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Comprehensive neurological evaluation of a cohort of patients with neurofibromatosis type 1 from a single institution
Neurofibromatosis type 1 (NF1) is a phenotypically heterogenous multisystem cancer predisposition syndrome manifesting in childhood and adolescents. Central nervous system (CNS) manifestations include structural, neurodevelopmental, and neoplastic disease. We aimed to (1) characterize the spectrum o...
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| Published in: | European journal of paediatric neurology 2023-03, Vol.43, p.52-61 |
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| creator | Angelova-Toshkina, Daniela Decker, Josua A. Traunwieser, Thomas Holzapfel, Johannes Bette, Stefanie Huber, Simon Schimmel, Mareike Vollert, Kurt Bison, Brigitte Kröncke, Thomas Bramswig, Nuria C. Wieczorek, Dagmar Gnekow, Astrid K. Frühwald, Michael C. Kuhlen, Michaela |
| description | Neurofibromatosis type 1 (NF1) is a phenotypically heterogenous multisystem cancer predisposition syndrome manifesting in childhood and adolescents. Central nervous system (CNS) manifestations include structural, neurodevelopmental, and neoplastic disease. We aimed to (1) characterize the spectrum of CNS manifestations of NF1 in a paediatric population, (2) explore radiological features in the CNS by image analyses, and (3) correlate genotype with phenotypic expression for those with a genetic diagnosis. We performed a database search in the hospital information system covering the period between January 2017 and December 2020. We evaluated the phenotype by retrospective chart review and imaging analysis. 59 patients were diagnosed with NF1 [median age 10.6 years (range, 1.1–22.6); 31 female] at last follow-up, pathogenic NF1 variants were identified in 26/29. 49/59 patients presented with neurological manifestations including 28 with structural and neurodevelopmental findings, 16 with neurodevelopmental, and 5 with structural findings only. Focal areas of signal intensity (FASI) were identified in 29/39, cerebrovascular anomalies in 4/39. Neurodevelopmental delay was reported in 27/59 patients, learning difficulties in 19/59. Optic pathway gliomas (OPG) were diagnosed in 18/59 patients, 13/59 had low-grade gliomas outside the visual pathways. 12 patients received chemotherapy. Beside the established NF1 microdeletion, neither genotype nor FASI were associated with the neurological phenotype. NF1 was associated with a spectrum of CNS manifestations in at least 83.0% of patients. Regular neuropsychological assessment complementing frequent clinical and ophthalmologic testing for OPG is necessary in the care of each child with NF1.
•Neurological manifestations were present in 83.0% of children/adolescents with NF1.•Cerebrovascular anomalies were identified in 6.8% of patients, 3.4% sustained a stroke.•Optic pathway and other low-grade gliomas were diagnosed in 30.5% and 22.0% patients.•Neither genotype nor FASI were associated with the neurological phenotype.•Regular neuropsychological and ophthalmological assessments are indicated. |
| doi_str_mv | 10.1016/j.ejpn.2023.02.006 |
| format | article |
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•Neurological manifestations were present in 83.0% of children/adolescents with NF1.•Cerebrovascular anomalies were identified in 6.8% of patients, 3.4% sustained a stroke.•Optic pathway and other low-grade gliomas were diagnosed in 30.5% and 22.0% patients.•Neither genotype nor FASI were associated with the neurological phenotype.•Regular neuropsychological and ophthalmological assessments are indicated.</description><identifier>ISSN: 1090-3798</identifier><identifier>EISSN: 1532-2130</identifier><identifier>DOI: 10.1016/j.ejpn.2023.02.006</identifier><identifier>PMID: 36905830</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Children ; Female ; Focal areas of signal intensity ; Genotype ; Humans ; Neurofibromatosis 1 - complications ; Neurofibromatosis 1 - genetics ; Neurofibromatosis type 1 ; Neurological manifestations ; Optic Nerve Glioma - diagnosis ; Optic Nerve Glioma - epidemiology ; Optic Nerve Glioma - genetics ; Phenotype ; Retrospective Studies</subject><ispartof>European journal of paediatric neurology, 2023-03, Vol.43, p.52-61</ispartof><rights>2023 European Paediatric Neurology Society</rights><rights>2023 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-c3d0f46a4a1902af5bc097784071645747a88e35791e9cd3a50e4ebed55ca28d3</citedby><cites>FETCH-LOGICAL-c356t-c3d0f46a4a1902af5bc097784071645747a88e35791e9cd3a50e4ebed55ca28d3</cites><orcidid>0000-0001-6876-1373 ; 0000-0002-2228-031X ; 0000-0003-4577-0503 ; 0000-0003-4889-1036 ; 0000-0002-7356-6887</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,783,787,27936,27937</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36905830$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Angelova-Toshkina, Daniela</creatorcontrib><creatorcontrib>Decker, Josua A.</creatorcontrib><creatorcontrib>Traunwieser, Thomas</creatorcontrib><creatorcontrib>Holzapfel, Johannes</creatorcontrib><creatorcontrib>Bette, Stefanie</creatorcontrib><creatorcontrib>Huber, Simon</creatorcontrib><creatorcontrib>Schimmel, Mareike</creatorcontrib><creatorcontrib>Vollert, Kurt</creatorcontrib><creatorcontrib>Bison, Brigitte</creatorcontrib><creatorcontrib>Kröncke, Thomas</creatorcontrib><creatorcontrib>Bramswig, Nuria C.</creatorcontrib><creatorcontrib>Wieczorek, Dagmar</creatorcontrib><creatorcontrib>Gnekow, Astrid K.</creatorcontrib><creatorcontrib>Frühwald, Michael C.</creatorcontrib><creatorcontrib>Kuhlen, Michaela</creatorcontrib><title>Comprehensive neurological evaluation of a cohort of patients with neurofibromatosis type 1 from a single institution</title><title>European journal of paediatric neurology</title><addtitle>Eur J Paediatr Neurol</addtitle><description>Neurofibromatosis type 1 (NF1) is a phenotypically heterogenous multisystem cancer predisposition syndrome manifesting in childhood and adolescents. Central nervous system (CNS) manifestations include structural, neurodevelopmental, and neoplastic disease. We aimed to (1) characterize the spectrum of CNS manifestations of NF1 in a paediatric population, (2) explore radiological features in the CNS by image analyses, and (3) correlate genotype with phenotypic expression for those with a genetic diagnosis. We performed a database search in the hospital information system covering the period between January 2017 and December 2020. We evaluated the phenotype by retrospective chart review and imaging analysis. 59 patients were diagnosed with NF1 [median age 10.6 years (range, 1.1–22.6); 31 female] at last follow-up, pathogenic NF1 variants were identified in 26/29. 49/59 patients presented with neurological manifestations including 28 with structural and neurodevelopmental findings, 16 with neurodevelopmental, and 5 with structural findings only. Focal areas of signal intensity (FASI) were identified in 29/39, cerebrovascular anomalies in 4/39. Neurodevelopmental delay was reported in 27/59 patients, learning difficulties in 19/59. Optic pathway gliomas (OPG) were diagnosed in 18/59 patients, 13/59 had low-grade gliomas outside the visual pathways. 12 patients received chemotherapy. Beside the established NF1 microdeletion, neither genotype nor FASI were associated with the neurological phenotype. NF1 was associated with a spectrum of CNS manifestations in at least 83.0% of patients. Regular neuropsychological assessment complementing frequent clinical and ophthalmologic testing for OPG is necessary in the care of each child with NF1.
•Neurological manifestations were present in 83.0% of children/adolescents with NF1.•Cerebrovascular anomalies were identified in 6.8% of patients, 3.4% sustained a stroke.•Optic pathway and other low-grade gliomas were diagnosed in 30.5% and 22.0% patients.•Neither genotype nor FASI were associated with the neurological phenotype.•Regular neuropsychological and ophthalmological assessments are indicated.</description><subject>Children</subject><subject>Female</subject><subject>Focal areas of signal intensity</subject><subject>Genotype</subject><subject>Humans</subject><subject>Neurofibromatosis 1 - complications</subject><subject>Neurofibromatosis 1 - genetics</subject><subject>Neurofibromatosis type 1</subject><subject>Neurological manifestations</subject><subject>Optic Nerve Glioma - diagnosis</subject><subject>Optic Nerve Glioma - epidemiology</subject><subject>Optic Nerve Glioma - genetics</subject><subject>Phenotype</subject><subject>Retrospective Studies</subject><issn>1090-3798</issn><issn>1532-2130</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kE9r3DAQxUVJaf60X6CHomMu644ky7Igl7CkbSDQS3sWWnmc1WJbjiRvyLevzCY95jIzPN57MD9CvjKoGLDm-6HCwzxVHLiogFcAzQdywaTgG84EnJUbNGyE0u05uUzpAAC65s0nci4aDbIVcEGWbRjniHuckj8inXCJYQiP3tmB4tEOi80-TDT01FIX9iHm9Z6LilNO9Nnn_SnU-10Mo80h-UTzy4yU0b4oJZf89Dgg9VPKPi9r32fysbdDwi-v-4r8_XH3Z_tr8_D75_329mHjhGxymR30dWNryzRw28udA61UW4NiTS1VrWzbopBKM9SuE1YC1rjDTkpneduJK3J96p1jeFowZTP65HAY7IRhSYartgGtuWLFyk9WF0NKEXszRz_a-GIYmBW3OZgVt1lxG-Cm4C6hb6_9y27E7n_kjW8x3JwMWL48eowmuULOYecjumy64N_r_wdd35Nv</recordid><startdate>202303</startdate><enddate>202303</enddate><creator>Angelova-Toshkina, Daniela</creator><creator>Decker, Josua A.</creator><creator>Traunwieser, Thomas</creator><creator>Holzapfel, Johannes</creator><creator>Bette, Stefanie</creator><creator>Huber, Simon</creator><creator>Schimmel, Mareike</creator><creator>Vollert, Kurt</creator><creator>Bison, Brigitte</creator><creator>Kröncke, Thomas</creator><creator>Bramswig, Nuria C.</creator><creator>Wieczorek, Dagmar</creator><creator>Gnekow, Astrid K.</creator><creator>Frühwald, Michael C.</creator><creator>Kuhlen, Michaela</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6876-1373</orcidid><orcidid>https://orcid.org/0000-0002-2228-031X</orcidid><orcidid>https://orcid.org/0000-0003-4577-0503</orcidid><orcidid>https://orcid.org/0000-0003-4889-1036</orcidid><orcidid>https://orcid.org/0000-0002-7356-6887</orcidid></search><sort><creationdate>202303</creationdate><title>Comprehensive neurological evaluation of a cohort of patients with neurofibromatosis type 1 from a single institution</title><author>Angelova-Toshkina, Daniela ; Decker, Josua A. ; Traunwieser, Thomas ; Holzapfel, Johannes ; Bette, Stefanie ; Huber, Simon ; Schimmel, Mareike ; Vollert, Kurt ; Bison, Brigitte ; Kröncke, Thomas ; Bramswig, Nuria C. ; Wieczorek, Dagmar ; Gnekow, Astrid K. ; Frühwald, Michael C. ; Kuhlen, Michaela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-c3d0f46a4a1902af5bc097784071645747a88e35791e9cd3a50e4ebed55ca28d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Children</topic><topic>Female</topic><topic>Focal areas of signal intensity</topic><topic>Genotype</topic><topic>Humans</topic><topic>Neurofibromatosis 1 - complications</topic><topic>Neurofibromatosis 1 - genetics</topic><topic>Neurofibromatosis type 1</topic><topic>Neurological manifestations</topic><topic>Optic Nerve Glioma - diagnosis</topic><topic>Optic Nerve Glioma - epidemiology</topic><topic>Optic Nerve Glioma - genetics</topic><topic>Phenotype</topic><topic>Retrospective Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Angelova-Toshkina, Daniela</creatorcontrib><creatorcontrib>Decker, Josua A.</creatorcontrib><creatorcontrib>Traunwieser, Thomas</creatorcontrib><creatorcontrib>Holzapfel, Johannes</creatorcontrib><creatorcontrib>Bette, Stefanie</creatorcontrib><creatorcontrib>Huber, Simon</creatorcontrib><creatorcontrib>Schimmel, Mareike</creatorcontrib><creatorcontrib>Vollert, Kurt</creatorcontrib><creatorcontrib>Bison, Brigitte</creatorcontrib><creatorcontrib>Kröncke, Thomas</creatorcontrib><creatorcontrib>Bramswig, Nuria C.</creatorcontrib><creatorcontrib>Wieczorek, Dagmar</creatorcontrib><creatorcontrib>Gnekow, Astrid K.</creatorcontrib><creatorcontrib>Frühwald, Michael C.</creatorcontrib><creatorcontrib>Kuhlen, Michaela</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of paediatric neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Angelova-Toshkina, Daniela</au><au>Decker, Josua A.</au><au>Traunwieser, Thomas</au><au>Holzapfel, Johannes</au><au>Bette, Stefanie</au><au>Huber, Simon</au><au>Schimmel, Mareike</au><au>Vollert, Kurt</au><au>Bison, Brigitte</au><au>Kröncke, Thomas</au><au>Bramswig, Nuria C.</au><au>Wieczorek, Dagmar</au><au>Gnekow, Astrid K.</au><au>Frühwald, Michael C.</au><au>Kuhlen, Michaela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comprehensive neurological evaluation of a cohort of patients with neurofibromatosis type 1 from a single institution</atitle><jtitle>European journal of paediatric neurology</jtitle><addtitle>Eur J Paediatr Neurol</addtitle><date>2023-03</date><risdate>2023</risdate><volume>43</volume><spage>52</spage><epage>61</epage><pages>52-61</pages><issn>1090-3798</issn><eissn>1532-2130</eissn><abstract>Neurofibromatosis type 1 (NF1) is a phenotypically heterogenous multisystem cancer predisposition syndrome manifesting in childhood and adolescents. Central nervous system (CNS) manifestations include structural, neurodevelopmental, and neoplastic disease. We aimed to (1) characterize the spectrum of CNS manifestations of NF1 in a paediatric population, (2) explore radiological features in the CNS by image analyses, and (3) correlate genotype with phenotypic expression for those with a genetic diagnosis. We performed a database search in the hospital information system covering the period between January 2017 and December 2020. We evaluated the phenotype by retrospective chart review and imaging analysis. 59 patients were diagnosed with NF1 [median age 10.6 years (range, 1.1–22.6); 31 female] at last follow-up, pathogenic NF1 variants were identified in 26/29. 49/59 patients presented with neurological manifestations including 28 with structural and neurodevelopmental findings, 16 with neurodevelopmental, and 5 with structural findings only. Focal areas of signal intensity (FASI) were identified in 29/39, cerebrovascular anomalies in 4/39. Neurodevelopmental delay was reported in 27/59 patients, learning difficulties in 19/59. Optic pathway gliomas (OPG) were diagnosed in 18/59 patients, 13/59 had low-grade gliomas outside the visual pathways. 12 patients received chemotherapy. Beside the established NF1 microdeletion, neither genotype nor FASI were associated with the neurological phenotype. NF1 was associated with a spectrum of CNS manifestations in at least 83.0% of patients. Regular neuropsychological assessment complementing frequent clinical and ophthalmologic testing for OPG is necessary in the care of each child with NF1.
•Neurological manifestations were present in 83.0% of children/adolescents with NF1.•Cerebrovascular anomalies were identified in 6.8% of patients, 3.4% sustained a stroke.•Optic pathway and other low-grade gliomas were diagnosed in 30.5% and 22.0% patients.•Neither genotype nor FASI were associated with the neurological phenotype.•Regular neuropsychological and ophthalmological assessments are indicated.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>36905830</pmid><doi>10.1016/j.ejpn.2023.02.006</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-6876-1373</orcidid><orcidid>https://orcid.org/0000-0002-2228-031X</orcidid><orcidid>https://orcid.org/0000-0003-4577-0503</orcidid><orcidid>https://orcid.org/0000-0003-4889-1036</orcidid><orcidid>https://orcid.org/0000-0002-7356-6887</orcidid></addata></record> |
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| subjects | Children Female Focal areas of signal intensity Genotype Humans Neurofibromatosis 1 - complications Neurofibromatosis 1 - genetics Neurofibromatosis type 1 Neurological manifestations Optic Nerve Glioma - diagnosis Optic Nerve Glioma - epidemiology Optic Nerve Glioma - genetics Phenotype Retrospective Studies |
| title | Comprehensive neurological evaluation of a cohort of patients with neurofibromatosis type 1 from a single institution |
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