Neurofibromatosis In Children Research Articles

Progress in diagnosis and treatment of neurofibromatosis in children

Neurofibromatosis type 1（NF1） is an autosomal dominant genetic disease in which a mutation in the NF1 gene on chromosome 17q11.2 results in inactivation or down-regulation of neurofibromin. This results in a series of neurocutaneous lesions characterized by neurofibromatosis. Patients with plexiform neurofibromas（PN）, as one of the main manifestations of NF1, often experience pain, dysfunction, skeletal deformities, changes in appearance and other symptoms. In severe cases, compression of the airways and vital organs occurs, and the PN is at risk of malignancy progression. At present, its treatment is still challenging. Surgery is the primary treatment for PN, but complete resection is often difficult. In recent years, chemotherapy for PN has become a hot topic. This article reviews the research progress in the pathogenesis, diagnosis and treatment of PN in recent years.

Neurofibromatosis in Children: Actually and Perspectives.

The three types of neurofibromatosis, namely type 1, type 2, and schwannomatosis, are generally associated with various benign tumors affecting the skin and the nervous system. On rare occasions, especially in patients with neurofibromatosis type 1 (NF1), malignant neoplasms may also be present, several of them possessing a more aggressive course than in individuals without this syndrome. As such, a clear delineation between the three variants of neurofibromatosis is crucial to establish the correct diagnosis and management, as well as predict the neoplasm-related outcomes. Neurofibromin, the principal product of the NF1 gene, is a potent inhibitor of cellular proliferation, having been linked to several key signaling pathways involved in tumor growth. Therefore, it may provide a useful therapeutic target for tumor management in these patients. In this article, we want to present the association between deficiency of neurofibromin and the consequences of the lack of this protein leading to different kinds of malignant tumors. The therapy is still uncertain and most therapeutic options are in development or clinical trials.

The first experience of using MEK inhibitors for type 1 neurofibromatosis in children in the Russian Federation in a hospital for short-term treatment at the National Medical Research Center

Neurofibromatosis is a genetic disorder that affects the bones, soft tissues, skin, and the nervous system. Neurofibromatosis has been described in 1882, however, there is still no specific treatment for this disease and no treatment protocols for the most frequent and life-threatening complications such as non-malignant tumors deriving from the cells of the peripheral nerve sheaths. Progress in molecular genetic study discovered the underlying genetic alteration in this tumor. This knowledge provides the base for clinical trials with new drugs. MEK-inhibitors are acting on the RAS-MAPK signaling pathway and have shown their efficacy in decreasing the size of inoperable tumors in children with type 1 neurofibromatosis (NF1). Although, this therapy does not completely reduce the tumor volume, it can significantly improve the quality of life. This article presents a clinical case of the trametinib efficacy in a child suffering from NF1-associated plexiform neurofibromas.

Role of high-resolution ultrasound in detection and monitoring of peripheral nerve tumor burden in neurofibromatosis in children

PurposePeripheral nerve sheath tumors are hallmark findings in neurofibromatosis types 1 and 2. With increasing size, they typically lead to neurological symptoms, and NF1 patients have a lifetime risk of 8–13% for developing malignant peripheral nerve sheath tumors. Medical imaging is therefore highly needed for early detection and exact localization of symptomatic or potentially malignant tumors. This review will give an overview of the ultrasound characteristics of peripheral nerve sheath tumors and findings in patients with neurofibromatosis types 1 and 2.MethodsA systematic search of electronic databases, reference lists, and unpublished literature was conducted including the keywords “schwannoma,” “neurofibroma,” “neurofibromatosis,” “benign and malignant peripheral nerve sheath tumor.”ResultsThe high-resolution allows a clear analysis of tumor echotexture, definition of margins, and the relation to the parent nerve. The use of color duplex/Doppler and contrast agent adds valuable information for the differentiation of benign and malignant tumors.ConclusionHigh-resolution ultrasound is a well-established, non-invasive, and easily repeatable first-line tool in diagnostic procedures of soft tissue tumors.

The Clinical Spectrum of Mosaic Neurofibromatosis in Children and Adolescents.

Segmental neurofibromatosis was initially described by Miller and Sparks (1977) as manifestations of neurofibromatosis limited to a dermatomal, localized distribution. Now termed mosaic neurofibromatosis, previous literature described this disease in children and adolescents with individual case reports and small-numbered case series. This study presents a large series of children and adolescents with mosaic neurofibromatosis. A retrospective chart review of a single institution medical record database was performed on all cases of mosaic neurofibromatosis diagnosed between the years 1998 and 2017. Eligible subjects were determined by 2 criteria: (1) segmental or unilateral expression of one of more signs of NF I according to those outlined in the NIH criteria and (2) were under 18 years of age at the time of diagnosis. Select information extracted include location of clinical features, NF manifestations (neurofibromas, plexiform neurofibromas, café-au-lait spots, freckling, Lisch nodules), presence of a diffuse area of cutaneous hyperpigmentation, and other significant medical conditions. Sixty-eight cases met established criteria. Average age at diagnosis was 8.28 ± 4.47 years. Thirty-seven (54%) were male and 31 (46%) were female. Localization of the dermatologic manifestations is as follows: left side in 28 (41%) cases, right side in 32 (47%) cases, and bilateral in 8 (11%) cases. Café-au-lait lesions appeared in 64 (94%) of cases and 14 (21%) had axillary and inguinal freckling. This study expands our understanding of the disease characteristics seen in children and adolescents with mosaic neurofibromatosis and confirms the need to focus on pigmentary changes in children with mosaic neurofibromatosis.

Analysis of clinical characteristics and surgical outcomes of neurofibromatosis in children

Objective To analyze the clinical characteristics and surgical outcomes of neurofibromatosis (NF) in children. Methods A total of 18 NF children who underwent tumor resection and were confirmed by pathological examination at Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University from January 2007 to March 2019 were retrospectively analyzed. Their ages ranged from 3 to 18 years. Among them, 17 cases were NF Ⅰ and 1 was NF Ⅱ. Two cases had positive family history. Clinical manifestations at admission included milky coffee spots in 15 cases, subcutaneous nodules in 14, limb numbness in 4, visual impairment in 4, bone invasion in 2 and lumbar meningocele associated with tethered cord (tumor was identified during lysis and reconstructive operation) in 1. There were 4 cases who suffered from intracranial tumors [parafalx in 1 case, cranio-orbital communication in 2 and bilateral cerebellopontine angles (CPA) in 1] and 4 having intraspinal tumors. For patients with local compression symptoms, progressive enlargement of the tumors, or biopsy purpose, palliative tumor resection was performed and surgical outcomes were followed up. Results Among 18 cases, early symptoms disappeared in 10 cases, were relieved in 3, and had no change in visual acuity in 4 (the same as preoperative conditions). Left hearing loss in the child with bilateral CPA tumors became severer than preoperative conditions due to left tumor resection. The follow-up duration was 2 to 143 months with an average of 74±37 months. Follow-up indicated a recurrence in 4 cases in the original surgical area (subcutaneous in 3 and CPA in 1), and a new subcutaneous lesion in 2 cases on body surface (neck in 1 and chest in 1). The 4 patients with intraspinal tumors recovered well without recurrence. Pathological results showed that Ki-67 positive cell index accounted for 1-8%. Conclusions Type NF Ⅰ is more common than NF type Ⅱ in children and often combined with multi-system tumors. Subcutaneous and CPA tumors tend to recur even after surgical resection. Palliative surgical decision should be made in order for the patients to maintain a satisfactory life quality. Key words: Neurofibromatoses; Child; Disease attributes; Neurosurgical procedures

Skeletal complications in the course of neurofibromatosis in children

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Jakubowska-Pietkiewicz E, Woźniak E, Chlebna-Sokół D, Michałus I. Skeletal complications in the course of neurofibromatosis in children. Pediatria Polska - Polish Journal of Paediatrics. 2019;94(3):151-157. doi:10.5114/polp.2019.86435. APA Jakubowska-Pietkiewicz, E., Woźniak, E., Chlebna-Sokół, D., & Michałus, I. (2019). Skeletal complications in the course of neurofibromatosis in children. Pediatria Polska - Polish Journal of Paediatrics, 94(3), 151-157. https://doi.org/10.5114/polp.2019.86435 Chicago Jakubowska-Pietkiewicz, Elżbieta, Elżbieta Woźniak, Danuta Chlebna-Sokół, and Izabela Michałus. 2019. "Skeletal complications in the course of neurofibromatosis in children". Pediatria Polska - Polish Journal of Paediatrics 94 (3): 151-157. doi:10.5114/polp.2019.86435. Harvard Jakubowska-Pietkiewicz, E., Woźniak, E., Chlebna-Sokół, D., and Michałus, I. (2019). Skeletal complications in the course of neurofibromatosis in children. Pediatria Polska - Polish Journal of Paediatrics, 94(3), pp.151-157. https://doi.org/10.5114/polp.2019.86435 MLA Jakubowska-Pietkiewicz, Elżbieta et al. "Skeletal complications in the course of neurofibromatosis in children." Pediatria Polska - Polish Journal of Paediatrics, vol. 94, no. 3, 2019, pp. 151-157. doi:10.5114/polp.2019.86435. Vancouver Jakubowska-Pietkiewicz E, Woźniak E, Chlebna-Sokół D, Michałus I. Skeletal complications in the course of neurofibromatosis in children. Pediatria Polska - Polish Journal of Paediatrics. 2019;94(3):151-157. doi:10.5114/polp.2019.86435.

Use of MSC in the Treatment of the Congenital Pseudoarthrosis in Children

Congenital pseudoatrhrosis of the tibia is one of the most frustrating conditions encountered in paediatric orthopaedic surgery because of the difficulty in achieving healing; There are different methods of treatment the most commonly used are: External fixator according Ilizarov’s technique, vascularised fibular grafting, bone grafting with intramedullary fixation, Boyd’s double bone grafting and also after several operation go bad and a significant shortening of the leg even the amputation has to be considered [1] [2]. Numerous treatment options have been explored with several degree of success. In this paper we show a combinated surgical technique using autogenous mesenchymal stem cells (MSC) by precursor of osteogenic differensation at the same time as adjuvant to the surgical stabilization by an external fixator or an intramedullary nailing. We used these combined technique in tibia congenital pseudoarthrosis with and without neurofibromatosis in children. In fact Bone Marrow has been shown to contain a population of rare mesenchymal stem cells that are capable of forming bone, cartilage and other connective tissues enhancing bone repair and regeneration.

Neurofibromatosis in children as seen in the University of Port Harcourt Teaching Hospital.

Neurofibromatosis in children as seen in the University of Port Harcourt Teaching Hospital.

Neurofibromatosis in children with Rhabdomyosarcoma: a report from the intergroup Rhabdomyosarcoma study IV*1

<h2>Abstract</h2> We identified all children enrolled in the Intergroup Rhabdomyosarcoma Study Group-IV with neurofibromatosis type I (NF1) and rhabdomyosarcoma. Among 1025 eligible patients, 5 (0.5 %) had NF1. Three children had relapses, two of whom died of progressive disease. Patients with NF1 and rhabdomyosarcoma should be treated with intensive contemporary therapy protocols.

Neurofibromatosis in children with Rhabdomyosarcoma: a report from the intergroup Rhabdomyosarcoma study IV

We identified all children enrolled in the Intergroup Rhabdomyosarcoma Study Group-IV with neurofibromatosis type I (NF1) and rhabdomyosarcoma. Among 1025 eligible patients, 5 (0.5 %) had NF1. Three children had relapses, two of whom died of progressive disease. Patients with NF1 and rhabdomyosarcoma should be treated with intensive contemporary therapy protocols.

Akustikusneurinom als Ursache einer progredienten kindlichen Hörstörung

Neurinomas of the vestibulocochlear nerve unrelated to neurofibromatosis in children are extremely rare. Only 20 cases in children under the age of 16 are reported in the literature. Progressive unilateral hearing loss, tinnitus, vertigo and neurological deficits due to cranial nerve or brainstem compression are clinical signs. We report on the case of a 12-years-old girl with an unilateral hearing loss, progressing to total deafness. Otoacoustic emissions were normal. In the MRI a large cerebellopontine angle tumor was found, identified as schwannoma of the vestibulocochlear nerve. The importance of MR Imaging in children with progressive unilateral hearing loss is demonstrated in this case.

The spectrum of neurofibromatosis in children: A pictorial essay

The spectrum of neurofibromatosis in children: A pictorial essay

Pitfalls of Spinal Deformities Associated With Neurofibromatosis in Children

A study of 116 patients younger than 12 years of age conclusively diagnosed as having neurofibromatosis was undertaken to determine the incidence of significant orthopedic problems. Deformities of the spine comprised the most common skeletal problem. Seventy-four patients (64%) had spinal deformities. Forty-six patients were treated by posterior spinal fusion. Ten required exploration for pseudarthrosis; six were found to have pseudarthrotic defects in the fusion mass. Eight patients had more kyphosis than scoliosis. Only three patients with kyphoscoliosis obtained a solid posterior spinal fusion after multiple surgical procedures. Anteroposterior and lateral roentgenograms of the cervical spine are recommended at the time of initial evaluation of all spinal deformities. Four patients had severe cervical spine deformities, only one of whom was initially identified as having a cervical spine disorder while under treatment for scoliosis. Three of these patients were seen by other surgical services for neck masses. Following removal of posterior elements, the osseous structures were unstable. Only one patient developed spondylolisthesis. Because of the exceedingly high incidence of pseudarthrosis and spinal instability following attempts at spinal fusion, certain guidelines have evolved for the management of these deformities. High-volume computed tomographic myelography in the prone, lateral, and supine positions or magnetic resonance imaging should be performed on all patients prior to surgical treatment. Anterior disc excision and bone graft followed by posterior arthrodesis with instrumentation are indicated if the kyphotic angle is greater than 50 degrees or if scoliosis is greater than 80 degrees. Even combined anterior and posterior arthrodesis operations did not guarantee successful permanent spinal stability in young patients with neurofibromatosis.

Neurofibromatosis in children with soft tissue sarcoma.

Case records of the 157 children with soft tissue sarcoma in the Manchester Children's Tumour Registry diagnosed between 1954 and 1983 were reviewed for reference to diagnostic features of neurofibromatosis (NF). Interviews were carried out with 124 families of these children. Four children in the series were identified as having NF. All four were boys, very young at diagnosis, and had rhabdomyosarcomas of the bladder or prostate. In addition, there were indications that a further nine children may have been affected. It is suggested that NF may be more common in children with soft tissue sarcoma than previously thought and that clinicians should be alert for signs and symptoms of NF in such children and their families. Affected children may be at increased risk of developing further malignancies.

Colonic obstruction in a child with von Recklinghausen's neurofibromatosis

A child is reported who developed partial colonic obstruction from an intussuscepting polypoid mass in the transverse colon. A 5 cm plexiform ganglioneurofibroma was found at laparotomy. Examination of the entire gastrointestinal tract revealed no other neurogenic tumors. Gastrointestinal involvement by neurofibromatosis in children is rare; however, children with von Recklinghausen's disease who complain of vague abdominal symptoms should be evaluated for gastrointestinal tumors.

Neurofibromatosis in Children

The clinical diagnosis of neurofibromatosis in childhood will usually be based on the presence of numerous café-au-lait spots. Early diagnosis allows for continuing follow-up and appropriate counselling. Symptomatic therapy can be provided if necessary. The disorder has a tendency via its mesodermal route to affect almost every system in the body; however, few laymen have even heard of the disorder and, except for the "Elephant Man" notoriety, are totally unaware of it, whereas muscular dystrophy, cystic fibrosis, and Down syndrome although occurring less frequently are well known to the general public. The management of neurofibromatosis in children covers an extremely wide spectrum: at times the management appears to be simple, involving little more than clinical evaluation and simple investigations. However, in view of the protean manifestations of the condition, a complete history including family history is obligatory, and investigation must include radiographic studies of the abdomen, chest, spine, and skull, the latter to include special views of the orbits and optic foramina. My investigation of this disorder has been extremely frustrating because of the progressive character of the disease. Nothing seems to alter the natural course of the disease. I cannot say that my investigative efforts have revealed any breakthroughs in treatment. An aggressive surgical approach to the myriad of lesions associated with this disease, especially neuromata or segmental problems, is probably advisable. The early treatment of tibial pseudarthrosis by polyprophylene orthotic and pulsating electromagnetic fields shows encouraging results over the short course, although I am not so sure as to whether or not the patients would do as well with the custom fit orthotic with or without the electronics. Early stabilization of spinal deformity has proven to be more than moderately successful and is strongly recommended following appropriate intraspinal evaluation. The management of tumors of the brain and spinal cord, as well as those associated with limb hypertrophy and congenital tibial pseudarthrosis, is undergoing innovations at this time which may result in a better cure rate. Procedures include the use of CT to evaluate tumors [Coleman et al. have attempted to differentiate neurofibromas from neurofibrosarcoma by contrast enhancement methods], the use of CO2 lasers to remove previously inoperable CNS tumors, microvascular bone transplantation and pulsating electromagnetic field to treat pseudarthrotic bones.4+he National

Radiology Rounds

Current Concepts in MedicineRadiology Rounds William A. CummingMD William A. Cumming Search for more papers by this author Published Online:1 Oct 1982https://doi.org/10.5144/0256-4947.1982.271SectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutFigure 1.: AP radiograph of thigh.Download FigureA 12-year-old boy has a large, solid tumor on the medial aspect of his thigh. This has been present for several months. In the past, he had a surgical procedure on his left knee because the left leg was longer than the right. He is otherwise in good health. He has some pigmented areas of skin at several sites on his body.Figure 2.: Pelvis.Download FigureSARCOMATOUS DEGENERATION IN NEUROFIBROMATOSISThe radiograph shows a large, smooth, rounded mass in the thigh and abnormal bony architecture in the adjacent femur. The cortices are irregularly thickened and, adjacent to the tumor, appear to be indented. There are linear, radiolucent streaks in the distal femoral shaft and similar streaks were present in the tibia. The distal femoral growth plate has been obliterated by surgical fusion in an attempt to stop growth of the left leg. The pelvis is deformed by an apparent acetabular protrusion and the bone of the left pubis and ischium is hypoplastic and irregularly sclerotic. Just above the left acetabulum the pelvis is unusually narrow and above this the left iliac wing is wide and flared. The lumbar spine shows anterior and posterior concavities of the vertebral bodies. All these findings are typical of neurofibromatosis.Figure 3.: Spine.Download FigureAlthough neurofibromatosis is a relatively common disease, fewer than five percent of patients develop malignant degeneration. Neurofibrosarcoma is the expected pathological diagnosis and this was confirmed histologically in this patient. A CT scan of the pelvis and abdomen shows retroperitoneal lymphatic spread of the tumor. Figure 4.Figure 4.: CT scan of the pelvis and abdomen.Download FigureARTICLE REFERENCES:1. Holt JF: "Edward B D Neuhauser lecture: neurofibromatosis in children" . Am J Roentgen 130 (4):6151978. Google Scholar Previous article Next article FiguresReferencesRelatedDetails Volume 2, Issue 4October 1982 Metrics History Published online1 October 1982 InformationCopyright © 1982, Annals of Saudi Medicine

The operative management of von Recklinghausenʼs neurofibromatosis in children, with special reference to lesions of the head and neck

The operative management of von Recklinghausenʼs neurofibromatosis in children, with special reference to lesions of the head and neck

The operative management of von Recklinghausen's neurofibromatosis in children, with special reference to lesions of the head and neck: J. C. Adkins and M. Ravitch. Surgery 82:342–348 (September), 1977

The operative management of von Recklinghausen's neurofibromatosis in children, with special reference to lesions of the head and neck: J. C. Adkins and M. Ravitch. Surgery 82:342–348 (September), 1977