scholarly journals Severe Phenotype in Patients with Large Deletions of NF1

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2963
Author(s):  
Laurence Pacot ◽  
Dominique Vidaud ◽  
Audrey Sabbagh ◽  
Ingrid Laurendeau ◽  
Audrey Briand-Suleau ◽  
...  
Keyword(s):  
Learning Disabilities ◽  
Neurofibromatosis Type ◽  
Reference Population ◽  
Severe Phenotype ◽  
Large Deletions ◽  
Clinical Investigations ◽  
Café Au Lait Spots ◽  
Lisch Nodules ◽  
Contiguous Gene ◽  
Nf1 Gene

Complete deletion of the NF1 gene is identified in 5–10% of patients with neurofibromatosis type 1 (NF1). Several studies have previously described particularly severe forms of the disease in NF1 patients with deletion of the NF1 locus, but comprehensive descriptions of large cohorts are still missing to fully characterize this contiguous gene syndrome. NF1-deleted patients were enrolled and phenotypically characterized with a standardized questionnaire between 2005 and 2020 from a large French NF1 cohort. Statistical analyses for main NF1-associated symptoms were performed versus an NF1 reference population. A deletion of the NF1 gene was detected in 4% (139/3479) of molecularly confirmed NF1 index cases. The median age of the group at clinical investigations was 21 years old. A comprehensive clinical assessment showed that 93% (116/126) of NF1-deleted patients fulfilled the NIH criteria for NF1. More than half had café-au-lait spots, skinfold freckling, Lisch nodules, neurofibromas, neurological abnormalities, and cognitive impairment or learning disabilities. Comparison with previously described “classic” NF1 cohorts showed a significantly higher proportion of symptomatic spinal neurofibromas, dysmorphism, learning disabilities, malignancies, and skeletal and cardiovascular abnormalities in the NF1-deleted group. We described the largest NF1-deleted cohort to date and clarified the more severe phenotype observed in these patients.

Neurofibromatosis Type 1

2017 ◽  
Author(s):  
David S. Wolf
Keyword(s):  
Learning Disabilities ◽  
Neurofibromatosis Type 1 ◽  
Autosomal Dominant ◽  
Neurofibromatosis Type ◽  
Vascular Abnormalities ◽  
Hyperactivity Disorder ◽  
Café Au Lait Spots ◽  
Lisch Nodules ◽  
Neurocutaneous Disorder

Neurofibromatosis type 1 is a common, autosomal dominant, monogenetic neurocutaneous disorder. It is characterized by café au lait spots, axillary and inguinal freckling, Lisch nodules, optic pathway gliomas, neurofibromas, and distinctive bony abnormalities. Also associated with this condition are other central nervous system tumors, scoliosis, hypertension, vascular abnormalities, and cognitive issues such as learning disabilities and attention deficit-hyperactivity disorder.

scholarly journals Bilateral and Symmetrical Anteromedial Bowing of the Lower Limbs in a Patient with Neurofibromatosis Type-I

2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Ali Al Kaissi ◽  
Klaus Klaushofer ◽  
Franz Grill ◽  
Rudolf Ganger
Keyword(s):  
Early Life ◽  
Neurofibromatosis Type ◽  
Lower Limbs ◽  
Wedge Osteotomy ◽  
Type I ◽  
Neurofibromatosis Type I ◽  
Café Au Lait Spots ◽  
Nf1 Gene ◽  
Recklinghausen Disease ◽  
Von Recklinghausen

An 8-year-old girl was referred to our department because of generalized bowing of long bones (radii, ulnae, and femora) and significant bilateral and symmetrical posteromedial bowing of the tibiae and fibulae. The femora were laterally bowed whereas the tibiae and fibulae showed posteromedial bowing between the middle and distal thirds of the tibia with posterior cortical thickening effectively causing the development of bilateral congenital anterolateral bowing of the tibiae and fibulae. We referred to closing-wedge osteotomy of the left tibia along with fibular osteotomy in order to realign the deformity. Due to the delayed appearance of skin stigmata in her early life, the diagnosis of neurofibromatosis was ruled out. At the age of 9 years, café-au-lait spots and axillary freckling were apparent. Genetic tests confirmed von Recklinghausen disease (neurofibromatosis type-I (NF1)) (gene has been localised to 17q22). Interestingly, bilateral and symmetrical anteromedial bowing of the tibiae and fibulae has not been described in patients with NF-I.

A clinical, genetic and audiological study of patients and families with bilateral acoustic neurofibromatosis

1993 ◽  
Vol 107 (1) ◽  
pp. 6-11 ◽  
Author(s):  
W. J. Neary ◽  
V. E. Newton ◽  
M. Vidler ◽  
R. T. Ramsden ◽  
R. H. Lye ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Neurofibromatosis Type ◽  
Team Approach ◽  
Clinical Genetic ◽  
Acoustic Neuromas ◽  
Café Au Lait Spots ◽  
Lisch Nodules ◽  
Hereditary Disorders

AbstractThe neurofibromatoses consist of at least two distinct autosomal dominant hereditary disorders. Neurofibromatosis type 1 (NF1) is due to a lesion on chromosome 17q. Neurofibromatosis type 2 (NF2) is caused by a defect on chromosome 22q. The hallmark of NF2 is the development, in the second and third decades, of bilateral acoustic neuromas. NF1 is characterized by the appearance of cafe-au-lait spots and neurofibromas in addition to iris hamartomas, or Lisch nodules, of the eye, during the first and second decades.Ten families were personally studied. A total of 16 members were found to be affected with NF2. A protocol for evaluation and review of subjects and relatives of NF2 families is proposed. A team approach, coordinating the expertise of multiple specialties is recommended.

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 Neurofibromatosis type 1 (NF1) gene: Beyond café au lait spots and dermal neurofibromas

2016 ◽  
Vol 26 (7) ◽  
pp. 645-648 ◽  
Author(s):  
Sirkku Peltonen ◽  
Roope A. Kallionpää ◽  
Juha Peltonen
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Café Au Lait Spots ◽  
Nf1 Gene

scholarly journals Comprehensive Mutation Scanning of NF1 in Apparently Sporadic Cases of Pheochromocytoma

2006 ◽  
Vol 91 (9) ◽  
pp. 3478-3481 ◽  
Author(s):  
Birke Bausch ◽  
Ann-Cathrin Koschker ◽  
Martin Fassnacht ◽  
Johanna Stoevesandt ◽  
Michael M. Hoffmann ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Susceptibility Gene ◽  
Neurofibromatosis Type ◽  
Germline Mutations ◽  
Mutation Scanning ◽  
Lisch Nodules ◽  
Rare Manifestation ◽  
Nf1 Gene ◽  
Sporadic Cases ◽  
Sporadic Pheochromocytoma

Abstract Background: Pheochromocytoma is a rare manifestation in patients with neurofibromatosis type 1 (NF 1). The 57-exon susceptibility gene NF1 has so far not been systematically scanned for unexpected germline mutations in individuals with sporadic pheochromocytoma. Methods: Twenty-seven patients with bilateral adrenal and/or extraadrenal abdominal pheochromocytoma not carrying germline mutations of the genes VHL, RET, SDHB, and SDHD were selected from the European-American pheochromocytoma registry. All 57 exons and flanking intronic regions of the NF1 gene were PCR amplified using newly designed primer pairs to exclude the amplification of pseudogenes. Intragenic mutation scanning was performed using denaturing HPLC and bidirectional direct sequencing. Results: Of the 27 apparently sporadic cases, one (4%) was found to have a pathogenic germline NF1 mutation, Leu303Arg. Clinical reevaluation of this individual, who had bilateral pheochromocytoma, revealed classic, but very mild, features of NF 1, one cutaneous neurofibroma, axillary freckling, and Lisch nodules of the iris as well as a few café-au-lait spots. Conclusions: In the absence of germline mutations in VHL, RET, SDHD, and SDHB, patients with pheochromocytoma, especially with bilateral disease, should be checked thoroughly for clinical lesions suggestive of underlying syndromes such as the cutaneous and ophthalmological features characteristic of NF 1.

scholarly journals Identification and characterization of four novel large deletions in the human neurofibromatosis type 1 (NF1) gene

2001 ◽  
Vol 18 (6) ◽  
pp. 549-550 ◽  
Author(s):  
Li Juan Fang ◽  
Dominique Vidaud ◽  
Michel Vidaud ◽  
Jean-Paul Thirion
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Large Deletions ◽  
Nf1 Gene ◽  
Identification And Characterization

scholarly journals Simultaneous Detection of NF1, SPRED1, LZTR1, and NF2 Gene Mutations by Targeted NGS in an Italian Cohort of Suspected NF1 Patients

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 671
Author(s):  
Donatella Bianchessi ◽  
Maria Cristina Ibba ◽  
Veronica Saletti ◽  
Stefania Blasa ◽  
Tiziana Langella ◽  
...  
Keyword(s):  
Simultaneous Detection ◽  
Gene Mutations ◽  
Neurofibromatosis Type ◽  
Pathogenic Variant ◽  
Large Deletions ◽  
Pathogenic Variants ◽  
Legius Syndrome ◽  
Nf1 Gene ◽  
One Year ◽  
Next Generation Sequencing Ngs

Neurofibromatosis type 1 (NF1) displays overlapping phenotypes with other neurocutaneous diseases such as Legius Syndrome. Here, we present results obtained using a next generation sequencing (NGS) panel including NF1, NF2, SPRED1, SMARCB1, and LZTR1 genes on Ion Torrent. Together with NGS, the Multiplex Ligation-Dependent Probe Amplification Analysis (MLPA) method was performed to rule out large deletions/duplications in NF1 gene; we validated the MLPA/NGS approach using Sanger sequencing on DNA or RNA of both positive and negative samples. In our cohort, a pathogenic variant was found in 175 patients; the pathogenic variant was observed in NF1 gene in 168 cases. A SPRED1 pathogenic variant was also found in one child and in a one year old boy, both NF2 and LZTR1 pathogenic variants were observed; in addition, we identified five LZTR1 pathogenic variants in three children and two adults. Six NF1 pathogenic variants, that the NGS analysis failed to identify, were detected on RNA by Sanger. NGS allows the identification of novel mutations in five genes in the same sequencing run, permitting unambiguous recognition of disorders with overlapping phenotypes with NF1 and facilitating genetic counseling and a personalized follow-up.

scholarly journals Malignant Peripheral Nerve Sheath Tumor in an Army Reservist With Neurofibromatosis Type 1

2020 ◽  
Author(s):  
Chung-Ting J Kou ◽  
Matthew Rendo ◽  
Devin R Broadwater ◽  
Bradley Beeler
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Negative Regulator ◽  
Ras Signaling ◽  
Nerve Sheath Tumor ◽  
Cutaneous Manifestations ◽  
Nerve Sheath ◽  
Café Au Lait Spots ◽  
Nf1 Gene

Abstract Neurofibromatosis type 1 (NF1) is an autosomal dominant condition affecting 1 in 3,500 people resulting from an NF1 gene mutation that encodes the nonfunctional protein neurofibromin mutant. Neurofibromin is a negative regulator of RAS signaling involved in cell survival and proliferation. NF1 typically presents at birth or in early childhood with multiple light brown (café au lait) spots and axillary freckling. With age, patients may develop scattered neurofibromas as well as additional neurological and malignant abnormalities. Additionally, the nonfunctional protein neurofibromin mutant may be involved in the pathogenesis of peripheral malignant nerve sheath tumors, which is a rare and life-threatening complication of NF1. While a disqualifying condition for military duty, it may not initially be clinically apparent until complications develop. Here, we present a case of malignant peripheral sheath in an U.S. Army African American reservist with NF1 in whom cutaneous manifestations of NF1 such as café au lait spots and axillary freckling were not identified on the initial military entrance processing examination.

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