The Neurofibromatoses.
Journal
Deutsches Arzteblatt international
ISSN: 1866-0452
Titre abrégé: Dtsch Arztebl Int
Pays: Germany
ID NLM: 101475967
Informations de publication
Date de publication:
15 May 2020
15 May 2020
Historique:
received:
18
04
2019
revised:
18
04
2019
accepted:
20
03
2020
entrez:
14
7
2020
pubmed:
14
7
2020
medline:
9
9
2020
Statut:
ppublish
Résumé
Neurofibromatosis of types 1 and 2 (NF1, NF2) and schwannomatosis are the diseases that make up the neurofibromatosis spectrum. With respective incidences of 1 in 3000, 1 in 33 000, and 1 in 60 000 births, they form part of the group of rare tumor-suppressor syndromes. They give rise to a greater tumor burden for the nervous system than any other type of neoplastic disease. New approaches to symptomatic treatment are emerging. This review is based on articles retrieved by a selective literature search on the pathogenesis, diagnosis, and treatment of the neurofibromatoses. NF1 and NF2 are monogenic diseases, while the genetics of schwannomatosis is complex. The three entities are clinically and pathophysiologically distinct. An important aspect of their tumor biology is the alternation of growth phases and growth pauses. Correlations between genotypes and phenotypes are variable, while new mutations and genetic mosaics are common. Ninety-nine percent of patients with NF1 have six or more café-au-lait spots by the age of 12 months; 90-95% of patients with NF2 develop bilateral vestibular schwannomas. In schwannomatosis, pain is the most prominent symptom; two-thirds of those affected develop spinal schwannomas. The severity and prognosis of these disorders are not closely correlated with the radiological findings; rather, neurologic deficits, malignant transformation, and psychosocial stress are of greater clinical importance. Advances in knowledge of pathophysiology have led to the development of targeted treatment approaches. Examples include the off-label treatment of vestibular schwannomas with bevacizumab and of plexiform neurofibromas with MEK inhibitors. Patients with neurofibromatoses need individualized care. They should be treated in centers of expertise where interdisciplinary consultation is available and new types of pharmacotherapy can be provided.
Sections du résumé
BACKGROUND
Neurofibromatosis of types 1 and 2 (NF1, NF2) and schwannomatosis are the diseases that make up the neurofibromatosis spectrum. With respective incidences of 1 in 3000, 1 in 33 000, and 1 in 60 000 births, they form part of the group of rare tumor-suppressor syndromes. They give rise to a greater tumor burden for the nervous system than any other type of neoplastic disease. New approaches to symptomatic treatment are emerging.
METHODS
This review is based on articles retrieved by a selective literature search on the pathogenesis, diagnosis, and treatment of the neurofibromatoses.
RESULTS
NF1 and NF2 are monogenic diseases, while the genetics of schwannomatosis is complex. The three entities are clinically and pathophysiologically distinct. An important aspect of their tumor biology is the alternation of growth phases and growth pauses. Correlations between genotypes and phenotypes are variable, while new mutations and genetic mosaics are common. Ninety-nine percent of patients with NF1 have six or more café-au-lait spots by the age of 12 months; 90-95% of patients with NF2 develop bilateral vestibular schwannomas. In schwannomatosis, pain is the most prominent symptom; two-thirds of those affected develop spinal schwannomas. The severity and prognosis of these disorders are not closely correlated with the radiological findings; rather, neurologic deficits, malignant transformation, and psychosocial stress are of greater clinical importance. Advances in knowledge of pathophysiology have led to the development of targeted treatment approaches. Examples include the off-label treatment of vestibular schwannomas with bevacizumab and of plexiform neurofibromas with MEK inhibitors.
CONCLUSION
Patients with neurofibromatoses need individualized care. They should be treated in centers of expertise where interdisciplinary consultation is available and new types of pharmacotherapy can be provided.
Identifiants
pubmed: 32657748
pii: arztebl.2020.0354
doi: 10.3238/arztebl.2020.0354
pmc: PMC7373809
doi:
pii:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
354-360Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Références
Arch Ophthalmol. 2007 Mar;125(3):389-94
pubmed: 17353411
Br J Neurosurg. 2005 Feb;19(1):5-12
pubmed: 16147576
Brain. 2008 Mar;131(Pt 3):606-15
pubmed: 17940085
Orphanet J Rare Dis. 2014 Sep 10;9:142
pubmed: 25205361
J Neurol. 2014 May;261(5):963-9
pubmed: 24619350
Can J Neurol Sci. 2005 May;32(2):225-31
pubmed: 16018159
Oncologist. 2012;17(10):1317-22
pubmed: 22927469
J Child Neurol. 2008 Sep;23(9):1002-10
pubmed: 18827266
Ann Neurol. 1997 Feb;41(2):143-9
pubmed: 9029062
Am J Med Genet A. 2010 Feb;152A(2):327-32
pubmed: 20082463
J Neurooncol. 2014 Jan;116(1):187-93
pubmed: 24142200
J Child Neurol. 2004 Nov;19(11):853-8
pubmed: 15658789
Clin Sarcoma Res. 2012 Oct 04;2(1):17
pubmed: 23036231
J Neurol Neurosurg Psychiatry. 2018 Nov;89(11):1215-1219
pubmed: 29909380
J Neurosurg. 2012 Jul;117(1):109-17
pubmed: 22503123
Otol Neurotol. 2012 Aug;33(6):1046-52
pubmed: 22805104
Neuro Oncol. 2012 Aug;14(8):1090-6
pubmed: 22711605
Child Neuropsychol. 2008 Sep;14(5):401-18
pubmed: 17963094
N Engl J Med. 2016 Dec 29;375(26):2550-2560
pubmed: 28029918
Dev Period Med. 2014 Jul-Sep;18(3):297-306
pubmed: 25182393
J Med Genet. 2015 Aug;52(8):557-62
pubmed: 26104281
Oncogene. 2016 Feb 4;35(5):537-48
pubmed: 25893302
Dev Med Child Neurol. 2002 Mar;44(3):164-70
pubmed: 12005317
Pediatrics. 2000 Mar;105(3 Pt 1):608-14
pubmed: 10699117
Adv Tech Stand Neurosurg. 2016;(43):3-36
pubmed: 26508404
Cell. 1993 Mar 12;72(5):791-800
pubmed: 8453669
Nat Genet. 2014 Feb;46(2):182-7
pubmed: 24362817
Clin Neurol Neurosurg. 2016 Jul;146:130-7
pubmed: 27208873
Int J Radiat Oncol Biol Phys. 2009 Jan 1;73(1):208-13
pubmed: 18687535
AJR Am J Roentgenol. 1995 Oct;165(4):951-5
pubmed: 7676998
Acta Neuropathol. 2016 Aug;132(2):289-307
pubmed: 27236462
Semin Pediatr Neurol. 2006 Mar;13(1):8-20
pubmed: 16818171
J Plast Reconstr Aesthet Surg. 2015 Sep;68(9):1199-203
pubmed: 26139580
Acta Neuropathol. 2002 Aug;104(2):179-87
pubmed: 12111361
Laryngoscope. 2007 Jun;117(6):1069-72
pubmed: 17545869
Am J Med Genet A. 2012 Jan;158A(1):215-9
pubmed: 22105938
Appl Clin Genet. 2013 Jul 24;6:53-61
pubmed: 23935382
Neurosurgery. 2008 May;62(5 Suppl):A37-42; discussion A42-3
pubmed: 18580779
Cancer. 2009 Jan 15;115(2):390-8
pubmed: 19109818
J Neurol. 2013 Jan;260(1):38-46
pubmed: 22760943
J Am Acad Dermatol. 2009 Jul;61(1):1-14; quiz 15-6
pubmed: 19539839
J Med Genet. 2003 Feb;40(2):109-14
pubmed: 12566519
J Bone Miner Res. 2012 Nov;27(11):2333-7
pubmed: 22692994
J Neurosurg. 2007 Apr;106(4 Suppl):255-60
pubmed: 17465357
Acta Neurochir (Wien). 2015 Nov;157(11):1983-90
pubmed: 26287269
Nat Genet. 2013 Mar;45(3):285-9
pubmed: 23334667
Neuro Oncol. 2015 Apr;17(4):566-73
pubmed: 25452392
Am J Hum Genet. 2001 May;68(5):1110-8
pubmed: 11283797
Brain. 2002 May;125(Pt 5):996-1004
pubmed: 11960890
Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):e607-11
pubmed: 22560549
Am J Hum Genet. 2007 Apr;80(4):805-10
pubmed: 17357086
Neuropediatrics. 2014 Aug;45(4):240-6
pubmed: 24504420
Lancet. 2009 Jun 6;373(9679):1974-86
pubmed: 19476995
Nature. 1993 Jun 10;363(6429):515-21
pubmed: 8379998
Otolaryngol Head Neck Surg. 2018 Mar;158(3):505-510
pubmed: 29160153
Otol Neurotol. 2006 Feb;27(2):197-208
pubmed: 16436990
Am J Med Genet A. 2013 Mar;161A(3):405-16
pubmed: 23401320
J Med Genet. 2011 Feb;48(2):93-7
pubmed: 20930055
Brain Pathol. 2014 Apr;24(3):205-20
pubmed: 24450866
Lancet Neurol. 2014 Aug;13(8):834-43
pubmed: 25030515
Acta Neurol Scand. 2016 Jun;133(6):475-80
pubmed: 26369495
Cancer Res. 2007 Jan 15;67(2):520-7
pubmed: 17234759
J Pediatr. 2004 May;144(5):666-8
pubmed: 15127010
Int J Clin Exp Pathol. 2012;5(9):852-62
pubmed: 23119102
Neurosurg Focus. 2009 Dec;27(6):E2
pubmed: 19951055
J Med Genet. 2000 Aug;37(8):632-6
pubmed: 10991696
J Med Genet. 2009 Apr;46(4):259-65
pubmed: 19066167
J Med Genet. 2002 May;39(5):311-4
pubmed: 12011145
Neurology. 2000 Oct 10;55(7):1067-8
pubmed: 11061281
Hum Genet. 2017 Feb;136(2):129-148
pubmed: 27921248
World Neurosurg. 2017 Feb;98:152-161
pubmed: 27777160
Acta Neuropathol. 2014 Sep;128(3):449-52
pubmed: 25008767
Neurology. 2005 Oct 11;65(7):1037-44
pubmed: 16217056
J Med Genet. 1989 Nov;26(11):704-11
pubmed: 2511318
Laryngoscope. 1996 Jun;106(6):694-9
pubmed: 8656953
J Neurosurg Spine. 2011 Apr;14(4):543-7
pubmed: 21294614
Pediatr Radiol. 2006 Oct;36(10):1048-56
pubmed: 16912896
Neurosurgery. 1997 Feb;40(2):248-60; discussion 260-2
pubmed: 9007856
Biochem Biophys Res Commun. 2003 Mar 7;302(2):238-45
pubmed: 12604337
Stereotact Funct Neurosurg. 2007;85(6):273-8
pubmed: 17709979
J Neuropathol Exp Neurol. 1998 Dec;57(12):1164-7
pubmed: 9862639
Hum Genet. 1997 Jan;99(1):88-92
pubmed: 9003501
Nat Neurosci. 2013 Apr;16(4):426-33
pubmed: 23455610
Neuropathology. 2012 Dec;32(6):611-6
pubmed: 22394059
Neurosurgery. 2007 Mar;60(3):460-8; discussion 468-70
pubmed: 17327790
Cancer Chemother Pharmacol. 2014 Jun;73(6):1197-204
pubmed: 24710627
Pediatr Radiol. 2008 Mar;38(3):305-10
pubmed: 18231788
AJR Am J Roentgenol. 2013 Jun;200(6):W646-53
pubmed: 23701098
Neurofibromatosis. 1988;1(3):172-8
pubmed: 3152465
Q J Med. 1992 Aug;84(304):603-18
pubmed: 1484939
Curr Protein Pept Sci. 2010 Sep;11(6):471-84
pubmed: 20491622
Arch Dis Child. 1999 Dec;81(6):496-9
pubmed: 10569966
J Pediatr Genet. 2016 Jun;5(2):98-104
pubmed: 27617150
J Autism Dev Disord. 2018 Jul;48(7):2278-2285
pubmed: 29423604
J Med Genet. 2015 Oct;52(10):699-705
pubmed: 26275417
Nat Rev Clin Oncol. 2013 Nov;10(11):616-24
pubmed: 23939548
Arch Neurol. 1988 May;45(5):575-8
pubmed: 3128965
Neuro Oncol. 2016 May;18(5):624-38
pubmed: 26851632
Behav Genet. 2006 Sep;36(5):660-4
pubmed: 16474913
J Med Genet. 2007 Jul;44(7):424-8
pubmed: 17307835