Multidisciplinary team for patients with neurocutaneous syndromes: The little discussed importance of dentistry.

Neurocutaneous syndromes comprise a heterogeneous group of congenital or hereditary conditions that are known to be associated with the risk of different disorders and complications. Two of the most common neurocutaneous syndromes are Neurofibromatosis type 1 (NF1) and Tuberous Sclerosis Complex (TSC). Although there appears to be a general consensus on the importance of a multidisciplinary approach in managing these cases, there is still very little emphasis in discussions addressed in the literature on the role of dentistry in accordance with the perspective of comprehensive care. Evidence-based propositions, together with a broad discussion of new insights in this regard, should have the ability to strongly impact related future perspectives, aiming for greater advances and better outcomes for these patients. In this review article, the authors discuss updated general aspects of NF1 and TSC, and the potential additional roles of dentistry, in addition to addressing suggestions for actions in dentistry at related levels of care, as well as priorities for future research.

Multidisciplinary Outpatient Clinic of Neurocutaneous Diseases: Five-year Experience of a Pediatric Tertiary Hospital in Portugal.

INTRODUCTION: Neurocutaneous syndromes (NCS) are a heterogeneous group of conditions with multiorgan involvement and diverse manifestations, evolving throughout life with significant morbidity. A multidisciplinary approach to NCS patients has been advocated, although a specific model is not yet established. The aim of this study was 1) to describe the organization of the recently created Multidisciplinary Outpatient Clinic of Neurocutaneous Diseases (MOCND) at a Portuguese pediatric tertiary hospital; 2) to share our institutional experience focusing on the most common conditions, neurofibromatosis type 1 (NF1) and tuberous sclerosis complex (TSC); 3) to analyze the advantages of a multidisciplinary center and approach in NCS. METHODS: Retrospective analysis of 281 patients enrolled in the MOCND over the first five years of activity (October 2016 to December 2021), reviewing genetics, family history, clinical features, complications, and therapeutic strategies for NF1 and TSC. RESULTS: The clinic works weekly with a core team of pediatricians and pediatric neurologists supported by other specialties as needed. Of the 281 patients enrolled, 224 (79.7%) had identifiable syndromes such as NF1 (n = 105), TSC (n = 35), hypomelanosis of Ito (n = 11), Sturge-Weber syndrome (n = 5), and others. In NF1 patients, 41.0% had a positive family history, all manifested café-au-lait macules, 38.1% neurofibromas with 45.0% being large plexiform neurofibromas. Sixteen were under treatment with selumetinib. Genetic testing was performed in 82.9% of TSC patients with pathogenic variants found in TSC2 gene in 72.4% patients (82.7% if considered contiguous gene syndrome). Family history was positive in 31.4%. All TSC patients presented hypomelanotic macules and fulfilled diagnostic criteria. Fourteen patients were being treated with mTOR inhibitors. CONCLUSION: Offering a systematic and multidisciplinary approach to NCS patients enables timely diagnosis, promotes a structured follow-up, and encourages discussion to outline management plans for optimal care to every patient, with significant impact on the quality of life of patients and families.

Neurological disease in xeroderma pigmentosum: prospective cohort study of its features and progression.

Xeroderma pigmentosum (XP) results from biallelic mutations in any of eight genes involved in DNA repair systems, thus defining eight different genotypes (XPA, XPB, XPC, XPD, XPE, XPF, XPG and XP variant or XPV). In addition to cutaneous and ophthalmological features, some patients present with XP neurological disease. It is unknown whether the different neurological signs and their progression differ among groups. Therefore, we aim to characterize the XP neurological disease and its evolution in the heterogeneous UK XP cohort. Patients with XP were followed in the UK National XP Service, from 2009 to 2021. Age of onset for different events was recorded. Cerebellar ataxia and additional neurological signs and symptoms were rated with the Scale for the Assessment and Rating of Ataxia (SARA), the Inventory of Non-Ataxia Signs (INAS) and the Activities of Daily Living questionnaire (ADL). Patients' mutations received scores based on their predicted effects. Data from available ancillary tests were collected. Ninety-three XP patients were recruited. Thirty-six (38.7%) reported neurological symptoms, especially in the XPA, XPD and XPG groups, with early-onset and late-onset forms, and typically appearing after cutaneous and ophthalmological symptoms. XPA, XPD and XPG patients showed higher SARA scores compared to XPC, XPE and XPV. SARA total scores significantly increased over time in XPD (0.91 points/year, 95% confidence interval: 0.61, 1.21) and XPA (0.63 points/year, 95% confidence interval: 0.38, 0.89). Hyporeflexia, hypopallesthaesia, upper motor neuron signs, chorea, dystonia, oculomotor signs and cognitive impairment were frequent findings in XPA, XPD and XPG. Cerebellar and global brain atrophy, axonal sensory and sensorimotor neuropathies, and sensorineural hearing loss were common findings in patients. Some XPC, XPE and XPV cases presented with abnormalities on examination and/or ancillary tests, suggesting underlying neurological involvement. More severe mutations were associated with a faster progression in SARA total score in XPA (0.40 points/year per 1-unit increase in severity score) and XPD (0.60 points/year per 1-unit increase), and in ADL total score in XPA (0.35 points/year per 1-unit increase). Symptomatic and asymptomatic forms of neurological disease are frequent in XP patients, and neurological symptoms can be an important cause of disability. Typically, the neurological disease will be preceded by cutaneous and ophthalmological features, and these should be actively searched in patients with idiopathic late-onset neurological syndromes. Scales assessing cerebellar function, especially walking and speech, and disability can show progression in some of the groups. Mutation severity can be used as a prognostic biomarker for stratification purposes in clinical trials.

Neurofibromatosis type1, type 2, tuberous sclerosis and Von Hippel-Lindau disease.

Neurocutaneous syndromes (also known as phakomatoses) are heterogenous group of disorders that involve derivatives of the neuroectoderm. Each disease has diagnostic and pathognomonic criteria, once identified, thorough clinical examination to the patient and the family members should be done. Magnetic resonance imaging (MRI) is used to study the pathognomonic findings withing the CNS (Evans et al. in Am J Med Genet A 152A:327-332, 2010). This chapter includes the 4 most common syndromes faced by neurosurgeons and neurologists; neurofibromatosis types 1 and 2, tuberous sclerosis and Von Hippel-Lindau disease. Each syndrome has specific genetic anomaly that involves a tumor suppressor gene and the loss of inhibition of specific pathways. The result is a spectrum of cutaneous manifestations and neoplasms.

Sjogren-Larsson syndrome brain volumetric reductions demonstrated with an automated software / Reduções volumétricas cerebrais da síndrome de Sjogren-Larsson demonstradas com um software automatizado

Abstract Background Sjogren-Larsson syndrome (SLS) is a neurocutaneous disease with an autosomal recessive inheritance, caused by mutations in the gene that encodes fatty aldehyde dehydrogenase (ALDH3A2), clinically characterized by ichthyosis, spastic diplegia, and cognitive impairment. Brain imaging plays an essential role in the diagnosis, demonstrating a nonspecific leukoencephalopathy. Data regarding brain atrophy and grey matter involvement is scarce and discordant. Objective We performed a volumetric analysis of the brain of two siblings with SLS with the aim of detecting deep grey matter nuclei, cerebellar grey matter, and brainstem volume reduction in these patients. Methods Volume data obtained from the brain magnetic resonance imaging (MRI) of the two patients using an automated segmentation software (Freesurfer) was compared with the volumes of a healthy control group. Results Statistically significant volume reduction was found in the cerebellum cortex, the brainstem, the thalamus, and the pallidum nuclei. Conclusion Volume reduction in grey matter leads to the hypothesis that SLS is not a pure leukoencephalopathy. Grey matter structures affected in the present study suggest a dysfunction more prominent in the thalamic motor pathways.

Resumo Antecedentes A Síndrome de Sjogren-Larsson (SSL) é uma doença neurocutânea de herança autossômica recessiva, causada por mutações no gene que codifica a aldeído graxo desidrogenase (ALDH3A2), caracterizada clinicamente por ictiose, diplegia espástica e comprometimento cognitivo. A imagiologia cerebral desempenha um papel essencial no diagnóstico, demonstrando uma leucoencefalopatia inespecífica. Dados sobre atrofia cerebral e envolvimento da substância cinzenta são escassos e discordantes. Objetivo Realizamos uma análise volumétrica do cérebro de dois irmãos com SLS com o objetivo de detectar núcleos profundos de substância cinzenta, substância cerebral cinzenta e redução do volume do tronco encefálico nestes pacientes. Métodos Os dados de volume obtidos da ressonância magnética (RM) cerebral dos dois pacientes usando um software de segmentação automática (Freesurfer) foram comparados com os volumes de um grupo controle saudável. Resultados Redução de volume estatisticamente significativa foi encontrada no córtex do cerebelo, no tronco cerebral, no tálamo e nos núcleos pálidos. Conclusão A redução do volume da substância cinzenta leva à hipótese de que a SSL não é uma leucoencefalopatia pura. As estruturas da substância cinzenta afetadas no presente estudo sugerem uma disfunção mais proeminente nas vias motoras talâmicas.

A Rare and Unusual Presentation of Neurofibromatosis Type 1: Using Available Tools To Distinguish Neurofibromas From Mimicking Pathologies on CT Scan and MRI.

Neurofibromatosis type 1 (NF-1) is the most common neurocutaneous syndrome. Despite its more common appearance relative to other phakomatoses, it has a large variety of disease manifestations that can, at times, make swift diagnosis more challenging if not readily recognized, especially when presenting in an atypical manner. Our case reveals an unusual presentation of NF-1. After initially presenting with a bug bite on the lip with progressive swelling and surrounding inflammatory changes despite treatment with oral antibiotics, a CT scan was performed and demonstrated inflammatory changes surrounding the lip with an adjacent inflammatory mass lesion. Due to hypoattenuating lesions within the retropharyngeal space and misinterpretation by the otorhinolaryngologist, aspiration was attempted but unsuccessful, and the patient's condition worsened. Subsequent MRI was able to confirm the presence of numerous neurofibromas. The patient gradually improved on an extended course of antibiotics and was discharged in stable condition. Familiarizing oneself with the more specific imaging characteristics of this relatively common neurocutaneous disorder can help prevent incorrect or delayed diagnosis and ensure proper management. Furthermore, identifying these features on CT scan and MRI can differentiate them from other mimicking pathologies on each modality. Recognition of a scarcely reported infected neurofibroma as an established diagnostic entity could be important to include in the differential of similar cases in the future and subsequently aid in proper diagnosis and management.

Magnetic resonance imaging of disorders with white matter changes in children and adolescents: a pictorial essay.

White matter changes are seen in a spectrum of disorders in children and adolescents. Understanding their distribution and appearance helps to reach diagnoses in daily radiologic practice. This pictorial essay will outline the magnetic resonance imaging (MRI) appearances of diseases with white matter changes including demyelinating diseases, dysmyelinating disorders/leukodystrophies, infections, autoimmune diseases, vascular causes, mitochondrial disorders and neurocutaneous syndromes, along with a brief overview of clinical aspects of the diseases such as typical age of presentation, etiology, symptoms and signs and treatment options. This article highlights important features in common white matter diseases in children and adolescents.

Sleep Problems in Children With Neurocutaneous Syndromes: A Cross-Sectional Study.

Introduction: The prevalence and patterns of sleep disturbances in neurocutaneous syndromes are variable and understudied. Methods: Cross-sectional study for 18 months at a tertiary care pediatric hospital, involving 100 children with neurocutaneous syndromes aged between 4 and 10 years using the Children's Sleep Habits Questionnaire-Abbreviated. Results: In 100 children with neurocutaneous syndromes, 47 (47%) had significant sleep problems. In subgroup analysis, 7 of 17 children with neurofibromatosis 1, 24 of 63 children with tuberous sclerosis complex, 10 of 12 children with Sturge-Weber syndrome, 2 of 3 children with linear nevus sebaceous syndrome, and each of the children with hypomelanosis of Ito, McCune-Albright syndrome, megalencephaly-capillary malformation syndrome, and unclassified neurocutaneous syndrome had significant sleep problems. Conclusion: The prevalence of sleep problems in our study population was not more than that observed in the general pediatric population. Prospective multicentric studies are needed to comprehend sleep problems in children with neurocutaneous syndromes.

Sebaceous nevus of Jadassohn: review and clinical-surgical approach.

BACKGROUND: Nevus sebaceous of Jadassohn is defined as a rare congenital malformation characterized as a non-hereditary hamartoma of the adnexal structures of the skin. Its etiology is not yet well understood, but it is believed to be related to post-zygotic mutations in the HRAS, NRAS and KRAS genes. OBJECTIVE: To describe the clinical manifestation of nevus sebaceous, as well as the main management techniques addressed in the medical literature. Moreover, the present study discusses a case report of a congenital linear nevus in the left retroauricular region found in a male patient, without extracutaneous manifestations. METHOD: A narrative review of the literature was carried out. DISCUSSION: Nevus sebaceous occurs as lesions with a linear or oval appearance, with a smooth or verrucous texture, generally alopecic and with very variable color. Moreover, nevus sebaceous is one of the components of the so-called linear nevus syndrome or Schimmelpenning-Feuerstein-Mims syndrome, which is associated with multisystemic complications. The treatment of the lesions is still controversial; however, most experts indicate surgical excision as the most frequently adopted treatment method, in addition to multidisciplinary follow-up when the diagnosis of Schimmelpenning-Feuerstein-Mims syndrome is established. CONCLUSION: The linear nevus syndrome constitutes a rare manifestation; however, its diagnosis should be considered in children born with nevus sebaceous. There is no consensus yet on the best therapy, but surgical removal has shown to be a viable option.

Value of a café-au-lait macules screening clinic: Experience from The Hospital for Sick Children in Toronto.

BACKGROUND/OBJECTIVES: Café-au-lait macules (CALMs) are a characteristic feature of neurofibromatosis type 1 (NF1), but also occur in other genetic disorders. Differential diagnosis of CALMs remains challenging and can be stressful for families. We sought to examine the role of an established CALMs screening clinic in diagnosing CALMs-related disorders. METHOD: We retrospectively reviewed patients seen between July 2012 and January 2019 in a CALMs screening clinic at The Hospital for Sick Children, a tertiary pediatric hospital in Toronto, Canada. Pediatric patients were referred because of multiple CALMs or suspected NF1. Selection was based on a chronological referral sample with no exclusions. A pediatric dermatologist examined all patients for CALMs and NF1 manifestations. Genetic testing was offered to confirm a clinical diagnosis or when clinical findings were inconclusive. RESULTS: Three hundred patients, of which 152 (50.7%) were female and had a mean age of 5.6 ± 4.8 years were seen during the study period. NF1 was diagnosed in 76 (25.3%) patients, mosaic NF1 in 38 (12.7%) patients, and 8 (2.7%) patients received other genetic diagnoses. One hundred and twelve (37.3%) patients were diagnosed with isolated CALMs not associated with an underlying genetic disease. Furthermore, 36 (12%) of our patients did not have CALMs. CONCLUSIONS: The CALMs screening clinic aided in the early diagnosis of genetic disorders such as NF1 and distinguished CALMs from other hyperpigmented lesions. We encourage the adoption of this clinic model in referral centers to streamline and optimize care of patients with presumptive diagnosis of CALMs.

Melanocytic lesions of the central nervous system: a case series / Lesiones melanocíticas del sistema nervioso central: una serie de casos

ABSTRACT Background: Melanocytic lesions of the central nervous system (CNS) are an infrequent, broad and diverse group of entities, both benign and malignant, found in all age groups, with imaging findings ranging from well-circumscribed focal lesions to diffuse leptomeningeal involvement. On MRI, they are usually distinguished by a high signal on T1WI sequences, given the paramagnetic effect of melanin, thus making it difficult to differentiate among them. Objective: To describe the imaging and epidemiological characteristics of a retrospective series of CNS melanocytic lesions. Methods: MR images of 23 patients with CNS melanocytic lesions diagnosed between January 2012 and June 2018 were analyzed. Results: Most patients were female (14/23; 61%), with a median age of 47 years (range: 3 weeks to 72 years). The primary melanocytic lesions accounted for 8/19 cases (42.1%), which included neurocutaneous melanosis, meningeal melanocytomas and primary malignant melanomas. Secondary melanocytic lesions (metastatic) accounted for 10/19 cases (52.6%). There was one case of a tumor with secondary melanization, from a melanocytic neuroectodermal tumor of infancy. There were also four cases of primary ocular melanomas. The most frequent findings were the cerebral location, high T1WI signal and marked contrast-enhancement. Conclusions: The present review describes the wide variety of melanocytic lesions that could affect the CNS, emphasizing the MRI characteristics. Knowledge of the imaging, clinical and epidemiological characteristics of CNS melanocytic lesions is essential for their correct interpretation, given the significant overlap between lesion features and the variable prognosis.

RESUMEN Antecedentes: Las lesiones melanocíticas del sistema nervioso central (SNC) corresponden a un grupo infrecuente, amplio y diverso de entidades, tanto benignas como malignas, encontradas en todos los grupos etarios, con hallazgos imagenológicos que van desde lesiones focales bien circunscritas hasta un compromiso leptomeníngeo difuso. A la RM se distinguen por la alta señal en la secuencia T1WI, dado el efecto paramagnético de la melanina, haciendo difícil la diferenciación entre ellas. Objetivo: Describir las características epidemiológicas y de de una serie retrospectiva de lesiones melanocíticas del SNC. Métodos: Revisión de imágenes de RM de 23 pacientes con lesiones melanocíticas del SNC diagnosticadas entre enero de 2012 y junio de 2018. Resultados: La mayoría de los pacientes fueron mujeres (14/23; 61%), con edades comprendidas entre las 3 semanas de vida hasta los 72 años. Las lesiones melanocíticas primarias representaron 8/19 (42,1%), incluyendo: melanosis neurocutáneas, melanocitomas meníngeos y melanomas malignos primarios. Las lesiones melanocíticas secundarias (metastásicas) representaron 10/19 casos (52,6%). Hubo un caso de tumor con melanización secundaria (tumor neuroectodermico melanocítico de la infancia). Se incluyeron cuatro casos de melanomas oculares primarios. Los hallazgos más frecuentes fueron la localización cerebral, el aumento de señal T1 y el acentuado realce con el gadolinio. Conclusiones: Se describe la amplia variedad de lesiones melanocíticas encontradas en el SNC, enfatizando sus características a la RM. El conocimiento de sus características imagenológicas, clínicas y epidemiológicas es fundamental para su correcta interpretación, dado la notable superposición entre las presentaciones de las lesiones y lo variable de sus pronósticos.

Dermoscopy of the iris: identification of Lisch nodules and contribution to the diagnosis of neurofibromatosis type 1

Abstract Neurofibromatosis is a common genodermatosis, whose diagnosis often involves the participation of a dermatologist. A case of a 38-year-old female patient with four café-au-lait macules and eleven neurofibromas on clinical examination is presented. Dermoscopy allowed the identification of Lisch nodules in the iris, bilaterally. The combination of these findings allowed the diagnosis of neurofibromatosis type 1, according to NIH criteria. Lisch nodules are melanocytic hamartomas of the iris, which must be evaluated through a visual augmentation method, usually employed in ophthalmology. Alternatively, dermoscopy can be used and contribute to the early diagnosis of neurofibromatosis type 1.

Dermoscopy of the iris: identification of Lisch nodules and contribution to the diagnosis of Neurofibromatosis type 1.

Neurofibromatosis is a common genodermatosis, whose diagnosis often involves the participation of a dermatologist. A case of a 38-year-old female patient with four café-au-lait macules and eleven neurofibromas on clinical examination is presented. Dermoscopy allowed the identification of Lisch nodules in the iris, bilaterally. The combination of these findings allowed the diagnosis of neurofibromatosis type 1, according to NIH criteria. Lisch nodules are melanocytic hamartomas of the iris, which must be evaluated through a visual augmentation method, usually employed in ophthalmology. Alternatively, dermoscopy can be used and contribute to the early diagnosis of neurofibromatosis type 1.

Multicenter Research Data of Epilepsy Management in Patients With Sturge-Weber Syndrome.

BACKGROUND: Epilepsy in typical Sturge-Weber syndrome (SWS) is common, and many questions remain regarding the treatment outcomes. We analyzed a large multicenter database with focus on neurological drug treatment in different demographic and SWS characteristic groups. METHODS: A total of 268 patients with brain involvement and a history of seizures were selected from a research data registry generated from a multicenter cross-sectional questionnaire. We examined associations between medication use and binary variables such as sex, ethnicity, and brain, skin, and eye involvement laterality. We analyzed group differences in mean number of antiseizure medications and age at diagnosis, enrollment, and seizure onset and examined differences in median SWS neurological scores in groups of interest. RESULTS: The most frequently used medications were levetiracetam (48.1%), low-dose aspirin (44.8%), oxcarbazepine (39.9%), and phenobarbital (14.9%). Lamotrigine was more frequently used in adults than in children (P = 0.001). History of neurosurgery was associated with no current antiseizure medication use (P = 0.001), whereas bilateral brain involvement and family history of seizures were associated with using a higher number of antiseizure medications (P = 0.002, P = 0.027, respectively). Subjects with bilateral brain involvement and early seizure onset were associated with using a higher number of antiseizure medications (P = 0.002) and phenobarbital use (0.003). CONCLUSIONS: Levetiracetam, low-dose aspirin, and oxcarbazepine were the most frequently used medications. More severely affected patients were frequently on a greater number of antiseizure medications. Surgery for epilepsy was associated with the ability to discontinue antiseizure medication. Longitudinal studies are needed to further investigate medication use in patients with SWS.

Síndromes neurocutáneos y leucemia linfoide aguda: a propósito de un caso / Neurocutaneous syndromes and acute lymphoid leukemia: a case report

Introducción: Los síndromes neurocutáneos comprenden un grupo heterogéneo de trastornos hereditarios que comprometen principalmente la piel y el sistema nervioso central. Dentro de estos se incluye la neurofibromatosis, la esclerosis tuberosa y la enfermedad de Von-Hippel Lindau. Se caracterizan por presencia de displasia en distintos tejidos y formación de tumores en diversos órganos. Se ha descrito también un riesgo relativo aumentado para leucemia linfoblástica aguda, leucemia mielomonocítica crónica y linfoma no Hodgkin. Objetivo: Describir caso de paciente con diagnóstico de síndrome neurocutáneo (esclerosis tuberosa) que desarrolló a los 6 años una leucemia linfoide aguda. Caso clínico: Paciente femenina, seis años de edad, con antecedentes de síndrome neurocutáneo tipo esclerosis tuberosa diagnosticado a los dos años de edad- Comenzó con síndrome febril, adenopatías cervicales y hepatoesplenomegalia. El hemograma mostró anemia, trombocitopenia grave y leucocitosis con presencia de blastos. En el medulograma se observó una infiltración de 90 por ciento de blastos linfoides, por lo que se diagnosticó como una leucemia linfoide aguda. Conclusiones: La coexistencia de síndromes neurocutáneos y leucemia linfoide aguda no es frecuente. Se describe una paciente con ambas enfermedades, que fallece a pesar del tratamiento(AU)

Introduction: Neurocutaneous syndromes comprise a heterogeneous set of hereditary disorders mainly affecting the skin and the central nervous system. Among the conditions included are neurofibromatosis, tuberous sclerosis and von Hippel-Lindau disease, characterized by dysplasia in various tissues and the formation of tumors in various organs. Increased relative risk has also been described for acute lymphoblastic leukemia, chronic myelomonocytic leukemia and non-Hodgkin lymphoma. Objective: Describe the case of a patient diagnosed with neurocutaneous syndrome (tuberous sclerosis) who developed acute lymphoid leukemia at age six. Clinical case: A case is presented of a female six-year-old patient with a history of neurocutaneous syndrome, tuberous sclerosis type, diagnosed at age two. The patient started with febrile syndrome, cervical adenopathies and hepatosplenomegaly. The blood count revealed anemia, severe thrombocytopenia and leukocytosis with the presence of blasts, whereas the medullogram showed 90 percent infiltration by lymphoid blasts, leading to the diagnosis of acute lymphoid leukemia. Conclusions: Coexistence of neurocutaneous syndromes and acute lymphoid leukemia is not frequent. A case is described of a patient with both conditions who died despite the treatment indicated(AU)

Fibrous Meningioma in a Patient with Encephalocraniocutaneous Lipomatosis: A Rare Case with Unique Features.

Encephalocraniocutaneous lipomatosis "ECCL" is a rare, sporadic neurocutaneous disorder that results from a lethal autosomal mutation surviving by somatic mosaicism. It is characterized by unilateral involvement of skin, eyes and central nervous system in addition to a propensity for mesenchymal tumors. A 30-year-old male with previously controlled epilepsy presented with recurrent seizures. Brain imaging revealed a left parietal parasagittal enhancing tumor, in addition to left sided gyriform calcifications, and bilateral cerebral atrophy and ventricular dilatation more prominent on the left side. He also presented multiple left sided sebaceous nevi and abundant subcutaneous lipomas in addition to left mandibular condylar cysts. The brain tumor was excised, and cytopathology revealed a WHO grade I fibrous meningioma. After a thorough evaluation and exclusion of alternative diagnoses, the patient was diagnosed with definite encephalocraniocutaneous lipomatosis as per Moog's criteria. Several cases of ECCL recently presented with different intracranial neoplasms. Here we report the first case of ECCL in association with meningioma.

Genetics of Common Pediatric Brain Tumors.

Central nervous system tumors are the most common solid tumors in pediatrics and represent the largest cause of childhood cancer-related mortality. Improvements have occurred in the management of these patients leading to better survival, but significant morbidity persists. With the era of next generation sequencing, considerable advances have occurred in the understanding of these tumors both biologically and clinically. This information has impacted diagnosis and management. Subgroups have been identified, improving risk stratification. Novel therapeutic approaches, specifically targeting the biology of these tumors, are being investigated to improve overall survival and decrease treatment-related morbidity. The intent of this review is to discuss the genetics of common pediatric brain tumors and the clinical implications. This review will include known genetic disorders associated with central nervous system tumors, neurofibromatosis, tuberous sclerosis, Li-Fraumeni syndrome, Gorlin syndrome, and Turcot syndrome, as well as somatic mutations of glioma, medulloblastoma, and ependymoma.

Multiple cardiac rhabdomyomas in tuberous sclerosis complex: case report and review of the literature

Cardiac rhabdomyoma is a benign tumor which constitutes the most common cardiovascular feature of the tuberous sclerosis complex, a multisystem genetically determined neurocutaneous disorder. Cardiac rhabdomyomas can be detected in the prenatal ultrasound, are usually asymptomatic and spontaneously regress within the first three years of life. Less often, the tumors' size, number, and location can produce a mass effect that may lead to blood flow abnormalities or organ dysfunction (heart failure and arrhythmia). In this setting, severe morbidity, and eventually, a lethal outcome despite clinical and surgical treatment may ensue. We describe a fatal case of multiple cardiac rhabdomyomas in a newborn girl. One of the rhabdomyomas was large and unfavorably located, causing significant obstruction of the left ventricular outflow tract. The autopsy identified, in addition to cardiac rhabdomyomas, brain glioneuronal hamartomas (cortical tubers), subependymal nodules and subependymal giant cell tumors, characteristic of the tuberous sclerosis complex. The newborn's family was investigated for the presence of typical clinical symptoms of the complex and image findings showed significant phenotypical variations and a broad symptom spectrum among the family members. This interesting case underscores the variability of tuberous sclerosis complex and the importance of performing a comprehensive postmortem examination in the identification of the cause of death, especially in the setting of familial disease.

Nevos melanocíticos congénitos / Congenital melanocytic nevus / Nevos melanocíticos congênitos

Resumen: Los nevos melanocíticos congénitos son una proliferación melanocítica benigna presente al nacimiento o que surgen en los primeros 2 o 3 años de vida. Habitualmente se clasifican, según su tamaño, en pequeños, medianos y grandes. Su importancia radica en el potencial riesgo de desarrollar melanoma, en la repercusión que tienen en la calidad de vida de quien los padece y en la asociación con disrafismo y tumores del sistema nervioso central. A mayor tamaño, mayor riesgo de desarrollar melanoma en el nevo o fuera de él. Describiremos las características epidemiológicas, clínicas dermatoscópicas y revisaremos el manejo y seguimiento de los nevos congénitos.

Summary: Congenital melanocytic nevi are a benign melanocytic proliferation present either from birth or during the first 2 or 3 years of life. They are usually classified according to size as: small, medium and large. Their importance lies on the potential risk of developing melanoma, on the impact they have on the patient's quality of life and on its association with dysraphism and tumors of the central nervous system. The larger the size of the nevi, the higher the risk of developing melanoma inside or outside the nevus. We will describe the epidemiological and dermatoscopic clinical characteristics and review the management and follow-up of congenital nevi.

Resumo: Os nevos melanocíticos congênitos são uma proliferação melanocítica benigna presente desde o nascimento ou durante os primeiros 2 ou 3 anos de vida. Eles são geralmente classificados de acordo com o seu tamanho como: pequenos, médios ou grandes. Sua importância está no risco potencial de desenvolver melanoma, no impacto que eles têm na qualidade de vida do paciente e na sua associação com disrafismo e tumores do sistema nervoso central. Quanto maior o tamanho dos nevos, maior o risco de desenvolver melanoma dentro ou fora do nevo. Descreveremos as características clínicas epidemiológicas e dermatoscópicas dos nevos congênitos e revisaremos o seu gerenciamento e acompanhamento.