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Selumetinib is clinically used for pediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas. Until recently, selumetinib had to be taken twice daily, after 2 hours of fasting and followed by 1 hour of fasting, which could be inconvenient. This population analysis evaluated the effect of low‐ and high‐fat meals on the pharmacokinetic (PK) parameters of selumetinib and its active metabolite N‐desmethyl selumetinib. The dataset comprised 511 subjects from 15 clinical trials who received ≥1 dose of selumetinib and provided ≥1 measurable postdose concentration of selumetinib and N‐desmethyl selumetinib. A 2‐compartment model with sequential 0‐ and 1st‐order delayed absorption and 1st‐order elimination adequately described selumetinib PK characteristics. A 1‐compartment model reasonably described N‐desmethyl selumetinib PK characteristics over time simultaneously with selumetinib. Selumetinib geometric mean area under the concentration–time curve ratio (1‐sided 90% confidence interval [CI] lower bound) was 76.9% (73.3%) with a low‐fat meal and 79.3% (76.3%) with a high‐fat meal versus fasting. The lower bound of the 1‐sided 90% CI demonstrated a difference of <30% between fed and fasted states. Considering the flat exposure‐response relationship within the dose range (20‐30 mg/m2), the observed range of exposure, and the variability in the SPRINT trial, this was not considered clinically relevant. [ABSTRACT FROM AUTHOR]

Background: Neurofibromatosis type 1 is an autosomal-dominant disease characterized by café-au-lait spots and neurofibromas, as well as various other symptoms in the bones, eyes, and nervous system. Due to its connection with vascular fragility, neurofibromatosis type 1 has been reported to be associated with vascular lesions, such as aneurysms. However, there have been few reports of abdominal visceral aneurysms associated with neurofibromatosis type 1. Furthermore, there have been no reports of robotic treatment of aneurysms associated with neurofibromatosis type 1. In this report, we describe the case of a patient with neurofibromatosis type 1 with a splenic artery aneurysm who was successfully treated with robotic surgery. Case presentation: This report describes a 41-year-old Asian woman with a history of neurofibromatosis type 1 who was referred to our hospital for evaluation of a 28 mm splenic artery aneurysm observed on abdominal ultrasound. The aneurysm was in the splenic hilum, and transcatheter arterial embolization was attempted; however, this was difficult due to the tortuosity of the splenic artery. Thus, we suggested minimally invasive robotic surgery for treatment and resection of the splenic artery aneurysm with preservation of the spleen. The postoperative course was uneventful, and the patient was discharged on the eighth day after surgery. At 1 year of follow-up, the patient was doing well, with no evidence of recurrence. Conclusion: We encountered a rare case of splenic artery aneurysm in a patient with neurofibromatosis type 1 who was successfully treated with robotic surgery. There is no consensus on treatment modalities for neurofibromatosis-related aneurysms, and endovascular treatment is considered safe and effective; however, surgery remains an important treatment modality. Especially in patients with stable hemodynamic status, robotic surgery may be considered as definitive treatment. To our knowledge, this is the first successfully treated case of a splenic artery aneurysm in a patient with neurofibromatosis type 1. [ABSTRACT FROM AUTHOR]

Purpose: Plexiform neurofibromas (PNF) are rare tumors arising from peripheral nerve sheath cells. PNF are a hallmark in patients with neurofibromatosis type 1 (NF1), a tumor predisposition syndrome. PNF often grow invasively and destructively, what may complicate surgical treatment. Data on frequency, location, and surgical procedures of patients with NF1-associated FPNF are scarce. This study provides treatment data of NF1 patients. Methods: Localization and treatment data of 69 NF1 patients with neck PNF were analyzed. Frequency of lesions was recorded in coded colors on schematic neck drawings. Results: The tumors showed no side preference, were located in the entire area under investigation, and did not respect anatomical units/dermatomes. However, the sternocleidomastoid region was particularly frequently affected. The mean number of surgical measures per patient was 1.33. Complications were extensive swelling, hematoma, and bleeding. Histological assessment usually confirmed the clinical assessment of neoplasm. However, histologic differentiation of PNST reveals differences in between tumors that have been unified in clinical assessment as PNF. Conclusion: The color-coded, schematic overview of the frequency distribution of surgical neck interventions in NF1 patients with PNF proved a useful tool to gain assessment of preferred treatment needs. The imaging procedure may be suitable for controlling the external aspect of natural tumor development (growth, effects of aging) in the same way as the documentation of the post-surgical course. Treatment plans for patients with these tumors should consider that repeated interventions may be necessary to achieve a longer-term stable result. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 is a genetic disorder impacting approximately 2.5 million people worldwide, often leading to development of numerous benign yet disfiguring cutaneous neurofibromas (cNF). Removal of cNF is limited to excision or laser ablation with common post-operation complications and scarring. The current case explores a new approach to removal or reduction of cNF by a minimally invasive and pain-reduced treatment modality. A 40-year-old female patient with numerous cNF across her body underwent a single treatment using a 20 MHz dermatologically focused ultrasound device on seven selected cNF on the upper back. Each cNF was treated in a single session of 20–60 s without anesthesia due to manageable pain. Only one minimal adverse reaction in the form of dyspigmentation in a single treated tumor was noted from treatment or during the healing of a thin scab that formed on each cNF a few days after treatment. At the 12-month follow-up, four out of seven treated cNF showed full remission, two showed partial or significant reduction in tumor volume, while two did not respond to treatment. The reason for the variability is not fully understood, but speculations include difference in tissue content, e.g., due to tumor age. The method is concluded to be a promising candidate for a new safe and minimally invasive treatment that can potentially be used for single-session removal/reduction of a large number of cNF. Further research should focus on refining treatment parameters and strategies to enhance response predictability. [ABSTRACT FROM AUTHOR]

Optic pathway glioma (OPG) occurs in as many as one-fifth of individuals with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Generally considered low-grade and slow growing, many children with NF1-OPGs remain asymptomatic. However, due to their location within the optic pathway, ~20-30% of those harboring NF1-OPGs will experience symptoms, including progressive vision loss, proptosis, diplopia, and precocious puberty. While treatment with conventional chemotherapy is largely effective at attenuating tumor growth, it is not clear whether there is much long-term recovery of visual function. Additionally, because these tumors predominantly affect young children, there are unique challenges to NF1-OPG diagnosis, monitoring, and longitudinal management. Over the past two decades, the employment of authenticated genetically engineered Nf1-OPG mouse models have provided key insights into the function of the NF1 protein, neurofibromin, as well as the molecular and cellular pathways that contribute to optic gliomagenesis. Findings from these studies have resulted in the identification of new molecular targets whose inhibition blocks murine Nf1-OPG growth in preclinical studies. Some of these promising compounds have now entered into early clinical trials. Future research focused on defining the determinants that underlie optic glioma initiation, expansion, and tumor-induced optic nerve injury will pave the way to personalized risk assessment strategies, improved tumor monitoring, and optimized treatment plans for children with NF1-OPG. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome, occurs when NF1 gene variants result in loss of neurofibromin, a negative regulator of RAS activity. Plexiform neurofibromas (PN) are peripheral nerve sheath tumors that develop in patients with NF1 and are associated with substantial morbidity and for which, until recently, the only treatment was surgical resection. However, surgery carries several risks and a proportion of PN are considered inoperable. Understanding the genetic underpinnings of PN led to the investigation of targeted therapies as medical treatment options, and the MEK1/2 inhibitor selumetinib has shown promising efficacy in pediatric patients with NF1 and symptomatic, inoperable PN. In a phase I/II trial, most children (approximately 70%) achieved reduction in tumor volume accompanied by improvements in patient-reported outcomes (decreased tumor-related pain and improvements in quality of life, strength, and range of motion). Selumetinib is currently the only licensed medical therapy indicated for use in pediatric patients with symptomatic, inoperable NF1-PN, with approval based on the results of this pivotal clinical study. Several other MEK inhibitors (binimetinib, mirdametinib, trametinib) and the tyrosine kinase inhibitor cabozantinib are also being investigated as medical therapies for NF1-PN. Careful consideration of multiple aspects of both disease and treatments is vital to reduce morbidity and improve outcomes in patients with this complex and heterogeneous disease, and clinicians should be fully aware of the risks and benefits of available treatments. There is no single treatment pathway for patients with NF1-PN; surgery, watchful waiting, and/or medical treatment are options. Treatment should be individualized based on recommendations from a multidisciplinary team, considering the size and location of PN, effects on adjacent tissues, and patient and family preferences. This review outlines the treatment strategies currently available for patients with NF1-PN and the evidence supporting the use of MEK inhibitors, and discusses key considerations in clinical decision-making. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is a multisystem disorder that causes multiple tumor formations throughout the nervous system. Common spinal dysplasias seen with NF1, such as dural ectasia (DE), often undergo modulation and predispose these patients to spondylolisthesis, making surgical treatment challenging. A patient with NF1 presented with a 12-year-history of back and left lower extremity radicular pain. Lumbar spine magnetic resonance imaging revealed developmental anomalies with severe DE and associated scalloping of the L4-S1 vertebral bodies and severe L5-S1 Meyerding grade 4 spondylolisthesis. During surgery, post-positioning x-rays demonstrated a grade 5 spondyloptosis. The patient underwent an L5-S1 stand-alone anterior lumbar interbody fusion (ALIF). The final construct was an ALIF cage with one screw into S1, without an anterior plate. By 3-months post-operative, there was complete resolution of preoperative symptoms and at 2 year follow-up the patient was asymptomatic with stable hardware and solid bony fusion. To the authors' knowledge, this is the first report of spondyloptosis treated with a stand-alone ALIF in a patient with NF1 and severe DE. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We report a 20‐year‐old man with neurofibromatosis type 1 presenting with frequent episodes of suprapubic pain. The episodes started 6 months ago, occurred 1 h a day, and were not related to urination. A prostate‐sparing cystectomy with orthotopic diversion was performed. Histopathological assessment of the specimen confirmed bladder plexiform neurofibromatosis. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 is an autosomal-dominant condition caused by NF1 gene inactivation. Clinical diagnosis is corroborated by genetic tests on gDNA and cDNA, which are inconclusive in approximately 3–5% of cases. Genomic DNA approaches may overlook splicing-affecting intronic variants and structural rearrangements, especially in regions enriched in repetitive sequences. On the other hand, while cDNA-based methods provide direct information about the effect of a variant on gene transcription, they are hampered by non-sense-mediated mRNA decay and skewed or monoallelic expression. Moreover, analyses on gene transcripts in some patients do not allow tracing back to the causative event, which is crucial for addressing genetic counselling, prenatal monitoring, and developing targeted therapies. We report on a familial NF1, caused by an insertion of a partial LINE-1 element inside intron 15, leading to exon 15 skipping. Only a few cases of LINE-1 insertion have been reported so far, hampering gDNA studies because of their size. Often, they result in exon skipping, and their recognition of cDNA may be difficult. A combined approach, based on Optical Genome Mapping, WGS, and cDNA studies, enabled us to detect the LINE-1 insertion and test its effects. Our results improve knowledge of the NF1 mutational spectrum and highlight the importance of custom-built approaches in undiagnosed patients. [ABSTRACT FROM AUTHOR]

Background: Neurofibromatoses are a rare group of autosomal dominant tumor suppressor phacomatoses syndromes. Neurofibromatosis type 1 (NF1 or Von Recklinghausen's disease) is the most commonly found type of neurofibromatosis, and constitutes the most commonly found autosomal dominant disease of the nervous system. Case presentation: We report a case of a 14-year-old boy who reported a 3-year-history of a slowly enlarging right lateral cervical mass. He has a medical history of a progressive limping gait disorder with scoliotic attitude. MRI identified a dumb-bell shaped intradural right cervical process through right paravertebral gutter on C2 to C4, a second intradural dorsal mass with the same characteristics through left paravertebral gutter on D4 and D5 and a large tissue-like mass infiltrating the lumbosacral subcutaneous soft tissues. A Surgical excision of the cervical and lumbar masses was performed with a good outcome after surgical excision. Conclusions: This case illustrates the need for a collaboration of both neurological and head and neck surgeons in terms of managing difficulties related to a cervical neurofibroma. Benign plexiform neurofibromas are rapidly growing tumors, particularly in children and adolescents, which makes all the importance of early detection and appropriate treatment. Repeated interventions are usually needed in order to adapt and stabilize the tumors extension. [ABSTRACT FROM AUTHOR]

Simple Summary: At present, no systematic study of the clinical spectrum and molecular characteristics of NF1 patients with spinal neurofibromatosis (SNF), a phenotypic subclass of neurofibromatosis 1 (NF1), has been carried out. Here, we provide evidence that SNF patients are at high risk of problematic neurofibromas, presenting not only bilateral neurofibromas involving all spinal roots, but also a higher incidence of internal neurofibromas and nerve root swelling. From a histopathological view, not only neurofibromas, but also neurogangliomas are present in SNF. The analysis of 19 families with at least 1 member affected by SNF showed a high phenotypic variability within the SNF families. Furthermore, we discovered a higher prevalence of missense mutations in SNF compared to classical NF1. Both clinical features and genetic testing can help in identifying cases at risk of SNF, and that are more likely to benefit from a spinal MRI scan. Spinal neurofibromatosis (SNF), a phenotypic subclass of neurofibromatosis 1 (NF1), is characterized by bilateral neurofibromas involving all spinal roots. In order to deepen the understanding of SNF's clinical and genetic features, we identified 81 patients with SNF, 55 from unrelated families, and 26 belonging to 19 families with at least 1 member affected by SNF, and 106 NF1 patients aged >30 years without spinal tumors. A comprehensive NF1 mutation screening was performed using NGS panels, including NF1 and several RAS pathway genes. The main features of the SNF subjects were a higher number of internal neurofibromas (p < 0.001), nerve root swelling (p < 0.001), and subcutaneous neurofibromas (p = 0.03), while hyperpigmentation signs were significantly less frequent compared with the classical NF1-affected cohorts (p = 0.012). Fifteen patients underwent neurosurgical intervention. The histological findings revealed neurofibromas in 13 patients and ganglioneuromas in 2 patients. Phenotypic variability within SNF families was observed. The proportion of missense mutations was higher in the SNF cases than in the classical NF1 group (21.40% vs. 7.5%, p = 0.007), conferring an odds ratio (OR) of 3.34 (CI = 1.33–10.78). Two unrelated familial SNF cases harbored in trans double NF1 mutations that seemed to have a subclinical worsening effect on the clinical phenotype. Our study, with the largest series of SNF patients reported to date, better defines the clinical and genetic features of SNF, which could improve the management and genetic counseling of NF1. [ABSTRACT FROM AUTHOR]

This article, published in the journal JCEM Case Reports, discusses a case of a 27-year-old pregnant woman who was diagnosed with pheochromocytoma, a rare tumor of the adrenal glands, during her pregnancy. The woman also had features of neurofibromatosis type 1, a genetic condition characterized by the development of tumors in the nervous system. The article highlights the importance of recognizing the symptoms of neurofibromatosis type 1, such as iris hamartomas, café-au-lait macules, and skinfold freckling, for early diagnosis. It also emphasizes that pheochromocytomas can be successfully managed during pregnancy with medical therapy. [Extracted from the article]

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that affects nearly 1 in 3000 infants. Neurofibromin inactivation and NF1 gene mutations are involved in various aspects of neuronal function regulation, including neuronal development induction, electrophysiological activity elevation, growth factor expression, and neurotransmitter release. NF1 patients often exhibit a predisposition to tumor development, especially in the nervous system, resulting in the frequent occurrence of peripheral nerve sheath tumors and gliomas. Recent evidence suggests that nerves play a role in the development of multiple tumor types, prompting researchers to investigate the nerve as a vital component in and regulator of the initiation and progression of NF1-related nervous system tumors. Conclusion: In this review, we summarize existing evidence about the specific effects of NF1 mutation on neurons and emerging research on the role of nerves in neurological tumor development, promising a new set of selective and targeted therapies for NF1-related tumors. [ABSTRACT FROM AUTHOR]

Neurofibromatosis (NF) is a group of disorders that is caused by a genetic mutation which is dominantly inherited neurogenetic disorder. They are of three types: NF1, NF2, and schwannomatosis. Out of these three, NF1 is the most common. NF1 mainly affects the skin, peripheral and central nervous system, bones, cardiovascular, and endocrine systems. Tuberculosis is a bacterial infection of the lung that is caused by Mycobacterium tuberculosis. It spreads by speaking, sneezing, and coughing in the air. Active pulmonary infections can spread to other people. Here, we represent a case of a 45-year-old male diagnosed with pulmonary tuberculosis (PTB) presenting with breathlessness, fever, loss of appetite, runny nose, nervousness, and dry cough. The patient had multiple swellings over the body with papules and nodules seen on different parts of the body. Cafe-au-lait macules were also present. After the all-over examination, the patient was diagnosed with smear-positive PTB with NF1. [ABSTRACT FROM AUTHOR]

Background: Superior rectal artery (SRA) aneurysms are rare. Although melena is the most common symptom, it has not been observed in cases of aneurysms located in the SRA trunk. Here, we report a case of a ruptured SRA trunk aneurysm successfully treated with coil embolization. Including our case, three of the four reported cases of SRA trunk aneurysms were related to neurofibromatosis type 1 (NF1). Case presentation: A 52-year-old woman with NF1 was referred to our hospital for the investigation of an abdominal mass with back pain. She had previously undergone a blood transfusion at another hospital for anemia without melena. Computed tomography angiography revealed a ruptured SRA trunk aneurysm measuring 3 cm in diameter and surrounded by a retroperitoneal hematoma. The aneurysm was isolated by embolizing the SRA trunk distally and proximally. Distal embolization was performed retrogradely from the internal iliac artery (IIA) via the middle rectal artery (MRA)-SRA anastomosis because the antegrade approach from the inferior mesenteric artery (IMA) failed. To our knowledge, this is the first case of successful coil embolization of an IMA branch through the IIA. Conclusion: SRA trunk aneurysms are rare; however, they are frequently associated with NF1. Antegrade distal embolization beyond the aneurysm is sometimes difficult to achieve. In such cases, a retrograde approach via MRA-SRA anastomosis can be the choice for isolating SRA trunk aneurysms. [ABSTRACT FROM AUTHOR]

Trametinib has been used in neurofibromatosis type 1 (NF1) patients, especially those with unresectable nerve tumors, but no systematic review based on the latest studies has been published. We conducted this meta-analysis to evaluate the effectiveness and safety of trametinib in treating NF1-related nerve tumors. Original articles reporting the efficacy and safety of trametinib in NF1 patents were identified in PubMed, EMBASE, and Web of Science up to 1 June 2022. Using R software and the 'meta' package, the objective response rates (ORRs) and disease control rates (DCRs) were calculated to evaluate the efficacy, and the pooled proportion of adverse events (AEs) was calculated. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence. Eight studies involving 92 patients were included, which had a very low to moderate quality of evidence. The pooled ORR was 45.3% (95% CI: 28.9–62.1%, I2 = 0%), and the DCR was 99.8% (95% CI: 95.5–100%, I2 = 0%). The most common AEs was paronychia, with a pooled rate of 60.7% (95% CI: 48.8–72.7%, I2 = 0%). Our results indicate the satisfactory ability to stabilize tumor progression but a more limited ability to shrink tumors of trametinib in NF1-related nerve tumors. The safety profile of trametinib is satisfactory. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is among the most common neurogenic disorders, characterized by loss of function mutations in the neurofibromin gene (NF1). NF1 patients are extremely susceptible to developing neurofibromas, which can transform into deadly malignant peripheral nerve sheath tumors (MPNSTs). At the center of these tumors are NF1-null Schwann cells. Here, we found that nanomedicine shows promise in the treatment of NF1-associated MPNSTs. We assessed the cytotoxicity of silver nanoparticles (AgNPs) in NF1-null NF1-associated MPNSTs, NF1-wildtype sporadic MPNST, and normal Schwann cells. Our data show that AgNP are selectivity cytotoxic to NF1-associated MPNSTs relative to sporadic MPNST and Schwann cells. Furthermore, we found that sensitivity to AgNPs is correlated with the expression levels of functional neurofibromin. The restoration of functional neurofibromin in NF1-associated MPNSTs reduces AgNP sensitivity, and the knockdown of neurofibromin in Schwann cells increases AgNP sensitivity. This finding is unique to AgNPs, as NF1 restoration does not alter sensitivity to standard of care chemotherapy doxorubicin in NF1-associated MPNSTs. Using an in vitro model system, we then found that AgNP can selectively eradicate NF1-associated MPNSTs in co-culture with Schwann cells at doses tolerable to normal cells. AgNP represents a novel therapy for the treatment of NF1-associated MPNSTs and addresses significant unmet clinical need. [ABSTRACT FROM AUTHOR]

Background: This paper discusses clinical features and management aspects of an extremely rare entity, neurofibroma of the external nose. Methods: Database searches were performed using PubMed, Embase and Google Scholar to identify previously published articles. Results: Twelve articles comprising 13 patients with neurofibroma of the external nose were included. The mean age of presentation was 31 years. Sixty-nine per cent of patients were diagnosed at final histopathology. External approach rhinoplasty was performed in 76.9 per cent of patients, while the intranasal approach was used in 15.3 per cent of patients. There was a 15.3 per cent association with neurofibromatosis type 1. Recurrence was noted in 23 per cent of patients. Conclusion: It may be challenging to diagnose this entity clinically because of its rarity and striking features on histopathology. Neurofibroma of the external nose should be kept in mind as a differential diagnosis for any soft progressive swelling over the nose. Management requires complete excision, with cosmesis and restoration of functions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and efficacy of selumetinib, a novel MEK inhibitor, for the treatment of plexiform neurofibromas (PN) in patients with neurofibromatosis type 1 (NF1). Data Sources: An English-based literature search of PubMed, EMBASE, and ClinicalTrials.gov was conducted using the terms selumetinib AND neurofibromatosis from inception to August 1, 2021. Study Selection and Data Extraction: Relevant prescribing information, abstracts, and articles identified through the search were considered for inclusion in this review. Data Synthesis: The open-label, multicenter, single-arm, phase II SPRINT trial demonstrated clinically significant improvements in PN-related complications. Of 50 symptomatic patients, 68% experienced a partial response, with a median change in tumor volume of −27.9% from baseline. Estimated progression-free survival at 3 years was 84%. Additionally, clinically meaningful improvements were seen on patient- and parent-reported assessments evaluating pain, range of motion, disfigurement, and quality of life. Overall, the adverse effect profile for selumetinib appears mild and manageable. Relevance to Patient Care and Clinical Practice: Selumetinib is the first FDA-approved treatment for inoperable PN in patients with NF1, demonstrating that MEK inhibition is a promising therapeutic strategy. Studies are ongoing to assess the effect of selumetinib on other NF1-associated tumor types and to determine the optimal dosing schedule and treatment duration. Cost and treatment burden must be considered when selecting selumetinib therapy. Conclusion: Selumetinib exhibits impressive antitumor activity and sustained clinical benefit in patients lacking other viable treatment options. Further studies are warranted to determine the optimal age of initiation, treatment duration, and overall cost-effectiveness of selumetinib. [ABSTRACT FROM AUTHOR]

The aim of this study is to analyze whether children with familial and sporadic neurofibromatosis type 1 (NF1) differ in psychosocial and socioeconomic aspects such as developmental delay as well as in comorbidities. Medical records of 250 children with NF1 at a median age of 10.6 years (range = 2–20 years at time of data collection) were retrospectively reviewed. Specifically, psychosocial and socioeconomic factors from 88 children with a family history for NF1 and 162 sporadic cases were compared. Comparing IQ, familial cases scored significantly lower than sporadic cases (89.8 vs. 96.5; p  = 0.015). IQ scores of children with familial and sporadic NF1 differ depending on level of parental education (mean IQ for high education 101.3 [familial] and 102.8 [sporadic] vs. low education 87.5 [familial] and 90.4 [sporadic]; p  < 0.001). No significant differences were found regarding the presence of developmental delay, learning disorders, autism spectrum disorder, or attention deficit hyperactivity disease. Children with inherited NF1 had a significantly lower IQ than sporadic cases. Children with familial NF1 more often had parents with a lower level of education, highlighting a possible impact of NF1 through generations. Also, the present study confirmed previous results in literature regarding high frequencies of learning disabilities, autism spectrum disease, and attention deficits in children with NF1. [ABSTRACT FROM AUTHOR]