examenophtalmologique retrouvait une gêne oculaire chez tous les patients, un ptosis, et une exophtalmie chez 2 patients. Un patient présentait un glaucome congénital. Trois patients présen-taient des nodules de Lisch, et un, une périsclérite. Une kérato-uvéite était retrouvée chez deux autres patients. Caractéristiques paracliniques : La tomodensitométrie montrait une atteinte osseuse (sphénoïdal et ou eth-moïdal, et ou du sinus maxillaire) chez tous les patients. L'IRM objectivait la tumeur plexiforme non encapsulé, infiltrant le tissu adipeux intra et extra conal, sans lésion du parenchyme cérébral. L'étude histologique confirmait le diagnostic de névrome plexiforme. Caractéristiques thérapeutiques et évolutives : La prise en charge était multidisciplinaire avec une exérèse chirurgicale à but fonctionnel et esthétique. L'évolution était favorable à court terme chez tous les patients. Une récidive chez un patient a nécessité une reprise chirurgicale qui s'est soldée par une rétraction de la fente palpé-brale, un ptérigion, un symblépharon, une kérato-uvéite et une chéloïde de l'angle extern

Utilidad del método clínico en el diagnóstico de algunos síndromes genéticos / Use fulness of the clinical method for diagnosing a group of clinical syndromes

Introducción: El método científico es un método general, constituido por varias etapas necesarias en el desarrollo de toda investigación científica. Es la forma de abordar la realidad y estudiar los fenómenos de la naturaleza, para descubrir su esencia y sus interrelaciones. El método clínico es la aplicación particular del método científico en el ejercicio de la práctica médica, y en las condiciones económicas actuales prevalecientes a nivel mundial resulta de inestimable valor su aplicación por las ventajas que reporta desde ese punto de vista, así como también por el bienestar del paciente que no es sometido a innecesarios y costosos procedimientos diagnósticos. Objetivo: Proporcionar al personal médico los criterios clínicos para lograr, mediante el uso del método clínico, el diagnóstico de algunos síndromes genéticos; los que han sido elaborados luego de una exhaustiva delineación clínica de estos. Métodos: Se realizó una revisión de los textos básicos de genética clínica y sindromología con independencia del año de su publicación y se realizó una búsqueda en las bases de datos Medline, Lilacs y Cochrane en el periodo comprendido entre 2012 y 2016. Conclusiones: Fueron reflejados los criterios establecidos para el diagnóstico clínico de catorce síndromes genéticos(AU)

Introduction: The scientific method is a general method which consists of several stages necessary for the development of all scientific research. It is the way to approach reality and to study the phenomena of nature, to discover their essence and interrelations. The clinical method is the particular application of the scientific method in the medical practice, and in the current economic conditions prevailing worldwide, its application is of inestimable value because of the advantages it brings from that point of view, as well as for the well-being of the patient, who would not be subjected to unnecessary and expensive diagnostic procedures. Objective: To provide the medical personnel with the clinical criteria to achieve, through the use of the clinical method, the diagnosis of some genetic syndromes. Such criteria have been elaborated after an exhaustive clinical description of those conditions. Methods: A review of basic texts of clinical genetics and syndromology was carried out regardless the year of publication. A search was carried out in the databases Medline, Lilacs and Cochrane, in the period between 2012 and 2016. Conclusions: The criteria established for the clinical diagnosis of fourteen genetic syndromes have been presented(AU)

Hallazgos clínicos y epidemiológicos en la neurofibromatosis tipo 1 y el complejo esclerosis tuberosa en una serie de pacientes pediátricos / Clinical and epidemiological findings in neurofibromatosis type 1 and tuberous sclerosis complex in a series of pediatric patients

Resumen: Introducción: La neurofibromatosis tipo 1 (NF1) es una entidad genética con una incidencia de 1 entre 2,500 a 3,500 nacimientos. Por su parte, el complejo esclerosis tuberosa (CET) presenta una incidencia de 1 entre 6,000 a 10,000 nacimientos. Ambas entidades neurocutáneas cursan con un patrón de herencia autosómico dominante, expresividad variable y la morbimortalidad se encuentra asociada a complicaciones multisistémicas. El objetivo de este trabajo fue exponer las características clínicas y epidemiológicas de una serie de pacientes pediátricos con diagnóstico de NF1 y CET atendidos en la Unidad de Genética Médica de la Universidad de Los Andes. Métodos: Este trabajo corresponde a una serie de casos de pacientes menores de 16 años atendidos en un período de 11 años, que cumplan con los criterios diagnósticos de NF1 y CET según los consensos para cada entidad. Resultados: Se estudiaron 89 pacientes, 73 con NF1 y 16 con CET. Presentaron dos criterios para NF1, 58 (79.45%) pacientes, y las máculas café con leche fueron las más frecuentes y presentes en todos los casos; 10 pacientes (62.50 %) presentaron dos criterios mayores para el CET, y las máculas hipocrómicas estuvieron igualmente presentes en todos los casos. Conclusiones: Este estudio muestra la forma de presentación clínica de las dos entidades neurocutáneas más frecuentes. Se discuten los criterios diagnósticos con el objeto de identificarlos a edades más tempranas y poder brindar una evaluación médica interdisciplinaria, tratamiento y un oportuno asesoramiento genético familiar.

Abstract: Background: Neurofibromatosis type 1 (NF1) is a genetic entity with an incidence of 1 in 2,500 to 3,500 births. Tuberous sclerosis complex (TSC) has an incidence between 1 in 6,000 to 10,000 births. Both neurocutaneous entities present an autosomal dominant inheritance pattern, variable expressivity and their morbidity and mortality is associated with multisystemic complications. The aim of this study was to present the clinical and epidemiological characteristics of a series of pediatric patients diagnosed with NF1 and TSC, who were treated in the Medical Genetics Unit of the Universidad of Los Andes. Methods: This work corresponds to a series of cases of patients under 16 years of age served in a period of 11 years, who met the diagnostic criteria of NF1 and CET according to the consensus for each entity. Results: We studied 89 patients, 73 with NF1 and 16 with TSC. 58 (79.45%) of the patients presented two criteria for NF1, with café-au-lait macules being the most frequent and present in all cases. 10 (62.50%) of the patients presented two major criteria for TSC; hypochromic macules were equally present in all cases. Conclusions: This study shows the clinical presentation of the two most frequent neurocutaneous entities. Diagnostic criteria are discussed in order to perform them at younger ages and to provide an interdisciplinary medical evaluation, treatment and timely family genetic counseling.

Neurofibroma Plexiforme Vesical em portador de Neurofibromatose: relato de caso / Bladder Plexiform Neurofibroma in Neurofibromatosis carrier: a case report / Neurofibroma Plexiforme Vesical en portador de Neurofibromatosis: relato de caso

Introdução: A neurofibromatose do tipo 1 (NF1) é uma doença hereditária de caráter autossômico dominante, com penetrância completa e relacionada a mutações no gene NF1 (17q11.2). Apresenta expressão extremamente variável e predisposição à ocorrência de tumores. Complicações como neurofibromas viscerais estão presentes em apenas 1% dos casos de NF1. Neurofibromas vesicais são extremamente raros. Relato do caso: O presente caso faz referência a um paciente do sexo masculino com 4 anos de idade que apresentava sinais e sintomas de disfunção urinária e intestinal associados a desvio da coluna lombossacra. Ao exame, foram identificadas características típicas de NF1 e os exames complementares permitiram o diagnóstico de um neurofibroma vesical. Posteriormente, foi concluído o diagnóstico de NF1. Conclusão: O diagnóstico de síndromes predisponentes ao câncer e o rastreio de tumores associados a essas condições são essenciais aos portadores dessas doenças.

Introduction: Type 1 neurofibromatosis is an inherited autosomal dominant disease with complete penetrance and is related to mutations in the NF1 gene (17q11.2). It presents extremely variable expression and predisposition to the occurrence of tumors. Complications such as visceral neurofibromas occurs in only 1% of NF1 cases. Vesical neurofibromas are extremely rare. Case report: Here in, we expose a case of a 4 years old boy, who presented signs and symptoms of urinary and intestinal dysfunction associated with lumbosacral spine deviation. His physical exam had neurofibromatosis type 1 features and the complementary exams revealed a vesical neurofibroma. Subsequently, a neurofibromatosis type 1 diagnosis was performed. Conclusion: Diagnose tumor predisposing syndromes and associated complications is essential for these patients.

Introducción: La neurofibromatosis tipo 1 es una enfermedad hereditaria de carácter autosómico dominante, con penetración completa y relacionada con mutaciones en el gen NF1 (17q11.2). Se presenta una expresión extremadamente variable y predisposición a la ocurrencia de tumores. Las complicaciones como los neurofibromas viscerales están presentes en sólo el 1% de los casos de NF1. Los neurofibromas vesicales son extremadamente raros. Relato del caso: Exponemos el caso de un niño de 4 años que presentaba signos y síntomas de disfunción urinaria e intestinal asociados a la desviación de la columna lumbosacra. En el examen se identificaron características típicas de neurofibromatosis y los exámenes complementarios permitieron el diagnóstico de un neurofibroma vesical. Se ha concluido el diagnóstico de neurofibromatosis del tipo 1. Conclusión: Diagnosticar los síndromes predisponentes del tumor y las complicaciones asociadas son esenciais para estos pacientes.

Melanocitoma del nervio óptico asociado a neurofibromatosis tipo 1. Reporte de caso / Melanocytoma of optic disk associated with type 1 neurofibromatosis. A case report

Objetivo: Exponer las principales características clínicas de un paciente con melanocitoma del nervio óptico, asociado a neurofibromatosis tipo 1 o enfermedad de Von Recklinghausen. Diseño del estudio: Reporte de caso. Método: Se revisó la historia clínica y los reportes de ayuda diagnósticas: Tomografía axial computarizada de orbitas simple y cerebral simple, ecografía ocular, campos visuales, Angiografía fluoresceínica, Tomografía óptica coherente de nervio óptico. Resultados: Se presenta el caso clínico de un paciente de 78 años de edad, con neurofibromatosis tipo 1, quien manifiesta visión borrosa en ojo izquierdo. Se realiza diagnóstico de melanocitoma del nervio óptico, que se caracteriza por ser una lesión altamente pigmentada y de buen pronóstico, con posibilidad de trasformación maligna. Generalmente no asociado con anomalías sistémicas. En la literatura actual no existe reporte de casos en los que se relacione a neurofibromatosis tipo 1. Conclusión: Esta revisión se concentra en exponer las manifestaciones clínicas del melanocitoma del nervio óptico asociado a una enfermedad sistémica, a través de un caso clínico por primera vez reportado en Colombia así como a nivel mundial. La importancia de publicar este reporte es facilitar un diagnóstico precoz, basados en la carente evidencia que existe y así no sea una enfermedad subdiagnosticada.

Purpose: To present the main clinical characteristics of a patient with melanocytoma of the optic disk, associated with neurofibromatosis type 1 also known as Von Recklinghausen's Disease. Study design: Case report. Method: Medical history and diagnostic studies were evaluated: Orbit and cerebral Computed tomography, visual fields, Fluorescein angiography and optic nerve tomography. Results: We present the clinical case of a 78-year-old patient with neurofibromatosis type 1, who manifests blurred vision in the left eye. Diagnosis of melanocytoma of the optic disk is made, this is a highly pigmented lesion with a good prognosis, it has the possibility of malignant transformation. Generally, not associated with systemic abnormalities. In the current literature there is no report of cases in which it is related to neurofibromatosis type 1. Conclusion: This case reviewfocuses on exposing the clinical manifestations of optic nerve melanocytoma associated with a systemic disease, through a clinical case reported for the fi rst time in Colombia as well as worldwide. The importance of publishing this report is to facilitate an early diagnosis, based on the lack of evidence that exists and that is not an underdiagnosed disease.

Neurofibromatosis tipo 1 (NF1) y su diagnóstico molecular como estrategia del diagnóstico diferencial y a edades tempranas / Molecular diagnosis as a strategy for differential diagnosis and at early ages of neurofibromatosis type 1 (NF1)

Neurofibromatosis type 1 (NF1), is a haploinsufficient and multisystemic disease, caused by inherited or sporadic mutations in the NF1 gene. Its incidence is one in 2,500 to 3,000 individuals, it has an autosomal dominant pattern of inheritance, high clinical variability, complete penetrance and age-dependent complications. Neurofibromin is the product of the NF1 gene and is believed to act as a tumor suppressor since the loss of its function has been associated with benign and malignant tumors in neural crest-derived tissues. Only two correlations between clinical phenotype and mutant alleles in the NF1 gene have been observed. The established criteria for disease diagnosis are very efficient in adults and children older than 3 years of age, but not for children under this age. Mutational analysis is therefore recommended to confirm the disease in young children with a negative family history. A pathogenic mutation in the NF1 should be added to the list of diagnostic criteria. Mutational analysis is also recommended for differential diagnosis and for prenatal or pre-implantation genetic diagnosis, taking into consideration the family history and the type of method to be applied. Molecular studies of this disease using different complimentary molecular techniques and bioinformatics tools have characterized NF1 gene mutations at both the DNA and mRNA levels, increasing the mutational spectrum. Consequently, about 1,289 defects have been reported to date, mainly nonsense/missense mutations, deletions and splice site defects.

Association between atypical parathyroid adenoma and neurofibromatosis

Primary hyperparathyroidism is a disease characterized by excessive production of parathyroid hormone (PTH), which is due to a parathyroid adenoma in 85% of cases. An atypical parathyroid adenoma, with some histopathological features of parathyroid carcinoma, may be found in some of the cases, although it may not fulfill all the criteria for this diagnosis. Neurofibromatosis type 1 (NF1) is an autosomal dominant systemic disease that may be associated with hyperparathyroidism. We report here the rare combination of a patient with NF1 and clinical manifestations of hyperparathyroidism due to an atypical parathyroid adenoma.

Oral Manifestations of Neurofibromatosis: A Rare Case Report.

Neurofibroma (NF) is a rare benign non-odontogenic tumor of the oral cavity. NF may present either as solitary lesions or as part of the generalized syndrome of NF or von Recklinghausen’s disease of the skin. The heterogeneous nature of NF was established by Riccardi et al. and he recognized at least seven types of NF. Among these proposed classifications of the disease, two distinct forms are generally accepted namely, a peripheral form known as NF Type I (NF-I), and a central form known as NF-II. NF-I represents the classic form of this disease, described by Recklinghawsen in 1882. Clinically, oral NF usually appears as slow growing, painless, pedunculated or sessile nodules. For illustration, a case of a NF with oral findings is been presented.

Hallazgos clínicos y oftalmológicos en niños con neurofibromatosis 1 / Clinical and ophthalmological findings in children with type 1 neurofibromatosis

Este trabajo tuvo por objetivos determinar la incidencia en nuestro medio de los criterios diagnósticos del National Institutes of Health (NIH) en niños con Neurofibromatosis 1 (NF1), comparar con estadísticas publicadas, analizar los hallazgos oftalmológicos, el valor de los estudios complementarios y establecer criterios de seguimiento. Métodos: Se trata de un estudio retrospectivo que incluyó 245 pacientes que ingresaron al Hospital de Pediatría Garrahan entre los años 1988 y 2010. Se diagnosticó NF1 en la primera consulta multidisciplinaria, utilizando los criterios de NIH, efectuándose en algunos niños neuroimágenes y potencial evocado visual (PEV). Resultados: El 92% de los pacientes presentó manchas café con leche; 40.8% neurofibromas, 75.5% nódulos de Lisch; 38.8% efeliloides; 16.3% glioma del nervio óptico; 16.3% displasia esquelética y 49% fueron hereditarios. Evidenciamos 1.76 miopías por cada hipermetropía. Conclusiones: Las frecuencias halladas coinciden con reportes previos, a excepción de las efeliloides, con incidencia menor. Realizamos de elección resonancia magnética nuclear (RMN), aún en pacientes asintomáticos, repitiéndolas bianualmente y examen oftalmológico cada seis meses hasta los ocho años. No indicamos actualmente PEV (AU)

The objective of this study was to determine the incidence of the National Institutes of Health (NIH) diagnostic criteria in children with Neurofibromatosis type 1 (NF1) in our setting, to compare them with the published statistical data, ophthalmological findings, the importance of complementary studies, and to establish follow-up criteria. Methods: We conducted a retrospective study including 245 patients that were admitted to the Pediatric Hospital Garrahan between 1988 and 2010. NF1 was diagnosed at the first multidisciplinary visit, using the NIH criteria. Neuroimaging and visual evoked potentials (VEP) were performed in some of the children. Results: 92% of the patients had café au laity spots; 40.8% neurofibromas; 75.5% Lisch nodules; 38.8% ephelides; 16.3% optic-nerve glioma; and 16.3% skeletal dysplasia. The disorder was hereditary in 49%. For each hypermetry,1.76 myopias were observed. Conclusions: These rates found were according to previous reports, except for ephelides, which were less common. Elective magnetic resonance imaging (MRI ) was performed, even in asymptomatic patients, and was repeated biannually and ophthalmological examination was done every six months until nine years of age. Currently, we do not indicate VEP

Plexiform Neurofibroma: An Unusual Diagnosis of Lip Swellings.

Neurofibromas (NF) are seen either as a solitary lesion or as part of the generalized syndrome of NF (NF-1, also known as Von Recklinghausen disease of the skin). In plexiform neurofibroma (PN), there is proliferation of Schwann cells from the inner aspect of the nerve sheath, thereby resulting in an irregularly thickened, distorted, tortuous structure. Oral involvement by a solitary and peripheral PN in patients with no other signs of NF is rarely seen. It is reported that only 4-7% of patients affected by NF display oral manifestations. A solitary PN in a patient with no other symptoms is a diagnostic challenge, more so when the location of the lesion is one of the rarest sites.

Neurofibromatosis Type I Associated with Malaria: A Case Report and Review of Literature.

Neurofibromatosis (von Recklinghausen disease) is a genetic disorder which is now not been considered to be most common due to a gradual increase in its number of cases worldwide. Its prevalence found is around 1 in 4000-5000 individuals with the incidence been found equally in all regions and reported in almost all ethnic groups. Two-three million cases are reported all over world so far with this disorder. It is an autosomal dominant trait with varied age range of the cases reported from 6 years to late adulthood. Disease occurs by a genetic mutation in the neurofibromatosis Type 1 (NF1) gene (tumor suppressor gene) which is located on chromosome no. 17 at 17q11.2, responsible for coding of neurofibromin, a cytoplasmic protein. The effect of this mutation is elicited in almost all systems of the body with mild to severe complications. About half of the cases reported are present with new mutations in the NF1 genes. A patient afflicted with NF1 has around 50-60% of chances of transmitting the disease to each of his/her offspring. Presenting here a case of the female patient diagnosed malaria associated with NF1.

Neurossarcoma plexiforme secundário à neurofibromatose tipo 1:relato de caso / Plexiform neurosarcoma secondary to Neurofibromatosis type 1: case report

A neurofibromatose tipo 1 é um transtorno neurocutâneo congênito caracterizado pela proliferação de tumores benignos da bainha dos nervos periféricos acompanhada de expressão inconstante a nível cutâneo, ósseo e nervoso. A evolução da doença é variável e dependente de possíveis complicações, sendo o prognóstico, em sua ausência, favorável. Os neurofibromas plexiformes são relativamente frequentes, constituindo complicação potencialmente grave, dependendo de sua localização e invasão de estruturas vizinhas. A transformação maligna desses tumores é rara, afetando 3 a 5% dos pacientes. O objetivo do estudo foi apresentar caso grave de neurofibromatose 1 com resultado fatal para o paciente, chamando a atenção para o diagnóstico das possíveis complicações. Paciente do gênero masculino, 20 anos, internado por massa cervical de etiologia a esclarecer. Com antecedentes de displasia tibial e duas exéreses de massas cutâneas não especificadas. Ao exame objetivo, apresentava múltiplas manchas café com leite, efélides axilares e inguinais, e nódulos na íris bilateralmente. Estabeleceu-se o diagnóstico de neurofibromatose1 em paciente sem história familiar, mediante dois resultados histopatológicos compatíveis. O estudo da massa revelou neurofibroma plexiforme cervicotorácico com malignização neurossarcomatosa, invadindo a veia jugular interna direita, artéria subclávia e plexo braquial, condicionando complicações hemorrágicas, posteriormente fatais. Apesar dos neurofibromas serem tumores benignos, estima-se que a esperança de vida dos pacientes com neurofibromatose 1 seja 15 anos menor do que a da população geral. A existência de complicações potencialmente fatais tornam indispensáveis a monitorização constante e o seguimento evolutivo das manifestações dessa doença

Neurofibromatosis type 1 is a congenital neurocutaneous disorder characterized by proliferation of benign peripheral nerve sheath tumors together with inconstant, cutaneous, osseous and neurological expression. Disease progression is variable and depends on eventual complications, with prognosis being favorable when they are absent. Plexiform neurofibroma is a relatively frequent and potentially severe complication, depending on its localization and surrounding structures. Malignant transformation is rare, affecting 3 to 5% of patients. The objective of this study was to present a severe case of neurofibromatosis 1, with fatal result for the patient, addressing the diagnosis of possible complications. Male patient, 20 years old, admitted due to cervical bulk of unknown origin, with a history of tibial dysplasia and two excisions of other unspecified cutaneous bulks. The physical examination showed multiple cafe-au-lait spots, axillary and inguinal ephelides, and bilateral iris Lisch nodules. Diagnosis of neurofibromatosis 1 was established in a patient without a family history, according to two compatible histopatological results. The investigation of the bulk demonstrated a plexiform cervical-thoracic neurofibroma with invasion of right internal jugular vein, subclavian artery and brachial plexus, with neurosarcomatous malignization, causing fatal hemorrhagic complications. In spite of neurofibromas being benign tumors, individuals with neurofibromatosis 1are predicted to have a lifespan of approximately 15 years less than the general population. Existence of potentially fatal complications makes close surveillance and follow-up of clinical manifestations crucial.

Neurofibromatosis type I and anti-phospholipid antibody syndrome: Report of one case / Neurofibromatosis tipo I y síndrome antifosfolípidos: Informe de un caso

Neurofibromatosis type I (NF1) has been only rarely reported in association with anti-phospholipid syndrome (APS). We report a 38 year-old female with NF1, who developed a cervix carcinoma at the age of 30 years and was successfully treated with conization, without requiring chemotherapy or radiation. She experienced two miscarriages prior to the diagnosis of the carcinoma. When she was 38 years old, an APS was diagnosed based on repeatedly positive lupus anticoagulant tests. The patient continued to smoke and using oral contraceptives. At 38 years of age she had a myocardial infarction, despite the use of oral anticoagulation. She required coronary stenting. Aspirin and clopidrogel were indicated thereafter.

Es inusual la asociación entre neurofibromatosis tipo I (NF1) y síndrome antifosfolípidos (APS). Presentamos una paciente mujer de 38 años con un NF1 que desarrolló un cáncer cervicouterino a los 30 años y que fue tratada exitosamente con una conización, sin requerir quimioterapia o radiación. La paciente tuvo dos abortos espontáneos antes del diagnóstico del carcinoma. A los 38 años, se le diagnosticó un APS, basado en pruebas de anticoagulante lúpico que resultaron positivas en repetidas oportunidades. La paciente continuó fumando y usando contraceptivos orales y, a pesar de estar con anticoagulantes orales, tuvo un infarto agudo de miocardio a los 38 años. Se colocó un stent coronario y se indicó aspirina y clopidogrel.

Neurofibromatose tipo I / Neurofibromatosis type I

A neurofibromatose tipo I é uma doença autossômica dominante cujo diagnóstico presuntivo é feito com base em critérios clínicos. As três principais manifestações: neurofibromas, manchas café com leite e nódulos de Lisch ocorrem em mais de 90% dos pacientes até a puberdade. Relatamos o caso de um paciente jovem com diagnóstico de neurofibromatose tipo I e história familiar positiva para a doença, comentando seus aspectos clínicos e achados nos exames de imagem.

The neurofibromatosis type 1 is a autosomal dominant disease which the diagnosis is made based on clinical criteria. Its three main features - neurofibromas, cafe au lait macules and Lisch nodules occur in up to 90% of the pacients until puberty. We documented a clinical case of a young male pacient who had the diagnosis of neurofibromatosis type 1 and family history, describing its clinical aspects and radiological features.

Prevalência de um fenótipo inédito na Neurofibromatose do Tipo 1 - Dados preliminares / Prevalence of a new phenotype in neurofibromatosis type 1 - Preliminary data

O diagnóstico precoce da neurofibromatose do tipo 1 (NF1) é útil no manejo clínico das complicações da doença: dificuldade de aprendizado, tumores no sistema nervoso, displasias ósseas, distúrbios auditivos e neurofibromas. No entanto, ao nascimento, a maioria dos pacientes com novas mutações apresenta somente manchas café-com-leite (MCL), ou seja, apenas um dos sete critérios diagnósticos adotados em consenso internacional. Portanto, qualquer outro sinal congênito de NF1 poderia ajudar a esclarecer o diagnóstico de NF1 e, consequentemente, o cuidado precoce às crianças. No atendimento de cerca de 600 pacientes com NF1 tem-se observado com certa frequência determinado sinal no segundo dedo dos pés (SSDP), consistindo em discreta elevação do segundo dedo e acavalamento sobre o terceiro dedo. Verificando que esse fenótipo ainda não fora descrito em pessoas com ou sem NF1, decidiu-se estudar se o SSDP seria manifestação fenotípica exclusiva ou mais prevalentena população com NF1. O método utilizado foi o envio de questionário pelo correio para 445 pessoas com pelo menos três critérios diagnósticos para NF1 e por correio eletrônico para 86 autodeclaradas sem NF1. O questionário continha foto com o SSDP, desenho explicativo e envelope selado com endereço para retorno e a pergunta se os pés do entrevistado seriam parecidos com a foto e/ou o desenho. Foram recebidas 167 respostas (39,2%). Nos pacientes com NF1 a prevalência de SSDP foi de 11,9% (11,1% em homens e 12,9% em mulheres, p>0,05),mas nove respostas manifestavam dúvidas (2%). Foram recebidas 60 respostas por e-mail de pessoas autodeclaradas sem NF1, nas quais a prevalência de SSDP foi de 3,3% (apenas dois homens ? pai e filho). Usando-se o teste do qui-quadrado, a diferença de prevalências do SSDP entre pacientes com NF1 parece ser maior do que nos controles (p=0,0503). Após o estudo, as imagens obtidas dos pés dos dois homens sem NF1, mas com SSDP positivo, mostraram hálux valgus em ambos os pés do pai (o que seria a causa do desvio dos dedos) e alteração similar ao SSDP apenas no pé esquerdo do filho. Em conclusão, se o SSDP semostrar verdadeiro sinal da NF1 em estudos subsequentes, ele será útil por estar presente ao nascimento (previamente ao aparecimento das efélides, do glioma óptico, dos neurofibromas cutâneos e dos nódulos de Lisch) e com mais prevalência do que as displasias ósseas.

The early diagnosis of neurofibromatosis type 1 (NF-1) is useful in the clinical management of the disease complications: learning difficulties, tumors in the nervous system, bone dysplasia, hearing disorders, and neurofibromas. However, at birth, most patients with new mutations present only café au lait spots (CLS), i.e. only one of the seven diagnosis criteria adopted in the international consensus. Therefore, any other NF-1 congenital signal could help clarifying its diagnosis and consequentlythe children?s early care. Following the attendance of about 600 NF-1 patients, we have frequently seen a determined signal in the second toe (SST), which consists of a discrete elevation of the second toe andsuperposition on the third one. After verifying that this kind of phenotype has not yet been described in people with or without NF-1, we have decided to study whether the SST would be a phenotypic manifestation that is exclusive or more prevalent in NF-1 population. It was sent a questionnaire as the applied method: a) via mailing to 445 people with at least 3 diagnostic criteria for NF-1; b) by forwarding the same questionnaire through e-mail for 86 people who self-declared being without NF-1. This instrument had a picture of the SST, an explanatorydrawing, and a sealed envelope with the correspondence address and the question if the interviewed person?s feet were alike to the picture and/or drawing. A total of 167 replies (39.2%) were received. In NF-1 patients, the SST prevalence was of 11.9% (11.1% for men and 12.9% for women, p>0.05), but nine answers had doubts (2%). We received 60 replies via e-mail from individuals who self-declared being without NF-1,wherein the SST prevalence was of 3.3% (only two men, father and son). By applying the chi-square test, the SST prevalence difference among patients with NF-1 seems to be higher than in controls (p=0.0503). After the study, the images that were acquired from the feet of both men without NF-1, but with positive SST, showed bunion in both feet of the father (which would be the cause of toe deviation), and a similar change inSST only on the son?s left foot. In conclusion, if the SST proves to be a real NF-1 sign in subsequent studies, it will be useful for being present at birth (before appearance of ephelides, optic glioma, cutaneous neurofibromas, and Lisch nodules), and for having a higher prevalence than the bone dysplasias.