Editing Neurofibromatosis

{{Short description|Three genetic disorders involving benign tumors of the nervous system}}
{{cs1 config|name-list-style=vanc}}
{{Use dmy dates|date=July 2018}}
{{Infobox medical condition (new)
| name            = Neurofibromatosis
| image           = Neurofibromatosis.jpg
| caption         = Back of an elderly woman with neurofibromatosis&nbsp;type&nbsp;1
| field           = [[Neurosurgery]], [[neurology]], [[Neuro-oncology]]
| pronounce       =
| symptoms        = Small lumps within the skin, [[scoliosis]], [[hearing loss]], [[vision loss]]<ref name=NIH2016/>
| complications   =
| onset           = Birth to early adulthood<ref name=NIH2016/>
| duration        = Life long<ref name=NIH2016/>
| types           = [[Neurofibromatosis type 1]] (NF1), [[neurofibromatosis type 2]] (NF2), [[schwannomatosis]]<ref name=NIH2016/>
| causes          = [[Genetics|Genetic]]<ref name=NIH2016/>
| risks           =
| diagnosis       = Symptoms, [[genetic testing]]<ref name=Gen2016/>
| differential    =
| prevention      =
| treatment       = Surgery, [[radiation therapy]]<ref name=Gen2016/>
| medication      =
| prognosis       = '''NF1''': variable, but most of the time normal life expectancy<ref name=NIH2016/><br>'''NF2''': shortened life expectancy<ref name=NIH2016/>
| frequency       = 1 in 3,000 people (United States)<ref name=NIH2016/>
| deaths          =
}}
<!-- Definition and symptoms -->
'''Neurofibromatosis''' ('''NF''') refers to a group of three distinct genetic conditions in which [[tumors]] grow in the [[nervous system]].<ref name="NIH2016">{{Cite web |date=3 February 2016 |title=Neurofibromatosis Fact Sheet |url=https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Neurofibromatosis-Fact-Sheet |url-status=live |archive-url=https://web.archive.org/web/20180123034742/https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Neurofibromatosis-Fact-Sheet |archive-date=23 January 2018 |access-date=16 April 2018 |website=NINDS}} {{PD-notice}}</ref> The tumors are non-cancerous ([[benign]]) and often involve the skin or surrounding bone.<ref name="NIH2016" /> Although symptoms are often mild, each condition presents differently. [[neurofibromatosis type I|Neurofibromatosis type I (NF1)]] is typically characterized by [[Café au lait spot|café au lait spots]] (light-brown flat patches of skin), [[Neurofibroma|neurofibromas]] (small bumps in or under the skin), [[scoliosis]] (side-way curvature of the back), and [[Headache|headaches]].<ref name="Gen2016">{{Cite web |date=16 August 2016 |title=Learning about Neurofibromatosis |url=https://www.genome.gov/14514225/ |url-status=live |archive-url=https://web.archive.org/web/20161010042216/https://www.genome.gov/14514225/ |archive-date=10 October 2016 |access-date=7 November 2016 |website=National Human Genome Research Institute (NHGRI)}}{{PD-notice}}</ref> [[neurofibromatosis type II|Neurofibromatosis type II (NF2)]], on the other hand, may present with early-onset [[hearing loss]], [[cataract]]s, [[tinnitus]], difficulty walking or maintaining balance, and [[muscle atrophy]].<ref name="Gen2016" /> The third type is called [[schwannomatosis]] and often presents in early adulthood with widespread pain, numbness, or tingling due to nerve compression.<ref name=Gene2019/>

<!-- Cause and diagnosis -->
The cause is a [[genetic mutation]] in certain [[oncogenes]].<ref name=NIH2016/> These can be [[heredity|inherited]], or in about half of cases [[Teratology|spontaneously occur during early development]].<ref name=NIH2016/> Different mutations result in the three types of NF.<ref name="Woodrow_2015">{{Cite journal |vauthors=Woodrow C, Clarke A, Amirfeyz R |date=1 June 2015 |title=Neurofibromatosis |url=https://www.orthopaedicsandtraumajournal.co.uk/article/S1877-1327(15)00017-2/fulltext |journal=Orthopaedics and Trauma |language=en |volume=29 |issue=3 |pages=206–210 |doi=10.1016/j.mporth.2015.02.004 |s2cid=239484110 |issn=1877-1327 |access-date=22 November 2019}}</ref> Neurofibromatosis arise from the [[Brain cell|supporting cells]] of the nervous system rather than the [[neurons]] themselves.<ref name=NIH2016/> In NF1, the tumors are [[neurofibromas]] (tumors of the peripheral nerves), while in NF2 and schwannomatosis [[schwannomas|tumors of Schwann cells]] are more common.<ref name=NIH2016/> Diagnosis is typically based on symptoms, examination, [[medical imaging]], and [[tissue biopsy|biopsy]].<ref name="Stat2019">{{Cite book |last1=Le |first1=C. |last2=Bedocs |first2=P. M. |date=January 2019 |title=Neurofibromatosis |pmid=29083784 |publisher=StatPearls}}</ref><ref name="Gene2019">{{Cite book |last1=Dhamija |first1=R. |last2=Plotkin |first2=S. |last3=Asthagiri |first3=A. |last4=Messiaen |first4=L. |last5=Babovic-Vuksanovic |first5=D. |last6=Adam |first6=M. P. |last7=Mirzaa |first7=G. M. |last8=Pagon |first8=R. A. |last9=Wallace |first9=S. E. |last10=Bean LJH |last11=Gripp |first11=K. W. |date=1993 |title=Schwannomatosis |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK487394/ |publisher=University of Washington, Seattle |pmid=29517885 |access-date=21 November 2019 |website=GeneReviews® |last12=Amemiya |first12=A.|chapter=LZTR1- and SMARCB1-Related Schwannomatosis }}</ref> [[Genetic testing]] may rarely be done to support the diagnosis.<ref name="Gen2016" />

<!-- Prevention and treatment -->
There is no known prevention or cure.<ref name="NIH2016" /><ref name="Gen2016" /> Surgery may be done to remove tumors that are causing problems or have become cancerous.<ref name="NIH2016" /> [[Radiation therapy|Radiation]] and [[chemotherapy]] may also be used if cancer occurs.<ref name="NIH2016" /> A [[cochlear implant]] or [[auditory brainstem implant]] may help some who have hearing loss due to the condition.<ref name="NIH2016" />

<!-- Epidemiology and history -->
In the United States, about 1 in 3,500 people have NF1 and 1 in 25,000 have NF2.<ref name="NIH2016" /> Males and females are affected equally often.<ref name="Gen2016" /> In NF1, symptoms are often present at birth or develop before 10 years of age.<ref name="NIH2016" /> While the condition typically worsens with time, most people with NF1 have a normal life expectancy.<ref name="NIH2016" /> In NF2, symptoms may not become apparent until early adulthood.<ref name="NIH2016" /> NF2 increases the risk of early death.<ref name=NIH2016/> Descriptions of the condition occur as far back as the 1st century.<ref name="evans">{{Cite book |url=https://books.google.com/books?id=Ng6MpB8sCUkC&pg=PA1 |title=Neurofibromatoses in clinical practice |vauthors=Ferner RE, Huson S, Evans DG |date=2011 |publisher=Springer |isbn=978-0-85729-628-3 |location=London |page=1 |access-date=9 October 2015 |archive-url=https://web.archive.org/web/20170910182704/https://books.google.com/books?id=Ng6MpB8sCUkC&lpg=PR4&pg=PA1 |archive-date=10 September 2017 |url-status=live}}</ref> It was formally described by [[Friedrich Daniel von Recklinghausen]] in 1882, after whom it was previously named.<ref name="Woodrow_2015" />

== Signs and symptoms ==
[[File:Lisch nodules.JPG|thumb|upright=1.3|[[Lisch nodule]]s as seen in NF1]]
[[File:Early neurofibromatosis.jpg|thumb|upright=1.3|Person with multiple small neurofibromas in the skin and a "café au lait spot" (bottom of photo, to the right of centre). A biopsy has been taken of one of the lesions.]]
Neurofibromatosis type 1 in early life may cause learning and [[behavior]] problems – about 60% of children who have NF1 have mild difficulty in school.<ref>{{Cite web |title=Neurofibromatosis |url=http://www.nhs.uk/conditions/Neurofibromatosis/pages/symptoms.aspx |url-status=live |archive-url=https://web.archive.org/web/20150925015544/http://www.nhs.uk/Conditions/Neurofibromatosis/Pages/Symptoms.aspx |archive-date=25 September 2015 |access-date=9 October 2015 |website=NHS Choices |publisher=NHS}}</ref> Signs the individual might have are as follows:<ref>{{Cite web |title=Neurofibromatosis |url=http://www.ninds.nih.gov/disorders/neurofibromatosis/detail_neurofibromatosis.htm |url-status=dead |archive-url=https://web.archive.org/web/20151004194320/http://www.ninds.nih.gov/disorders/neurofibromatosis/detail_neurofibromatosis.htm |archive-date=4 October 2015 |access-date=9 October 2015 |website=NINDS |publisher=NIH}}</ref><ref name="NINDS2">{{Cite web |date=23 February 2015 |title=NINDS Neurofibromatosis Information Page |url=http://www.ninds.nih.gov/disorders/neurofibromatosis/neurofibromatosis.htm |url-status=dead |archive-url=https://web.archive.org/web/20150404180516/http://www.ninds.nih.gov/disorders/neurofibromatosis/neurofibromatosis.htm |archive-date=4 April 2015 |access-date=2015-04-21}}</ref>
* Six or more light brown dermatological spots ("[[café au lait spot]]s")
* At least two [[neurofibroma]]s
* At least two growths on the eye's iris
* Abnormal growth of the spine ([[scoliosis]])
* [[Lisch nodule|Lisch nodules]]
* Tumors on the adrenal glands called [[Pheochromocytoma|pheochromocytomas]]

People with neurofibromatosis type 2 can exhibit the same type of skin symptoms as type 1, but not necessarily in every case.<ref name=":5">{{Cite journal |vauthors=Guha M |date=March 2011 |title=The Gale Encyclopedia of Genetic Disorders |journal=Reference Reviews |edition=3rd |location=Detroit, MI |publisher=Gale |volume=25 |issue=3 |pages=40–42 |doi=10.1108/09504121111119022 |isbn=978-1-4144-7602-5 |veditors=Fundukian LJ}}</ref> Symptoms may include pain due to pressure on nerves, [[tinnitus]], weakness in fingers, numbness, headaches. The symptom most characteristic of NF2 is hearing loss.<ref>{{Cite journal |last1=Selvanathan |first1=SK |last2=Shenton |first2=A |last3=Ferner |first3=R |last4=Wallace |first4=AJ |last5=Huson |first5=SM |last6=Ramsden |first6=RT |last7=Evans |first7=DG |date=2010-01-11 |title=Further genotype – phenotype correlations in neurofibromatosis 2 |url=http://dx.doi.org/10.1111/j.1399-0004.2009.01315.x |journal=Clinical Genetics |volume=77 |issue=2 |pages=163–170 |doi=10.1111/j.1399-0004.2009.01315.x |pmid=19968670 |s2cid=11130733 |issn=0009-9163}}</ref> The hearing loss occurs due to the pressure of tumors on the acoustic nerve. The same pressure can cause headaches, dizziness, and nausea.<ref name=":5" />

The main symptom of schwannomatosis is localized pain. This pain is due to tissues and nerves experiencing more pressure because of nearby tumors.<ref name=":42" />

<gallery mode="packed" heights="338" widths="338">
File:Neurofibromatosis type II tumor types.png|Figure of various morbidities associated with neurofibromatosis type II.<ref name="pmid33445724">{{cite journal |author1=Bachir S |author2=Shah S |author3=Shapiro S |author4=Koehler A |author5=Mahammedi A |author6=Samy RN | display-authors=etal| title=Neurofibromatosis Type 2 (NF2) and the Implications for Vestibular Schwannoma and Meningioma Pathogenesis. | journal=Int J Mol Sci | year= 2021 | volume= 22 | issue= 2 | page=690| pmid=33445724 | doi=10.3390/ijms22020690 | pmc=7828193 | doi-access=free}}</ref>
</gallery>

==Cause==
[[File:Autosomal dominant - en.svg|thumb|Diagram of autosomal dominant inheritance pattern]]
The three types of neurofibromatosis are caused by different mutations on chromosomes. NF1 is caused by a mutation on the NF1 gene on the arm of chromosome 17.<ref name="Woodrow_2015" /> NF2 is caused by a mutation on the NF2 tumor suppressor gene on chromosome 22.<ref name="Woodrow_2015" /> Schwannomatosis is caused by various mutations on chromosome 22.<ref name="Woodrow_2015" />

Neurofibromatosis is an [[autosomal dominant]] disorder, which means only one copy of the affected [[gene]] is needed for the disorder to develop.<ref name="Woodrow_2015" /> If one parent has neurofibromatosis, his or her children have a 50% chance of developing the condition as well. The severity of the parent's condition does not affect the child; the affected child may have mild NF1 even though it was inherited from a parent with a severe form of the disorder.<ref>{{Cite web |title=Neurofibromatosis type 1 - Causes |url=http://www.nhs.uk/conditions/neurofibromatosis/pages/causes.aspx |url-status=live |archive-url=https://web.archive.org/web/20150924065741/http://www.nhs.uk/Conditions/Neurofibromatosis/Pages/Causes.aspx |archive-date=24 September 2015 |access-date=2015-10-09 |website=NHS Choices}}</ref> The types of neurofibromatosis are:
* [[Neurofibromatosis type I]], in which the nerve tissue grows tumors (neurofibromas) that may be benign, but may cause serious damage by compressing nerves and other tissues.<ref>{{Cite web |date=5 October 2015 |title=Neurofibromatosis type 1 |url=http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1 |url-status=live |archive-url=https://web.archive.org/web/20150910222428/http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1 |archive-date=10 September 2015 |access-date=2015-10-09 |website=Genetics Home Reference}}</ref>
* [[Neurofibromatosis type II]], in which bilateral acoustic neuromas (tumors of the vestibulocochlear nerve or cranial nerve 8 (CN VIII) also known as schwannoma) develop, often leading to hearing loss.<ref>{{Cite web |date=5 October 2015 |title=Neurofibromatosis type 2 |url=http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-2 |url-status=live |archive-url=https://web.archive.org/web/20150910222433/http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-2 |archive-date=10 September 2015 |access-date=2015-10-09 |website=Genetics Home Reference}}</ref> 
* [[Schwannomatosis]], in which painful schwannomas develop on spinal and peripheral nerves.<ref>{{Cite book |url=https://books.google.com/books?id=FQFGnXv41h0C |title=Practical Surgical Neuropathology: A Diagnostic Approach |vauthors=Perry A, Brat DJ |date=1 January 2010 |publisher=Elsevier Health Sciences |isbn=978-0-443-06982-6 |page=435 |archive-url=https://web.archive.org/web/20160502120635/https://books.google.com/books?id=FQFGnXv41h0C |archive-date=2 May 2016 |url-status=live}}</ref>

==Pathophysiology==
The pathophysiology is varied, and each NF type has a different one:

* '''Neurofibromatosis type I''' is the most common of the three types and is caused by genetic changes in the NF1 gene located on chromosome 17 (17q11.2). This gene encodes a cytoplasmic protein known the neurofibromin, which functions as a [[tumor suppressor]] and therefore serves as a signal regulator of [[cell proliferation]] and differentiation.<ref>{{Cite journal |last1=Wallace |first1=Margaret R. |last2=Marchuk |first2=Douglas A. |last3=Andersen |first3=Lone B |last4=Letcher |first4=Roxanne |last5=Odeh |first5=Hana M. |last6=Saulino |first6=Ann M. |last7=Fountain |first7=Jane W. |last8=Brereton |first8=Anne |last9=Nicholson |first9=Jane |last10=Mitchell |first10=Anna L. |last11=Brownstein |first11=Bernard H. |last12=Collins |first12=Francis S. |date=1990-07-13 |title=Type 1 Neurofibromatosis Gene: Identification of a Large Transcript Disrupted in Three NF1 Patients |url=http://dx.doi.org/10.1126/science.2134734 |journal=Science |volume=249 |issue=4965 |pages=181–186 |doi=10.1126/science.2134734 |pmid=2134734 |bibcode=1990Sci...249..181W |issn=0036-8075}}</ref><ref>{{Cite web |title=Orphanet: Neurofibromatosis type 1 |url=http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=636 |url-status=live |archive-url=https://web.archive.org/web/20151006061921/http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=636 |archive-date=6 October 2015 |access-date=2015-10-13 |website=www.orpha.net}}</ref> A dysfunction or lack of neurofibromin can affect regulation, and cause uncontrolled cell proliferation, leading to the tumors (neurofibromas) that characterize NF1. The neurofibromas caused by NF consist of Schwann cells, fibroblasts, perineuronal cells, mast cells and axons embedded in an extracellular matrix.<ref name=":2">{{Cite journal |vauthors=Ferner RE |date=February 2007 |title=Neurofibromatosis 1 |journal=European Journal of Human Genetics |volume=15 |issue=2 |pages=131–138 |doi=10.1038/sj.ejhg.5201676 |pmid=16957683 |doi-access=free}}</ref><ref>{{Cite journal |vauthors=Boyd KP, Korf BR, Theos A |date=July 2009 |title=Neurofibromatosis type 1 |journal=Journal of the American Academy of Dermatology |volume=61 |issue=1 |pages=1–14 |doi=10.1016/j.jaad.2008.12.051 |pmc=2716546 |pmid=19539839}}</ref> Another function of neurofibromin is to bind to microtubules that play a role in the release of [[adenylyl cyclase]] and its activity.<ref name=":2" /> Adenylyl cyclase plays an essential role in cognition.<ref name=":2" /> Neurofibromin's role in the activity of adenylyl cyclase explains why patients with NF experience cognitive impairment.<ref name=":2" />

* '''Neurofibromatosis type II''' is caused by a mutation on chromosome 22 (22q12).<ref name=":3">{{Cite journal |vauthors=Lin AL, Gutmann DH |date=November 2013 |title=Advances in the treatment of neurofibromatosis-associated tumours |journal=Nature Reviews. Clinical Oncology |volume=10 |issue=11 |pages=616–624 |doi=10.1038/nrclinonc.2013.144 |pmid=23939548 |s2cid=21986493}}</ref> The mutation falls on the NF2 tumor suppressor gene.<ref name=":3" /> The gene normally encodes a cytoplasmic protein known as [[Merlin (protein)|merlin]]. The normal function of merlin is to regulate the activity of multiple growth factors, the mutated copy of the gene leads to merlin's loss of function.<ref name=":3" /> The loss of function leads to increased activity of growth factors normally regulated by merlin, leading to the formation of the tumors associated with NF2.<ref name=":3" />

* '''Schwannomatosis''' is caused by a mutation on the [[SMARCB1]] gene.<ref name=":42">{{Cite journal |display-authors=6 |vauthors=Plotkin SR, Blakeley JO, Evans DG, Hanemann CO, Hulsebos TJ, Hunter-Schaedle K, Kalpana GV, Korf B, Messiaen L, Papi L, Ratner N, Sherman LS, Smith MJ, Stemmer-Rachamimov AO, Vitte J, Giovannini M |date=March 2013 |title=Update from the 2011 International Schwannomatosis Workshop: From genetics to diagnostic criteria |journal=American Journal of Medical Genetics. Part A |volume=161A |issue=3 |pages=405–416 |doi=10.1002/ajmg.a.35760 |pmc=4020435 |pmid=23401320}}</ref> This gene is located near the NF2 tumor suppressor gene leading to the thought that schwannomatosis and NF2 were the same condition. The two conditions show different mutations on two different genes. The normal function of the SMARCB1 gene is to encode a protein called SMARCB1 that is part of a larger protein complex whose function is not completely understood.<ref name=":42" /> The complex including SMARCB1 plays a role in tumor suppression.<ref name=":42" /> The mutation of the SMARCB1 gene causes a loss of function in the complex leading to the formation of tumors indicative of schwannomatosis.<ref name=":42" />

==Diagnosis==

The neurofibromatoses are considered as [[RASopathy|RASopathies]] and as members of the ''[[neurocutaneous syndrome]]s'' (''phakomatoses'').<ref name="ka">{{Cite book |title=Master the Board USMLE Step 2 CK |vauthors=Fischer C, Bagheri F, Manchandani R, Pinsker R, Chauhan S, Patel P, Maruf M, Satani D, Doshi K, Alwani A, Pathak M, Thurm C, Babury M, Patel MC, Shalanov A, Sarkar S, Raouf S, Nahar J, Patel P |publisher=KAPLAN Medical |year=2010 |isbn=978-1-60714-653-7 |page=287 |display-authors=6}}</ref>
The diagnosis of neurofibromatosis is done via the following means:<ref>{{Cite web |title=Neurofibromatosis. What is neurofibromatosis? Type 1 (NF1) {{!}} Patient |url=http://patient.info/doctor/neurofibromatosis-pro |url-status=live |archive-url=https://web.archive.org/web/20151004171048/http://patient.info/doctor/neurofibromatosis-pro |archive-date=4 October 2015 |access-date=2015-10-09 |website=Patient}}</ref>

{{columns-list|colwidth=30em|
* [[Radiograph]]
* [[MRI]] or [[CT scan]]
* [[EEG]]
* [[Slit-lamp]] examination
* [[Genetic testing]]
* [[Histology]]
}}

===Differential diagnosis===
Conditions similar to NF include:

{{columns-list|colwidth=30em|
* [[LEOPARD syndrome]]<ref>{{Cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK1109/ |title=Neurofibromatosis 1 |vauthors=Friedman JM |date=2014 |publisher=University of Washington, Seattle |veditors=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Gripp KW, Mirzaa GM, Amemiya A |location=Seattle (WA) |pmid=20301288 |archive-url=https://web.archive.org/web/20170118123311/https://www.ncbi.nlm.nih.gov/books/NBK1109/ |archive-date=18 January 2017 |url-status=live}}</ref>
* [[Legius syndrome]]<ref>{{Cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK47312/ |title=Legius Syndrome |vauthors=Legius E, Stevenson D |date=2015 |publisher=University of Washington, Seattle |veditors=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Gripp KW, Mirzaa GM, Amemiya A |location=Seattle (WA) |pmid=20945555 |archive-url=https://web.archive.org/web/20170910182704/https://www.ncbi.nlm.nih.gov/books/NBK47312/ |archive-date=10 September 2017 |url-status=live}}</ref>
* [[Proteus syndrome]]<ref name="elsobky2015">{{Cite journal |vauthors=El-Sobky TA, Elsayed SM, El Mikkawy DM |date=December 2015 |title=Orthopaedic manifestations of Proteus syndrome in a child with literature update |journal=Bone Reports |volume=3 |pages=104–108 |doi=10.1016/j.bonr.2015.09.004 |pmc=5365241 |pmid=28377973}}</ref>
* [[Macrodystrophia lipomatosa]]{{citation needed|date=January 2021}}
* [[Klippel–Trénaunay syndrome]]{{citation needed|date=January 2021}}
* [[Parkes Weber syndrome]]{{citation needed|date=January 2021}}
}}

==Treatment==
Surgical removal of tumors is an option; however, the risks involved should be assessed first.<ref>{{Cite web |title=Neurofibromatosis type 2 - Treatment |url=http://www.nhs.uk/Conditions/neurofibromatosis-type-2/Pages/Treatment.aspx |url-status=live |archive-url=https://web.archive.org/web/20151222143129/http://www.nhs.uk/Conditions/neurofibromatosis-type-2/Pages/Treatment.aspx |archive-date=22 December 2015 |access-date=2015-10-11 |website=NHS Choices}}</ref> With regard to OPG (optic pathway gliomas), the preferred treatment is chemotherapy. However, radiotherapy is not recommended in children who present with this disorder.<ref>{{Cite web |title=Complex Neufibrmatosis type 1 |url=http://www.england.nhs.uk/wp-content/uploads/2013/06/b13-comp-neurofib-1.pdf |url-status=live |archive-url=https://web.archive.org/web/20151223050931/https://www.england.nhs.uk/wp-content/uploads/2013/06/b13-comp-neurofib-1.pdf |archive-date=23 December 2015 |access-date=13 October 2015 |website=NHS.uk |publisher=NHS}}</ref> It is recommended that children diagnosed with NF1 at an early age have an examination each year, which allows any potential growths or changes related to the disorder to be monitored.<ref>{{Cite web |title=Neurofibromatosis type 1 - Treatment |url=http://www.nhs.uk/Conditions/Neurofibromatosis/Pages/Treatment.aspx |url-status=live |archive-url=https://web.archive.org/web/20150926003955/http://www.nhs.uk/Conditions/Neurofibromatosis/Pages/Treatment.aspx |archive-date=26 September 2015 |access-date=2015-10-11 |website=NHS Choices}}</ref>

==Prognosis==
[[File:Adam Pearson-64485.jpg|thumb|[[Adam Pearson (actor)|Adam Pearson]], a British actor with neurofibromatosis]]
In most cases, symptoms of NF1 are mild, and individuals live normal and productive lives. In some cases, however, NF1 can be severely debilitating and may cause cosmetic and [[psychological]] issues. The course of NF2 varies greatly among individuals.  In some cases of NF2, the damage to nearby vital structures, such as other [[cranial nerves]] and the [[brain stem]], can be life-threatening.  Most individuals with schwannomatosis have significant pain.  In some extreme cases, the pain will be severe and disabling.<ref name="NINDS2" />

==Epidemiology==
In the United States, about 1 in 3,500 people have NF1, 1 in 25,000 have NF2, and 1 in 40,000 have schwannomatosis.<ref name="NIH2016" /> Males and females are affected equally often in all three conditions.<ref name="Gen2016" /> In NF1, symptoms are often present at birth or develop before 10 years of age.<ref name="NIH2016" /> While the condition typically worsens with time, most people with NF1 have a normal life expectancy.<ref name="NIH2016" /> In NF2, symptoms may not become apparent until early adulthood.<ref name="NIH2016" /> NF2 increases the risk of early death.<ref name="NIH2016" /> Schwannomatosis symptoms develop in early childhood and can worsen with time. Typically life expectancy is unaffected in those with schwannomatosis.<ref name="Gene2019" />

==History==
Descriptions of what is believed to be the condition go as far back as the 1st century.<ref name = evans/> The conditions were formally described by [[Friedrich Daniel von Recklinghausen]] in 1882, after whom it was previously named.<ref name="Woodrow_2015" />

== References ==
{{Reflist}}

== Further reading ==
* {{Cite book |url=https://books.google.com/books?id=pWlHAAAAQBAJ |title=Neurofibromatosis Type 1: Molecular and Cellular Biology |vauthors=Upadhyaya M, Cooper D |date=29 January 2013 |publisher=Springer Science & Business Media |isbn=978-3-642-32864-0}}

== External links ==
{{Scholia|topic}}
{{Commons}}	

* [https://www.ninds.nih.gov/Disorders/All-Disorders/Neurofibromatosis-Information-Page National Institute of Neurological Disorders and Stroke - information on Neurofibromatosis]

{{Medical condition classification and resources
 | DiseasesDB      =
 | ICD10           = {{ICD10|Q|85|0|q|80}}
 | ICD9            = {{ICD9|237.7}}
 | ICDO            = {{ICDO|9540|0}}
 | OMIM            = 162200
 | OMIM_mult       = {{OMIM|101000||none}},{{OMIM|162091||none}}
 | MedlinePlus     =
 | eMedicineSubj   = derm
 | eMedicineTopic  = 287
 | MeshID          = D017253
}}
{{Nervous tissue tumors}}
{{Phakomatoses}}
{{Authority control}}

[[Category:Genodermatoses]]
[[Category:PNS neoplasia]]
[[Category:Wikipedia medicine articles ready to translate]]