This case report is one of the rare cases of bilateral pheochromocytoma associated with neurofibromatosis type 1. The interest lies in the clinical form in which the diagnosis was revealed. We report the case of a 38-year-old woman admitted for severe hypertension resistant to triple therapy. Clinical examination revealed Cafe-au-lait spots, which are pigmented birthmarks that appear as patches on the skin with a light to dark brown colour. More than six spots are present in an estimated 95% of people diagnosed with neurofibromatosis type 1 (NF1). Abdominal computed tomography (CT) showed bilateral adrenal tumor involvement. The diagnosis of pheochromocytoma was made by measuring urinary Vanillylmandelic acid (VMA). The evolution was favorable after the excision of the tumor, with normalization of blood pressure. In conclusion: resistant hypertension with café au lait spots may indicate pheochromocytoma, especially bilateral, suggesting an underlying genetic condition like NF1, warranting systematic screening.
En este reporte se documenta un caso raro de feocromocitoma bilateral asociado a neurofibromatosis tipo 1. El interés radica en la forma clínica en la que se reveló el diagnóstico. Presentamos el caso de una mujer de 38 años que ingresa por hipertensión arterial severa resistente a triple terapia. El examen clínico reveló manchas café con leche, que son marcas de nacimiento pigmentadas que aparecen como manchas en la piel y que son de un color marrón claro a oscuro. Se estima que el 95% de las personas diagnosticadas con neurofibromatosis tipo 1 (NF1) presentan más de seis manchas. La tomografía computarizada (TC) abdominal mostró afectación tumoral suprarrenal bilateral. El diagnóstico de feocromocitoma se realizó mediante la medición del ácido vanilmandélico (VMA) urinario. La evolución fue favorable tras la extirpación del tumor, con normalización de la presión arterial. En conclusión, la hipertensión resistente con manchas café con leche puede indicar feocromocitoma, especialmente si es bilateral, lo que sugiere una afección genética subyacente como la NF1, que justifica un tamizaje sistemático.

BACKGROUND: The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1manifestations (e.g., neurocognitive function, growth reduction, and café-au-lait spots) are unknown.
METHODS: This open-label, phase 2 trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥ 3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hrs for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated.
RESULTS: Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22±5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥ 20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P <0.05). Prepubertal patients showed increases in height score and growth velocity (P <0.05). Café-au-lait spot intensity decreased significantly (P <0.05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation.
CONCLUSIONS: Selumetinib decrease PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in non-malignant diverse NF1 manifestations.

Neurofibromatosis-Noonan syndrome is a rare RASopathy syndrome. It occurs due to the mutation in the NF1 gene and the patients present with the phenotypic features of both Neurofibromatosis and Noonan syndrome. Here a case of an early adolescent girl is described who presented with the chief complaint of primary amenorrhoea and on evaluation was diagnosed to be a patient of Neurofibromatosis-Noonan syndrome. The index case was short-statured with a short and broad neck. Physical examination revealed a pointed pinna, hypertelorism, telecanthus, characteristic facies, and multiple freckles all over the body. She also had numerous atypical café-au-lait spots. Whole genome sequencing revealed Neurofibromatosis-Noonan syndrome which was likely a pathogenic variant causative of the typical phenotype present with a mutation in the neurofibromin gene (NF1) on chromosome 17q11. We discuss here the management and follow-up of the case.

Aneurysmal coronary artery disease (ACAD) has been reported rarely in patients with neurofibromatosis type 1 (NF1), mostly in adults. We report on a female newborn affected by NF1 with ACAD disclosed during investigation for an abnormal prenatal ultrasound along with a review of the previously reported cases. The proposita had multiple café-au-lait spots and had no cardiac symptoms. Echocardiography, and cardiac computed tomography angiography confirmed aneurysms on the left coronary artery, left anterior descending coronary artery, and of the sinus of Valsalva. Molecular analysis detected the pathogenic variant NM_001042492.3(NF1):c.3943C>T (p.Gln1315*). Literature findings on ACAD in NF1 indicated that this mostly occurs in males, showing predilection for the development of aneurysms at the left anterior descending coronary artery, and manifesting predominantly as acute myocardial infarction, inclusively in teenagers, though it may be also asymptomatic as in our case. This report documents the first case of ACAD in a patient with NF1 diagnosed at birth, emphasizing that its early diagnosis is essential to prevent potential life-threatening events attributable directly to coronary lesions.

Neurofibromatosis type 1 (NF1) is one of the most common inherited disorders. It is caused by mutations in the neurofibromin-1 gene ( NF1 ) and affects the formation and growth of nerve tissues. More than 3,600 pathogenic variants in the NF1 gene have been identified from patients with most of the germline variants are from the Western populations. We found 16 patients (15 Chinese and 1 Asian Indian) who had heterozygous variants in NF1 through targeted next-generation sequencing. There were 15 different variants: 4 frameshift, 4 nonsense, 5 missense, and 2 splice variants. One nonsense variant and three frameshift variants had never been reported in any population or patient database. Twelve of the 16 patients met the NF1 diagnostic criteria, and each was found to have a pathogenic or likely pathogenic variant. Three different missense variants of unknown significance were discovered in the other four patients who did not meet NF1 diagnostic criteria. Our findings add four novel variants to the list of genetic mutations linked to NF1\'s various clinical manifestations.

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McCune-Albright syndrome (MAS) is a complex endocrinopathy with polyostotic fibrous dysplasia and café-au-lait spots. Pathological femoral shaft fracture along with MAS is not a common occurrence. Bisphosphonates can be used for the management of pathological fractures. A seven-year-old male child presented with pathological femoral shaft fracture with MAS (café-au-lait macules and hyperthyroidism). The patient was managed conservatively with closed reduction along with hip spica and oral alendronate. Fracture consolidation occurred within six to eight weeks with improvement in bone pains. Oral alendronate can be used as an adjuvant to conservative therapy for pathological fracture in MAS in children.

Neurofibromatosis type 1 (NF1) is one of the most common genetic neurocutaneous disorders. The hallmark of this disease is skin lesions in the form of café-au-lait spots, ephelides, and the characteristic cutaneous neurofibromas. Other common manifestations include bone abnormalities, \"NF1 vasculopathy,\" and neurocognitive disorders. In addition, patients are at an increased risk for a wide variety of malignant neoplasms, including the malignant transformation of plexiform neurofibromas. It is necessary to know the various clinical characteristics of this disorder and to provide an early, multidisciplinary follow-up and treatment approach in order to provide optimal care to these patients, who present with a multisystemic disease that is potentially severe. This review summarizes the diagnosis and main clinical characteristics and suggests a protocol for screening and follow-up of adult patients with NF1.

Neurofibromatosis type 1 (NF1) or von Recklinghausen disease is one of the most common autosomal dominant genetic diseases. It is characterized by \'café-au-lait\' spots and multiple tumors starting from the central and peripheric nervous system. The diagnosis is determined on two out of seven criteria: i) A total of 6 or more light brown spots larger than 5 mm in diameter (pre-puberty) or 15 mm in diameter (post-puberty); ii) a total of 2 or more neurofibromas or one plexiform neurofibroma; iii) axillary or inguinal freckling; iv) optic glioma; v) a total of 2 or more Lisch nodules; vi) bone abnormalities: tibia pseudarthrosis or dysplasia of the sphenoid wing; and vii) a relative of first degree having an NF1 diagnosis. A total of ~50% of patients have significant musculoskeletal manifestation, with scoliosis and congenital pseudarthrosis of tibia most common. Management of the orthopaedic manifestations of NF1 is often difficult. Due to NF1 influencing multiple organ systems, patients are likely to benefit most from a multidisciplinary treatment strategy.

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.