Nörofibromatozis
Özet
Nörofibromatozis; santral ve periferik sinir sistemi başta olmak üzere cilt, kemik ve kas-iskelet sistemini etkileyen, sıklıkla otozomal dominant kalıtılan multisistemik bir nörokütanöz hastalıktır. Hastalık, NF1, NF2, Schwannomatoz ve Legius sendromu gibi farklı klinik formlarla kendini gösterir ve tanı süreci detaylı klinik değerlendirme ile radyolojik veya genetik incelemeleri içerir. Malign tümör gelişimi, öğrenme güçlükleri ve kardiyovasküler problemler gibi ciddi komplikasyonlar nedeniyle erken teşhis ve multidisipliner takip hayati öneme sahiptir. Kesin bir tedavisi olmamakla birlikte, semptomatik yaklaşımlar ve kişiselleştirilmiş cerrahi veya medikal müdahalelerle morbidite yönetilmektedir.
Neurofibromatosis is a multisystem neurocutaneous disorder, typically inherited in an autosomal dominant pattern, that affects the central and peripheral nervous systems, skin, bones, and musculoskeletal system. It manifests in various forms, including NF1, NF2, Schwannomatosis, and Legius syndrome, necessitating a multidisciplinary approach for diagnosis through clinical evaluation, imaging, and genetic testing. The condition presents risks for serious complications like malignant tumors, cognitive impairments, and cardiovascular issues, making early detection and ongoing monitoring essential. As there is no definitive cure, management focuses on symptomatic care and personalized interventions to address specific complications and improve quality of life.
Referanslar
Kresak J, Walsh M. Neurofibromatosis: A Review of NF1, NF2, and Schwannomatosis. J Pediatr Genet. 2016;05(02):098-104. doi:10.1055/s-0036-1579766
Farschtschi S, Mautner V-F, McLean ACL, Schulz A, Friedrich RE, Rosahl SK. The Neurofibromatoses. Dtsch Arztebl Int. 2020;117(20):354-360. doi:10.3238/arztebl.2020.0354
Ruggieri M. The different forms of neurofibromatosis. Child’s Nerv Syst. 1999;15(6-7):295-308. doi:10.1007/s003810050398
Riccardi VM. Neurofibromatosis: clinical heterogeneity. Curr Probl Cancer. 1982;7(2):1-34. doi:10.1016/s0147-0272(82)80016-0
Hirbe AC, Gutmann DH. Neurofibromatosis type 1: A multidisciplinary approach to care. Lancet Neurol. 2014;13(8):834-843. doi:10.1016/S1474-4422(14)70063-8
Evans DG, Howard E, Giblin C, et al. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A. 2010;152A(2):327-332. doi:10.1002/ajmg.a.33139
Le C, Bedocs PM. Neurofibromatosis. In: Neurofibromatosis. StatPearls Publishing LLC.; 2021. https://www.ncbi.nlm.nih.gov/books/NBK459329/#_NBK459329_pubdet_
Thiele EA KB. Phakomatoses and allied conditions. In: Swaiman’s Pediatric Neurology Principles and Practice. 6th ed. Elsevier; 2018:362-372.
Boyd KP, Korf BR, Theos A. Neurofibromatosis type 1. J Am Acad Dermatol. 2009;61(1):1-6. doi:10.1016/j.jaad.2008.12.051
Korf BR. Neurofibromatosis. Handb Clin Neurol. 2013;111:333-340. doi:10.1016/B978-0-444-52891-9.00039-7
Dunning-Davies BM, Parker APJ. Annual review of children with neurofibromatosis type 1. Arch Dis Child Educ Pract Ed. 2016;101(2):102-111. doi:10.1136/archdischild-2014-308084
Messiaen LM, Callens T, Mortier G, et al. Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects. Hum Mutat. 2000;15(6):541-555. doi:10.1002/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N
Brabbing-Goldstein D, Ben-Shachar S. Ante-natal counseling in phacomatoses. Child’s Nerv Syst ChNS Off J Int Soc Pediatr Neurosurg. 2020;36(10):2269-2277. doi:10.1007/s00381-020-04776-3
Neurofibromatosis type 1. Nat Rev Dis Prim. 2017;3(1):17005. doi:10.1038/nrdp.2017.5
DeBella K, Szudek J, Friedman JM. Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children. Pediatrics. 2000;105(3 Pt 1):608-614. doi:10.1542/peds.105.3.608
Wilson BN, John AM, Handler MZ, Schwartz RA. Neurofibromatosis type 1: New developments in genetics and treatment. J Am Acad Dermatol. Published online August 2020. doi:10.1016/j.jaad.2020.07.105
Wu-Chou YH, Hung TC, Lin YT, et al. Neurofibromatosis 1 Summary Genetic counseling Suggestive Findings. Gene Rev. 2000;25(1):33-40.
Nunley KS, Gao F, Albers AC, Bayliss SJ, Gutmann DH. Predictive Value of Café au Lait Macules at Initial Consultation in the Diagnosis of Neurofibromatosis Type 1. Arch Dermatol. 2009;145(8):883-887. doi:10.1001/archdermatol.2009.169
National Institutes of Health Consensus Development Conference Statement: neurofibromatosis. Bethesda, Md., USA, July 13-15, 1987. Neurofibromatosis. 1988;1(3):172-178.
Anderson S. Café au Lait Macules and Associated Genetic Syndromes. J Pediatr Heal care Off Publ Natl Assoc Pediatr Nurse Assoc Pract. 2020;34(1):71-81. doi:10.1016/j.pedhc.2019.05.001
Seminog O, Goldacre M. Risk of benign tumours of nervous system, and of malignant neoplasms, in people with neurofibromatosis: Population-based record-linkage study. Br J Cancer. 2012;108. doi:10.1038/bjc.2012.535
Ortonne N, Wolkenstein P, Blakeley JO, et al. Cutaneous neurofibromas: Current clinical and pathologic issues. Neurology. 2018;91(2 Suppl 1):S5-S13. doi:10.1212/WNL.0000000000005792
Walker L, Thompson D, Easton D, et al. A prospective study of neurofibromatosis type 1 cancer incidence in the UK. Br J Cancer. 2006;95(2):233-238. doi:10.1038/sj.bjc.6603227
Roth TM, Petty EM, Barald KF. The role of steroid hormones in the NF1 phenotype: focus on pregnancy. Am J Med Genet A. 2008;146A(12):1624-1633. doi:10.1002/ajmg.a.32301
Nguyen R, Kluwe L, Fuensterer C, Kentsch M, Friedrich RE, Mautner V-F. Plexiform neurofibromas in children with neurofibromatosis type 1: frequency and associated clinical deficits. J Pediatr. 2011;159(4):652-5.e2. doi:10.1016/j.jpeds.2011.04.008
Cunha KSG, Barboza EP, Dias EP, Oliveira FM. Neurofibromatosis type I with periodontal manifestation. A case report and literature review. Br Dent J. 2004;196(8):457-460. doi:10.1038/sj.bdj.4811175
Higham CS, Dombi E, Rogiers A, et al. The characteristics of 76 atypical neurofibromas as precursors to neurofibromatosis 1 associated malignant peripheral nerve sheath tumors. Neuro Oncol. 2018;20(6):818-825. doi:10.1093/neuonc/noy013
Ferrari F, Masurel A, Olivier-Faivre L, Vabres P. Juvenile xanthogranuloma and nevus anemicus in the diagnosis of neurofibromatosis type 1. JAMA dermatology. 2014;150(1):42-46. doi:10.1001/jamadermatol.2013.6434
Vaassen P, Rosenbaum T. Nevus Anemicus As an Additional Diagnostic Marker of Neurofibromatosis Type 1 in Childhood. Neuropediatrics. 2016;47(3):190-193. doi:10.1055/s-0036-1579786
Miraglia E, Moliterni E, Iacovino C, et al. Cutaneous manifestations in neurofibromatosis type 1. Clin Ter. 2020;171(5):e371-e377. doi:10.7417/CT.2020.2242
Friedrich RE, Nuding MA. Optic Pathway Glioma and Cerebral Focal Abnormal Signal Intensity in Patients with Neurofibromatosis Type 1: Characteristics, Treatment Choices and Follow-up in 134 Affected Individuals and a Brief Review of the Literature. Anticancer Res. 2016;36(8):4095-4121.
Listernick R, Ferner RE, Piersall L, Sharif S, Gutmann DH, Charrow J. Late-onset optic pathway tumors in children with neurofibromatosis 1. Neurology. 2004;63(10):1944-1946. doi:10.1212/01.wnl.0000144341.16830.01
Guillamo J-S, Créange A, Kalifa C, et al. Prognostic factors of CNS tumours in Neurofibromatosis 1 (NF1): a retrospective study of 104 patients. Brain. 2003;126(Pt 1):152-160. doi:10.1093/brain/awg016
Mahdi J, Goyal MS, Griffith J, Morris SM, Gutmann DH. Nonoptic pathway tumors in children with neurofibromatosis type 1. Neurology. 2020;95(8):e1052-e1059. doi:10.1212/WNL.0000000000009458
Vagge A, Nelson LB, Capris P, Traverso CE. Choroidal Freckling in Pediatric Patients Affected by Neurofibromatosis Type 1. J Pediatr Ophthalmol Strabismus. 2016;53(5):271-274. doi:10.3928/01913913-20160719-05
Ferrari A, Bisogno G, Macaluso A, et al. Soft-tissue sarcomas in children and adolescents with neurofibromatosis type 1. Cancer. 2007;109(7):1406-1412. doi:10.1002/cncr.22533
James AW, Shurell E, Singh A, Dry SM, Eilber FC. Malignant Peripheral Nerve Sheath Tumor. Surg Oncol Clin N Am. 2016;25(4):789-802. doi:10.1016/j.soc.2016.05.009
Pannu AK, Sharma N. Neurofibromatosis type 1 and disseminated malignant peripheral nerve sheath tumor. QJM. 2017;110(9):583-584. doi:10.1093/qjmed/hcx071
Sung L, Anderson JR, Arndt C, Raney RB, Meyer WH, Pappo AS. Neurofibromatosis in children with rhabdomyosarcoma: A report from the intergroup rhabdomyosarcoma study IV. J Pediatr. 2004;144(5):666-668. doi:10.1016/j.jpeds.2004.02.026
Ylä-Outinen H, Loponen N, Kallionpää RA, Peltonen S, Peltonen J. Intestinal tumors in neurofibromatosis 1 with special reference to fatal gastrointestinal stromal tumors (GIST). Mol Genet genomic Med. 2019;7(9):e927. doi:10.1002/mgg3.927
Stewart DR, Sloan JL, Yao L, et al. Diagnosis, management, and complications of glomus tumours of the digits in neurofibromatosis type 1. J Med Genet. 2010;47(8):525-532. doi:10.1136/jmg.2009.073965
Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007;44(2):81-88. doi:10.1136/jmg.2006.045906
Sharif S, Moran A, Huson SM, et al. Women with neurofibromatosis 1 are at a moderately increased risk of developing breast cancer and should be considered for early screening. J Med Genet. 2007;44(8):481-484. doi:10.1136/jmg.2007.049346
Delucia TA, Yohay K, Widmann RF. Orthopaedic aspects of neurofibromatosis: update. Curr Opin Pediatr. 2011;23(1):46-52. doi:10.1097/MOP.0b013e32834230ce
Kang E, Yoon HM, Lee BH. Neurofibromatosis type I: points to be considered by general pediatricians. Clin Exp Pediatr. 2021;64(4):149-156. doi:10.3345/cep.2020.00871
Elefteriou F, Kolanczyk M, Schindeler A, et al. Skeletal abnormalities in neurofibromatosis type 1: approaches to therapeutic options. Am J Med Genet A. 2009;149A(10):2327-2338. doi:10.1002/ajmg.a.33045
Tucker T, Schnabel C, Hartmann M, et al. Bone health and fracture rate in individuals with neurofibromatosis 1 (NF1). J Med Genet. 2009;46(4):259-265. doi:10.1136/jmg.2008.061895
Heervä E, Leinonen P, Kuorilehto T, et al. Neurofibromatosis 1-related osteopenia often progresses to osteoporosis in 12 years. Calcif Tissue Int. 2013;92(1):23-27. doi:10.1007/s00223-012-9661-y
Crawford AH, Herrera-Soto J. Scoliosis Associated with Neurofibromatosis. Orthop Clin North Am. 2007;38(4):553-562. doi:10.1016/j.ocl.2007.03.008
Hsieh H-Y, Wu T, Wang C-J, Chin S-C, Chen Y-R. Neurological complications involving the central nervous system in neurofibromatosis type 1. Acta Neurol Taiwan. 2007;16(2):68-73.
Nix JS, Blakeley J, Rodriguez FJ. An update on the central nervous system manifestations of neurofibromatosis type 1. Acta Neuropathol. 2020;139(4):625-641. doi:10.1007/s00401-019-02002-2
Summers MA, Quinlan KG, Payne JM, Little DG, North KN, Schindeler A. Skeletal muscle and motor deficits in Neurofibromatosis Type 1. J Musculoskelet Neuronal Interact. 2015;15(2):161-170.
North KN, Riccardi ; V, Samango-Sprouse ; C, et al. Consensus statement from the NF1 Cognitive Disorders Task Force. Neurology. Published online 1997:481121-481127.
Lehtonen A, Howie E, Trump D, Huson SM. Behaviour in children with neurofibromatosis type 1: cognition, executive function, attention, emotion, and social competence. Dev Med Child Neurol. 2013;55(2):111-125. doi:10.1111/j.1469-8749.2012.04399.x
Cohen JS, Levy HP, Sloan J, Dariotis J, Biesecker BB. Depression among adults with neurofibromatosis type 1: prevalence and impact on quality of life. Clin Genet. 2015;88(5):425-430. doi:10.1111/cge.12551
Friedman JM, Arbiser J, Epstein JA, et al. Cardiovascular disease in neurofibromatosis 1: Report of the NF1 Cardiovascular Task Force. Genet Med. 2002;4(3):105-111. doi:10.1097/00125817-200205000-00002
Riccardi VM. Type 1 neurofibromatosis and the pediatric patient. Curr Probl Pediatr. 1992;22(2):66-106. doi:10.1016/0045-9380(92)90053-2
Oderich GS, Sullivan TM, Bower TC, et al. Vascular abnormalities in patients with neurofibromatosis syndrome type I: clinical spectrum, management, and results. J Vasc Surg. 2007;46(3):475-484. doi:10.1016/j.jvs.2007.03.055
Malav IC, Kothari SS. Renal artery stenosis due to neurofibromatosis. Ann Pediatr Cardiol. 2009;2(2):167-169. doi:10.4103/0974-2069.58323
Murphy ES, Xie H, Merchant TE, Yu JS, Chao ST, Suh JH. Review of cranial radiotherapy-induced vasculopathy. J Neurooncol. 2015;122(3):421-429. doi:10.1007/s11060-015-1732-2
Ejerskov C, Krogh K, Ostergaard JR, Joensson I, Haagerup A. Gastrointestinal Symptoms in Children and Adolescents With Neurofibromatosis Type 1. J Pediatr Gastroenterol Nutr. 2018;66(6):872-875. doi:10.1097/MPG.0000000000001860
Gill DS, Hyman SL, Steinberg A, North KN. Age-related findings on MRI in neurofibromatosis type 1. Pediatr Radiol. 2006;36(10):1048-1056. doi:10.1007/s00247-006-0267-2
Sabol Z, Rešić B, Juraški RG, et al. Clinical sensitivity and specificity of multiple T2-hyperintensities on brain magnetic resonance imaging in diagnosis of neurofibromatosis type 1 in children: Diagnostic accuracy study. Croat Med J. 2011;52(4):488-496. doi:10.3325/cmj.2011.52.488
Payne JM, Pickering T, Porter M, et al. Longitudinal assessment of cognition and T2-hyperintensities in NF1: an 18-year study. Am J Med Genet A. 2014;164A(3):661-665. doi:10.1002/ajmg.a.36338
D’Arco F, D’Amico A, Caranci F, Di Paolo N, Melis D, Brunetti A. Cerebrovascular stenosis in neurofibromatosis type 1 and utility of magnetic resonance angiography: our experience and literature review. Radiol Med. 2014;119(6):415-421. doi:10.1007/s11547-013-0358-8
Miller DT, Freedenberg D, Schorry E, Ullrich NJ, Viskochil D, Korf BR. Health Supervision for Children With Neurofibromatosis Type 1. Pediatrics. 2019;143(5). doi:10.1542/peds.2019-0660
Korf, BR, Lobbous M ML. Neurofibromatosis type 1(NF1): Pathogenesis, clinical features, and diagnosis. Up to Date. Published online 2021.
Yarar C. Nörofibromatozlar. Türkiye Klin. 2021;1(978-625-401-263-1):101-113.
Ferner RE, Gutmann DH. Neurofibromatosis type 1 (NF1): diagnosis and management. Handb Clin Neurol. 2013;115:939-955. doi:10.1016/B978-0-444-52902-2.00053-9
Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet (London, England). 2013;381(9863):333-342. doi:10.1016/S0140-6736(12)61023-X
Tartaglia M, Gelb BD, Zenker M. Noonan syndrome and clinically related disorders. Best Pract Res Clin Endocrinol Metab. 2011;25(1):161-179. doi:10.1016/j.beem.2010.09.002
Evans DGR, Baser ME, McGaughran J, Sharif S, Howard E, Moran A. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet. 2002;39(5):311-314. doi:10.1136/jmg.39.5.311
Lion-François L, Gueyffier F, Mercier C, et al. The effect of methylphenidate on neurofibromatosis type 1: a randomised, double-blind, placebo-controlled, crossover trial. Orphanet J Rare Dis. 2014;9:142. doi:10.1186/s13023-014-0142-4
Ardern-Holmes S, Fisher G, North K. Neurofibromatosis Type 2. J Child Neurol. 2017;32(1):9-22. doi:10.1177/0883073816666736
Ruggieri M, Huson SM. The clinical and diagnostic implications of mosaicism in the neurofibromatoses. Neurology. 2001;56(11):1433-1443. doi:10.1212/WNL.56.11.1433
Evans DGR, Moran A, King A, Saeed S, Gurusinghe N, Ramsden R. Incidence of vestibular schwannoma and neurofibromatosis 2 in the North West of England over a 10-year period: higher incidence than previously thought. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc [and] Eur Acad Otol Neurotol. 2005;26(1):93-97. doi:10.1097/00129492-200501000-00016
Evans DGR. Neurofibromatosis type 2 (NF2): a clinical and molecular review. Orphanet J Rare Dis. 2009;4:16. doi:10.1186/1750-1172-4-16
Hexter A, Jones A, Joe H, et al. Clinical and molecular predictors of mortality in neurofibromatosis 2: a UK national analysis of 1192 patients. J Med Genet. 2015;52(10):699-705. doi:10.1136/jmedgenet-2015-103290
Asthagiri AR, Parry DM, Butman JA, et al. Neurofibromatosis type 2. Lancet (London, England). 2009;373(9679):1974-1986. doi:10.1016/S0140-6736(09)60259-2
Schulz A, Zoch A, Morrison H. A neuronal function of the tumor suppressor protein merlin. Acta Neuropathol Commun. 2014;2(1):1-10. doi:10.1186/s40478-014-0082-1
Evans DGR. Neurofibromatosis 2 [Bilateral acoustic neurofibromatosis, central neurofibromatosis, NF2, neurofibromatosis type II]. Genet Med. 2009;11(9):599-610. doi:10.1097/GIM.0b013e3181ac9a27
Evans DGR, Baser ME, O’Reilly B, et al. Management of the patient and family with neurofibromatosis 2: a consensus conference statement. Br J Neurosurg. 2005;19(1):5-12. doi:10.1080/02688690500081206
Gugel I, Grimm F, Zipfel J, et al. Age at Onset and Presenting Symptoms of Neurofibromatosis Type 2 as Prognostic Factors for Clinical Course of Vestibular Schwannomas. Cancers (Basel). 2020;12(9). doi:10.3390/cancers12092355
Lin AL, Gutmann DH. Advances in the treatment of neurofibromatosis-associated tumours. Nat Rev Clin Oncol. 2013;10(11):616-624. doi:10.1038/nrclinonc.2013.144
Bendon CL, Furniss D, Giele HP. Comparison of outcomes of peripheral nerve schwannoma excision in neurofibromatosis type 2 patients and non-neurofibromatosis type 2 patients: A case control study. J Plast Reconstr Aesthet Surg. 2015;68(9):1199-1203. doi:10.1016/j.bjps.2015.05.026
Evans DG, Birch JM, Ramsden RT. Paediatric presentation of type 2 neurofibromatosis. Arch Dis Child. 1999;81(6):496-499. doi:10.1136/adc.81.6.496
Maccollin M, Mautner V. The Diagnosis and M a n a g e m e n t of Neurofibromatosis 2 in Childhood. 1998;5(93):243-252.
Sperfeld AD, Hein C, Schröder JM, Ludolph AC, Hanemann CO. Occurrence and characterization of peripheral nerve involvement in neurofibromatosis type 2. Brain. 2002;125(Pt 5):996-1004. doi:10.1093/brain/awf115
Bouzas EA, Freidlin V, Parry DM, Eldridge R, Kaiser-Kupfer MI. Lens opacities in neurofibromatosis 2: further significant correlations. Br J Ophthalmol. 1993;77(6):354-357. doi:10.1136/bjo.77.6.354
Rosser BT. Neurocutaneous Disorders. 2018;(February):96-129.
Goutagny S, Kalamarides M. Meningiomas and neurofibromatosis. J Neurooncol. 2010;99(3):341-347. doi:10.1007/s11060-010-0339-x
Slattery WH 3rd, Fisher LM, Hitselberger W, Friedman RA, Brackmann DE. Hearing preservation surgery for neurofibromatosis Type 2-related vestibular schwannoma in pediatric patients. J Neurosurg. 2007;106(4 Suppl):255-260. doi:10.3171/ped.2007.106.4.255
Neff BA, Wiet RM, Lasak JM, et al. Cochlear implantation in the neurofibromatosis type 2 patient: long-term follow-up. Laryngoscope. 2007;117(6):1069-1072. doi:10.1097/MLG.0b013e31804b1ae7
Renzi S, Michaeli O, Salvador H, et al. Bevacizumab for NF2-associated vestibular schwannomas of childhood and adolescence. Pediatr Blood Cancer. 2020;67(5):e28228. doi:10.1002/pbc.28228
Morris KA, Golding JF, Axon PR, et al. Bevacizumab in neurofibromatosis type 2 (NF2) related vestibular schwannomas: a nationally coordinated approach to delivery and prospective evaluation. Neuro-oncology Pract. 2016;3(4):281-289. doi:10.1093/nop/npv065
Lu-Emerson C, Plotkin SR. The neurofibromatoses. Part 2: NF2 and schwannomatosis. Rev Neurol Dis. 2009;6(3):E81-6.
Merker VL, Esparza S, Smith MJ, Stemmer-Rachamimov A, Plotkin SR. Clinical features of schwannomatosis: a retrospective analysis of 87 patients. Oncologist. 2012;17(10):1317-1322. doi:10.1634/theoncologist.2012-0162
Evans DG, Bowers NL, Tobi S, et al. Schwannomatosis: a genetic and epidemiological study. J Neurol Neurosurg Psychiatry. 2018;89(11):1215-1219. doi:10.1136/jnnp-2018-318538
Plotkin SR, Wick A. Neurofibromatosis and Schwannomatosis. Semin Neurol. 2018;38(1):73-85. doi:10.1055/s-0038-1627471
Koontz NA, Wiens AL, Agarwal A, Hingtgen CM, Emerson RE, Mosier KM. Schwannomatosis: the overlooked neurofibromatosis? AJR Am J Roentgenol. 2013;200(6):W646-53. doi:10.2214/AJR.12.8577
Hilton DA, Hanemann CO. Schwannomas and their pathogenesis. Brain Pathol. 2014;24(3):205-220. doi:10.1111/bpa.12125
Lin J, Martel W. Cross-sectional imaging of peripheral nerve sheath tumors: characteristic signs on CT, MR imaging, and sonography. AJR Am J Roentgenol. 2001;176(1):75-82. doi:10.2214/ajr.176.1.1760075
Brems H, Legius E. Legius syndrome, an Update. Molecular pathology of mutations in SPRED1. Keio J Med. 2013;62(4):107-112. doi:10.2302/kjm.2013-0002-re
Brems H, Pasmant E, Van Minkelen R, et al. Review and update of SPRED1 mutations causing Legius syndrome. Hum Mutat. 2012;33(11):1538-1546. doi:10.1002/humu.22152
Evans DG, Bowers N, Burkitt-Wright E, et al. Comprehensive RNA Analysis of the NF1 Gene in Classically Affected NF1 Affected Individuals Meeting NIH Criteria has High Sensitivity and Mutation Negative Testing is Reassuring in Isolated Cases With Pigmentary Features Only. EBioMedicine. 2016;7:212-220. doi:10.1016/j.ebiom.2016.04.005
Denayer E, Legius E. Legius syndrome and its relationship with neurofibromatosis type 1. Acta Derm Venereol. 2020;100(100-year theme Genodermatoses):161-167. doi:10.2340/00015555-3429
