{{Infobox Malattia
|RaraIT=RBG010
|ICD9=
}}

La '''neurofibromatosi''' è una malattia ereditaria che colpisce le cellule nervose e muco-cutanee dovuta a turbe dell'istogenesi.<br>

E' caratterizzata dalla presenza di numerosi tumori benigni fibrosi (fibromi) della pelle e del tessuto nervoso.

Si distinguono 2 tipi, il tipo 1, detto anche tipo 2 che è molto più rara e colpisce anche i nervi ottici, uditivi e il cervello.

Le due forme sono caratterizzate da ereditarietà autosomica dominante. La NF1 è 10 volte più comune della NF2. Interessa oltre il 90% dei casi e colpisce un nato ogni 3.000: si calcolano oltre un milione e mezzo di malati nel mondo, di cui almeno 20.000 in Italia. 

La NF1 colpisce una persona su 1500, nel 20% dei casi provoca malformazioni gravi e nel 15% dei soggetti provoca la morte prima del compimento trent'anni, spesso non è diagnosticata poiché provoca solo problemi estetici. Uno dei sintomi della malattia sono delle macchie di color caffelatte sulla superficie cutanea. <br>
La diagnosi può esser sospettata sin dai primi anni di vita per la presenza sulla pelle di almeno 6 macchie color caffè-latte. Con il passare del tempo compaiono i neurofibromi, nella forma di noduli localizzati in varie parti del corpo. 

Nel 20% dei casi si associano alcune gravi manifestazioni (tumori cerebrali ed extracerebrali - in particolare del nervo ottico, del surrene, delle ossa - scoliosi, convulsioni, ritardo mentale, ipertensione, bassa statura, pubertà anticipata ecc.), mentre il 30-40% dei soggetti presenta dei disturbi di apprendimento (scarsa memoria o concentrazione, difficoltà di lettura, di scrittura o di linguaggio) che necessitano di un supporto adeguato sin dalla prima infanzia. 

L'imprevedibile decorso della malattia e la mancanza di una cura risolutiva impongono di effettuare periodici controlli medici multispecialistici presso sedi qualificate, grazie ai quali poter eventualmente intervenire con cure sintomatiche, tanto più efficaci se precoci. 

{{Infobox_Disease |
  Name           = Neurofibromatosis |
  Image          = Neurofibromatosis.jpg|
  Caption        = Back of an old woman with Neurofibromatosis.|
  DiseasesDB     = |
  ICD10          =  |
  ICD9           =  |
  ICDO           = 9540/0 |
  OMIM           = |
  MedlinePlus    = |
  eMedicineSubj  = derm |
  eMedicineTopic = 287 |
  MeshID         = D017253 |
}}

'''Neurofibromatosis''' is a genetically-transmitted disease in which nerve cells (Schwann cells) grow tumors (neurofibromas) that may be harmless or may cause serious damage by compressing nerves and other tissues. The tumors may cause bumps under the skin, colored spots, skeletal problems, pressure on spinal nerve roots, and other neurological problems. <ref>http://www.merck.com/mmhe/sec06/ch088/ch088d.html Merck Manual Home Edition, 	
"Neurofibromatosis"</ref> 

Neurofibromatosis is autosomal dominant, which means that it is autosomal (it affects males and females equally often) and dominant (only one copy of the affected gene is needed to get the disorder). Therefore, if only one parent has neurofibromatosis, his or her children have a 50% chance of developing the condition as well. Disease severity in affected individuals, however, can vary (this is called variable expressivity). Moreover, in around half of cases there is no other affected family member because a new mutation has occurred.

==Types==
* Incidence is 1:3,000
* Incidence is 1:25,000
* Incidence is unknown but thought to be 1:40,000

==Diagnostic Criteria==
===Neurofibromatosis type 1===
Neurofibromatosis type 1 - mutation of neurofibromin chromosome 17q11.2
* Multiple neurofibromas on the skin and under the skin; the subcutaneous lumps are characteristic of the disease and increase in number with age.
* Freckling of the groin and the arm pit.
* A predisposition to particular tumors (both benign and malignant). These tumors are called neurofibromas.  
* Café au lait spots (pigmented birthmarks). Six or more measuring 1/4 of an inch in childhood and 3/4 of an inch in adulthood.
* Skeletal abnormalities such as bowing of the legs might occur
* iris), freckling in the iris.
* Tumor on the optic nerve, also known as an Optic Glioma
* Plexiform neurofibroma, a large tumor involving multiple nerves.
*Bowing of the tibia

thumb|right|plexiform neurofibroma
thumb|Patient with multiple small cutaneous neurofibromas 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 2===
Neurofibromatosis type 2 - mutation of merlin chromosome 22q12
* bilateral tumors, acoustic neuromas on the vestibulocochlear nerve
* the hallmark of NF 2 is hearing loss due to acoustic neuromas around the age of twenty
* the tumors may cause:
** headache
** balance problems, and Vertigo
** facial weakness/paralysis
** patients with NF2 may also develop other brain tumors, as well as spinal tumors
** Deafness and Tinnitus

===Schwannomatosis===
Schwannomatosis - gene involved has yet to be identified
# Multiple Schwannomas occur.
# The Schwannomas develop on cranial, spinal and peripheral nerves.
# Chronic pain, and sometimes numbness, tingling and weakness.
# About 1/3 of patients have segmental Schwannomatosis, which means that the Schwannomas are limited to a single part of the body, such as an arm, a leg or the spine.
# Unlike the other forms of NF, the Schwannomas do not develop on vestibular nerves, and as a result, no loss of hearing is associated with Schwannomatosis.
# Patients with Schwannomatosis do not have learning disabilities related to the disease.

==Genetics and Hereditability ==
thumb|right|[[NF-1 and NF-2 may be inherited in an autosomal dominant fashion, as well as through random mutation.]]
Neurofibromatosis type 1 is due to  mutation on chromosome 17q11.2 , the gene product being Neurofibromin ( a GTPase activating enzyme).<ref>Fauci, et al ''Harrison's Principle of Internal Medicine'' 16th Ed. p 2453 </ref>

Neurofibromatosis type 2 is due to Merlin, a cytoskeletal protein.

Both NF1 and NF2 are autosomal dominant disorders, meaning that only one copy of the mutated gene need be inherited to pass the disorder. A child of a parent with NF1 or NF2 and an unaffected parent will have a 50% chance of inheriting the disorder.
 
Complicating the question of heritability is the distinction between genotype and phenotype, that is, between the genetics and the actual manifestation of the disorder. In the case of NF1, no clear links between genotype and phenotype have been found, and the severity and specific nature of the symptoms may vary widely among family members with the disorder.<ref>Korf, Bruce E. and Allan E. Rubenstein. 2005. ''Neurofibromatosis: A Handbook for Patients, Families, and Health Care Professionals.''</ref> In the case of NF2, however, manifestations are similar among family members; a strong genotype-phenotype correlation is believed to exist (ibid).

Both NF1 and NF2 can also appear to be spontaneous mutation, with no family history. These cases account for about one half of neurofibromatosis  cases (ibid).

==How NF Can Affect You==
People with Neurofibromatosis can be affected in many different ways. 
* There is a high incidence of learning disabilities in people with NF. It is believed that at least 50% of people with NF have learning disabilities of some type. 
*The tumors that occur can grow anywhere a nerve is present. This means that: 
**They can grow in places that are very visible to people that a patient may encounter on the street. 
**The tumors can also grow in places that can cause other medical issues that may require them to be removed for the patient's safety.
*Affected individuals may need multiple surgeries, depending on where the tumors are located.

==Treatment==
There is no cure for the disease itself. Instead, people with neurofibromatosis are followed by a team of specialists to manage symptoms or complications. Surgery may be needed when the tumors compress organs or other structures. Less than 10% people with neurofibromatosis develop cancerous growths; in these cases, chemotherapy can be tried.<ref name="JAMApatient">[http://jama.ama-assn.org/cgi/content/full/300/3/352 Neurofibromatosis]. JAMA patient page,  Vol. 300 No. 3, July 16, 2008.</ref>

==History==
Neurofibromatosis was discovered in 1882 by the German pathologist Friedrich Daniel von Recklinghausen. He wrote on it and published it in ''Hämochromatose, ''Tageblatt der Naturforschenden Versammlung''.<ref></ref>