Background: Neurofibromatosis type 1 (NF1) is a complex neurocutaneous disorder caused by pathogenic variants in the NF1 gene. Although genotype–phenotype correlation studies are increasing, robust clinically relevant correlations have remained limited. Methods: We conducted a retrospective analysis of data obtained from a cohort of 204 Hungarian individuals, with a mean age of 16 years (age range: 1–33 years). The data were collected over 15 years. Results: Among the cohort of 204 patients, 148 subjects fulfilled ≥2 criteria established by the National Health Institute. Genetic testing was performed in 70 patients, with an 82.8% detection rate, of which 13 patients were excluded. Among the remaining 45 pathogenic variants, 17 (37.7%) frameshift, 11 (24.4%) nonsense, 8 (17.8%) splice-site, 4 (8.9%) missense mutations, and 5 (11.11%) copy number variations (CNVs) were detected. Café-au-lait macules were present in all patients (100%). Intracranial malformations were the second most common feature (55.6%), followed by Lisch nodules (35.6%), neurofibromas (33.3%), and skeletal abnormalities (31.1%). Conclusions: In our cohort, patients with splice-site variants (8/45, 17.8%) demonstrated a notably more severe phenotype compared to findings reported in other studies, with a high prevalence of plexiform neurofibromas (37.5%), intracranial findings (62.5%), skeletal abnormalities (50%), Lisch nodules (50%), and even pseudarthrosis (25%). Correlating with the literature, missense variants represented a mild phenotype, while patients with microdeletion syndrome revealed a more severe phenotype.

Plexiform neurofibromas occurring in approximately 20–50% of all neurofibromatosis type-1 (NF1) cases are histologically benign tumors, but they can be fatal due to compression of vital structures or transformation to malignant sarcomas or malignant peripheral nerve sheath tumors. All sizeable plexiform neurofibromas are thought to result from an early second mutation giving rise to a loss of heterozygosity of the NF1 gene. In this unusual case, a 12-year-old girl presented with a rapidly growing, extremely extensive plexiform neurofibroma with segmental distribution over the entire right arm, extending to the right chest wall and mediastinum, superimposed on classic cutaneous lesions of NF1. After several surgical interventions, the patient was efficiently treated with an oral selective MEK inhibitor, selumetinib, which resulted in a rapid reduction of the tumor volume. Molecular analysis of the NF1 gene revealed a c.2326-2 A>G splice-site mutation in the clinically unaffected skin, peripheral blood sample, and plexiform neurofibroma, which explains the general clinical symptoms. Furthermore, a novel likely pathogenic variant, c.4933dupC (p.Leu1645Profs*7), has been identified exclusively in the girl’s plexiform neurofibromas. This second-hit mutation can explain the extremely extensive segmental involvement.

Purpose: The aims of this study were to compare the clinical manifestations of neurofibromatosis type 1 in the Hungarian population with global data and to establish a standardised diagnostic and follow-up protocol for neurofibromatosis type 1 patients in Hungary. Materials/Methods: We retrospectively analysed the clinical and genetic data of 262 individuals diagnosed with multiple café-au-lait macules or neurofibromatosis type 1 at the Heim Pál National Paediatric Institute between 1 January 2010 and 31 January 2025. The study assessed neurofibromatosis type 1 diagnostic criteria, associated complications, genetic testing outcomes, and disease burden in order to refine diagnostic accuracy and optimise follow-up strategies. Results: Of the 231 individuals fulfilling at least one National Institutes of Health diagnostic criterion, 175 met at least two criteria confirming neurofibromatosis type 1. Genetic testing was performed on 88 patients, and pathogenic variants were identified in 80% of them. Plexiform neurofibromas were detected in 17.7% of patients, optic pathway gliomas in 11.4%, and skeletal abnormalities in 38.2%. Neurodevelopmental disorders were frequently observed, including cognitive impairment, attention deficit hyperactivity disorder, and autism spectrum disorder. Focal areas of signal intensity were present in 56% of patients. A comprehensive follow-up protocol was developed, emphasising early diagnosis, regular dermatological, ophthalmological, neurodevelopmental and orthopaedic assessment, and imaging-based surveillance in high-risk cases. Conclusions: Our findings provide epidemiological data on the Hungarian neurofibromatosis type 1 population and confirm the need for standardised surveillance and interdisciplinary management. Integrating genetic insights and innovative therapeutic options into clinical practice may enhance patient outcomes and guide future treatment strategies.

Background: Livedoid vasculopathy (LV) and cutaneous arteritis (CA) are rare cutaneous diseases. A consideration of these two conditions as different entities is debatable, because thrombosis and inflammation are closely related in their pathogenesis mechanisms. Varying reports on the effectiveness of anticoagulant and immunosuppressant therapies in LV and CA also point to diagnostic challenge and overlap in these conditions.Objectives: We sought to assess the therapeutic effect of anticoagulation therapy in adult patients with CA, who were recalcitrant to immunosuppressive modalities.Methods: A monocentric retrospective analysis of adult patients who were diagnosed with CA between 2010 and 2018, was carried out.Results: We describe 8 cases of long‐term recalcitrant CA, in whom anticoagulation therapy significantly reduced the pain and cutaneous symptoms. All patients had cutaneous symptoms compatible with CA along with clinical features also characteristic of LV, including underlying procoagulative disorders in the majority (87.5%), as confirmed by screening for thrombophilia. We also review current concepts regarding LV and CA, and suggest vascular occlusion is a common link between these two entities.Conclusions: Although current knowledge advocates segregating vasculopathy from vasculitis by means of histopathological examination in LV and CA, clinical experience suggests some overlap and common complex underlying pathomechanisms.