Au Lait Research Articles

Clinical aspects of Neurofibromatosis type 1 seen in the Department of Dermatology at University Hospital Antananarivo, Madagascar

RésuméIntroductionLa neurofibromatose type 1 (NF1) est une maladie autosomique dominante, à expression multisystémique. Sa prévalence varie selon les pays et peu de données sur la NF1 sont connues à Madagascar.MéthodologieUne étude transversale rétrospective a été réalisée au service de dermatologie du Centre hospitalier universitaire Joseph Raseta Befelatanana d'Antananarivo, Madagascar, sur une période de 6 ans (de janvier 2014 à décembre 2019). Ont été inclus dans cette étude les patients vus en consultation porteurs de NF1 dont le diagnostic a été confirmé et chez lesquels une enquête généalogique a pu être faite.RésultatsVingt-huit cas de neurofibromatose ont été inclus avec un sexe-ratio H/F de 0,87. L’âge moyen était de 24 ans avec des extrêmes de 11 et 54 ans. La tranche d’âge 16-35 ans était la plus touchée. Dix-sept patients présentaient la forme sporadique. Tous les patients présentaient des taches café au lait et des neurofibromes cutanés, 15 patients portaient des nodules iridiens de Lisch. Les difficultés d'apprentissage, l’épilepsie et la scoliose étaient les complications les plus représentées.ConclusionLes manifestations cliniques de la NF1 sont extrêmement variables. Même si les complications systémiques sont rares, le suivi des patients est indispensable.

A Case of 27-Year-Old Localized Solitary Neurofibroma of the Base Tongue; A Case Report

Introduction: Neurofibromas, benign peripheral nerve sheath tumors, are the most common among neural lesion. Neurofibromas are rare in head and neck location, although it may involve any part of oral cavity. However, tongue is the most common region. Case Presentation: A 27 year-old man was admitted to Otorhinolaryngology Department due to a swelling in the base of his tongue, since two weeks before. This mass was painless, and without any associated symptoms. He was suffered from a mild eating disorder, too. He had no any positive past medical history, and only a large soft 6×5 cm mass was found at the base of his tongue without bleeding in the oral cavity. Excisional biopsy was performed for him under general anesthesia and the tumor was easily enucleated. The final diagnosis was neurofibroma. After the diagnosis of neurofibroma, the physical reexamination revealed a series of café au lait spots on his skin. Conclusion: the neurofibroma should be considered by otorhinolaryngologist, as a differential diagnosis of tongue mass, and more accurate physical examination are recommended for better management.

Woman With Left Pulsatile Exophthalmos

Neurofibromatosis is rarely seen in emergency departments unless it becomes symptomatic. There are 3 types of neurofibromatosis. Neurofibromatosis type 1 (NF-1; von Recklinghausen disease) is the most common of the 3 types of neurofibromatosis disease. In the disease, there are skin, peripheral and central nervous system, bone, and soft tissue involvements, and there is an increase in the susceptibility to cancer. 1 Hirbe A.C. Gutmann D.H. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol. 2014; 13: 834-843https://doi.org/10.1016/S1474-4422(14)70063-8 Abstract Full Text Full Text PDF PubMed Scopus (261) Google Scholar NF-1 is seen once in 3000 births, showing autosomal dominant inheritance and affecting many systems simultaneously. 2 Ghalayani P. Saberi Z. Sardari F. Neurofibromatosis type I (von Recklinghausen’s disease): a family case report and literature review. Dent Res J (Isfahan). 2012; 9 (PMC3491339): 483-488 Google Scholar The NF-1 gene is located on chromosome 17 and encodes a type of tumor suppressor protein called neurofibromin. As a result of incomplete or incorrect folding of this protein, benign and rarely malignant nerve tumors are seen from the early stages of life. Because the disease affects many systems at the same time, the diagnostic criteria have been shaped in this direction. Diagnostic criteria include café au lait spots, neurofibromas, axillary and/or inguinal freckles, optic glioma, Lisch nodules (iris hamartomas), typical bone lesions, and NF-1 disease in first-degree relatives. 3 Ferner R.E. Huson S.M. Thomas N. et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007; 44: 81-88https://doi.org/10.1136/jmg.2006.045906 Crossref PubMed Scopus (645) Google Scholar In uncertain cases, genetic testing may be requested to confirm the diagnosis. Metin Yadigaroglu is Assistant Professor, Faculty of Medicine, Department of Emergency Medicine, Samsun University, Samsun, Turkey. Twitter: @mtnydgrdr. Melih Imamoglu is Assistant Professor, Faculty of Medicine, Department of Emergency Medicine, Karadeniz Technical University, Trabzon, Turkey. Twitter: @melihimam. Muhammet Fatih Beser is Emergency Specialist, Faculty of Medicine, Department of Emergency Medicine, Karadeniz Technical University, Trabzon, Turkey. Twitter: @drfatih. Sinan Pasli is Assistant Professor, Faculty of Medicine, Department of Emergency Medicine, Karadeniz Technical University, Trabzon, Turkey.

Multiscale confocal photoacoustic dermoscopy to evaluate skin health.

Photoacoustic dermoscopy (PAD) is a promising branch of photoacoustic microscopy (PAM) that can provide a range of functional and morphologic information for clinical assessment and diagnosis of dermatological conditions. However, most PAM setups are unsuitable for clinical dermatology because their single-scale mode and narrow frequency band result in insufficient imaging depth or poor spatiotemporal resolution when visualizing the internal texture of the skin. We developed a multiscale confocal photoacoustic dermoscopy (MC-PAD) with a multifunction opto-sono objective that could achieve high quality dermatological imaging. Using the objective to coordinate the spatial resolution and penetration depth, the MC-PAD was used to visualize pathophysiological biomarkers and vascular morphology from the epidermis (EP) to the dermis, which enabled us to quantify skin abnormalities without using exogenous contrast agents for human skin. The MC-PAD was shown to have the ability to differentiate between different types of cells (such as red blood cells and melanoma cells), image and quantify pigment of the skin, and visualize skin morphology and blood capillary landmarks. The MC-PAD detected a significant difference in the structures of some pigmented and vascular lesions of skin diseases compared with that of healthy skin (P<0.01). The café au lait macule (CALM) skin type was found to have a relatively higher melanin concentration and thicker stratum basale (SB) in the EP than healthy skin. The dermal vascular network of skin that had a port wine stain (PWS) had greater diameters and a denser distribution than healthy skin, as reported in clinical trials. The MC-PAD has a broad range of applications for the diagnosis of human skin diseases and evaluation of the curative effect of treatments, and it can offer new perspectives in biomedical sciences.

The genetics and diagnosis of pediatric neurocutaneous disorders: Neurofibromatosis and tuberous sclerosis complex

Neurofibromatosis (NF) and tuberous sclerosis complex (TSC) are the two most common neurocutaneous disorders, both transmitted as autosomal dominant or, in the case of NF, also as a mosaic condition. The causative genetic mutations in these neurocutaneous disorders can lead to benign skin changes or uninhibited growth and proliferation in multiple organ systems due to the loss of tumor suppression in mitogen-activated protein kinase and mammalian target of rapamycin signaling pathways. Common clinical features in NF include pigmented lesions, known as café au lait patches, neurofibromas, intertriginous freckles (Crowe's sign), and benign fibrous growths, such as hamartomas in multiple organ systems. Common clinical features in TSC include hypopigmented macules, known as ash leaf spots, in addition to neurologic sequelae, such as autism, seizures, and developmental delays. Advances in genetic sequencing technologies have allowed an exponential expansion in the understanding of NF and TSC.Consensus criteria have been established for both diagnoses that can be confirmed in most cases through gene testing. Once diagnosed, the clinical and diagnostic value of disease-specific surveillance include early identification of benign and malignant tumors. Genetic counseling is important for informed reproductive decision-making for patients and at-risk family members. The improvement in understanding of pathways of pathogenic disease development and oncogenesis in both conditions have produced a new series of therapeutic options that can be used to control seizures and tumor growth. Tremendous advances in life expectancy and quality of life are now a reality due to early introduction of seizure control and novel medications. While we lack cures, early institution of interventions, such as seizure control in tuberous sclerosis, appears to be disease-modifying and holds immense promise to offer patients better lives.

Abstract 48: A typical neurofibromatosis type 1 presenting as overgrowth syndrome

A 6 years old boy presented to the endocrinology department as unilateral left leg overgrowth since birth. Limb discrepancy had been negligible at birth but became evident as the child gained height and further he developed a limping gait by 2 years of age. On examination, he had multiple café au lait spots of > 5 mm over the body and hyperpigmentation on anterolateral aspect of left leg which turned out to be a venous malformation on color Doppler and MRI of the leg. There was no other neuro cutaneous marker and no family history of similar illness or any other neuro cutaneous lesions or any abdominal malignancy. A probable diagnosis of segmental overgrowth syndrome was made with associated café au laits. We wanted to rule out syndromic cause for the same, so patient was advised clinical whole exome sequencing. Genetic result revealed atypical NF1 with heterogenous 3’ splice site variation in intron 36 of the NF1 gene. We hereby report rare presentation of neurofibromatosis as segmental overgrowth syndrome.

Abstract 87: Novel mutation in leptin receptor causing monogenic obesity

Hereby we present a case of monogenic obesity in a 3 ½ year old boy. Child was born of third degree consanguinity with birth weight of 3kg. He had excessive weight gain since five months of age with food seeking behaviour, recurrent upper respiratory tract infections since infancy, renal calculi and features of obstructive sleep apnoea. He had normal developmental milestones. His 5 ½ year old sister also had obesity since infancy with a present BMI of 41.64 kg/m2 and recurrent upper respiratory tract infections. No other similar family history. On examination, his height was 103 cm (SDS 0.98). He weighed 40 kg with BMI of 37.7 kg/m2 (Z score +6.9). General examination showed grade 4 acanthosis nigricans, low set ears, and café au lait spot on the abdominal wall. Bone age was appropriate for chronological age. Investigations revealed dyslipidemia and fatty hepatomegaly. Screening tests for secondary causes were negative. In view of strong suspicion of genetic etiology, clinical exome sequencing was done which showed a novel mutation c.850-1G>A in Intron 7 of LEPR suggestive of leptin receptor defect.

Abstract 126: Myriad endocrine manifestations of a rare syndrome

Background: McCune-Albright syndrome (MAS) is a rare disorder of striking complexity with a prevalence of 1 in 100,000. It arises from somatic, gain-of-function mutations in GNAS.Aims and Objectives: The Present case series highlights varied manifestations of Mc Cune Albright syndrome.Case Details: C1: 6 y/o female presented with bleeding per vaginum, breast development. H/o pain in Right hip with difficulty in walking since 3 years. C2: 8 y/o female, presented with progressive genu varum and multiple dental caries. H/o vaginal bleeding and breast enlargement. C3: 6 y/o girl presented with inability to walk, bony pains. H/o multiple fractures with trivial trauma. C4: 16 year boy presented with acral enlargement, coarsening of facial features accelerated height gain. Clinical examination revealed acromegaloid features, gynaecomastia, expressive galactorrhea, goiter. Investigations showed elevated GH, IGF1, PRL. MRI brain showed pituitary enlargement. Clinical examination revealed multiple café au lait macules in all the cases and rachitic changes, hypophosphatemia with low TmP GFR in C2, C3; subclinical hyperthyroidism in C3. Hormonal profile was suggestive of GIPP. Bone scan showed polyostotic fibrous dysplasia.Conclusion: The broad phenotypic spectrum can make MAS a challenging disorder. All endocrinopathies should be evaluated and managed accordingly.

Giant Perineal Plexiform Neurofibroma in an 8-Year-Old African Male

Background: The perineal presentation of plexiform neurofibroma is exceptional, with only two cases reported to date. Case report: We present an 8-year-old African male with a large perineal tumor of years of evolution. He had no associated symptoms. Café au lait stains were observed on examination, without other findings of relevance. The patient had no preoperative radiological studies. Partial excision of the lesion was performed. Histopathological study of the specimen revealed a plexiform neurofibroma. Discussion: The lack of diagnostic suspicion due to the atypical nature of the location, the anatomical complexity of surgical resection and the potential urological and rectal involvement make this lesion a diagnostic-therapeutic challenge. Among the differential diagnoses, schwannoma, congenital lipoma, hamartoma and lipoblastoma should be considered.

A Case of Chiari Type 1 Malformation and Syringomyelia in Neurofibromatosis Type 1 Patient

A 26-year-old woman presented with skin pigmentation and numbness on the upper arm. More than six café au lait spots over 15 mm diameter could be seen throughout her skin. Neurofibromatosis (NF) type 1 was diagnosed based on genetic study. The brain magnetic resonance imaging (MRI) showed Chiari type 1 malformation and syringomyelia was noted in the C2 to T7 level in the spinal MRI. We suggest Chiari malformation and syringomyelia could be a rare manifestation in a patient with NF type 1.

Di‐genic inheritance of germline POLE and PMS2 pathogenic variants causes a unique condition associated with pediatric cancer predisposition

Polymerase proofreading-associated polyposis (PPAP) and Lynch syndrome, caused by mutated POLE and mismatch repair (MMR) genes, respectively, are associated with adult-onset cancer. PPAP and MMR-deficient tumors are both hypermutated, and each has a unique mutational signature. We describe a 4.5-year-old boy with multiple café au lait spots who presented with metastatic Sonic Hedgehog-activated medulloblastoma, with partial response to intensive chemotherapy and immunotherapy. The tumor showed microsatellite stability, loss of PMS2 nuclear expression, and an exceptionally high tumor mutational burden of 276 Mut/Mb. Germline molecular analysis revealed an inherited heterozygous pathogenic POLE variant and a de novo heterozygous PMS2 pathogenic variant. The tumor featured the MMR, POLE, and POLE+MMR mutational signatures. This is the first description of a di-genic condition, which we named "POL-LYNCH syndrome," manifested by an aggressive ultra-mutant pediatric medulloblastoma with a unique genomic signature.

Primary pilocytic astrocytoma of the cerebellopontine angle in pediatric patient with neurofibromatosis type 1: a case report

BackgroundCerebellopontine angle tumor (CPA) in pediatrics is rare as compared to adults. We describe a case of pediatric pilocytic astrocytoma presented as a right CPA mass with a concurrent clinical diagnosis of neurofibromatosis type 1 (NF1).Case presentationA 14-year-old boy with a newly diagnosed hypertension presented with a short history of headache and blurring vision. Neurological examination revealed bilateral papilloedema, partial right third nerve palsy and mild sensorineuronal hearing deficits. Skin examination identified multiple café au lait spots with cutaneous neurofibromas. Preoperative neuroimaging suggested the diagnosis of an extraaxial CPA mass consistent with meningioma, with obstructive hydrocephalus. A left ventriculoperitoneal shunt was inserted and the child was subjected for a suboccipital retrosigmoid approach for tumor resection. The histopathological features, however, were typical for pilocytic astrocytoma.ConclusionsA careful evaluation of the clinical presentation and radiological images of CPA lesions is necessary prior to surgical embarkment. To the best of our knowledge, this case is the first report of pilocytic astrocytoma in the CPA in pediatric with NF1.

Neurofibromatosis Type 1: About a Series of 5 Cases

We report in this series 5 cases of neurofibromatosis type 1 (NF1). The mean age of the patients was 14.8 years (±9.65) with extremes ranging from 3 to 27 years. Three patients were female (60%) and two were male (40%). Three of our patients (60%) had no history of NF1 and two were monophthalmic because of plexiform neurofibromas involving the eyelid. Both cutaneous and plexiform neurofibromas were found in all our patients. The latter were of variable location: one on the chin, two on the left temporofacial region and two on the left upper eyelid. They were the cause of complications such as blindness in two patients. Café au lait macule (CALMs) was also present in all our patients. No cases of optic nerve glioma were found in the 3 patients (60%) who underwent an orbitocerebral CT scan. Lish nodules were observed in 4 patients (80%). With the exception of the 3-year-old female patient who was not old enough to go to school, all the other four patients dropped out of school because of the stigma attached to them.

Cerebral developmental venous anomalies in children with mismatch repair deficiency

Constitutional mismatch repair deficiency (CMMRD) is one of the rare cancer predisposition syndromes. The aim of this study was to evaluate the cerebral developmental venous anomalies in children with central nervous system tumors associated with CMMRD, an area in which there is extremely little experience. Data from children diagnosed with medulloblastoma and high grade central nervous sytem tumor were retrospectively collected. According to the European CMMRD criteria, nine patients were diagnosed as CMMRD syndrome and the others consisted of the group without CMMRD. All radiological examinations of these children were retrospectively reviewed. Whole exome sequencing was performed to index cases` germline DNA. Nine children from four families, six females and three males, were studied. The median age at the first tumor diagnosis was 4.5 years (range, 9 months to 14 years). All CMMRD patients had café au lait spots, but none fulfilled the diagnostic criteria for neurofibromatosis. The patients developed high-grade glial tumor (n: 7) and medulloblastoma (n: 2). The affected genes in the three families were MSH6 [c.478C > T (p.Gln160Ter)], MSH6 [c.2871dupC (p.Phe958LeufsTer5)] and MLH1 [c.236G > A(p.Arg79Lys)], respectively. Seven patients had multiple developmental venous anomalies; six patients had leptomeningeal enhancement; and five patients had cavernomas. None of these findings were present in the group without CMMRD. Constitutional mismatch repair deficiency should be considered when multiple developmental venous anomalies, cavernomas, and leptomeningeal enhancement are detected, especially in patients with café au lait spots.

Mucosal Lesions Related to Toombak Dipping in the Sudanese

Background: Mucosal changes related to smokeless tobacco dipping appear to be influenced by many factors; including duration of dipping, frequency of dipping, chemical ingredients of the dipped stuff, in addition to possible genetic and racial factors. In the Sudan the habit of using smokeless tobacco (Toombak) is very common, and it is associated with pathological mucosal changes classified into five distinct clinical presentations: Presentation I; wrinkling with slight discoloration, Presentation II; Café au lait discoloration (Brownish discoloration), Presentation III; smoke-white discoloration, Presentation IV; grizzle discoloration, and Presentation V; cotton-white discoloration. Material and Methods: In this observational prospective study, a survey of oral cancer across 16 different localities was held in the Sudan. A total of 285 Toombak dippers agreed to be examined and of them 161 patients were found to have Toombak dipper-lesions. The clinical presentations of these lesions were identified and recorded into 5 different presentation categories. Furthermore, 64 specimens were cut and stained with Haematoxylin and Eosin (H&amp;E). Microscopic diagnosis was obtained using both WHO-5-Point grading classification and the binary system. The history of the time span was matched with the related clinical and microscopic findings. Results: Regarding the 161 cases; the lower vestibule was the preferred dipping site in 75(46.6%) cases. The average Age of Commencement (AoC) was 24.5 years. The average Estimated Contact Hours (ECH) was 22,338 ± 40,824 hours; equal to 2.55 contact years in lifetime. The dominant mucosal clinical presentation was wrinkling with/without slight discolouration; found in 54 cases, and accounting for 33.6% of the sample. Of the 64 specimens, 51 cases showed hyperkeratosis, 11 cases showed mild dysplasia and the remaining three cases showed severe dysplasia; two cases were cotton- white presentations, and one case was a grizzle presentation. Conclusion: Twenty per cent of Toombak dippers-lesions showed dysplastic cells. The grizzle and the cotton- white clinical presentations are associated with high-risk dysplasia. A significant relationship was found between the clinical presentation and the AoC. No significant relationship was found between the clinical presentation and the Impact of Time Duration (TD), in terms of life-time duration of dipping, number of dippings/day, dip-duration and the Estimated Contact Hours (ECH).

COVID-19 pregnant woman with widespread neurofibromatosis and suprasellar craniopharyngioma presenting for in labour: A challenging scenario

A 29 year old G3P2L2 presented at term in active labour and was tested to be COVID-19 positive. On examination she had multiple papules all over the limbs /abdomen; groin freckles and café au lait spots on the abdomen/lower limbs. She was evaluated for these lesions for the first time in this pregnancy at 20 weeks gestation and MRI brain had shown supra-sellarcraniopharyngioma. She didn’t return for ophthalmology/neurology opinion due to pandemic restrictions. So how does one deliver this patient?. Can vaginal delivery be allowed in the scenario of craniopharyngioma and the possibility of raised intracranial pressure during Valsalva?.

Prospective varieties of dahlia cultural (Dahlia x cultorum Thorsr. et Reis.) when growing for shearing in conditions of protected ground

Relevance. In terms of the richness of colors, shapes and sizes of inflorescences and relative unpretentiousness during cultivation, as well as the duration of flowering of a dahlia, the cultural has no equal. Basically, this flower crop is grown in the open field and used for landscaping areas. Dahlias, due to their decorative properties, are a promising crop for cutting. But the growth in the volume of industrial cultivation of cut dahlias has long been constrained by two negative factors - the low life expectancy of cut flowers, and the fact that not all varieties of cultivated dahlias are suitable for cultivation in greenhouses. Therefore, the search for varieties that meet the aforementioned properties is an especially urgent task.Material and methods. The material for the study was 10 varieties of Dahlia × cultorum Dutch selection. They belong to different groups of dahlias – spherical: Souvenir d'Eté, The Voice, Jowey Winnie; decorative – Orion, Café au Lait, Fleurel, Karma Choc and pompom dahlias: Little William, Cornel Bronze, Petra's Wedding, All tubers were planted in phytotron beds. Phenological observations of plants were carried out according to the Methodology of State Variety Testing of Ornamental Crops. During the growing season, the following indicators were determined: the onset of phenological phases of development, the dynamics of plant growth, the number and size of inflorescences, the length of the peduncle, the duration of flowering.Results. It was found that all the studied varieties of cultural dahlias have a high decorative effect and are suitable for growing for cutting in greenhouse conditions. Growing plants in a phytotron allows you to get a high-quality cut almost two months ahead of time, as well as have a longer and more abundant flowering. It was found that the Café au Lait cultivar is not entirely suitable for cut cultivation in greenhouses or requires the development of cultivation technology that is individual for this cultivar. It was found that the Fleurel variety surpasses other studied varieties in terms of decorativeness, inflorescence size, peduncle length, onset time and flowering duration. A significant disadvantage of the variety is its high growth and fragility of the peduncles. The most popular cut varieties were Fleurel, Petra's Wedding, Jowey Winnie and Little William. It was found that the studied varieties of cultural dahlias were distinguished not only by high decorativeness, but also by high durability in a vase from 5 to 7 days.

Solitary congenital neurofibroma with overlying melanocytic hyperplasia.

The common embryonic origin of neuroid and melanocytic cells justifies the simultaneous presence of the two cell types in the same neoformation (3). Neurofibroma (NF) can be solitary, diffuse when it has a large extension, and plexiform when it appears as a collection of multiple nodules and cordoniform structures. 10% of diffuse NFs and almost all plexiform NFs are associated with neurofibromatosis (1, 2). Then there is the so-called pigmented or melanotic NF, in which a part of the cells making up the neoplasm is loaded with melanin; this finding is present exclusively in syndromic NF, ie associated with neurofibromatosis. Thus, screening for neurofibromatosis is warranted in the case of plexiform, diffuse, multi-element and melanotic NF (4). In 28% of syndromic NFs and in 4.6% of sporadic NFs there is also a proliferation of epidermal melanocytes, most often in the form of lentiginous melanocytic hyperplasia, but exceptionally in the form of junctional nevus (4). Before assuming that melanocytic hyperplasia is related to NF, it must be considered that melanocytic hyperplasia is also found in cafe au lait spots and therefore we could face a cafe au lait spot superimposed on the NF; this hypothesis should be discarded since lentiginous hyperplasia is also found in sporadic NF and because in any case the histological finding does not always correspond to a clinically evident hyperpigmentation. A casual collision between two different pathologies could also be hypothesized, but this hypothesis is discarded because the limits of melanocytic hyperplasia coincide perfectly with those of the underlying NF (4).

CONSTITUTIONAL MISSMATCH DEFECT REPAIR DISORDER (CMMRD) IN PEDIATRIC HIGH GRADE GLIOMA

Pediatric high grade gliomas(HGG) have dismal prognosis with median survival of 9-15 months after standard radio-chemptherapy. Recent molecular investigations revealed a missmatch repair defect called Constitutional Mismatch Repair Deficiency (CMMRD), which induce pediatric HGG. In CMMRD, there are mutations at least one of the mismatch repair(MMR) genes in both tumoral and non-tumoral DNA. Patients generally have cafe au lait spots resembling the ones in NF-1. Forty-four pediatric high-grade glioma cases operated in our clinic between 2015-2021 were included in the study. PMS2, MLH1, MSH6, MSH2 immunohistochemical antibodies were applied to the sections prepared from paraffin blocks with tumors of these 44 cases. Next generation Sequencing (NGS) Custom Panel for Brain Tumors was performed with DNA and RNA obtained from neoplastic tissue of 2 cases and germline NGS analysis was performed with DNA obtained from peripheral blood in 1 case. MMR protein expression loss was detected in 11 (25%) cases. In 5 (45%) of these 11 cases, MMR protein loss was detected in both neoplastic and non-neoplastic tissue, and these cases were considered as CMMRD. NGS performed in 2 of these 5 cases revealed a hypermutant profile. At least one MMR protein loss was found only in the neoplastic tissue in 6 (55%) of 11 cases, and PMS2 deficiency was the most common. In 1 of these 6 cases, MSH6 deficiency was shown as germline by NGS. CMMRD and MMRD, are disorders with close relationship with pediatric high grade gliomas. Since CMMRD cases also may have cafe au lait spots, they should not be misdiagnosed as NF 1. Temozolomide induce more aggressive tumors in CMMRD ve MMRD, therefore its use is not suggested in those cases. Preliminary literature data advocate use of immunotherapy instead. All pediatric HGG cases should be evaluated for CMMRD and MMRD with molecular investigations to understand their biology.

Mandibular neurofibroma with osseous deformities in a 3-year-old child with neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a rare autosomal dominant genetic disorder. It is a multisystem neurocutaneous condition represented by multiple benign tumors of the nerves and skin known as neurofibromas and cafe' au lait spots. However, neurofibroma localized in the mandible is rare. We present a case of a 3-year-old, Egyptian girl with NF1. The girl presented with right mandibular swelling of undetermined duration and multiple hyperpigmented spots on the skin. This case report shows the important role of dentists, as demonstrated in the present case, in the diagnosis and management of this disease, since the diagnosis was made during dental consultation and subsequently managed by the team.