Legius Syndrome and its Relationship with Neurofibromatosis Type 1

Denayer, Ellen; Legius, Eric

doi:10.2340/00015555-3429

Cited by 17 publications

(9 citation statements)

References 43 publications

(55 reference statements)

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“…Legius syndrome (MIM#611431) is characterized by the occurrence of CALM with or without axillary or inguinal freckles and therefore resembles NF1. Learning disabilities, attention deficits and hyperactivity may also occur in patients with Legius syndrome even though they are generally less frequent and less severe than in NF1 (Brems and Legius 2013 ; Denayer and Legius 2020 ). Other NF1-associated features such as Lisch nodules, neurofibromas, NF1-specific bone lesions, optic pathway gliomas, and malignant peripheral nerve sheath tumours are however absent in patients with Legius syndrome (Brems et al 2007 , 2012 ; Messiaen et al 2009 ; Pasmant et al 2009 ; Spurlock et al 2009 ; Laycock-van Spyk et al 2011 ; Brems and Legius 2013 ; Denayer and Legius 2020 ).…”

Section: Differential Diagnosis Of Nf1 Versus Legius Syndrome and Cmmrdmentioning

confidence: 99%

“…It was most important to be able to distinguish between the two conditions since they differ markedly in terms of the severity of their clinical manifestations. In contrast to NF1, frequent surveillance for tumours is not necessary in children and adults with Legius syndrome (Denayer and Legius 2020 ).…”

Section: Differential Diagnosis Of Nf1 Versus Legius Syndrome and Cmmrdmentioning

confidence: 99%

See 1 more Smart Citation

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

Kehrer‐Sawatzki

Cooper

2021

Hum Genet

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Neurofibromatosis 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.

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Section: Differential Diagnosis Of Nf1 Versus Legius Syndrome and Cmmrdmentioning

confidence: 99%

Section: Differential Diagnosis Of Nf1 Versus Legius Syndrome and Cmmrdmentioning

confidence: 99%

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

Kehrer‐Sawatzki

Cooper

2021

Hum Genet

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“…However, neurofibromas, Lisch nodules and gliomas of the visual pathway -typical of NF1are not found. Correct differentiation of Legius syndrome from neurofibromatosis 1 is extremely important due to differences in prognosis, which is significantly better in the case of Legius syndrome compared to NF1 [40,41]. The genetic background of Legius syndrome involves mutations in the SPRED1 gene located on the long arm of chromosome 15 (locus q13.2).…”

Section: Differential Diagnosismentioning

confidence: 99%

“…The genetic background of Legius syndrome involves mutations in the SPRED1 gene located on the long arm of chromosome 15 (locus q13.2). Similarly as in NF1, the SPRED1 protein is a negative regulator of the RAS-MAPK pathway [41,42].…”

Section: Differential Diagnosismentioning

confidence: 99%

Phacomatoses, genetic testing for personalisation of clinical management (part 1.)

Kofla-Dłubacz

Stawarski

Pytrus

et al. 2021

Nowotwory. Journal of Oncology

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Genetically determined disorders of tissue development, which are derived from the ecto-, endo-and mesoderm and develop in the early stages of foetal life, referred to as phacomatoses, constitute a large group of diseases predisposing to development of neoplasms. Early diagnosis, including identification of mutations and clinical evaluation, enables introduction of multidisciplinary care for patients with a confirmed diagnosis. Thus, the long-term prognosis and quality of patients' life can be improved. The most common phacomatoses include neurofibromatosis types 1 and 2 and schwannomatosis.

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“…The only reliable method for differential diagnosis is genetic testing. SPRED1 located on chromosome 15q14 belongs to the RAS-MAPK pathway and is involved in the inactivation of RAS together with neurofibromin [7].…”

Section: Introductionmentioning

confidence: 99%

Application of Combined Long Amplicon Sequencing (CoLAS) for Genetic Analysis of Neurofibromatosis Type 1: A Pilot Study

Togi

Ura

Niida

2021

CIMB

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Elaborate analyses of the status of gene mutations in neurofibromatosis type 1 (NF1) are still difficult nowadays due to the large gene sizes, broad mutation spectrum, and the various effects of mutations on mRNA splicing. These problems cannot be solved simply by sequencing the entire coding region using next-generation sequencing (NGS). We recently developed a new strategy, named combined long amplicon sequencing (CoLAS), which is a method for simultaneously analysing the whole genomic DNA region and, also, the full-length cDNA of the disease-causative gene with long-range PCR-based NGS. In this study, CoLAS was specifically arranged for NF1 genetic analysis, then applied to 20 patients (five previously reported and 15 newly recruited patients, including suspicious cases) for optimising the method and to verify its efficacy and benefits. Among new cases, CoLAS detected not only 10 mutations, including three unreported mutations and one mosaic mutation, but also various splicing abnormalities and allelic expression ratios quantitatively. In addition, heterozygous mapping by polymorphisms, including introns, showed copy number monitoring of the entire NF1 gene region was possible in the majority of patients tested. Moreover, it was shown that, when a chromosomal level microdeletion was suspected from heterozygous mapping, it could be detected directly by breakpoint-specific long PCR. In conclusion, CoLAS not simply detect the causative mutation but accurately elucidated the entire structure of the NF1 gene, its mRNA expression, and also the splicing status, which reinforces its high usefulness in the gene analysis of NF1.

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Legius Syndrome and its Relationship with Neurofibromatosis Type 1

Cited by 17 publications

References 43 publications

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

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

Phacomatoses, genetic testing for personalisation of clinical management (part 1.)

Application of Combined Long Amplicon Sequencing (CoLAS) for Genetic Analysis of Neurofibromatosis Type 1: A Pilot Study

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