Difference between revisions of "Neurofibromatosis"

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'''Neurofibromatosis''' is a genetic conditions, also known as '''von Recklinghausen's disease'''.  It is abbreviated as '''NF'''.
'''Neurofibromatosis''' is a genetic conditions, also known as '''von Recklinghausen's disease'''.  It is abbreviated as '''NF'''.


It comes in two flavours:
It comes in several flavours:
#Neurofibromatosis type 1 - NF1 (peripheral).
#Neurofibromatosis type 1 - NF1 (peripheral).
#Neurofibromatosis type 2 - NF2 (central).
#Neurofibromatosis type 2 - NF2 (central).
#Neurofibromatosis type 3 - Schwannomatosis.


==Neurofibromatosis type 1==
==Neurofibromatosis type 1==
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===Diagnosis===
===Diagnosis===
Features (need 2/7 to diagnose):<ref>URL: [http://emedicine.medscape.com/article/1177266-overview http://emedicine.medscape.com/article/1177266-overview]. Accessed on: 3 May 2010.</ref>
Features (need 2/7 to diagnose):<ref>URL: [http://emedicine.medscape.com/article/1177266-overview http://emedicine.medscape.com/article/1177266-overview]. Accessed on: 3 May 2010.</ref>
#Two or more [[neurofibroma]]s or one plexiform neurofibroma.
#Two or more [[neurofibroma]]s or one [[plexiform neurofibroma]].
#*May give rise to a [[malignant peripheral nerve sheath tumour]].
#*May give rise to a [[malignant peripheral nerve sheath tumour]].
#Café-au-lait spots.
#Café-au-lait spots.
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====Mnemonic====
====Mnemonic====
''CAFE SPOT'':<ref>URL: [http://www.paeds.co.uk/wiki/index.php?title=Mnemonics#Neurofibromatosis_Type_1_diagnostic_criteria http://www.paeds.co.uk/wiki/index.php?title=Mnemonics#Neurofibromatosis_Type_1_diagnostic_criteria]. Accessed on: 30 May 2011.</ref>
Diagnostic criteria ''CAFE SPOT'':<ref>URL: [http://www.paeds.co.uk/wiki/index.php?title=Mnemonics#Neurofibromatosis_Type_1_diagnostic_criteria http://www.paeds.co.uk/wiki/index.php?title=Mnemonics#Neurofibromatosis_Type_1_diagnostic_criteria]. Accessed on: 30 May 2011.</ref>
* '''C'''afé-au-lait spots.
* '''C'''afé-au-lait spots.
* '''A'''xillary or inguinal freckling.
* '''A'''xillary or inguinal freckling.
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* '''E'''ye hamartomas (Lisch nodules).
* '''E'''ye hamartomas (Lisch nodules).
* '''S'''keletal abnormalities, e.g. ''s''phenoid dysplasia, leg bowing.
* '''S'''keletal abnormalities, e.g. ''s''phenoid dysplasia, leg bowing.
* '''P'''ositive family history.
* '''P'''ositive family history. †
* '''O'''ptic '''T'''umour (optic nerve glioma).
* '''O'''ptic '''T'''umour (optic nerve glioma).
Note:
* † One could include ''paraganglioma'' here.
===Other associations===
*[[Pancreatic neuroendocrine tumour]].<ref name=pmid15249710>{{Cite journal  | last1 = Alexakis | first1 = N. | last2 = Connor | first2 = S. | last3 = Ghaneh | first3 = P. | last4 = Lombard | first4 = M. | last5 = Smart | first5 = HL. | last6 = Evans | first6 = J. | last7 = Hughes | first7 = M. | last8 = Garvey | first8 = CJ. | last9 = Vora | first9 = J. | title = Hereditary pancreatic endocrine tumours. | journal = Pancreatology | volume = 4 | issue = 5 | pages = 417-33; discussion 434-5 | month =  | year = 2004 | doi = 10.1159/000079616 | PMID = 15249710 }}</ref>
*[[Gastrointestinal stromal tumour]].<ref name=pmid20848108>{{cite journal |author=Agaimy A, Hartmann A |title=[Hereditary and non-hereditary syndromic gastointestinal stromal tumours] |language=German |journal=Pathologe |volume=31 |issue=6 |pages=430–7 |year=2010 |month=October |pmid=20848108 |doi=10.1007/s00292-010-1354-6 |url=}}</ref>
*[[Glomus tumour]].<ref name=pmid25426397>{{cite journal |authors=Harrison B, Sammer D |title=Glomus tumors and neurofibromatosis: a newly recognized association |journal=Plast Reconstr Surg Glob Open |volume=2 |issue=9 |pages=e214 |date=September 2014 |pmid=25426397 |pmc=4229273 |doi=10.1097/GOX.0000000000000144 |url=}}</ref>


===Possible association===
===Possible association===
*[[Gangliocytic paraganglioma]].<ref name=pmid12754392>{{Cite journal  | last1 = Castoldi | first1 = L. | last2 = De Rai | first2 = P. | last3 = Marini | first3 = A. | last4 = Ferrero | first4 = S. | last5 = De Luca | first5 = V. | last6 = Tiberio | first6 = G. | title = Neurofibromatosis-1 and Ampullary Gangliocytic Paraganglioma Causing Biliary and Pancreatic Obstruction. | journal = Int J Gastrointest Cancer | volume = 29 | issue = 2 | pages = 93-98 | month =  | year = 2001 | doi =  | PMID = 12754392 }}</ref>
*[[Gangliocytic paraganglioma]].<ref name=pmid12754392>{{Cite journal  | last1 = Castoldi | first1 = L. | last2 = De Rai | first2 = P. | last3 = Marini | first3 = A. | last4 = Ferrero | first4 = S. | last5 = De Luca | first5 = V. | last6 = Tiberio | first6 = G. | title = Neurofibromatosis-1 and Ampullary Gangliocytic Paraganglioma Causing Biliary and Pancreatic Obstruction. | journal = Int J Gastrointest Cancer | volume = 29 | issue = 2 | pages = 93-98 | month =  | year = 2001 | doi =  | PMID = 12754392 }}</ref>
===Images===
<gallery>
File:Early_neurofibromatosis.jpg | Café-au-lait spot (WC/Haymanj)
File:NF-1-Tache_cafe-au-lait.jpg | Café-au-lait spot (WC/Accrochoc)
File:Lisch_nodules.gif | Lisch nodule (iris hamartoma) in the eye (WC/filip em)
File:Neurofibroma03.jpg | Multiple neurofibromas of the skin in NF1 (WC/Enigma51)
File:Neurofibroma02.jpg | Multiple neurofibromas of the skin in NF1 (WC/Enigma51)
File:Neurofibroma_large_NF1.jpg | Large neurofibroma in a NF1 case (WC/jensflorian)
File:Neurofibromatosis,_bowel.jpg | Neurofibromatosis in the bowel (WC/Dr. Robertson)
File:MPNST Pathology gross.jpg | Malignant peripheral nerve sheath tumor of the forearm (WC/drbloodmoney)
</gallery>


==Neurofibromatosis type 2==
==Neurofibromatosis type 2==
*Caused by mutations in the ''NF2 gene'';<ref name=omim101000>{{OMIM|101000}}</ref> this gene is also known as ''merlin''.<ref name=omim607379>{{OMIM|607379}}</ref>
*Reduced life expectancy.
*Mean age at diagnosis: 35years.
===Diagnosis===
Features (need 1/3 to diagnose):<ref>URL: [http://emedicine.medscape.com/article/1178283-overview http://emedicine.medscape.com/article/1178283-overview]. Accessed on: 3 May 2010.</ref>
Features (need 1/3 to diagnose):<ref>URL: [http://emedicine.medscape.com/article/1178283-overview http://emedicine.medscape.com/article/1178283-overview]. Accessed on: 3 May 2010.</ref>
#Bilateral CNVIII masses on imaging.
#Bilateral CNVIII masses on imaging.
#Unilateral CNVIII mass + first-degree relative with NF2.
#Unilateral CNVIII mass + first-degree relative with NF2.
#First-degree relative with NF2 ''and'' 2/4 of the following:     
#First-degree relative with NF2 ''and'' 2/4 of the following:     
## [[Meningioma]] (meningothelial meningioma).<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm]. Accessed on: 26 October 2010.</ref>
## [[Meningioma]] (meningothelial meningioma) up to 50% of the cases.<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm]. Accessed on: 26 October 2010.</ref>
## Glioma.
## Glioma, mostly spinal [[ependymoma]]s (up tp 20% of NF2 cases affected).
## [[Schwannoma]].
## [[Schwannoma]].
## Juvenile cataract.
## Juvenile cataract.
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*[[meningioma|'''M'''eningiomas]].  
*[[meningioma|'''M'''eningiomas]].  
*[[ependymoma|'''E'''pendymomas]].
*[[ependymoma|'''E'''pendymomas]].
Other:
*Cerebral microhamartomas.
*Schwannosis (Schwann cell proliferations).
*Peripheral neuropathy.
===Meningioangiomatosis===
*Cortical proliferations of meningeothelial cells around small vessels.
*May occur within NF2 and sporadic.
*Associated with seizures and/or headaches.
**Often asymptomatic.
<gallery>
File:Meningoangiomatosis low mag.jpg | Meningioangiomatosis, low mag. (WC/jensflorian)
File:Meningoangiomatosis higher mag.jpg | Meningioangiomatosis, higher mag.(WC/jensflorian)
</gallery>


==See also==
==See also==
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*[[Neurocutaneous syndromes]].
*[[Neurocutaneous syndromes]].
*[[Berry aneurysm]].
*[[Berry aneurysm]].
==Schwannomatosis==
*Autosomal dominant.
*Prevalence: 1:155000 (UK).
*Distinct entity from NF2, mainly due to absence of vestibular schwannomas.
*Mean age at diagnosis: 40years.
*Life expectancy better compared to NF2.
===Diagnosis===
Features:<ref>{{Cite journal  | last1 = Evans | first1 = DG. | last2 = Bowers | first2 = NL. | last3 = Tobi | first3 = S. | last4 = Hartley | first4 = C. | last5 = Wallace | first5 = AJ. | last6 = King | first6 = AT. | last7 = Lloyd | first7 = SKW. | last8 = Rutherford | first8 = SA. | last9 = Hammerbeck-Ward | first9 = C. | title = Schwannomatosis: a genetic and epidemiological study. | journal = J Neurol Neurosurg Psychiatry | volume =  | issue =  | pages =  | month = Jun | year = 2018 | doi = 10.1136/jnnp-2018-318538 | PMID = 29909380 }}</ref>
#Two or more non-intradermal [[schwannoma]]s.
#Radiological exclusion of vestibular schwannoma.
#NF2-mutation excluded.
#One schwannoma or meningioma and one relative with confirmed schwannomatosis.
#Germline SMARCB1 or LZTR1 variant and histologically confirmed [[schwannoma]] or [[meningioma]].
===IHC===
*INI1 mosaic pattern in schwannomas.<ref>{{Cite journal  | last1 = Caltabiano | first1 = R. | last2 = Magro | first2 = G. | last3 = Polizzi | first3 = A. | last4 = Praticò | first4 = AD. | last5 = Ortensi | first5 = A. | last6 = D'Orazi | first6 = V. | last7 = Panunzi | first7 = A. | last8 = Milone | first8 = P. | last9 = Maiolino | first9 = L. | title = A mosaic pattern of INI1/SMARCB1 protein expression distinguishes Schwannomatosis and NF2-associated peripheral schwannomas from solitary peripheral schwannomas and NF2-associated vestibular schwannomas. | journal = Childs Nerv Syst | volume = 33 | issue = 6 | pages = 933-940 | month = Jun | year = 2017 | doi = 10.1007/s00381-017-3340-2 | PMID = 28365909 }}</ref>


==References==
==References==
{{reflist|2}}
{{reflist|2}}


[[Category:Weird stuff]]
[[Category:Neuropathology]]
[[Category:Syndrome]]
[[Category:Syndromes]]

Latest revision as of 14:20, 24 August 2021

Neurofibromatosis is a genetic conditions, also known as von Recklinghausen's disease. It is abbreviated as NF.

It comes in several flavours:

  1. Neurofibromatosis type 1 - NF1 (peripheral).
  2. Neurofibromatosis type 2 - NF2 (central).
  3. Neurofibromatosis type 3 - Schwannomatosis.

Neurofibromatosis type 1

  • Autosomal dominant.

Diagnosis

Features (need 2/7 to diagnose):[1]

  1. Two or more neurofibromas or one plexiform neurofibroma.
  2. Café-au-lait spots.
  3. Freckles in axilla or inguinal area.
  4. Optic nerve glioma.
  5. Iris hamartomas (Lisch nodules).
  6. Sphenoid dysplasia or typical long-bone abnormalities (e.g. bowing).
  7. First-degree relative with NF1.

Mnemonic

Diagnostic criteria CAFE SPOT:[2]

  • Café-au-lait spots.
  • Axillary or inguinal freckling.
  • neuroFibroma (two or more) or plexiform neurofibroma (one).
  • Eye hamartomas (Lisch nodules).
  • Skeletal abnormalities, e.g. sphenoid dysplasia, leg bowing.
  • Positive family history. †
  • Optic Tumour (optic nerve glioma).

Note:

  • † One could include paraganglioma here.

Other associations

Possible association

Images

  • Café-au-lait spot (WC/Haymanj)

  • Café-au-lait spot (WC/Accrochoc)

  • Lisch nodule (iris hamartoma) in the eye (WC/filip em)

  • Multiple neurofibromas of the skin in NF1 (WC/Enigma51)

  • Multiple neurofibromas of the skin in NF1 (WC/Enigma51)

  • Large neurofibroma in a NF1 case (WC/jensflorian)

  • Neurofibromatosis in the bowel (WC/Dr. Robertson)

  • Malignant peripheral nerve sheath tumor of the forearm (WC/drbloodmoney)

Neurofibromatosis type 2

  • Caused by mutations in the NF2 gene;[7] this gene is also known as merlin.[8]
  • Reduced life expectancy.
  • Mean age at diagnosis: 35years.

Diagnosis

Features (need 1/3 to diagnose):[9]

  1. Bilateral CNVIII masses on imaging.
  2. Unilateral CNVIII mass + first-degree relative with NF2.
  3. First-degree relative with NF2 and 2/4 of the following:
    1. Meningioma (meningothelial meningioma) up to 50% of the cases.[10]
    2. Glioma, mostly spinal ependymomas (up tp 20% of NF2 cases affected).
    3. Schwannoma.
    4. Juvenile cataract.

Mnemonic MISME:[11]

Other:

  • Cerebral microhamartomas.
  • Schwannosis (Schwann cell proliferations).
  • Peripheral neuropathy.


Meningioangiomatosis

  • Cortical proliferations of meningeothelial cells around small vessels.
  • May occur within NF2 and sporadic.
  • Associated with seizures and/or headaches.
    • Often asymptomatic.

  • Meningioangiomatosis, low mag. (WC/jensflorian)

  • Meningioangiomatosis, higher mag.(WC/jensflorian)

See also


Schwannomatosis

  • Autosomal dominant.
  • Prevalence: 1:155000 (UK).
  • Distinct entity from NF2, mainly due to absence of vestibular schwannomas.
  • Mean age at diagnosis: 40years.
  • Life expectancy better compared to NF2.

Diagnosis

Features:[12]

  1. Two or more non-intradermal schwannomas.
  2. Radiological exclusion of vestibular schwannoma.
  3. NF2-mutation excluded.
  4. One schwannoma or meningioma and one relative with confirmed schwannomatosis.
  5. Germline SMARCB1 or LZTR1 variant and histologically confirmed schwannoma or meningioma.

IHC

  • INI1 mosaic pattern in schwannomas.[13]

References

  1. ↑ URL: http://emedicine.medscape.com/article/1177266-overview. Accessed on: 3 May 2010.
  2. ↑ URL: http://www.paeds.co.uk/wiki/index.php?title=Mnemonics#Neurofibromatosis_Type_1_diagnostic_criteria. Accessed on: 30 May 2011.
  3. ↑ Alexakis, N.; Connor, S.; Ghaneh, P.; Lombard, M.; Smart, HL.; Evans, J.; Hughes, M.; Garvey, CJ. et al. (2004). "Hereditary pancreatic endocrine tumours.". Pancreatology 4 (5): 417-33; discussion 434-5. doi:10.1159/000079616. PMID 15249710.
  4. ↑ Agaimy A, Hartmann A (October 2010). "[Hereditary and non-hereditary syndromic gastointestinal stromal tumours]" (in German). Pathologe 31 (6): 430–7. doi:10.1007/s00292-010-1354-6. PMID 20848108.
  5. ↑ Harrison B, Sammer D (September 2014). "Glomus tumors and neurofibromatosis: a newly recognized association". Plast Reconstr Surg Glob Open 2 (9): e214. doi:10.1097/GOX.0000000000000144. PMC 4229273. PMID 25426397. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229273/.
  6. ↑ Castoldi, L.; De Rai, P.; Marini, A.; Ferrero, S.; De Luca, V.; Tiberio, G. (2001). "Neurofibromatosis-1 and Ampullary Gangliocytic Paraganglioma Causing Biliary and Pancreatic Obstruction.". Int J Gastrointest Cancer 29 (2): 93-98. PMID 12754392.
  7. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 101000
  8. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 607379
  9. ↑ URL: http://emedicine.medscape.com/article/1178283-overview. Accessed on: 3 May 2010.
  10. ↑ URL: http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm. Accessed on: 26 October 2010.
  11. ↑ URL: http://emedicine.medscape.com/article/342667-overview. Accessed on: 20 February 2012.
  12. ↑ Evans, DG.; Bowers, NL.; Tobi, S.; Hartley, C.; Wallace, AJ.; King, AT.; Lloyd, SKW.; Rutherford, SA. et al. (Jun 2018). "Schwannomatosis: a genetic and epidemiological study.". J Neurol Neurosurg Psychiatry. doi:10.1136/jnnp-2018-318538. PMID 29909380.
  13. ↑ Caltabiano, R.; Magro, G.; Polizzi, A.; Praticò, AD.; Ortensi, A.; D'Orazi, V.; Panunzi, A.; Milone, P. et al. (Jun 2017). "A mosaic pattern of INI1/SMARCB1 protein expression distinguishes Schwannomatosis and NF2-associated peripheral schwannomas from solitary peripheral schwannomas and NF2-associated vestibular schwannomas.". Childs Nerv Syst 33 (6): 933-940. doi:10.1007/s00381-017-3340-2. PMID 28365909.
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