scholarly journals Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

2021 ◽  
Author(s):  
Eric Legius ◽  
Ludwine Messiaen ◽  
Pierre Wolkenstein ◽  
Patrice Pancza ◽  
Robert A. Avery ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Neurofibromatosis Type 1 ◽  
Young Patients ◽  
Neurofibromatosis Type ◽  
Consensus Recommendation ◽  
International Consensus ◽  
Legius Syndrome ◽  
Multistep Process ◽  
Patient Advocacy Groups

Abstract Purpose By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS.

scholarly journals Challenges in the diagnosis of neurofibromatosis type 1 (NF1) in young children facilitated by means of revised diagnostic criteria including genetic testing for pathogenic NF1 gene variants

2021 ◽  
Author(s):  
Hildegard Kehrer-Sawatzki ◽  
David N. Cooper
Keyword(s):  
Young Children ◽  
Diagnostic Criteria ◽  
Neurofibromatosis Type 1 ◽  
Early Adulthood ◽  
Neurofibromatosis Type ◽  
Clinical Feature ◽  
Pathogenic Variants ◽  
Legius Syndrome ◽  
Nf1 Gene

AbstractNeurofibromatosis type 1 (NF1) is the most frequent disorder associated with multiple café-au-lait macules (CALM) which may either be present at birth or appear during the first year of life. Other NF1-associated features such as skin-fold freckling and Lisch nodules occur later during childhood whereas dermal neurofibromas are rare in young children and usually only arise during early adulthood. The NIH clinical diagnostic criteria for NF1, established in 1988, include the most common NF1-associated features. Since many of these features are age-dependent, arriving at a definitive diagnosis of NF1 by employing these criteria may not be possible in infancy if CALM are the only clinical feature evident. Indeed, approximately 46% of patients who are diagnosed with NF1 later in life do not meet the NIH diagnostic criteria by the age of 1 year. Further, the 1988 diagnostic criteria for NF1 are not specific enough to distinguish NF1 from other related disorders such as Legius syndrome. In this review, we outline the challenges faced in diagnosing NF1 in young children, and evaluate the utility of the recently revised (2021) diagnostic criteria for NF1, which include the presence of pathogenic variants in the NF1 gene and choroidal anomalies, for achieving an early and accurate diagnosis.

scholarly journals Clinical features and disease severity in patients with mosaic neurofibromatosis type 1: a single-center study and literature review

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
C. Ejerskov ◽  
M. Raundahl ◽  
P. A. Gregersen ◽  
M. M. Handrup
Keyword(s):  
Cognitive Impairment ◽  
Learning Disability ◽  
Diagnostic Criteria ◽  
Clinical Features ◽  
Neurofibromatosis Type 1 ◽  
Plexiform Neurofibroma ◽  
Neurofibromatosis Type ◽  
Language Delay

Abstract Background The mosaic form of neurofibromatosis type 1 (NF1) is called mosaic NF1 (MNF1). No specific MNF1 follow-up guidelines exist. It is debatable if patients with MNF1 should be clinically examined and undergo follow-up in accordance with the standard NF1 guidelines, as MNF1 patients more often may develop more benign phenotypes and thereby less disease-associated complications including cognitive impairment. We discussed the need for a specific MNF1 follow-up guideline with focus on frequency of plexiform neurofibromas and NF1-associated complications. Method A systematic retrospective data collection in a MNF1 cohort from one of two Danish national centers of NF1 Expertise was completed. Data collected included demographics, clinical features including NF1 diagnostic criteria and NF1-associated complications. Recent literature in the field was reviewed. Results We identified 17 patients with MNF1 with a median age of 37 years [4; 66]. Eleven (65%) were females. Five patients (30%) had a plexiform neurofibroma. The median age at detection of plexiform neurofibroma was 30 years [14; 60]. Nine (53%) had at least one NF1-related complication; scoliosis, hypertension, ADHD, learning disability, language delay, autism and delay in gross and fine motor function development. We reviewed nine articles. In total, 126 cases were described within three case-series. Nineteen (15%) had a plexiform neurofibroma and in total, 23 NF1-associated complications were reported including language delay, learning disability and skeletal abnormalities. Furthermore, from the literature it was evident that the diagnosing of MNF1 varies among physicians and across countries. Conclusion Patients with MNF1 present with plexiform neurofibromas and other NF1-related complications with a frequency requiring that follow-up of MNF1 patients should be in accordance with the standard NF1 guideline in both childhood and adulthood. Physicians should be aware of cognitive impairment as a complication to MNF1. To develop a specific MNF1 follow-up guideline, there is a need for an international consensus on the diagnostic criteria for MNF1 and a follow-up study conducted in a larger MNF1 cohort.

scholarly journals Clinical features and disease severity in patients with mosaic neurofibromatosis type 1: a single-center study and literature review

2021 ◽  
Author(s):  
Cecilie Ejerskov ◽  
Maj Raundahl ◽  
Pernille Axel Gregersen ◽  
Mette Møller Handrup
Keyword(s):  
Cognitive Impairment ◽  
Learning Disability ◽  
Diagnostic Criteria ◽  
Clinical Features ◽  
Neurofibromatosis Type 1 ◽  
Plexiform Neurofibroma ◽  
Neurofibromatosis Type ◽  
Language Delay

Abstract BackgroundThe mosaic form of neurofibromatosis type 1 (NF1) is called mosaic NF1 (MNF1). No specific MNF1 follow-up guidelines exist. It is debatable if patients with MNF1 should be clinically examined and undergo follow-up in accordance with the standard NF1 guidelines, as MNF1 patients more often may develop more benign phenotypes and thereby less disease-associated complications including cognitive impairment. We discussed the need for a specific MNF1 follow-up guideline with focus on frequency of plexiform neurofibromas and NF1-associated complications.MethodA systematic retrospective data collection in a MNF1 cohort from one of two Danish national centers of NF1 Expertise was completed. Data collected included demographics, clinical features including NF1 diagnostic criteria and NF1-associated complications. Recent literature in the field was reviewed.ResultsWe identified 17 patients with MNF1 with a median age of 37 years [4; 66]. Eleven (65%) were females. Five patients (30%) had a plexiform neurofibroma. The median age at detection of plexiform neurofibroma was 30 years [14; 60]. Nine (53%) had at least one NF1-related complication; scoliosis, hypertension, ADHD, learning disability, language delay, autism and delay in gross and fine motor function development. We reviewed nine articles. In total, 126 cases were described within three case-series. Nineteen (15%) had a plexiform neurofibroma and in total, 23 NF1-associated complications were reported including language delay, learning disability and skeletal abnormalities. Furthermore, from the literature it was evident that the diagnosing of MNF1 varies among physicians and across countries. ConclusionPatients with MNF1 present with plexiform neurofibromas and other NF1-related complications with a frequency requiring that follow-up of MNF1 patients should be in accordance with the standard NF1 guideline in both childhood and adulthood. Physicians should be aware of cognitive impairment as a complication to MNF1. To develop a specific MNF1 follow-up guideline, there is a need for an international consensus on the diagnostic criteria for MNF1 and a follow-up study conducted in a larger MNF1 cohort.

scholarly journals Secondary Knee Osteoarthritis due to Neurofibromatosis Type 1 Treated with above the Knee Amputation: A Case Report

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Jay Patel ◽  
Jeffrey Whiting ◽  
Daniel Jones
Keyword(s):  
Knee Osteoarthritis ◽  
Neurofibromatosis Type 1 ◽  
Young Patients ◽  
Neurofibromatosis Type ◽  
Functional Improvement ◽  
Poor Bone Quality ◽  
Knee Amputation ◽  
Device Use ◽  
Severe Grade

Background. Neurofibromatosis Type 1 (NF-1) has a variety of associated orthopaedic manifestations that have been previously reported. We report a case of severe, grade 4 knee osteoarthritis (OA) with recurrent subluxation and joint laxity due to multiple extra-articular neurofibromas ultimately treated with Above the Knee Amputation (AKA).Case Description. A 39-year-old man presented with multiple neurofibromas and lymphedema leading to degenerative changes of the knee. Conservative treatment failed due to the severity of the knee degeneration and patient discomfort. Likewise, arthroplasty was not possible due to poor bone quality and joint instability. Therefore, AKA was selected to relieve symptoms and provide functional improvement. six months after the procedure the patient has increased functional capacity for ambulation and activities of daily living, as well as significant decrease in pain and discomfort.Clinical Relevance. Extra-articular neurofibromas causing severe secondary OA in relatively young patients can be functionally improved with AKA and prosthetic device use.

Neurofibromatosis-associated nerve sheath tumors

2006 ◽  
Vol 20 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Judith A. Murovic ◽  
Daniel H. Kim ◽  
David G. Kline
Keyword(s):  
Diagnostic Criteria ◽  
Current Literature ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Imaging Findings ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Examination Protocol ◽  
Nerve Sheath

In this paper the authors describe a patient with neurofibromatosis Type 1 (NF1) who presented with sequelae of this disease. They also review the current literature on NF1 and NF2 published between 2001 and 2005. The method used to obtain information for the case report consisted of a family member interview and a review of the patient's chart. For the literature review the authors used the search engine Ovid Medline to identify papers published on the topic between 2001 and 2005. Neurofibromatosis Type 1 appears in approximately one in 2500 to 4000 births, is caused by a defect on 17q11.2, and results in neurofibromin inactivation. The authors reviewed the current literature with regard to the following aspects of this disease: 1) diagnostic criteria for NF1; 2) criteria for other NF1-associated manifestations; 3) malignant peripheral nerve sheath tumors (PNSTs); 4) the examination protocol for a patient with an NF1-related NST; 5) imaging findings in patients with NF1; 6) other diagnostic studies; 7) surgical and adjuvant treatment for NSTs and malignant PNSTs; and 8) hormone receptors in NF1-related tumors. Pertinent illustrations are included. Neurofibromatosis Type 2 occurs much less frequently than NF1, that is, in one in 33,000 births. Mutations in NF2 occur on 22q12 and result in inactivation of the tumor suppressor merlin. The following data on this disease are presented: 1) diagnostic criteria for NF2; 2) criteria for other NF2 manifestations; 3) malignant PNSTs in patients with NF2; 4) examination protocol for the patient with NF2 who has an NST; and 5) imaging findings in patients with NF2. Relevant illustrations are included. It is important that neurosurgeons be aware of the sequelae of NF1 and NF2, because they may be called on to treat these conditions.

scholarly journals Retrospective Multicentric Study on Non-Optic CNS Tumors in Children and Adolescents with Neurofibromatosis Type 1

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1426
Author(s):  
Claudia Santoro ◽  
Stefania Picariello ◽  
Federica Palladino ◽  
Pietro Spennato ◽  
Daniela Melis ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Age At Onset ◽  
Young Patients ◽  
Progression Free Survival ◽  
Neurofibromatosis Type ◽  
Cns Tumors ◽  
Optic Pathway Glioma ◽  
Low Grade ◽  
Multicentric Study

The natural history of non-optic central nervous system (CNS) tumors in neurofibromatosis type 1 (NF1) is largely unknown. Here, we describe prevalence, clinical presentation, treatment, and outcome of 49 non-optic CNS tumors observed in 35 pediatric patients (0–18 years). Patient- and tumor-related data were recorded. Overall survival (OS) and progression-free survival (PFS) were evaluated. Eighteen patients (51%) harbored an optic pathway glioma (OPG) and eight (23%) had multiple non-optic CNS lesions. The majority of lesions (37/49) were managed with a wait-and-see strategy, with one regression and five reductions observed. Twenty-one lesions (42.9%) required surgical treatment. Five-year OS was 85.3%. Twenty-four patients progressed with a 5-year PFS of 41.4%. Patients with multiple low-grade gliomas progressed earlier and had a lower 5-year PFS than those with one lesion only (14.3% vs. 57.9%), irrespective of OPG co-presence. Non-optic CNS tumors are common in young patients with NF1. Neither age and symptoms at diagnosis nor tumor location influenced time to progression in our series. Patients with multiple lesions tended to have a lower age at onset and to progress earlier, but with a good OS.

scholarly journals Malignant Peripheral Nerve Sheath Tumor of the Inguinum and Angiosarcoma of the Scalp in a Child with Neurofibromatosis Type 1

2017 ◽  
Vol 2017 ◽  
pp. 1-4
Author(s):  
Marija Milković Periša ◽  
Tihana Džombeta ◽  
Jasminka Stepan Giljević ◽  
Božo Krušlin
Keyword(s):  
Peripheral Nerve ◽  
Neurofibromatosis Type 1 ◽  
Malignant Tumors ◽  
Young Patients ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumor ◽  
Peripheral Nerve Sheath Tumor ◽  
Nerve Sheath ◽  
The Right

Benign and malignant tumors are common in the setting of neurofibromatosis type 1 (NF1). Malignant peripheral nerve sheath tumor (MPNST) and angiosarcoma are rare tumors in children and adolescents and mostly occur in young patients in relation to NF1. Both histological types can be present in the same tumor mass in patients with NF1. We present a case of 12.5-year-old girl with NF1 who first presented with MPNST of the right inguinal region and 1.5 years later with unrelated angiosarcoma of the scalp.

scholarly journals Legius Syndrome in a 13 Month Old Boy: A Case Report

2017 ◽  
Vol 2 (1) ◽  
Keyword(s):  
Learning Disabilities ◽  
Case Report ◽  
Developmental Delay ◽  
Neurofibromatosis Type 1 ◽  
Autosomal Dominant ◽  
Clinical Manifestations ◽  
Neurofibromatosis Type ◽  
Café Au Lait Spots ◽  
Legius Syndrome

Legius syndrome is autosomal dominant and caused by mutations in the SPRED1 gene. Clinical manifestations include multiple cafe-au-lait spots, axillary/ inguinal freckling and a degree of macrocephaly, without the non-pigmentary signs of neurofibromatosis type 1 (NF1). Learning disabilities, developmental delay and ADHD are also known.

scholarly journals Evaluation of the Clinical Profile and Malignancies in Children With Neurofibromatosis Type 1

2021 ◽  
Author(s):  
Nihal Şahin ◽  
Ugur Demirsoy ◽  
Funda Corapcioglu
Keyword(s):  
Risk Factor ◽  
Diagnostic Criteria ◽  
Neurofibromatosis Type 1 ◽  
Bone Dysplasia ◽  
Female Gender ◽  
Neurofibromatosis Type ◽  
Clinical Findings ◽  
Degree Relative ◽  
Risk Of Malignancy

Abstract Purpose: Neurofibromatosis type 1 (NF 1) is a significant disease as it is one of the most common autosomal dominant disorders in childhood. Several systems are affected due to significant progression. This study aimed to analyze the clinical findings in children with NF 1 and investigate the characteristics of those with malignancy. Methods: Medical records of 55 children with NF 1 that were followed up for ten years (2004-2015) in our center were analyzed. We assessed clinical and demographical characteristics of patients, presence NF 1 diagnostic criteria, NF 1 related complications, and malignancies. The patients without malignancy are classified in group 1 while patients with malignancy are in group 2. Results: The mean age was 7.68 ± 4.65 years. Female gender was dominant in both groups. Café au lait spots were present in all patients. Axillary-inguinal freckling was observed in 76.4% of patients, followed by neurofibromas in 30.9%, Lisch nodules in 29.1%, bone dysplasia in 14.5%, optic gliomas (OG) in 23.6%, and a history of first degree relative with NF 1 in 63.6%. Central nervous system (CNS) tumors were present in 40%. Tumors beyond CNS were acute myeloid leukemia and schwannoma. None of the diagnostic criteria was a risk factor for malignancy. Having >3 criteria was the risk factor for malignancy in NF-1 (OR:5.891, CI 95%: 1.676-20.705, p=0.006).Conclusions: The major problem is malignancies in NF -1 patients. There are no clearly defined risk factors predicting malignancies in NF-1 at present. However, we found the risk of malignancy higher in patients with more diagnostic criteria.

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