Lisch nodule: Difference between revisions

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__NOTOC__
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'''For patient information, click [[Lisch nodule (patient information)|here]]'''
{{CMG}}; {{AE}} {{Swathi}}
{{Lisch nodule}}
{{CMG}} {{Swathi}}


{{SK}} Sakurai-lisch nodule
{{SK}} Sakurai-lisch nodule
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==Historical Perspective==
==Historical Perspective==
*In 1882, [[Neurofibromatosis 1|Neurofibromatosis]] ([[NF]]), described by Friedrich Daniel [[Von Recklinghausen neurofibromatosis|Von Recklinghausen]].
*[[File:Lisch Nodule.jpg|alt=Lisch nodules|thumb|Multiple small, oval, yellow-brown [[papules]] (Lisch nodules) in the right [[Iris (anatomy)|iris]](Red arrows). case courtesy by E. G. Adams et al.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350217/|title=Multiple, Unilateral Lisch Nodules in the Absence of Other Manifestations of Neurofibromatosis Type 1|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>]]In 1882, [[Neurofibromatosis 1|Neurofibromatosis]] ([[NF]]), described by Friedrich Daniel [[Von Recklinghausen neurofibromatosis|Von Recklinghausen]].<ref name="pmid23793209">{{cite journal| author=Antônio JR, Goloni-Bertollo EM, Trídico LA| title=Neurofibromatosis: chronological history and current issues. | journal=An Bras Dermatol | year= 2013 | volume= 88 | issue= 3 | pages= 329-43 | pmid=23793209 | doi=10.1590/abd1806-4841.20132125 | pmc=3754363 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23793209  }}</ref><ref name="Hosoi1931">{{cite journal|last1=Hosoi|first1=Kiyoshi|title=MULTIPLE NEUROFIBROMATOSIS (von RECKLINGHAUSEN'S DISEASE)|journal=Archives of Surgery|volume=22|issue=2|year=1931|pages=258|issn=0272-5533|doi=10.1001/archsurg.1931.01160020081004}}</ref>
*[[NF]] is a neuroectodermal abnormality constituted by a [[set]] of [[clinical]] [[symptoms]] that compromise the [[skin]], [[nervous system]], [[bones]], [[eyes]] and other sites.
*[[NF]] is a neuroectodermal abnormality constituted by a [[set]] of [[clinical]] [[symptoms]] that compromise the [[skin]], [[nervous system]], [[bones]], [[eyes]] and other sites.
*Lisch Nodules were named after the infamous Austrian [[ophthalmology|ophthalmologist]] Karl Lisch(1907-1999) who was also called as "Ophthalmological Pope".
*Lisch Nodules were named after the infamous Austrian [[ophthalmology|ophthalmologist]] Karl Lisch(1907-1999) who was also called as "Ophthalmological Pope".
*Besides general [[ophthalmology]], Lisch was interested in [[scientific]] [[research]]. He published more than 120 [[scientific]] papers in German [[Science (journal)|science]] journals.
*Besides general [[ophthalmology]], Lisch was interested in [[scientific]] [[research]]. He published more than 120 [[scientific]] papers in German [[Science (journal)|science]] journals.
*In 1937, Karl Lisch published an article on the [[iris]] [[hamartomas]] and their association with [[neurofibromatosis 1]], now known as "Lisch nodules", while at the University Eye Clinic in Munich.
*In 1937, Karl Lisch published an article on the [[iris]] [[hamartomas]] and their association with [[neurofibromatosis 1]], now known as "Lisch nodules", while at the University Eye Clinic in Munich.
*Lisch'a article described his [[Observation|observations]] in 3 [[patients]] with [[neurofibromatosis]]:
*Lisch'a article described his [[Observation|observations]] in 3 [[patients]] with [[neurofibromatosis]]:<ref name="pmid20418991">{{cite journal| author=Gabhane SK, Kotwal MN, Bobhate SK| title=Segmental neurofibromatosis: a report of 3 cases. | journal=Indian J Dermatol | year= 2010 | volume= 55 | issue= 1 | pages= 105-8 | pmid=20418991 | doi=10.4103/0019-5154.60366 | pmc=2856359 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20418991  }}</ref><ref name="Dimitrova2009">{{cite journal|last1=Dimitrova|first1=Valentina|title=A CASE OF NEUROFIBROMATOSIS TYPE 1|journal=Journal of IMAB - Annual Proceeding (Scientific Papers)|volume=14, 1|issue=2008|year=2009|pages=63–67|issn=1312773X|doi=10.5272/jimab.14-1-2010.63}}</ref>
**[[Patient]] 1: A 39 [[year]] [[Old age|old]] [[male]] who had been affected with several [[nodules]] and [[Pigmented lesions|pigmented]] [[lesions]] on the [[skin]], typical of [[neurofibromatosis]], since the [[age]] of 15 [[Year|years]]. His mother and his sisters had a similar [[disorder]]. Lisch observed several [[brown]] [[nodules]] on the surface of the [[iris]]. The [[nodules]] could be seen even without the [[slit lamp]] due to the greyish-blue [[color]] of the [[iris]].
**[[Patient]] 1: A 39 [[year]] [[Old age|old]] [[male]] who had been affected with several [[nodules]] and [[Pigmented lesions|pigmented]] [[lesions]] on the [[skin]], typical of [[neurofibromatosis]], since the [[age]] of 15 [[Year|years]]. His mother and his sisters had a similar [[disorder]]. Lisch observed several [[brown]] [[nodules]] on the surface of the [[iris]]. The [[nodules]] could be seen even without the [[slit lamp]] due to the greyish-blue [[color]] of the [[iris]].
**[[Patient]] 2: 27 [[year]] [[Old age|old]] [[patient]] with similar [[cutaneous]] and [[iris]] [[lesions]] could be detected along with a [[family]] [[History and Physical examination|history]] of [[neurofibromatosis]]. In comparison to the first [[patient]] the [[iris]] [[nodules]] were much more pigmented.
**[[Patient]] 2: 27 [[year]] [[Old age|old]] [[patient]] with similar [[cutaneous]] and [[iris]] [[lesions]] could be detected along with a [[family]] [[History and Physical examination|history]] of [[neurofibromatosis]]. In comparison to the first [[patient]] the [[iris]] [[nodules]] were much more pigmented.
**[[Patient]] 3: A 44 [[year]] [[Old age|old]] [[male]] suffered form [[bilateral]] [[optic]] [[nerve]] [[gliomas]] with [[Chiasma|chiasmal]] involvement. The [[slit lamp]] [[examination]] revealed tiny [[iris]] [[nodules]] in both [[eyes]].
**[[Patient]] 3: A 44 [[year]] [[Old age|old]] [[male]] suffered form [[bilateral]] [[optic]] [[nerve]] [[gliomas]] with [[Chiasma|chiasmal]] involvement. The [[slit lamp]] [[examination]] revealed tiny [[iris]] [[nodules]] in both [[eyes]].


==Lisch nodule classification==
==Classification==


* There is no established system for the classification of Lisch nodules.
* There is no established system for the classification of Lisch nodules.


==Pathophysiology==
==Pathophysiology==
*A [[hamartoma]] is defined as a [[benign]] [[tumor]] or [[nodular]] [[growth]] that is composed of [[Proliferation|proliferating]] [[Maturation|mature]] [[histologically]] normal [[cells]] that normally reside at the affected [[tissue]].
*A [[hamartoma]] is defined as a [[benign]] [[tumor]] or [[nodular]] [[growth]] that is composed of [[Proliferation|proliferating]] [[Maturation|mature]] [[histologically]] normal [[cells]] that normally reside at the affected [[tissue]].<ref name="pmid19650418">{{cite journal| author=Terzi YK, Oguzkan-Balci S, Anlar B, Aysun S, Guran S, Ayter S| title=Reproductive decisions after prenatal diagnosis in neurofibromatosis type 1: importance of genetic counseling. | journal=Genet Couns | year= 2009 | volume= 20 | issue= 2 | pages= 195-202 | pmid=19650418 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19650418  }}</ref><ref name="pmid19516012">{{cite journal| author=Boley S, Sloan JL, Pemov A, Stewart DR| title=A quantitative assessment of the burden and distribution of Lisch nodules in adults with neurofibromatosis type 1. | journal=Invest Ophthalmol Vis Sci | year= 2009 | volume= 50 | issue= 11 | pages= 5035-43 | pmid=19516012 | doi=10.1167/iovs.09-3650 | pmc=2883270 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19516012  }}</ref><ref name="pmid19539839">{{cite journal| author=Boyd KP, Korf BR, Theos A| title=Neurofibromatosis type 1. | journal=J Am Acad Dermatol | year= 2009 | volume= 61 | issue= 1 | pages= 1-14; quiz 15-6 | pmid=19539839 | doi=10.1016/j.jaad.2008.12.051 | pmc=2716546 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19539839  }}</ref><ref name="TheosKorf2006">{{cite journal|last1=Theos|first1=Amy|last2=Korf|first2=Bruce R.|title=Pathophysiology of Neurofibromatosis Type 1|journal=Annals of Internal Medicine|volume=144|issue=11|year=2006|pages=842|issn=0003-4819|doi=10.7326/0003-4819-144-11-200606060-00010}}</ref>
*[[NF1]] is due to [[mutations]] in the [[NF1]] [[gene]], located at [[chromosome]] 17q11.2
*[[NF1]] is due to [[mutations]] in the [[NF1]] [[gene]], located at [[chromosome]] 17q11.2.<ref name="pmid20422842">{{cite journal| author=Cohen R, Shuper A| title=[Developmental manifestation in children with neurofibromatosis type 1]. | journal=Harefuah | year= 2010 | volume= 149 | issue= 1 | pages= 49-52, 61 | pmid=20422842 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20422842  }}</ref><ref name="pmid115721742">{{cite journal| author=de Goede-Bolder A, Cnossen MH, Dooijes D, van den Ouweland AM, Niermeijer MF| title=[From gene to disease; neurofibromatosis type 1]. | journal=Ned Tijdschr Geneeskd | year= 2001 | volume= 145 | issue= 36 | pages= 1736-8 | pmid=11572174 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11572174  }}</ref>
*Lisch nodules are generally not present in central NF([[neurofibromatosis]])/NF([[neurofibromatosis]])-2.
*[[Neurofibromin]], the [[protein]] product encoded by the [[gene]], is expressed in many [[tissues]], including [[brain]], [[kidney]], [[spleen]], and [[thymus]].
*[[Neurofibromin]], the [[protein]] product encoded by the [[gene]], is expressed in many [[tissues]], including [[brain]], [[kidney]], [[spleen]], and [[thymus]].
*[[Mutations]] in the [[NF1]] [[gene]] result in loss of production or reduced [[Function (biology)|function]] of [[protein]]; this causes a wide spectrum of clinical findings, including NF1-associated tumors.
*[[Mutations]] in the [[NF1]] [[gene]] result in loss of production or reduced [[Function (biology)|function]] of [[protein]]; this causes a wide spectrum of clinical findings, including [[NF1]]-associated [[Tumor|tumors]].<ref name="LubsBauer1991">{{cite journal|last1=Lubs|first1=Marie-Louise E.|last2=Bauer|first2=Mislen S.|last3=Formas|first3=Maria E.|last4=Djokic|first4=Borivoje|title=Lisch Nodules in Neurofibromatosis Type 1|journal=New England Journal of Medicine|volume=324|issue=18|year=1991|pages=1264–1266|issn=0028-4793|doi=10.1056/NEJM199105023241807}}</ref><ref name="Dimitrova20092">{{cite journal|last1=Dimitrova|first1=Valentina|title=A CASE OF NEUROFIBROMATOSIS TYPE 1|journal=Journal of IMAB - Annual Proceeding (Scientific Papers)|volume=14, 1|issue=2008|year=2009|pages=63–67|issn=1312773X|doi=10.5272/jimab.14-1-2010.63}}</ref>
*[[Histopathology|Histopathologically]], Lisch nodules are composed of [[melanocytes]] and [[spindle cells]], usually concentrated on the superficial layers of the [[iris]] stroma.
*[[Histopathology|Histopathologically]], Lisch nodules are composed of [[melanocytes]] and [[spindle cells]], usually concentrated on the superficial layers of the [[iris]] [[stroma]].<ref name="pmid28979620">{{cite journal| author=Abaloun Y, Ajhoun Y| title=[Lisch nodule in neurofibromatosis type 1]. | journal=Pan Afr Med J | year= 2017 | volume= 27 | issue=  | pages= 218 | pmid=28979620 | doi=10.11604/pamj.2017.27.218.11517 | pmc=5622834 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28979620  }}</ref><ref name="pmid150961513">{{cite journal| author=Richetta A, Giustini S, Recupero SM, Pezza M, Carlomagno V, Amoruso G et al.| title=Lisch nodules of the iris in neurofibromatosis type 1. | journal=J Eur Acad Dermatol Venereol | year= 2004 | volume= 18 | issue= 3 | pages= 342-4 | pmid=15096151 | doi=10.1111/j.1468-3083.2004.00915.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15096151  }}</ref><ref name="RichettaGiustini2004">{{cite journal|last1=Richetta|first1=A|last2=Giustini|first2=S|last3=Recupero|first3=SM|last4=Pezza|first4=M|last5=Carlomagno|first5=V|last6=Amoruso|first6=G|last7=Calvieri|first7=S|title=Lisch nodules of the iris in neurofibromatosis type 1|journal=Journal of the European Academy of Dermatology and Venereology|volume=18|issue=3|year=2004|pages=342–344|issn=0926-9959|doi=10.1111/j.1468-3083.2004.00915.x}}</ref>
*The [[spindle cells]] are larger than the normal iris [[melanocytes]].
*The [[spindle cells]] are larger than the normal [[Iris (anatomy)|iris]] [[melanocytes]].
*[[Immunohistochemical]] studies show positive reaction against [[vimentin]], [[smooth muscle]] [[actin]] and neuron specific [[enolase]].
*[[Immunohistochemical]] studies show positive reaction against the following
**[[Vimentin]]
**[[Smooth muscle]] [[actin]]  
**[[Neuron]] specific [[enolase]].


== Lisch nodule causes ==
== Causes ==


* Lisch Nodules commonly associated with [[neurofibromatosis]] and is caused by [[Genetics|genetic]] defects or [[mutations]] that either are passed on by a parent or occur spontaneously at [[conception]].
* Lisch Nodules commonly associated with [[neurofibromatosis]] and is caused by [[Genetics|genetic]] defects or [[mutations]] that either are passed on by a parent or occur spontaneously at [[conception]].


==Lisch nodule differential diagnosis==
==Differential diagnosis==


* Lisch nodules must be differentiated from [[Iris (anatomy)|Iris]] mammillations, [[Iridocorneal endothelial syndrome]], Rieger's anomaly or syndrome, [[Iris (anatomy)|Iris]] [[nevi]], [[Melanoma]], [[Inflammatory]] conditions such as [[Sarcoidosis]], [[Leprosy]], [[Tuberculosis]] and [[Syphilis]].<ref name="pmid6992584">{{cite journal| author=Radius RL, Herschler J| title=Histopathology in the iris-nevus (Cogan-Reese) syndrome. | journal=Am J Ophthalmol | year= 1980 | volume= 89 | issue= 6 | pages= 780-6 | pmid=6992584 | doi=10.1016/0002-9394(80)90165-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6992584  }}</ref><ref name="pmid3190109">{{cite journal| author=Makley TA, Kapetansky FM| title=Iris nevus syndrome. | journal=Ann Ophthalmol | year= 1988 | volume= 20 | issue= 8 | pages= 311-5 | pmid=3190109 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3190109  }}</ref>
* Lisch nodules must be differentiated from [[Iris (anatomy)|Iris]] mammillations, [[Iridocorneal endothelial syndrome]], Rieger's anomaly or syndrome, [[Iris (anatomy)|Iris]] [[nevi]], [[Melanoma]], [[Inflammatory]] conditions such as [[Sarcoidosis]], [[Leprosy]], [[Tuberculosis]] and [[Syphilis]].<ref name="pmid6992584">{{cite journal| author=Radius RL, Herschler J| title=Histopathology in the iris-nevus (Cogan-Reese) syndrome. | journal=Am J Ophthalmol | year= 1980 | volume= 89 | issue= 6 | pages= 780-6 | pmid=6992584 | doi=10.1016/0002-9394(80)90165-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6992584  }}</ref><ref name="pmid3190109">{{cite journal| author=Makley TA, Kapetansky FM| title=Iris nevus syndrome. | journal=Ann Ophthalmol | year= 1988 | volume= 20 | issue= 8 | pages= 311-5 | pmid=3190109 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3190109  }}</ref>
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== Epidemiology and Demographics ==
== Epidemiology and Demographics ==


*NF1 is an autosomal dominant genetic disorder with an incidence of approximately 1 in 2600 to 3000 individuals.
=== Incidence ===
**Approximately one-half of the cases are familial (inherited)
**The remainder are the result of de novo (sporadic) mutations.
**The de novo mutations occur primarily in paternally derived chromosomes, and the likelihood of de novo NF1 increases with advanced paternal age
*Lisch nodules are predominantly visible in children usually after the age of six years.
*Lisch Nodule incidence in NF1 increases with age and their prevalence raises by about 10% per year of life, up to age 9.
*Lisch nodules are found in 93% of adults with NF-1 but have not been described in NF-2.
*Lisch Nodules may be found in a very limited number of individuals without NF.
*Multiple Lisch nodules appear to be found only in patients with peripheral neurofibromatosis (neurofibromatosis type 1, or von Recklinghausen's disease), an autosomal disorder with a prevalence of 1 in 3500.


* The [[incidence]] of Lisch nodules is approximately 1 in 2600 to 3000 individuals worldwide.<ref name="LubsBauer19912">{{cite journal|last1=Lubs|first1=Marie-Louise E.|last2=Bauer|first2=Mislen S.|last3=Formas|first3=Maria E.|last4=Djokic|first4=Borivoje|title=Lisch Nodules in Neurofibromatosis Type 1|journal=New England Journal of Medicine|volume=324|issue=18|year=1991|pages=1264–1266|issn=0028-4793|doi=10.1056/NEJM199105023241807}}</ref><ref name="pmid196504182">{{cite journal| author=Terzi YK, Oguzkan-Balci S, Anlar B, Aysun S, Guran S, Ayter S| title=Reproductive decisions after prenatal diagnosis in neurofibromatosis type 1: importance of genetic counseling. | journal=Genet Couns | year= 2009 | volume= 20 | issue= 2 | pages= 195-202 | pmid=19650418 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19650418  }}</ref>
*Approximately one-half of the cases are [[familial]] ([[inherited]]).<ref name="pmid20082463">{{cite journal| author=Evans DG, Howard E, Giblin C, Clancy T, Spencer H, Huson SM et al.| title=Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. | journal=Am J Med Genet A | year= 2010 | volume= 152A | issue= 2 | pages= 327-32 | pmid=20082463 | doi=10.1002/ajmg.a.33139 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20082463  }}</ref><ref name="pmid150961512">{{cite journal| author=Richetta A, Giustini S, Recupero SM, Pezza M, Carlomagno V, Amoruso G et al.| title=Lisch nodules of the iris in neurofibromatosis type 1. | journal=J Eur Acad Dermatol Venereol | year= 2004 | volume= 18 | issue= 3 | pages= 342-4 | pmid=15096151 | doi=10.1111/j.1468-3083.2004.00915.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15096151  }}</ref>
*<nowiki/>The remainder are the result of [[De novo|de novo (]]<nowiki/>sporadic) [[mutations]].


==Risk Factors==
=== Prevalence ===
*The biggest risk factor for Lisch nodules associated with neurofibromatosis is a family history of the disorder.   
 
**NF1 and NF2 are both autosomal dominant disorders, which means that any child of a parent with the disorder has a 50 percent chance of inheriting the genetic mutation.
*<nowiki/>The [[prevalence]] of Lisch nodules is approx<nowiki/>imately 1 in 3500 individuals worldwide.<ref name="pmid15655144">{{cite journal| author=Lammert M, Friedman JM, Kluwe L, Mautner VF| title=Prevalence of neurofibromatosis 1 in German children at elementary school enrollment. | journal=Arch Dermatol | year= 2005 | volume= 141 | issue= 1 | pages= 71-4 | pmid=15655144 | doi=10.1001/archderm.141.1.71 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15655144 }}</ref>
**About half of people with NF1 and NF2 inherited the disease from the affected parent.
 
*People with NF1 and NF2 that don't have affected relatives likely have a new gene mutation.
=== Age ===
*Neurofibromatosis is caused by genetic defects (mutations) that either are passed on by a parent or occur spontaneously at conception.
 
**The NF1 gene is located on chromosome 17. This gene produces a protein called neurofibromin that helps regulate cell growth.  The mutated gene causes a loss of neurofibromin, which allows cells to grow uncontrolled.
* Lisch nodules are predominantly visible in children usually after the age of six years.<ref name="pmid204228422">{{cite journal| author=Cohen R, Shuper A| title=[Developmental manifestation in children with neurofibromatosis type 1]. | journal=Harefuah | year= 2010 | volume= 149 | issue= 1 | pages= 49-52, 61 | pmid=20422842 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20422842  }}</ref>
**The NF2 gene is located on chromosome 22, and produces a protein called merlin (also called schwannomin), which suppresses tumors.  The mutated gene causes a loss of merlin, leading to uncontrolled cell growth.
 
**Two genes are known to cause schwannomatosis. Mutations of the genes SMARCB1 and LZTR1, which suppress tumors, are associated with this type of neurofibromatosis.
*Lisch Nodule [[incidence]] in [[NF1]] increases with age and their prevalence raises by about 10% per year of life, up to age 9.
*Lisch nodules are found in 93% of adults with [[Neurofibromatosis type I|NF-1]] but have not been described in [[Neurofibromatosis type II|NF-2.]]
*Lisch Nodules may be found in a very limited number of individuals without [[NF]].
*The [[De novo mutation|de novo mutations]] occur primarily in paternally derived [[Chromosome|chromosomes]], and the likelihood of de novo [[NF1]] increases with advanced [[Paternal age effect|paternal]] age.
 
== Risk Factors ==
 
*The biggest [[risk factor]] for Lisch nodules associated with [[neurofibromatosis]] is a family history of the disorder.


==Screening==
==Screening==
*Lisch Nodules are not regularly screened, they’re usually detected when other signs and symptoms of neurofibromatosis appear. 
*However, Lisch nodules are seen in 95% of children with NF1 by age 20
*They can often be seen with no magnification, especially in adults, who usually have multiple, bilateral nodules
*A slit-lamp examination, however, is required to distinguish them from nevi on the iris, which are flat or minimally elevated, densely pigmented lesions with blurred margins.


* Lisch Nodules are not regularly [[Screening|screened]], they’re usually detected when other [[signs]] and [[Symptom|symptoms]] of [[neurofibromatosis]] appear.<ref name="LubsBauer19913">{{cite journal|last1=Lubs|first1=Marie-Louise E.|last2=Bauer|first2=Mislen S.|last3=Formas|first3=Maria E.|last4=Djokic|first4=Borivoje|title=Lisch Nodules in Neurofibromatosis Type 1|journal=New England Journal of Medicine|volume=324|issue=18|year=1991|pages=1264–1266|issn=0028-4793|doi=10.1056/NEJM199105023241807}}</ref>
*However, Lisch nodules are seen in 95% of children with [[NF1]] by age 20.<ref name="pmid3103673">{{cite journal| author=Huson S, Jones D, Beck L| title=Ophthalmic manifestations of neurofibromatosis. | journal=Br J Ophthalmol | year= 1987 | volume= 71 | issue= 3 | pages= 235-8 | pmid=3103673 | doi=10.1136/bjo.71.3.235 | pmc=1041127 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3103673  }}</ref>


==[[Lisch nodule natural history|Natural History, Complications and Prognosis]]==
== Natural History, Complications and Prognosis ==


*The prognosis is excellent for eyes that contain iris Lisch nodules, unless associated with other ocular lesions including optic nerve gliomas and epiretinal membranes.
=== Natural History ===
*NF1 and NF2 vary based on location of chromosome mutation, tumor type and location, non-tumor manifestations and management techniques; however, clinical presentations of both subtypes may overlap, making diagnosis difficult
*Both NF1 and NF2 are acquired through an inherited autosomal dominant transmission or sporadic mutation, with presentation of NF1 more common than NF2.
*Therefore, members of the same family with NF may have different disease presentations from each other, as they do not always carry the same gene mutations.
*Lisch nodules rarely cause ocular complications and patients are typically asymptomatic
*NF patients may also present with plexiform neurofibroma, retinal tumors and optic nerve pathway gliomas as optical lesions


==Diagnosis==
* The symptoms of Lisch Nodules usually develop in the first decade of life, and mostly [[asymptomatic]].
 
=== Complications ===
 
* Common [[complications]] of Lisch Nodules include:<ref name="pmid15096151">{{cite journal| author=Richetta A, Giustini S, Recupero SM, Pezza M, Carlomagno V, Amoruso G et al.| title=Lisch nodules of the iris in neurofibromatosis type 1. | journal=J Eur Acad Dermatol Venereol | year= 2004 | volume= 18 | issue= 3 | pages= 342-4 | pmid=15096151 | doi=10.1111/j.1468-3083.2004.00915.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15096151  }}</ref><ref name="Dimitrova20093">{{cite journal|last1=Dimitrova|first1=Valentina|title=A CASE OF NEUROFIBROMATOSIS TYPE 1|journal=Journal of IMAB - Annual Proceeding (Scientific Papers)|volume=14, 1|issue=2008|year=2009|pages=63–67|issn=1312773X|doi=10.5272/jimab.14-1-2010.63}}</ref>
**[[Optic]] [[Glioma|gliomas]]
**[[Pseudarthrosis]]
** Progressive [[vision loss]]
**[[Choroidal|Choroid]] [[hamartomas]]
**[[Retinal]] [[tumors]]
**Prominent [[corneal]] [[Nerve|nerves]]
 
=== Prognosis ===
 
*[[Prognosis]] is generally good of patients with Lisch Nodules.
 
== Diagnosis ==
'''Diagnostic Criteria for neurofibromatosis 1'''
'''Diagnostic Criteria for neurofibromatosis 1'''


'''(NIH consensus development conference 1988)'''
* ([[National Institute of Health]] Consensus Development Conference 1988)<ref name="pmid6789269">{{cite journal| author=Lewis RA, Riccardi VM| title=Von Recklinghausen neurofibromatosis. Incidence of iris hamartomata. | journal=Ophthalmology | year= 1981 | volume= 88 | issue= 4 | pages= 348-54 | pmid=6789269 | doi=10.1016/s0161-6420(81)35034-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6789269  }}</ref><ref name="pmid31036732">{{cite journal| author=Huson S, Jones D, Beck L| title=Ophthalmic manifestations of neurofibromatosis. | journal=Br J Ophthalmol | year= 1987 | volume= 71 | issue= 3 | pages= 235-8 | pmid=3103673 | doi=10.1136/bjo.71.3.235 | pmc=1041127 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3103673  }}</ref><ref name="pmid289796202">{{cite journal| author=Abaloun Y, Ajhoun Y| title=[Lisch nodule in neurofibromatosis type 1]. | journal=Pan Afr Med J | year= 2017 | volume= 27 | issue=  | pages= 218 | pmid=28979620 | doi=10.11604/pamj.2017.27.218.11517 | pmc=5622834 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28979620  }}</ref><ref name="pmid3100979">{{cite journal| author=Flüeler U, Boltshauser E, Kilchhofer A| title=Iris hamartomata as diagnostic criterion in neurofibromatosis. | journal=Neuropediatrics | year= 1986 | volume= 17 | issue= 4 | pages= 183-5 | pmid=3100979 | doi=10.1055/s-2008-1052525 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3100979  }}</ref><ref name="pmid204228423">{{cite journal| author=Cohen R, Shuper A| title=[Developmental manifestation in children with neurofibromatosis type 1]. | journal=Harefuah | year= 2010 | volume= 149 | issue= 1 | pages= 49-52, 61 | pmid=20422842 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20422842  }}</ref><ref name="pmid16583938">{{cite journal| author=Sabol Z, Kipke-Sabol L| title=[Neurofibromatosis type 1 (von Recklinghausen's disease or peripheral neurofibromatosis): from phenotype to gene]. | journal=Lijec Vjesn | year= 2005 | volume= 127 | issue= 11-12 | pages= 303-11 | pmid=16583938 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16583938  }}</ref><ref name="pmid18280349">{{cite journal| author=Yang CC, Happle R, Chao SC, Yu-Yun Lee J, Chen W| title=Giant café-au-lait macule in neurofibromatosis 1: a type 2 segmental manifestation of neurofibromatosis 1? | journal=J Am Acad Dermatol | year= 2008 | volume= 58 | issue= 3 | pages= 493-7 | pmid=18280349 | doi=10.1016/j.jaad.2007.03.013 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18280349  }}</ref><ref name="pmid11572174">{{cite journal| author=de Goede-Bolder A, Cnossen MH, Dooijes D, van den Ouweland AM, Niermeijer MF| title=[From gene to disease; neurofibromatosis type 1]. | journal=Ned Tijdschr Geneeskd | year= 2001 | volume= 145 | issue= 36 | pages= 1736-8 | pmid=11572174 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11572174  }}</ref>
** 6 or more [[Café au lait spot|café au lait macules]]<ref name="pmid196504183">{{cite journal| author=Terzi YK, Oguzkan-Balci S, Anlar B, Aysun S, Guran S, Ayter S| title=Reproductive decisions after prenatal diagnosis in neurofibromatosis type 1: importance of genetic counseling. | journal=Genet Couns | year= 2009 | volume= 20 | issue= 2 | pages= 195-202 | pmid=19650418 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19650418  }}</ref>
***[[Cafe-au-lait spots|Cafe au lait macules]] should be  >0.5 cm in length in children
***[[Cafe-au-lait spots|Cafe au lait macules]] should be >1.5 cm in length in adults
** 2 or more [[cutaneous]] [[Neurofibroma|neurofibromas]] or one [[plexiform neurofibroma]]
**[[Axillary]] or [[groin]] freckling
**[[Optic]] gliomas
**2 or more Lisch [[nodules]] especially [[Iris (anatomy)|iris]] [[hamartomas]] which can be seen on [[slit lamp]] examination
**[[Bonyl|Bony]] [[dysplasia]] with or without [[pseudarthrosis]]
**First degree relative with [[NF1]]


*6 or more café au lait macules (>0.5 cm in children or >1.5 cm in adults)
* The [[diagnosis]] is primarily based on clinical assessment and two or more of the features are required to confirm the [[diagnosis]].
*2 or more cutaneous/subcutaneous neurofibromas or one plexiform neurofibroma
*Axillary or groin freckling
*Optic pathway glioma
*2 or more Lisch nodules (iris hamartomas seen on slit lamp examination)
*Bony dysplasia (sphenoid wing dysplasia, bowing of long bone ± pseudarthrosis)
*First degree relative with NF1


The diagnosis is based on clinical assessment and two or more of the features are required.
== Physical Examination ==


*[[File:Lisch nodules.jpg|alt=Lisch nodules and near-infrared reflectance image|thumb|Lisch nodules and near-infrared reflectance image (case 4). At least five Lisch nodules were detected and were classified as scale III (A). Note that 14 bright, patchy [[lesions]] were detected by near-infrared reflectance (B). The hyper-reflective point at the center of the image is an [[optical]] artifact. Case courtesy by Shinji Makino et al<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883548/|title=Correlations between choroidal abnormalities, Lisch nodules, and age in patients with neurofibromatosis type 1|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>]]Lisch nodules occur in 90% of adults with [[Neurofibromatosis type I|neurofibromatosis]] 1.<ref name="pmid67892693">{{cite journal| author=Lewis RA, Riccardi VM| title=Von Recklinghausen neurofibromatosis. Incidence of iris hamartomata. | journal=Ophthalmology | year= 1981 | volume= 88 | issue= 4 | pages= 348-54 | pmid=6789269 | doi=10.1016/s0161-6420(81)35034-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6789269  }}</ref><ref name="pmid31036733">{{cite journal| author=Huson S, Jones D, Beck L| title=Ophthalmic manifestations of neurofibromatosis. | journal=Br J Ophthalmol | year= 1987 | volume= 71 | issue= 3 | pages= 235-8 | pmid=3103673 | doi=10.1136/bjo.71.3.235 | pmc=1041127 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3103673 }}</ref><ref name="pmid289796203">{{cite journal| author=Abaloun Y, Ajhoun Y| title=[Lisch nodule in neurofibromatosis type 1]. | journal=Pan Afr Med J | year= 2017 | volume= 27 | issue=  | pages= 218 | pmid=28979620 | doi=10.11604/pamj.2017.27.218.11517 | pmc=5622834 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28979620  }}</ref><ref name="pmid182803492">{{cite journal| author=Yang CC, Happle R, Chao SC, Yu-Yun Lee J, Chen W| title=Giant café-au-lait macule in neurofibromatosis 1: a type 2 segmental manifestation of neurofibromatosis 1? | journal=J Am Acad Dermatol | year= 2008 | volume= 58 | issue= 3 | pages= 493-7 | pmid=18280349 | doi=10.1016/j.jaad.2007.03.013 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18280349  }}</ref><ref name="pmid204228424">{{cite journal| author=Cohen R, Shuper A| title=[Developmental manifestation in children with neurofibromatosis type 1]. | journal=Harefuah | year= 2010 | volume= 149 | issue= 1 | pages= 49-52, 61 | pmid=20422842 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20422842  }}</ref><ref name="Dimitrova20094">{{cite journal|last1=Dimitrova|first1=Valentina|title=A CASE OF NEUROFIBROMATOSIS TYPE 1|journal=Journal of IMAB - Annual Proceeding (Scientific Papers)|volume=14, 1|issue=2008|year=2009|pages=63–67|issn=1312773X|doi=10.5272/jimab.14-1-2010.63}}</ref>
==Lisch Nodule Physical Examination Findings==  
*[[Eye]]-findings include orange-brown colored specks.
*Lisch nodules occur in 90% of adults with neurofibromatosis 1.   
*Lisch nodules are usually elevated and tan in appearance.
*Eye-findings include orange-brown colored specks.
*Lisch nodules are [[benign]] [[hamartomas]] that can be seen without magnification.
*They are usually elevated and tan in appearance.
*Also known as [[Melanoma|melanocytic]] [[hamartomas]] of the iris, often associated with [[Neurofibromatosis type I|neurofibromatosis]] (NF) I.<ref name="pmid14560838">{{cite journal| author=Nichols JC, Amato JE, Chung SM| title=Characteristics of Lisch nodules in patients with neurofibromatosis type 1. | journal=J Pediatr Ophthalmol Strabismus | year= 2003 | volume= 40 | issue= 5 | pages= 293-6 | pmid=14560838 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14560838  }}</ref>
*These are benign hamartomas that can be seen without magnification.
*Other associated [[Ophthalmology|ophthalmologic]] findings are [[Optic glioma|optic gliomas]].
*Also known as melanocytic hamartomas of the iris, often associated with neurofibromatosis (NF) I
*[[Optic glioma|Optic gliomas]] can alter [[color vision]] and can produce progressive [[vision loss]].
*Other associated ophthalmologic findings are optic gliomas  
**Optic gliomas can alter color vision and can produce progressive sight loss


==Lisch nodule Diagnostic Studies==
==Diagnostic Studies==
*On slit-lamp examination, they have a smooth, dome-shaped appearance and are usually light brown, although some can be very pale.   
*On [[slit-lamp]] examination, they have a smooth, dome-shaped appearance and are usually light brown, although some can be very pale.<ref name="pmid67892692">{{cite journal| author=Lewis RA, Riccardi VM| title=Von Recklinghausen neurofibromatosis. Incidence of iris hamartomata. | journal=Ophthalmology | year= 1981 | volume= 88 | issue= 4 | pages= 348-54 | pmid=6789269 | doi=10.1016/s0161-6420(81)35034-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6789269  }}</ref><ref name="pmid31036734">{{cite journal| author=Huson S, Jones D, Beck L| title=Ophthalmic manifestations of neurofibromatosis. | journal=Br J Ophthalmol | year= 1987 | volume= 71 | issue= 3 | pages= 235-8 | pmid=3103673 | doi=10.1136/bjo.71.3.235 | pmc=1041127 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3103673  }}</ref><ref name="pmid289796204">{{cite journal| author=Abaloun Y, Ajhoun Y| title=[Lisch nodule in neurofibromatosis type 1]. | journal=Pan Afr Med J | year= 2017 | volume= 27 | issue=  | pages= 218 | pmid=28979620 | doi=10.11604/pamj.2017.27.218.11517 | pmc=5622834 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28979620 }}</ref><ref name="pmid204228425">{{cite journal| author=Cohen R, Shuper A| title=[Developmental manifestation in children with neurofibromatosis type 1]. | journal=Harefuah | year= 2010 | volume= 149 | issue= 1 | pages= 49-52, 61 | pmid=20422842 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20422842  }}</ref>
*Slit lamp examination can differentiate them from nevi on the iris by demonstrating elevated lesion instead of flat ones.
*[[Slit lamp]] examination can differentiate them from [[nevi]] on the [[iris]] by demonstrating elevated [[lesion]] instead of flat ones.<ref name="pmid19354164">{{cite journal| author=Crişan M, Talu S, Florea M, Coprean D, Cosgarea R, Crişan D| title=[Lisch nodules. Markers for a non-invasive diagnosis in Recklinghausen neurofibromatosis]. | journal=Oftalmologia | year= 2008 | volume= 52 | issue= 4 | pages= 56-61 | pmid=19354164 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19354164  }}</ref>
*Lisch nodules develop during childhood, after the appearance of café-au-lait spots but before peripheral neurofibromas  
*Lisch nodules develop during childhood, after the appearance of [[Café au lait spot|café-au-lait spots]] but before peripheral [[Neurofibroma|neurofibromas]].
*This is useful in confirming the diagnosis of NF1 in children with no family history and only multiple café-au-lait spots
*[[File:Bundles of wavy spindle cells with serpentine nuclei .jpg|alt=Lisch nodule|thumb|(a) Microsection showing bundles of wavy [[spindle cells]] with serpentine nuclei in fascicles (H&E, ×10x), (b) Strong [[S-100 protein|S-100]] positivity of [[Tumor cell|tumor]] cells (×40x), (c) [[Café au lait spot|café au lait macule]] (arrow) in the back, (d) axillary [[freckle]], (e) Lisch nodule (arrow) in [[slit-lamp]] examination, and (f) father of patient with multiple cutaneous [[Neurofibroma|neurofibromas]]. Case courtesy by Rachna Rath et al.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921149/|title=Multifocal Head and Neck Neurofibromas with Osseous Abnormalities and Muscular Hypoplasia in a Child with Neurofibromatosis: Type I|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>]]This is useful in confirming the [[diagnosis]] of [[NF1]] in children with no [[family history]] and only multiple [[Café-au-lait spot|café-au-lait spots]].<ref name="pmid182803493">{{cite journal| author=Yang CC, Happle R, Chao SC, Yu-Yun Lee J, Chen W| title=Giant café-au-lait macule in neurofibromatosis 1: a type 2 segmental manifestation of neurofibromatosis 1? | journal=J Am Acad Dermatol | year= 2008 | volume= 58 | issue= 3 | pages= 493-7 | pmid=18280349 | doi=10.1016/j.jaad.2007.03.013 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18280349  }}</ref><ref name="pmid196504184">{{cite journal| author=Terzi YK, Oguzkan-Balci S, Anlar B, Aysun S, Guran S, Ayter S| title=Reproductive decisions after prenatal diagnosis in neurofibromatosis type 1: importance of genetic counseling. | journal=Genet Couns | year= 2009 | volume= 20 | issue= 2 | pages= 195-202 | pmid=19650418 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19650418  }}</ref>


==Treatment==
==Treatment==
{{CMG}}{{Swathi}}


=== Medical Therapy ===
*There is no treatment for the underlying disease nor any necessity to treat these small [[benign]] [[lesions]] which do not interfere with [[visual]] function.<ref name="Dimitrova20095">{{cite journal|last1=Dimitrova|first1=Valentina|title=A CASE OF NEUROFIBROMATOSIS TYPE 1|journal=Journal of IMAB - Annual Proceeding (Scientific Papers)|volume=14, 1|issue=2008|year=2009|pages=63–67|issn=1312773X|doi=10.5272/jimab.14-1-2010.63}}</ref>
*Lifelong monitoring is necessary because of the widespread manifestations and serious threat of [[complications]] such as:
**[[Visual]] [[impairment]]
**[[Renal]] [[hypertension]]
**[[Ischemia]] of major [[Organ (anatomy)|organs]].
== Primary Prevention ==
* There are no established measures for the [[primary prevention]] of Lisch nodules.


[[Lisch nodule medical therapy|Medical Therapy]] 
== Secondary Prevention ==
*There is no treatment for the underlying disease nor any necessity to treat these small benign lesions which do not interfere with visual function, but lifelong monitoring is necessary because of the widespread manifestations and serious threat of complications such as visual impairment, renal hypertension and ischemia of major organs. 


==Case Studies==
* There are no established measures for the [[secondary prevention]] of Lisch nodules.
[[Lisch nodule case study one|Case #1]]


[[Category:Disease]]
[[Category:Disease]]
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Latest revision as of 14:02, 27 September 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Swathi Venkatesan, M.B.B.S.[2]

Synonyms and keywords: Sakurai-lisch nodule

Overview

Lisch nodules are well defined melanocytic hamartomas of the iris. Lisch nodules generally appear as dome-shaped gelatinous masses. Lisch nodules masses are more commonly develop on the surface of the iris, also known as iris hamartomas. Lisch nodules are gold-tan to brown in color, they may grow up to 2 mm in diameter and can be of different sizes on the same iris. Lisch nodules arise from mast cells, pigmented cells and fibroblast-like cells. The presence of Lisch nodules is the most common clinical sign of Neurofibromatosis 1; ninety-three percent of cases are bilaterally affected and an average of 25 nodules can be counted on each iris. Once iris hamartomas have developed, they remain stable throughout life. In 80% of eyes, Lisch nodules may be found in the inferior quadrants of the iris and this may be related to greater sun exposure, one of the postulated factors in the development of these benign tumefactions.

Historical Perspective

Classification

  • There is no established system for the classification of Lisch nodules.

Pathophysiology

Causes

Differential diagnosis

Epidemiology and Demographics

Incidence

Prevalence

  • The prevalence of Lisch nodules is approximately 1 in 3500 individuals worldwide.[23]

Age

  • Lisch nodules are predominantly visible in children usually after the age of six years.[24]
  • Lisch Nodule incidence in NF1 increases with age and their prevalence raises by about 10% per year of life, up to age 9.
  • Lisch nodules are found in 93% of adults with NF-1 but have not been described in NF-2.
  • Lisch Nodules may be found in a very limited number of individuals without NF.
  • The de novo mutations occur primarily in paternally derived chromosomes, and the likelihood of de novo NF1 increases with advanced paternal age.

Risk Factors

Screening

  • However, Lisch nodules are seen in 95% of children with NF1 by age 20.[26]

Natural History, Complications and Prognosis

Natural History

  • The symptoms of Lisch Nodules usually develop in the first decade of life, and mostly asymptomatic.

Complications

Prognosis

  • Prognosis is generally good of patients with Lisch Nodules.

Diagnosis

Diagnostic Criteria for neurofibromatosis 1

  • The diagnosis is primarily based on clinical assessment and two or more of the features are required to confirm the diagnosis.

Physical Examination

Diagnostic Studies

Treatment

Medical Therapy

Primary Prevention

Secondary Prevention

References

  1. "Multiple, Unilateral Lisch Nodules in the Absence of Other Manifestations of Neurofibromatosis Type 1".
  2. Antônio JR, Goloni-Bertollo EM, Trídico LA (2013). "Neurofibromatosis: chronological history and current issues". An Bras Dermatol. 88 (3): 329–43. doi:10.1590/abd1806-4841.20132125. PMC 3754363. PMID 23793209.
  3. Hosoi, Kiyoshi (1931). "MULTIPLE NEUROFIBROMATOSIS (von RECKLINGHAUSEN'S DISEASE)". Archives of Surgery. 22 (2): 258. doi:10.1001/archsurg.1931.01160020081004. ISSN 0272-5533.
  4. Gabhane SK, Kotwal MN, Bobhate SK (2010). "Segmental neurofibromatosis: a report of 3 cases". Indian J Dermatol. 55 (1): 105–8. doi:10.4103/0019-5154.60366. PMC 2856359. PMID 20418991.
  5. Dimitrova, Valentina (2009). "A CASE OF NEUROFIBROMATOSIS TYPE 1". Journal of IMAB - Annual Proceeding (Scientific Papers). 14, 1 (2008): 63–67. doi:10.5272/jimab.14-1-2010.63. ISSN 1312-773X.
  6. Terzi YK, Oguzkan-Balci S, Anlar B, Aysun S, Guran S, Ayter S (2009). "Reproductive decisions after prenatal diagnosis in neurofibromatosis type 1: importance of genetic counseling". Genet Couns. 20 (2): 195–202. PMID 19650418.
  7. Boley S, Sloan JL, Pemov A, Stewart DR (2009). "A quantitative assessment of the burden and distribution of Lisch nodules in adults with neurofibromatosis type 1". Invest Ophthalmol Vis Sci. 50 (11): 5035–43. doi:10.1167/iovs.09-3650. PMC 2883270. PMID 19516012.
  8. Boyd KP, Korf BR, Theos A (2009). "Neurofibromatosis type 1". J Am Acad Dermatol. 61 (1): 1–14, quiz 15-6. doi:10.1016/j.jaad.2008.12.051. PMC 2716546. PMID 19539839.
  9. Theos, Amy; Korf, Bruce R. (2006). "Pathophysiology of Neurofibromatosis Type 1". Annals of Internal Medicine. 144 (11): 842. doi:10.7326/0003-4819-144-11-200606060-00010. ISSN 0003-4819.
  10. Cohen R, Shuper A (2010). "[Developmental manifestation in children with neurofibromatosis type 1]". Harefuah. 149 (1): 49–52, 61. PMID 20422842.
  11. de Goede-Bolder A, Cnossen MH, Dooijes D, van den Ouweland AM, Niermeijer MF (2001). "[From gene to disease; neurofibromatosis type 1]". Ned Tijdschr Geneeskd. 145 (36): 1736–8. PMID 11572174.
  12. Lubs, Marie-Louise E.; Bauer, Mislen S.; Formas, Maria E.; Djokic, Borivoje (1991). "Lisch Nodules in Neurofibromatosis Type 1". New England Journal of Medicine. 324 (18): 1264–1266. doi:10.1056/NEJM199105023241807. ISSN 0028-4793.
  13. Dimitrova, Valentina (2009). "A CASE OF NEUROFIBROMATOSIS TYPE 1". Journal of IMAB - Annual Proceeding (Scientific Papers). 14, 1 (2008): 63–67. doi:10.5272/jimab.14-1-2010.63. ISSN 1312-773X.
  14. Abaloun Y, Ajhoun Y (2017). "[Lisch nodule in neurofibromatosis type 1]". Pan Afr Med J. 27: 218. doi:10.11604/pamj.2017.27.218.11517. PMC 5622834. PMID 28979620.
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  16. Richetta, A; Giustini, S; Recupero, SM; Pezza, M; Carlomagno, V; Amoruso, G; Calvieri, S (2004). "Lisch nodules of the iris in neurofibromatosis type 1". Journal of the European Academy of Dermatology and Venereology. 18 (3): 342–344. doi:10.1111/j.1468-3083.2004.00915.x. ISSN 0926-9959.
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