Difference between revisions of "Neurofibromatosis"

Line 1:

'''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 2 - NF2 (central).

#Neurofibromatosis type 3 - Schwannomatosis.

==Neurofibromatosis type 1==

Line 9:

Line 10:

===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>

#Two or more [[neurofibroma]]s or one [[plexiform neurofibroma]].

#*May give rise to a [[malignant peripheral nerve sheath tumour]].

#Café-au-lait spots.

#Freckles in axilla or inguinal area.

#Optic nerve glioma.

#Iris hamartomas (Lisch nodules).

#Sphenoid dysplasia or typical long-bone abnormalities (e.g. bowing).

#First-degree relative with NF1.

====Mnemonic====

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.

* '''A'''xillary or inguinal freckling.

* neuro'''F'''ibroma (two or more) ''or'' plexiform neurofibroma (one).

* '''E'''ye hamartomas (Lisch nodules).

* '''S'''keletal abnormalities, e.g. ''s''phenoid dysplasia, leg bowing.

* '''P'''ositive family history. †

* '''O'''ptic '''T'''umour (optic nerve glioma).

Note:

* † One could include ''paraganglioma'' here.

===Images===

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>

===Others===

*[[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>

===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>

==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>

#Bilateral CNVIII masses on imaging.

#Unilateral CNVIII mass + first-degree relative with NF2.

#First-degree relative with NF2 ''and'' 2/4 of the following:

## [[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, mostly spinal [[ependymoma]]s (up tp 20% of NF2 cases affected).

## [[Schwannoma]].

## Juvenile cataract.

Mnemonic ''MISME'':<ref>URL: [http://emedicine.medscape.com/article/342667-overview http://emedicine.medscape.com/article/342667-overview]. Accessed on: 20 February 2012.</ref>

*'''M'''ultiple '''I'''nherited [[schwannoma|'''S'''chwannomas]].

*[[meningioma|'''M'''eningiomas]].

*[[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.

File:Meningoangiomatosis low mag.jpg | Meningioangiomatosis, low mag. (WC/jensflorian)

File:Meningoangiomatosis higher mag.jpg | Meningioangiomatosis, higher mag.(WC/jensflorian)

</gallery>

==See also==

*[[Soft tissue lesions]].

*[[Neurocutaneous syndromes]].

*[[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==

[[Category:Neuropathology]]

[[Category:Syndromes]]

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]].

Difference between revisions of "Neurofibromatosis"

Navigation menu

Search

@@ Line 1: / Line 1: @@
 '''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 2 - NF2 (central).
+#Neurofibromatosis type 3 - Schwannomatosis.
 ==Neurofibromatosis type 1==
@@ Line 9: / Line 10: @@
 ===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>
+#Two or more [[neurofibroma]]s or one [[plexiform neurofibroma]].
+#*May give rise to a [[malignant peripheral nerve sheath tumour]].
+#Café-au-lait spots.
+#Freckles in axilla or inguinal area.
+#Optic nerve glioma.
+#Iris hamartomas (Lisch nodules).
+#Sphenoid dysplasia or typical long-bone abnormalities (e.g. bowing).
+#First-degree relative with NF1.
+====Mnemonic====
+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.
+* '''A'''xillary or inguinal freckling.
+* neuro'''F'''ibroma (two or more) ''or'' plexiform neurofibroma (one).
+* '''E'''ye hamartomas (Lisch nodules).
+* '''S'''keletal abnormalities, e.g. ''s''phenoid dysplasia, leg bowing.
+* '''P'''ositive family history. †
+* '''O'''ptic '''T'''umour (optic nerve glioma).
+Note:
+* † One could include ''paraganglioma'' here.
+===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>
+===Others===
+*[[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>
+===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>
+==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>
+#Bilateral CNVIII masses on imaging.
+#Unilateral CNVIII mass + first-degree relative with NF2.
+#First-degree relative with NF2 ''and'' 2/4 of the following:
+## [[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, mostly spinal [[ependymoma]]s (up tp 20% of NF2 cases affected).
+## [[Schwannoma]].
+## Juvenile cataract.
+Mnemonic ''MISME'':<ref>URL: [http://emedicine.medscape.com/article/342667-overview http://emedicine.medscape.com/article/342667-overview]. Accessed on: 20 February 2012.</ref>
+*'''M'''ultiple '''I'''nherited [[schwannoma|'''S'''chwannomas]].
+*[[meningioma|'''M'''eningiomas]].
+*[[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==
+*[[Soft tissue lesions]].
+*[[Neurocutaneous syndromes]].
+*[[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==
+{{reflist|2}}
+[[Category:Neuropathology]]
+[[Category:Syndromes]]
 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]].