Phakomatoses Are a Massive Topic. (Don’T Believe Me? Take a Glance at the Number of Slides in This Set.) Try to Get Through the Whole Set Once a Month Or So

Phakomatoses are a massive topic. (Don’t believe me? Take a glance at the number of slides in this set.) Try to get through the whole set once a month or so. There’s a TLDR at the end, so when it’s crunch time (ie, the last few weeks before the OKAPs, WQE or Boards), just flip through the TLDR a few times every day to keep it fresh. You got this! 2

Phakomatoses are known also as what sort of syndrome? 3

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes 4

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? 5

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? With multiple lesions in two or more organ systems, usually including the CNSabb. , diff eyesword and skinword 6

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? With multiple lesions in two or more organ systems, usually including the CNS , diff eyesword and skinword 7

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? With multiple lesions in two or more organ systems, usually including the CNS , diff eyes and skinword 8

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? With multiple lesions in two or more organ systems, usually including the CNS , eyes and skin 9

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? With multiple lesions in two or more organ systems, usually including the CNS , eyes and skin

Are the lesions in phakomatoses predominantly choristomas or hamartomas? 10

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? With multiple lesions in two or more organ systems, usually including the CNS , eyes and skin

Are the lesions in phakomatoses predominantly choristomas or hamartomas? Most (but not all) are hamartomas (some are choristomas) 11

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? With multiple lesions in two or more organ systems, usually including the CNS , eyes and skin

Are the lesions in phakomatoses predominantly choristomas or hamartomas? Most (but not all) are hamartomas (some are choristomas) What’s the difference between a hamartoma and a choristoma? A hamartomaone of them is a nest of abnormal cells in a normal location, whereas a choristomathe other is a nest of relatively-normal cells in an abnormal location 12

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? With multiple lesions in two or more organ systems, usually including the CNS , eyes and skin

Are the lesions in phakomatoses predominantly choristomas or hamartomas? Most (but not all) are hamartomas (some are choristomas) What’s the difference between a hamartoma and a choristoma? A hamartoma is a nest of abnormal cells in a normal location, whereas a choristoma is a nest of relatively-normal cells in an abnormal location 13

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? With multiple lesions in two or more organ systems, usually including the CNS , eyes and skin

Are the lesions in phakomatoses predominantly choristomas or hamartomas? Most (but not all) are hamartomas (some are choristomas) What’s the difference between a hamartoma and a choristoma? A hamartoma is a nest of abnormal cells in a normal location, whereas a choristoma is a nest of relatively-normal cells in an abnormal location

That a lesion is a hamartoma or choristoma indicates what about its onset? That it is congenital

That a lesion is a hamartoma or choristoma indicates what about its status vis a vis malignancy? That it is benign 14

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? With multiple lesions in two or more organ systems, usually including the CNS , eyes and skin

Are the lesions in phakomatoses predominantly choristomas or hamartomas? Most (but not all) are hamartomas (some are choristomas) What’s the difference between a hamartoma and a choristoma? A hamartoma is a nest of abnormal cells in a normal location, whereas a choristoma is a nest of relatively-normal cells in an abnormal location

That a lesion is a hamartoma or choristoma indicates what about its onset? That it is congenital

That a lesion is a hamartoma or choristoma indicates what about its status vis a vis malignancy? That it is benign 15

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? With multiple lesions in two or more organ systems, usually including the CNS , eyes and skin

Are the lesions in phakomatoses predominantly choristomas or hamartomas? Most (but not all) are hamartomas (some are choristomas) What’s the difference between a hamartoma and a choristoma? A hamartoma is a nest of abnormal cells in a normal location, whereas a choristoma is a nest of relatively-normal cells in an abnormal location

That a lesion is a hamartoma or choristoma indicates what about its onset? That it is congenital

That a lesion is a hamartoma or choristoma indicates what about its status vis a vis malignancy? That it is benign 16

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? With multiple lesions in two or more organ systems, usually including the CNS , eyes and skin

Are the lesions in phakomatoses predominantly choristomas or hamartomas? Most (but not all) are hamartomas (some are choristomas) What’s the difference between a hamartoma and a choristoma? A hamartoma is a nest of abnormal cells in a normal location, whereas a choristoma is a nest of relatively-normal cells in an abnormal location

That a lesion is a hamartoma or choristoma indicates what about its onset? That it is congenital

That a lesion is a hamartoma or choristoma indicates what about its status vis a vis malignancy? That it is benign 17

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? With multiple lesions in two or more organ systems, usually including the CNS , eyes and skin

Are the lesions in phakomatoses predominantly choristomas or hamartomas? Hamartomas

Is there a single, universally accepted definition of the term phakomatosis? 18

Phakomatoses are known also as what sort of syndrome? Neuro-oculocutaneous syndromes

In general terms, how do phakomatoses present? With multiple lesions in two or more organ systems, usually including the CNS , eyes and skin

Are the lesions in phakomatoses predominantly choristomas or hamartomas? Hamartomas

Is there a single, universally accepted definition of the term phakomatosis? Unfortunately not, and for this reason, the conditions so labelled will vary from source to source 19

A phakomatosis by any other name…by what Q other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

 Tuberous sclerosis: Bournville disease

 Sturge-Weber syndrome: Encephalotrigeminal angiomatosis

 von Hippel-Lindau: Retinal angiomatosisStart here with the other name for NF1

 Incontinentia pigmenti: Bloch-Sulzberger syndrome

 Neurofibromatosis type 2: None in common use of which I am aware

 Racemose angioma: Wyburn-Mason syndrome

 Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 20

A phakomatosis by any other name…by what A other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

 Tuberous sclerosis: Bournville disease

 Sturge-Weber syndrome: Encephalotrigeminal angiomatosis

 von Hippel-Lindau: Retinal angiomatosisStart here with the other name for NF1

 Incontinentia pigmenti: Bloch-Sulzberger syndrome

 Neurofibromatosis type 2: None in common use of which I am aware

 Racemose angioma: Wyburn-Mason syndrome

 Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 21

A phakomatosis by any other name…by what Q other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-SulzbergerNext for TS syndrome

NF2  Neurofibromatosis type 2: None in common use of which I am aware

RA  Racemose angioma: Wyburn-Mason syndrome

AT  Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 22

A phakomatosis by any other name…by what A other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-SulzbergerNext for TS syndrome

NF2  Neurofibromatosis type 2: None in common use of which I am aware

RA  Racemose angioma: Wyburn-Mason syndrome

AT  Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 23

A phakomatosis by any other name…by what Q other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-Sulzberger syndrome

NF2  Neurofibromatosis type 2: None in common useEtc of which I am aware

RA  Racemose angioma: Wyburn-Mason syndrome

AT  Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 24

A phakomatosis by any other name…by what A other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: RetinalOther angiomatosis names you might encounter for SWS: Encephalofacial angiomatosis IP  Incontinentia pigmenti: Bloch-SulzbergerCerebrofacial angiomatosis syndrome

NF2  Neurofibromatosis type 2: None in common use of which I am aware

RA  Racemose angioma: Wyburn-Mason syndrome

AT  Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 25

A phakomatosis by any other name…by what Q other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-Sulzberger syndrome

NF2  Neurofibromatosis type 2: None in common use of which I am aware

RA  Racemose angioma: Wyburn-Mason syndrome

AT  Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 26

A phakomatosis by any other name…by what A other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-Sulzberger syndrome

NF2  Neurofibromatosis type 2: None in common use of which I am aware

RA  Racemose angioma: Wyburn-Mason syndrome

AT  Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 27

A phakomatosis by any other name…by what Q other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-Sulzberger syndrome

NF2  Neurofibromatosis type 2: None in common use of which I am aware

RA  Racemose angioma: Wyburn-Mason syndrome

AT  Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 28

A phakomatosis by any other name…by what A other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-Sulzberger syndrome

NF2  Neurofibromatosis type 2: None in common use of which I am aware

RA  Racemose angioma: Wyburn-Mason syndrome

AT  Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 29

A phakomatosis by any other name…by what Q other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-Sulzberger syndrome

NF2  Neurofibromatosis type 2: None in common use of which I am aware

RA  Racemose angioma: Wyburn-Mason syndrome

AT  Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 30

A phakomatosis by any other name…by what A other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-Sulzberger syndrome

NF2  Neurofibromatosis type 2: MISME syndrome

RA  Racemose angioma: Wyburn-Mason syndrome

AT  Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 31

A phakomatosis by any other name…by what Q other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-Sulzberger syndrome

NF2  Neurofibromatosis type 2: MISME syndrome

RA  Racemose angioma:MISME Wyburn-Mason is an acronym. What syndrome does it stand for? --M AT  Ataxia-telangiectasia:-- I Louis-Bar syndrome --S Abbreviations used henceforth --M --E 32

A phakomatosis by any other name…by what A other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-Sulzberger syndrome

NF2  Neurofibromatosis type 2: MISME syndrome

RA  Racemose angioma:MISME Wyburn-Mason is an acronym. What syndrome does it stand for? --Multiple AT  Ataxia-telangiectasia:-- Inherited Louis-Bar syndrome --Schwannomas, Abbreviations used henceforth --Meningiomas (and) --Ependymomas 33

A phakomatosis by any other name…by what Q other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-Sulzberger syndrome

NF2  Neurofibromatosis type 2: MISME syndrome

RA  Racemose angioma: Wyburn-Mason syndrome

AT  Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 34

A phakomatosis by any other name…by what A other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-Sulzberger syndrome

NF2  Neurofibromatosis type 2: MISME syndrome

RA  Racemose angioma: Wyburn-Mason syndrome

AT  Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 35

A phakomatosis by any other name…by what Q other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-Sulzberger syndrome

NF2  Neurofibromatosis type 2: MISME syndrome

RA  Racemose angioma: Wyburn-Mason syndrome

AT  Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 36

A phakomatosis by any other name…by what A other name is each syndrome known?

Abbreviations used henceforth

NF1  Neurofibromatosis type 1: von Rechlinghausen syndrome

TS  Tuberous sclerosis: Bournville disease

SWS Sturge-Weber syndrome: Encephalotrigeminal angiomatosis vH-L von Hippel-Lindau: Retinal angiomatosis

IP  Incontinentia pigmenti: Bloch-Sulzberger syndrome

NF2  Neurofibromatosis type 2: MISME syndrome

RA  Racemose angioma: Wyburn-Mason syndrome

AT  Ataxia-telangiectasia: Louis-Bar syndrome

Abbreviations used henceforth 37

 Phakomatoses: Inheritance patterns  These four are AD…  NF2  NF1  von Hippel-Lindau  Tuberous sclerosis  this one is AR…  Ataxia-telangiectasia  this one is X-linked dominant…  Incontinentia pigmenti  and these two are sporadic/nonhereditary  Sturge-Weber  Racemose angioma 38

 Phakomatoses: Inheritance patterns  These four are AD…  NF2  NF1  von Hippel-Lindau  Tuberous sclerosis  This one is AR…  Ataxia-telangiectasia  this one is X-linked dominant…  Incontinentia pigmenti  and these two are sporadic/nonhereditary  Sturge-Weber  Racemose angioma 40

 Phakomatoses: Inheritance patterns  These four are AD…  NF2  NF1  von Hippel-Lindau  Tuberous sclerosis  This one is AR…  Ataxia-telangiectasia  This one is X-linked dominant…  Incontinentia pigmenti  and these two are sporadic/nonhereditary  Sturge-Weber  Racemose angioma 42

 Phakomatoses: Inheritance patterns  These four are AD…  NF2  NF1  von Hippel-Lindau  Tuberous sclerosis  This one is AR…  Ataxia-telangiectasia  This one is X-linked dominant…  Incontinentia pigmenti  And these two are sporadic/nonhereditary  Sturge-Weber  Racemose angioma 44

 Phakomatoses: Inheritance patterns  These four are AD…  NF2  NF1  von Hippel-Lindau  Tuberous sclerosis  This one is AR…  Ataxia-telangiectasia  This one is X-linked dominant…  Incontinentia pigmenti  And these two are sporadic/nonhereditary  Sturge-Weber  Racemose angioma 45

 Phakomatoses: Inheritance patterns  These four are AD…  NF2  NF1  von Hippel-Lindau What does X-linked dominant transmission mean? It means the conditionTuberous manifests sclerosis in every conception possessing at least one X chromosome (ie, everyone)

But almost allThis IP pts areone female. is IfAR IP is X-link… ed dominant, why don’t male infants present with it? The mutation causingAtaxia-telangiectasia IP is lethal to males in utero. That’s about as ‘manifest’ as it gets.  This one is X-linked dominant…  Incontinentia pigmenti  And these two are sporadic/nonhereditary  Sturge-Weber  Racemose angioma 46

 Phakomatoses: Inheritance patterns  These four are AD… Hold the phone! NF2 To say that ‘almost’ all pts are female means that some IP pts are male. If IP is X-linked dominant and lethal in hemizygous individuals, how could there be any male pts? There are two waysNF1 by which a male child could be liveborn with IP: --If the (phenotypically) male child possesses two X chromosomes (eg, Klinefelter syndrome, XXY) and is therefore heterozygous von Hippel-Lindau for IP; or What--it can does occur X-linked in males dominant via a sporadic transmission post-zygotic mean? mutation that renders the male child an IP ‘mosaic’ It means the conditionTuberous manifests sclerosis in every conception possessing at least one X chromosome (ie, everyone)

But almost Thisall IP pts oneare female. is IfAR IP is …X-linked dominant, why don’t male infants present with it? The mutation causingAtaxia-telangiectasia IP is lethal to males in utero. That’s about as ‘manifest’ as it gets.  This one is X-linked dominant…  Incontinentia pigmenti  And these two are sporadic/nonhereditary  Sturge-Weber  Racemose angioma 50

 Phakomatoses: Inheritance patterns  These four are AD… Hold the phone! NF2 To say that ‘almost’ all pts are female means that some IP pts are male. If IP is X-linked dominant and lethal in hemizygous individuals, how could there be any male pts? There are two waysNF1 by which a male child could be liveborn with IP: --If the (phenotypically) male child possesses two X chromosomes (eg, Klinefelter syndrome, XXY) and is therefore heterozygous von Hippel-Lindaufor IP; or What--it can does occur X-linked in males dominant via a sporadic transmission post-zygotic mean? mutation that renders the male child an IP ‘mosaic’ It means the conditionTuberous manifests sclerosis in every conception possessing at least one X chromosome (ie, everyone)

‘An x-linked recessive condition, lethal in genetically typical males such that all pts are female except for Klinefelter Phakomatoses: males.’ There is only one other conditionInheritance in the BCSC that patterns fits this description—what is it? Aicardi syndrome  These four are AD… In a nutshell, what sort of condition is Aicardi syndrome? Hold the phone! NF2 To say that ‘almost’ all pts are female means that some IP pts are male. If IP is X-linked A dominantneurodevelopmental and lethal in disorder hemizygous marked individuals, by profound how ocular could andthere CNS be anymanifestationsmale pts? There are two waysNF1 by which a male child could be liveborn with IP: What--If the is the (phenotypically) classic triad of male Aicardi child syndrome? possesses two X chromosomes (eg, Klinefelter syndrome, XXY) and is --Infantiletherefore epilepsy/spasms heterozygous von Hippel-Lindaufor IP; or --AbsenceWhat--it can does occur or X-linkeddysgenesis in males dominant via of thea sporadic corpus transmission post-zygoticcallosum mean? mutation that renders the male child an IP ‘mosaic’ --ChorioretinalIt means the conditionlacunaeTuberous manifests sclerosis in every conception possessing at least one X chromosome (ie, everyone)

‘An x-linked recessive condition, lethal in genetically typical males such that all pts are female except for Klinefelter Phakomatoses: males.’ There is only one other conditionInheritance in the BCSC that patterns fits this description—what is it? Aicardi syndrome  These four are AD… In a nutshell, what sort of condition is Aicardi syndrome? Hold the phone! NF2 To say that ‘almost’ all pts are female means that some IP pts are male. If IP is X-linked A dominantneurodevelopmental and lethal in disorder hemizygous marked individuals, by profound how ocular could andthere CNS be anymanifestationsmale pts? There are two waysNF1 by which a male child could be liveborn with IP: What--If the is the (phenotypically) classic triad of male Aicardi child syndrome? possesses two X chromosomes (eg, Klinefelter syndrome, XXY) and is --Infantiletherefore epilepsy/spasms heterozygous von Hippel-Lindaufor IP; or --Absence or dysgenesis of the corpus callosum What--it can does occurAicardi X-linked in males dominant syndrome via a sporadic transmission post-zygotic has mean?its ownmutation slide-set that renders (FELT20)—the male child an IP ‘mosaic’ --ChorioretinalIt means the conditionlacunaeTuberous manifests sclerosis in every conception possessing at least one X chromosome (ie, everyone) see it for more on this condition But almost Thisall IP pts oneare female. is IfAR IP is …X-linked dominant, why don’t male infants present with it? The mutation causingAtaxia-telangiectasia IP is lethal to males in utero. That’s about as ‘manifest’ as it gets.  This one is X-linked dominant…  Incontinentia pigmenti  And these two are sporadic/nonhereditary  Sturge-Weber  Racemose angioma 58

Of course, even the inherited conditions can occur sporadically. For each,  Phakomatoses: whatInheritance percent of cases patterns are sporadic?  These four are AD… % Sporadic  NF2 ?  NF1 ?  von Hippel-Lindau ?  Tuberous sclerosis ?  This one is AR…  Ataxia-telangiectasia ?  This one is X-linked dominant…  Incontinentia pigmenti ?  And these two are sporadic/nonhereditary  Sturge-Weber  Racemose angioma 59

Of course, even the inherited conditions can occur sporadically. For each,  Phakomatoses: whatInheritance percent of cases patterns are sporadic?  These four are AD… % Sporadic  NF2 50  NF1 50  von Hippel-Lindau 20  Tuberous sclerosis 80  This one is AR…  Ataxia-telangiectasia ~0  This one is X-linked dominant…  Incontinentia pigmenti 60  And these two are sporadic/nonhereditary  Sturge-Weber  Racemose angioma 60

Of course, even the inherited conditions can occur sporadically. For each,  Phakomatoses: whatInheritance percent of cases patterns are sporadic?  These four are AD… % Sporadic  NF2 50  NF1 50  von Hippel-Lindau 20  Tuberous sclerosis 80 Why is the sporadic-occurrence rate of A-T essentially zero?  Because it is an autosomal- This one is AR… recessive condition, and thus can  Ataxia-telangiectasia ~0 occur sporadically only if someone heterozygous for it  This one is X-linked dominant…happens to suffer a mutation of the other copy of the responsible  Incontinentia pigmenti 60 gene--a very unlikely event.  And these two are sporadic/nonhereditary  Sturge-Weber  Racemose angioma 61

Of course, even the inherited conditions can occur sporadically. For each,  Phakomatoses: whatInheritance percent of cases patterns are sporadic?  These four are AD… % Sporadic  NF2 50  NF1 50  von Hippel-Lindau 20  Tuberous sclerosis 80 Why is the sporadic-occurrence rate of A-T essentially zero?  Because it is an autosomal- This one is AR… recessive condition, and thus can  Ataxia-telangiectasia ~0 occur sporadically only if someone heterozygous for it  This one is X-linked dominant…happens to suffer a mutation of the other copy of the responsible  Incontinentia pigmenti 60 gene--a very unlikely event.  And these two are sporadic/nonhereditary  Sturge-Weber  Racemose angioma 62 Phakomatoses

NF1 central vs --Peripheralperipheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 63 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytesone cell type or neuroglialdiff cell type cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 65 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules,How are these JXG cellnodules, lines related and congenita embryologically?l ectropion --Optic nerve glioma: AlwaysBoth symptomatic derive from neural-crestby age 10 cellsyears. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 67 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules,How are these JXG cellnodules, lines related and congenita embryologically?l ectropion --Optic nerve glioma: AlwaysBoth symptomatic derive from neural-crestby age 10 cellsyears. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 68 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules,How are these JXG cellnodules, lines related and congenita embryologically?l ectropion --Optic nerve glioma: AlwaysBoth symptomatic derive from neural-crestby age 10 years. cells Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10

Given this, it should come as no surprise that NF is associated with other manifestations of disordered neural-crest embryology, including and especially: something of two long words --Oculodermal melanocytosis (aka nevussomething of Ota) --Choroidal melanoma --Conjunctival melanoma stemming from PAM 69 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules,How are these JXG cellnodules, lines related and congenita embryologically?l ectropion --Optic nerve glioma: AlwaysBoth symptomatic derive from neural-crestby age 10 years. cells Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10

Given this, it should come as no surprise that NF is associated with other manifestations of disordered neural-crest embryology, including and especially: --Oculodermal melanocytosis (aka nevus of Ota) --Choroidal melanoma --Conjunctival melanoma stemming from PAM 70 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules,How are these JXG cellnodules, lines related and congenita embryologically?l ectropion --Optic nerve glioma: AlwaysBoth symptomatic derive from neural-crestby age 10 years. cells Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10

Given this, it should come as no surprise that NF is associated with other manifestations of disordered neural-crest embryology, including and especially: --Oculodermal melanocytosis (aka nevus of Ota) --Choroidal melanomayikes --Conjunctival melanoma stemming from PAM 71 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules,How are these JXG cellnodules, lines related and congenita embryologically?l ectropion --Optic nerve glioma: AlwaysBoth symptomatic derive from neural-crestby age 10 years. cells Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10

--Conjunctival melanomayikes stemming from PAMabb. 73 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules,How are these JXG cellnodules, lines related and congenita embryologically?l ectropion --Optic nerve glioma: AlwaysBoth symptomatic derive from neural-crestby age 10 years. cells Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10

Given this, it should come as no surprise that NF is associated with other manifestations of disordered neural-crest embryology, including and especially: --Oculodermal melanocytosis (aka nevus of Ota) --Choroidal melanoma What does PAM stand for in this context? --Conjunctival melanoma stemming from PAM Primary acquired melanosis 75 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules,How are these JXG cellnodules, lines related and congenita embryologically?l ectropion --Optic nerve glioma: AlwaysBoth symptomatic derive from neural-crestby age 10 years. cells Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10

Given this, it should come as no surprise that NF is associated with other manifestations of disordered neural-crest embryology, including and especially: --Oculodermal melanocytosis (aka nevus of Ota) --Choroidal melanoma What does PAM stand for in this context? --Conjunctival melanoma stemming from PAM Primary acquired melanosis 76 Phakomatoses

Lisch nodules Café au lait spots

NF1: Melanocytic lesions 79 Phakomatoses

Plexiform neurofibroma Nodular neurofibroma

Optic nerve glioma NF1: Neuroglial lesions 82 Phakomatoses

In what fundamental way do these lesions differ (other than the cell type of origin, duh)? The melanocytic lesions are of no clinical significance beyond establishing the diagnosis, whereas the neuroglial lesions are associated with significant ocular and/or systemic morbidity 83 Phakomatoses

In what fundamental way do these lesions differ (other than the cell type of origin, duh)? The melanocyticm’cytic v N-G lesions are of no clinical significance beyond establishing the diagnosis,

whereas the neuroglialm’cytic v N-G lesions are associated with significant ocular and/or systemic morbidity 84 Phakomatoses

Do the neuroglial lesions in NF1 carry a risk of malignant transformation? Yes, especially the plexiform neurofibromas, which can give rise to lesions known as ‘malignant peripheral nerve-sheath tumors’

What is the lifetime risk of such a transformation? About 10% 86 Phakomatoses

Do the neuroglial lesions in NF1 carry a risk of malignant transformation? Yes, especially the plexiform neurofibromas , which can give rise to lesions known as ‘malignant peripheralfive words nerve-sheath tumors’

What is the lifetime risk of such a transformation? About 10% 87 Phakomatoses

Do the neuroglial lesions in NF1 carry a risk of malignant transformation? Yes, especially the plexiform neurofibromas , which can give rise to lesions known as ‘malignant peripheral nerve-sheath tumors’

What is the lifetime risk of such a transformation? About 10% 88 Phakomatoses

Do the neuroglial lesions in NF1 carry a risk of malignant transformation? Yes, especially the plexiform neurofibromas , which can give rise to lesions known as ‘malignant peripheral nerve-sheath tumors’

What is the lifetime risk of such a transformation? About 10% 89 Phakomatoses

Do the neuroglial lesions in NF1 carry a risk of malignant transformation? Yes, especially the plexiform neurofibromas , which can give rise to lesions known as ‘malignant peripheral nerve-sheath tumors’

What is the lifetime risk of such a transformation? About 10% 90 Phakomatoses

Four non-neural-crest-derived malignancies are associated with NF1 (albeit uncommonly). What are they? --Leukemia --Rhabdomyosarcoma --Pheochromocytoma --Wilms tumor 91 Phakomatoses

Four non-neural-crest-derived malignancies are associated with NF1 (albeit uncommonly). What are they? --Leukemia --Rhabdomyosarcoma --Pheochromocytoma --Wilms tumor 92 Phakomatoses

Four non-neural-crest-derived malignancies are associated with NF1 (albeit uncommonly). What are they? --Leukemia --Rhabdomyosarcoma --Pheochromocytoma --Wilms tumor 93 Phakomatoses

Four non-neural-crest-derived malignancies are associated with NF1 (albeit uncommonly). What are they? --Leukemia --Rhabdomyosarcoma --Pheochromocytoma --Wilms tumor 94 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lidclassic plexiform lid finding fibroma and/or irisless classic ectropion iris finding --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 95 Phakomatoses

Plexiform neurofibroma Ectropion uveae

NF1 97 Phakomatoses

How strong is the association with glaucoma; ie, what percent of NF1 cases with an upper-lid plexiform fibroma and/or ectropion will have ipsilateral glaucoma? About 50 98 Phakomatoses

How strong is the association with glaucoma; ie, what percent of NF1 cases with an upper-lid plexiform fibroma and/or ectropion will have ipsilateral glaucoma? About 50 99 Phakomatoses

How strong is the association with glaucoma; ie, what percent of NF1 cases with an upper-lid plexiform fibroma and/or ectropion will have ipsilateral glaucoma? About 50 100 Phakomatoses

How strong is the association with glaucoma; ie, what percent of NF1 cases with an upper-lid plexiform fibroma and/or ectropion will have ipsilateral glaucoma? About 50 101 Phakomatoses

What rule of thumb adheres regarding the appearance of Lisch nodules? Lisch nodules are lighter than the rest of the iris when the iris in question is dark, but darker than the rest when the iris is light 104 Phakomatoses

Darker on light iris Lighter on dark iris

NF1: Lisch nodules 106 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion What does JXG stand for in this context? --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion Juvenile xanthogranuloma --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 107 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion What does JXG stand for in this context? --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion Juvenile xanthogranuloma --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 108 Phakomatoses

NF1: JXG nodules 109 Phakomatoses

What are the two hallmarks of JXG histology? The presence of…Touton giant cells The presence of…’foamy macrophages’

At what age does JXG present? The majority before age 1 year, and almost all by age 2

How does JXG usually present? (Hint: It’s not ophthalmic) As orange skin papules 110 Phakomatoses

What are the two hallmarks of JXG histology? The presence of…Touton giant cells The presence of…’foamy macrophages’

At what age does JXG present? The majority before age 1 year, and almost all by age 2

How does JXG usually present? (Hint: It’s not ophthalmic) As orange skin papules 111 Phakomatoses

What are the two hallmarks of JXG histology? The presence of… The presence of…’foamy macrophages’

At what age does JXG present? The majority before age 1 year, and almost all by age 2

How does JXG usually present? (Hint: It’s not ophthalmic) As orange skin papules 112 Phakomatoses

What are the two hallmarks of JXG histology? The presence of…Touton giant cells The presence of…’foamy macrophages’

At what age does JXG present? The majority before age 1 year, and almost all by age 2

How does JXG usually present? (Hint: It’s not ophthalmic) As orange skin papules 113 Phakomatoses

NF1: Touton giant cells 114 Phakomatoses

What are the two hallmarks of JXG histology? The presence of…Touton giant cells The presence of…’foamy macrophages’

At what age does JXG present? The majority before age 1 year, and almost all by age 2

How does JXG usually present? (Hint: It’s not ophthalmic) As orange skin papules 115 Phakomatoses

What are the two hallmarks of JXG histology? The presence of…Touton giant cells The presence of…’foamy macrophages’

At what age does JXG present? The majority before age 1 year, and almost all by age 2

How does JXG usually present? (Hint: It’s not ophthalmic) As orange skin papules 116 Phakomatoses

What are the two hallmarks of JXG histology? The presence of…Touton giant cells The presence of…’foamy macrophages’

At what age does JXG present? The majority before age 1 year, and almost all by age 2

How does JXG usually present? (Hint: It’s not ophthalmic) As orange skin papules 117 Phakomatoses

What are the two hallmarks of JXG histology? The presence of…Touton giant cells The presence of…’foamy macrophages’

At what age does JXG present? The majority before age 1 year, and almost all by age 2

How does JXG usually present? (Hint: It’s not ophthalmic) As orange skin papules 118 Phakomatoses

NF1: JXG nodules 119 Phakomatoses

NF1: Optic nerve gliomas bilaterally. Note the ‘kinked’ appearance 122 Phakomatoses

Of those, about how many will be symptomatic? About 1/3

With what symptoms will they present? Vision loss and/or proptosis

Are optic-nerve gliomas typically life-threatening? No

What about NF1 pts with chiasmal gliomas--do they fare better than their non-NF1 counterparts? Much better 123 Phakomatoses

Of those, about how many will be symptomatic? About 1/3

With what symptoms will they present? Vision loss and/or proptosis

Are optic-nerve gliomas typically life-threatening? No

What about NF1 pts with chiasmal gliomas--do they fare better than their non-NF1 counterparts? Much better 124 Phakomatoses

Of those, about how many will be symptomatic? About 1/3

With what symptoms will they present? Vision loss and/or proptosis

Are optic-nerve gliomas typically life-threatening? No

What about NF1 pts with chiasmal gliomas--do they fare better than their non-NF1 counterparts? Much better 125 Phakomatoses

Of those, about how many will be symptomatic? About 1/3

With what symptoms will they present? Vision loss and/or proptosis

Are optic-nerve gliomas typically life-threatening? No

What about NF1 pts with chiasmal gliomas--do they fare better than their non-NF1 counterparts? Much better 126 Phakomatoses

Of those, about how many will be symptomatic? About 1/3

With what symptoms will they present? Vision loss and/or proptosis

Are optic-nerve gliomas typically life-threatening? No

What about NF1 pts with chiasmal gliomas--do they fare better than their non-NF1 counterparts? Much better 127 Phakomatoses

Of those, about how many will be symptomatic? About 1/3

With what symptoms will they present? Vision loss and/or proptosis

Are optic-nerve gliomas typically life-threatening? No

What about NF1 pts with chiasmal gliomas--do they fare better than their non-NF1 counterparts? Much better 128 Phakomatoses

Of those, about how many will be symptomatic? About 1/3

With what symptoms will they present? Vision loss and/or proptosis

Are optic-nerve gliomas typically life-threatening? No

What about NF1 pts with chiasmal gliomas--do they fare better than their non-NF1 counterparts? Much better 129 Phakomatoses

Of those, about how many will be symptomatic? About 1/3

With what symptoms will they present? Vision loss and/or proptosis

Are optic-nerve gliomas typically life-threatening? No

What about NF1 pts with chiasmal gliomas--do they fare better than their non-NF1 counterparts? Much better 130 Phakomatoses

Of those, about how many will be symptomatic? About 1/3

With what symptoms will they present? Vision loss and/or proptosis

Are optic-nerve gliomas typically life-threatening? No

What about NF1 pts with chiasmal gliomas--do they fare better than their non-NF1 counterparts? Much better 131 Phakomatoses

Of those, about how many will be symptomatic? About 1/3

With what symptoms will they present? Vision loss and/or proptosis

Are optic-nerve gliomas typically life-threatening? No

What about NF1 pts with chiasmal gliomas--do they fare better than their non-NF1 counterparts? Much better 132 Phakomatoses

In other words, about 10% of 1 year olds will have Lisch nodules, 40% of 4 yo, 60% of 6 yo, etc. By the age of 10 years, essentially 100% of NF1 pts will manifest Lisch nodules. 135 Phakomatoses

What is the eponymous name of this triad? Vogt’s triad 139 Phakomatoses

What is the eponymous name of this triad? Vogt’s triad 140 Phakomatoses

What is the eponymous name of this triad? Vogt’s triad 141 Phakomatoses

What is the eponymous name of this triad? Vogt’s triad 142 Phakomatoses

What is the eponymous name of this triad? Vogt’s triad 143 Phakomatoses

What is the eponymous name of this triad? Vogt’s triad 144 Phakomatoses

What is the eponymous name of this triad? Vogt’s triad 145 Phakomatoses

What is the eponymous name of this triad? Vogt’s triad 146 Phakomatoses

What is the eponymous name of this triad? Vogt’s triad 147 Phakomatoses

What is the eponymous name of this triad? Vogt’s triad 148 Phakomatoses

Tuberous sclerosis: Adenoma sebaceum 151 Phakomatoses

Tuberous sclerosis: Ash leaf spots 152 Phakomatoses

Tuberous sclerosis: Shagreen patch 153 Phakomatoses

Adenoma sebaceum ? Appear in infancy

Shagreen patches ? Usually in lumbosacral region

Ash-leaf spots ? Appear in childhood 154 Phakomatoses

Adenoma sebaceum Appear in infancy

Shagreen patches Usually in lumbosacral region

Ash-leaf spots Appear in childhood 155 Phakomatoses

Adenoma sebaceum ? Which lesion(s) is/are raised, Shagreen patches ? and which is/are flat? Ash-leaf spots ? 156 Phakomatoses

Adenoma sebaceum Raised Which lesion(s) is/are raised, Shagreen patches and which is/are flat? Ash-leaf spots Flat 157 Phakomatoses

Adenoma sebaceum ? Which lesion(s) is/are Shagreen patches ? hyperpigmented, and which is/are hypopigmented? Ash-leaf spots ? 158 Phakomatoses

Adenoma sebaceum Hyperpigmented Which lesion(s) is/are Shagreen patches hyperpigmented, and which is/are hypopigmented? Ash-leaf spots Hypopigmented 159 Phakomatoses

Adenoma sebaceum ? Which lesion(s) fluoresce Shagreen patches ? under a Woods lamp, and which do/does not? Ash-leaf spots ? 160 Phakomatoses

Adenoma sebaceum Don’t fluoresce Which lesion(s) fluoresce Shagreen patches under a Woods lamp, and which do/does not? Ash-leaf spots Fluoresce 161 Phakomatoses

Adenoma sebaceum ? Which lesion(s) is/are Shagreen patches ? considered pathognomonic for TS, and which is/are not? Ash-leaf spots ? 162 Phakomatoses

Adenoma sebaceum Not Which lesion(s) is/are Shagreen patches considered pathognomonic for TS, and which is/are not? Ash-leaf spots Pathognomonic 163 Phakomatoses

Why is it called a ‘tuber’? Because it’s shaped like a potato (sort of)

What basic geometric shape do tubers often take? A triangle

Which way does the apex of the triangle point? Toward a ventricle 166 Phakomatoses

Why is it called a ‘tuber’? Because it’s shaped like a potato (sort of)

What basic geometric shape do tubers often take? A triangle

Which way does the apex of the triangle point? Toward a ventricle 167 Phakomatoses

Tuberous sclerosis: Cortical tuber 168 Phakomatoses

Why is it called a ‘tuber’? Because it’s shaped like a potato (sort of)

What basic geometric shape do tubers often take? A triangle

Which way does the apex of the triangle point? Toward a ventricle 169 Phakomatoses

Why is it called a ‘tuber’? Because it’s shaped like a potato (sort of)

What basic geometric shape do tubers often take? A triangle

Which way does the apex of the triangle point? Toward a ventricle 170 Phakomatoses

Why is it called a ‘tuber’? Because it’s shaped like a potato (sort of)

What basic geometric shape do tubers often take? A triangle

Which way does the apex of the triangle point? Toward a ventricle 171 Phakomatoses

Why is it called a ‘tuber’? Because it’s shaped like a potato (sort of)

What basic geometric shape do tubers often take? A triangle

Which way does the apex of the triangle point? Toward a ventricle 172 Phakomatoses

Why is it called a ‘tuber’? Because it’s shaped like a potato (sort of)

What basic geometric shape do tubers often take? A triangle

Which way does the apex of the triangle point? Toward a ventricle 173 Phakomatoses

Why is it called a ‘tuber’? Because it’s shaped like a potato (sort of)

What basic geometric shape do tubers often take? A triangle

Which way does the apex of the triangle point? Toward a ventricle 174 Phakomatoses

Tuberous sclerosis: Astrocytic hamartoma 182 Phakomatoses

Can they present bilaterally? Yes

Can multiple phakomas be found in one eye? Yes

Are the pathognomonic for TS? No 183 Phakomatoses

Can they present bilaterally? Yes

Can multiple phakomas be found in one eye? Yes

Are the pathognomonic for TS? No 184 Phakomatoses

Can they present bilaterally? Yes

Can multiple phakomas be found in one eye? Yes

Are the pathognomonic for TS? No 185 Phakomatoses

Can they present bilaterally? Yes

Can multiple phakomas be found in one eye? Yes

Are the pathognomonic for TS? No 186 Phakomatoses

Can they present bilaterally? Yes

Can multiple phakomas be found in one eye? Yes

Are the pathognomonic for TS? No 187 Phakomatoses

Can they present bilaterally? Yes

Can multiple phakomas be found in one eye? Yes

Are the pathognomonic for TS? No 188 Phakomatoses

Can they present bilaterally? Yes

Can multiple phakomas be found in one eye? Yes

Are the pathognomonic for TS? No 189 Phakomatoses

Can they present bilaterally? Yes

Can multiple phakomas be found in one eye? Yes

Are the pathognomonic for TS? No 190 Phakomatoses

Can they present bilaterally? Yes

Can multiple phakomas be found in one eye? Yes

Are they pathognomonic for TS? No 191 Phakomatoses

Can they present bilaterally? Yes

Can multiple phakomas be found in one eye? Yes

Are they pathognomonic for TS? No 192 Phakomatoses

Can they present bilaterally? Phakomas typically present with one of two appearances--whatYes are they? --Smooth, nearly flat, with poorly-defined margins --Irregular, elevated, and sharply demarcated Can multiple phakomas be found in one eye? Yes

Are they pathognomonic for TS? No 193 Phakomatoses

Are they pathognomonic for TS? No 194 Phakomatoses

Are they pathognomonic for TS? No 195 Phakomatoses

The appearance of this lesion-type has been likened to thatAre ofthe a pathognomonicfruit, and a foodstuff. for TS? What are they? --Fruit: No --Foodstuff: 196 Phakomatoses

The appearance of this lesion-type has been likened to thatAre ofthe a pathognomonicfruit, and a foodstuff. for TS? What are they? --Fruit: ‘Mulberry’ No --Foodstuff: 197 Phakomatoses

NF1Tapioca (pudding)--Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --ClassicMulberry triad is epiloia By what other name is the astrocytic hamartoma --Skin: Adenoma sebaceum of face; ash-leaf spotsof theand retina shagreen known? patches on torso --CNS: Cortical tubers, other benign tumors Retinal phakoma --Benign tumors of heart and kidney as well What proportion of TS pts develop a phakoma? --Retinal tumor is astrocytic hamartoma 1/3 to 1/2

The appearance of this lesion-type has been likened to thatAre ofthe a pathognomonicfruit, and a foodstuff. for TS? What are they? --Fruit: ‘Mulberry’ No --Foodstuff: ‘Tapioca’ 198 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --Classic triad is epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: Cortical tubers, other benign tumors --Benign tumors of heart and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still consideredtrick a questionphakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 199 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --Classic triad is epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: Cortical tubers, other benign tumors --Benign tumors of heart and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 200 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --Classic triad is epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: Cortical tubers, other benign tumors --Benign tumors of heart and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomastumor type , classically of cerebellumtumor location (if absent, is called vonnot von Hippel Hippel-Lindau disease syndrome ) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 201 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --Classic triad is epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: Cortical tubers, other benign tumors --Benign tumors of heart and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 202 Phakomatoses

von Hippel-Lindau: Cerebellar hemangioblastoma 203 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --Classic triad is epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: Cortical tubers, other benign tumors --Benign tumors of heart and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cystsfinding and tumorsfinding in multiple organs, including malignancies: Pheo, 2renal-cell different malignancies Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 204 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --Classic triad is epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: Cortical tubers, other benign tumors --Benign tumors of heart and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large(short feeder for Pheochromocytoma)/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 205 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --Classic triad is epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: Cortical tubers, other benign tumors --Benign tumors of heart and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillarysomething hemangioblastoma something ; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 206 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --Classic triad is epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: Cortical tubers, other benign tumors --Benign tumors of heart and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 207 Phakomatoses

von Hippel-Lindau: Capillary hemangioblastoma 208 Phakomatoses

NF1 --PeripheralBy what otherNF name is this lesion known (it’s a subtle change)? --MostCapillary lesions hemangioma due to abnormal(ie, nomelanocytes ‘-blasto-’) or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --IrisCan lesions the retinal include lesions Lisch benodules, present JXG bilaterally? nodules, and congenital ectropion --OpticYes, nerve in about glioma: 1/2 Alwaysof cases symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Can there be multiple lesions in the same eye? Tuberous sclerosis --ClassicYes, these triad occuris epiloia in about(but all 1/3 3 presentof cases in only ~30%) --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS:Are allCortical retinal tubers, hemangio(blasto)mas other benign tumors associated with vHL? --BenignNo, they tumors can beof heartsporadic and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 209 Phakomatoses

--OpticYes, nerve in about glioma: 1/2#/# Alwaysof cases symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Can there be multiple lesions in the same eye? Tuberous sclerosis --ClassicYes, these triad occuris epiloia in about(but all 1/3 3 presentof cases in only ~30%) --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS:Are allCortical retinal tubers, hemangio(blasto)mas other benign tumors associated with vHL? --BenignNo, they tumors can beof heartsporadic and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 212 Phakomatoses

NF1 --PeripheralBy what otherNF name is this lesion known (it’s a subtle change)? --MostCapillary lesions hemangioma due to abnormal(ie, nomelanocytes ‘-blasto-’) or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --IrisCan lesions the retinal include lesions Lisch benodules, present JXG bilaterally? nodules, and congenital ectropion --OpticYes, nerve in about glioma: 1/2 Alwaysof cases symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Can there be multiple lesions in the same eye? Tuberous sclerosis --ClassicYes, these triad occuris epiloia in about(but all 1/3#/# 3 presentof cases in only ~30%) --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS:Are allCortical retinal tubers, hemangio(blasto)mas other benign tumors associated with vHL? --BenignNo, they tumors can beof heartsporadic and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 215 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --Classic triad is epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: Cortical tubers, other benign tumors --Benign tumors of heart and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRFabb.  ERDabb.  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 219 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --Classic triad is epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: Cortical tubers, other benign tumors --Benign tumors of heart and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management(subretinal fluid) (exudative retinal detachment) --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 220 Phakomatoses

von Hippel-Lindau: Edema 221 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --Classic triad is epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: Cortical tubers, other benign tumors --Benign tumors of heart and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1frequency year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 222 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --Classic triad is epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: Cortical tubers, other benign tumors --Benign tumors of heart and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 223 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --Classic triad is epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: Cortical tubers, other benign tumors --Benign tumors of heart and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year o --Systemic: Complete PE q1year with renaltest 1u/s, 24 urinetest 2for VMA; MRI brain q3frequency years until age 40yrs ; after that, MRI brain q5frequency years 224 Phakomatoses

NF1 --Peripheral NF --Most lesions due to abnormal melanocytes or neuroglial cells --Glaucoma associated with ipsilateral upper-lid plexiform fibroma and/or iris ectropion --Iris lesions include Lisch nodules, JXG nodules, and congenital ectropion --Optic nerve glioma: Always symptomatic by age 10 years. Classic CT appearance: Kinked ON --Rule of thumb for Lisch nodule prevalence: Age in years x 10 Tuberous sclerosis --Classic triad is epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: Cortical tubers, other benign tumors --Benign tumors of heart and kidney as well --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management (Vanillylmandelic acid ) --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 225 Phakomatoses

Tuberous sclerosisIs vH-L a potentially fatal condition? --Classic triad isYes epiloia --Skin: Adenoma sebaceum of face; ash-leaf spots and shagreen patches on torso --CNS: CorticalTwo tubers, components other benign are mosttumors likely to result in death. What are they? --Benign tumors of heart and kidney as well The cerebellar hemangioma and the renal carcinoma --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 226 Phakomatoses

Tuberous sclerosisIs vH-L a potentially fatal condition? --ClassicThe cerebellar triad isYes epiloia hemangioma??!! I thought that was a benign lesion. How could it be fatal? --Skin:It is Adenoma a benign lesion. sebaceum However, of face;it is notoriously ash-leaf ‘leaky,’spots andand the shagreen accumulating patches exudate on torso can lead to compression of vital intracranial structures --CNS: CorticalTwo tubers, components other benign are mosttumors likely to result in death. What are they? --Benign tumors of heart and kidney as well The cerebellar hemangioma and the renal carcinoma --Retinal tumor is astrocytic hamartoma; can appear smooth or lumpy (mulberry) von Hippel-Lindau --Skin: None! Despite this, is still considered a phakomatosis (and a classic one to boot) --CNS: Hemangioblastomas, classically of cerebellum (if absent, is called von Hippel disease) --Cysts and tumors in multiple organs, including malignancies: Pheo, renal-cell Ca --Retinal tumor is capillary hemangioblastoma; has large feeder/drainage vessels --Tumor leaks  SRF  ERD  decreased VA; treat with laser or cryo --Management --Ocular: DFE q1 year --Systemic: Complete PE q1year with renal u/s, 24o urine for VMA; MRI brain q3 years until age 40 ; after that, MRI brain q5 years 230 Phakomatoses

NF2 --Central NF Which is more common, NF1 or NF2? --Classic finding:NF1 bilateral is about acoustic 10x more neuromas common --Eye findings: Common: PSC/cortical cataracts; Rare: combined hamartoma of retina and RPE; Rarer: Lisch nodules 232 Phakomatoses

NF2 peripheral --Centralvs central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: combined hamartoma of retina and RPE; Rarer: Lisch nodules 234 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: combined hamartoma of retina and RPE; Rarer: Lisch nodules 235 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acousticnot neuromas eye --Eye findings: Common: PSC/cortical cataracts; Rare: combined hamartoma of retina and RPE; Rarer: Lisch nodules 236 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: combined hamartoma of retina and RPE; Rarer: Lisch nodules 237 Phakomatoses

14 y.o. with NF2 His 50 y.o. uncle with NF2

Tuberous sclerosis: Astrocytic hamartoma. Note large feeder/drainage vessels 238 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare:What sortcombined of tumor hamartoma is the acoustic of neuroma retina and of NF2; RPE; ie, Rarer:what specific Lisch cell nodules type is involved? A schwanomma 239 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: combined hamartomaWhat are of the retina three and most RPE; common Rarer: symptoms Lisch nodulesof acoustic neuroma?

#1: Reduced hearingeh?

#2: Tinnitusbzzzz… #3: Balancesteady… issues 241 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/corticalanterior segment cataracts; Rare: combined hamartoma of retina and RPE; Rarer: Lisch nodules 243 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: combined hamartoma of retina and RPE; Rarer: Lisch nodules 244 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: combined hamartoma of retina and RPE; Rarer: Lisch nodules Are the cataracts visually significant? Yes

Do they manifest prior to or after the acoustic neuromas? Usually prior

At what age do they become clinically significant? Usually in the 30s

Are they unilateral, or bilateral? Both presentations are common 245 Phakomatoses

Do they manifest prior to or after the acoustic neuromas? Usually prior

At what age do they become clinically significant? Usually in the 30s

Are they unilateral, or bilateral? Both presentations are common 246 Phakomatoses

Do they manifest prior to or after the acoustic neuromas? Usually prior

At what age do they become clinically significant? Usually in the 30s

Are they unilateral, or bilateral? Both presentations are common 247 Phakomatoses

Do they manifest prior to or after the acoustic neuromas? Usually prior

At what age do they become clinically significant? Usually in the 30s

Are they unilateral, or bilateral? Both presentations are common 248 Phakomatoses

Do they manifest prior to or after the acoustic neuromas? Usually prior

At what age do they become clinically significant? Usually in the 30s

Are they unilateral, or bilateral? Both presentations are common 249 Phakomatoses

Do they manifest prior to or after the acoustic neuromas? Usually prior

At what age do they become clinically significant? Usually in the 30s

Are they unilateral, or bilateral? Both presentations are common 250 Phakomatoses

Do they manifest prior to or after the acoustic neuromas? Usually prior

At what age do they become clinically significant? Usually in the 30s

ProAre tip: they If you unilateral, see a pt or<30 bilateral? years old with significant PSCs and/or corticalBoth presentations cataracts, consider are common whether s/he might have NF2! 251 Phakomatoses

Do they manifest prior to or after the acoustic neuromas? Usually prior

At what age do they become clinically significant? Usually in the 30s

Are they unilateral, or bilateral? Both presentations are common 252 Phakomatoses

Do they manifest prior to or after the acoustic neuromas? Usually prior

At what age do they become clinically significant? Usually in the 30s

Are they unilateral, or bilateral? Both presentations are common 253 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: combined hamartomaposterior segment of retina and RPE; Rarer: Lisch nodules 254 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules 255 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lischant seg: nodules two words 256 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules 257 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Melanocytic lesions Neuroglial lesions --Café au lait spots --Nodular neurofibromas --Axillary/inguinal freckles --Plexiform neurofibromas --Lisch nodules --Optic glioma --Choroidal lesions --Prominent corneal nerves

One key difference between NF1 and NF2 is this: In NF1, both melanocytic and neuroglial lesions are common, whereas… 258 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules Neuroglial lesions Melanocytic lesions --Nodular neurofibromas --Café au lait spots --Axillary/inguinal freckles --Plexiform neurofibromas --Lisch nodules --Choroidal lesions --Optic glioma --Prominent corneal nerves

One key difference between NF1 and NF2 is this: In NF1, both melanocytic and neuroglial lesions are common, whereas… In NF2, neuroglial lesions predominate. 259 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules Neuroglial lesions Melanocytic lesions --Nodular neurofibromas --Café au lait spots --Axillary/inguinal freckles --Plexiform neurofibromas --Lisch nodules --Choroidal lesions --Optic glioma --Prominent corneal nerves

One key difference between NF1 and NF2 is this: In NF1, both melanocytic and neuroglial lesions are common, whereas… In NF2, neuroglial lesions predominate.

Do melanocytic lesions occur in NF2 at all? Yes. The occasional café au lait spot and/or Lisch nodule shows up now and then 260 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules Neuroglial lesions Melanocytic lesions --Nodular neurofibromas --Café au lait spots --Axillary/inguinal freckles --Plexiform neurofibromas --Lisch nodules --Choroidal lesions --Optic glioma --Prominent corneal nerves

One key difference between NF1 and NF2 is this: In NF1, both melanocytic and neuroglial lesions are common, whereas… In NF2, neuroglial lesions predominate.

Do melanocytic lesions occur in NF2 at all? Yes. The occasional café au lait spot and/or Lisch nodule shows up now and then 261 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules This propensity for manifesting mainly as CNS tumors is why NF2 is referred Neuroglial lesions toDo as NF2 ‘central’ pts get peripheral-nerve NFMelanocytic lesions tumors --Nodular neurofibromas like NF1 pts? --Café au lait spots Neuroglial--Plexiform neurofibromas lesions --Axillary/inguinal freckles --Optic glioma Yes, but at much --Lischlower nodules rates --Choroidal lesions --Nodular neurofibromas? OK then, other than acoustic neuromas, --Prominent corneal nerves what sorts of neuroglial lesions occur in NF2? --Schwannomas--Plexiform neurofibromas? of the SC CNS neuroglial lesions; eg, spinal-cord --Meningiomas--Optic glioma? (intracranial) schwannomas, intracranial meningiomas, --Ependymomas--Prominent corneal nerves? and ependymomas 266 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules Neuroglial lesions Do NF2 pts get peripheral-nerveMelanocytic lesions tumors --Nodular neurofibromas like NF1 pts? --Café au lait spots Neuroglial--Plexiform neurofibromas lesions --Axillary/inguinal freckles --Optic glioma Yes, but at much --Lischlower nodules rates --Choroidal lesions --Nodular neurofibromas? OK then, other than acoustic neuromas, --Prominent corneal nerves what sorts of neuroglial lesions occur in NF2? ----PlexiformSchwannomas neurofibromas?of the SC CNS neuroglial lesions; eg, spinal-cord --Meningiomas--Optic glioma? (intracranial) schwannomas, intracranial meningiomas, --Ependymomas--Prominent corneal nerves? and ependymomas NF2 is also known as MISME syndrome. MISME is an acronym. What does it stand for? --Multiple -- Inherited --Schwannomas --M --E 269 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules Neuroglial lesions Do NF2 pts get peripheral-nerveMelanocytic lesions tumors --Nodular neurofibromas like NF1 pts? --Café au lait spots Neuroglial--Plexiform neurofibromas lesions --Axillary/inguinal freckles --Optic glioma Yes, but at much --Lischlower nodules rates --Choroidal lesions --Nodular neurofibromas? OK then, other than acoustic neuromas, --Prominent corneal nerves what sorts of neuroglial lesions occur in NF2? ----PlexiformSchwannomas neurofibromas?of the SC CNS neuroglial lesions; eg, spinal-cord ----OpticMeningiomas glioma? (intracranial) schwannomas, intracranial meningiomas, --Ependymomas--Prominent corneal nerves? and ependymomas NF2 is also known as MISME syndrome. MISME is an acronym. What does it stand for? --Multiple -- Inherited --Schwannomas --Meningiomas, and --E 270 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules Neuroglial lesions Do NF2 pts get peripheral-nerveMelanocytic lesions tumors --Nodular neurofibromas like NF1 pts? --Café au lait spots Neuroglial--Plexiform neurofibromas lesions --Axillary/inguinal freckles --Optic glioma Yes, but at much --Lischlower nodules rates --Choroidal lesions --Nodular neurofibromas? OK then, other than acoustic neuromas, --Prominent corneal nerves what sorts of neuroglial lesions occur in NF2? ----PlexiformSchwannomas neurofibromas?of the SC CNS neuroglial lesions; eg, spinal-cord ----OpticMeningiomas glioma? (intracranial) schwannomas, intracranial meningiomas, ----ProminentEpendymomas corneal nerves? and ependymomas NF2 is also known as MISME syndrome. MISME is an acronym. What does it stand for? --Multiple -- Inherited --Schwannomas --Meningiomas, and --Ependymomas 271 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules Neuroglial lesions Do NF2 pts get peripheral-nerveMelanocytic lesions tumors --Nodular neurofibromas like NF1 pts? --Café au lait spots Neuroglial--Plexiform neurofibromas lesions --Axillary/inguinal freckles --Optic glioma Yes, but at much --Lischlower nodules rates --Choroidal lesions --Nodular neurofibromas? OK then, other than acoustic neuromas, --Prominent corneal nerves what sorts of neuroglial lesions occur in NF2? ----PlexiformSchwannomas neurofibromas?of the SC CNS neuroglial lesions; eg, spinal-cord ----OpticMeningiomas glioma? (intracranial) schwannomas, intracranial meningiomas, ----ProminentEpendymomas corneal nerves? and ependymomas What is an ependymoma? NF2 is also known as MISME syndrome. MISME is an acronym. A glioma consisting of ependymal cells What does it stand for? --Multiple OK smart guy, what are ependymal cells? -- Inherited The epithelial-like glial cells that form the inner lining of the --Schwannomas cerebral ventricles and the central canal of the spinal cord --Meningiomas, and --Ependymomas 272 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules Neuroglial lesions Do NF2 pts get peripheral-nerveMelanocytic lesions tumors --Nodular neurofibromas like NF1 pts? --Café au lait spots Neuroglial--Plexiform neurofibromas lesions --Axillary/inguinal freckles --Optic glioma Yes, but at much --Lischlower nodules rates --Choroidal lesions --Nodular neurofibromas? OK then, other than acoustic neuromas, --Prominent corneal nerves what sorts of neuroglial lesions occur in NF2? ----PlexiformSchwannomas neurofibromas?of the SC CNS neuroglial lesions; eg, spinal-cord ----OpticMeningiomas glioma? (intracranial) schwannomas, intracranial meningiomas, ----ProminentEpendymomas corneal nerves? and ependymomas What is an ependymoma? NF2 is also known as MISME syndrome. MISME is an acronym. A glioma consisting of ependymal cells What does it stand for? --Multiple OK smart guy, what are ependymal cells? -- Inherited The epithelial-like glial cells that form the inner lining of the --Schwannomas cerebral ventricles and the central canal of the spinal cord --Meningiomas, and --Ependymomas 273 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules Neuroglial lesions Do NF2 pts get peripheral-nerveMelanocytic lesions tumors --Nodular neurofibromas like NF1 pts? --Café au lait spots Neuroglial--Plexiform neurofibromas lesions --Axillary/inguinal freckles --Optic glioma Yes, but at much --Lischlower nodules rates --Choroidal lesions --Nodular neurofibromas? OK then, other than acoustic neuromas, --Prominent corneal nerves what sorts of neuroglial lesions occur in NF2? ----PlexiformSchwannomas neurofibromas?of the SC CNS neuroglial lesions; eg, spinal-cord ----OpticMeningiomas glioma? (intracranial) schwannomas, intracranial meningiomas, ----ProminentEpendymomas corneal nerves? and ependymomas What is an ependymoma? NF2 is also known as MISME syndrome. MISME is an acronym. A glioma consisting of ependymal cells What does it stand for? --Multiple OK smart guy, what are ependymal cells? -- Inherited The epithelial-like glial cells that form the inner lining of the --Schwannomas cerebral ventricles and the central canal of the spinal cord --Meningiomas, and --Ependymomas 274 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules Neuroglial lesions Do NF2 pts get peripheral-nerveMelanocytic lesions tumors --Nodular neurofibromas like NF1 pts? --Café au lait spots Neuroglial--Plexiform neurofibromas lesions --Axillary/inguinal freckles --Optic glioma Yes, but at much --Lischlower nodules rates --Choroidal lesions --Nodular neurofibromas? OK then, other than acoustic neuromas, --Prominent corneal nerves what sorts of neuroglial lesions occur in NF2? ----PlexiformSchwannomas neurofibromas?of the SC CNS neuroglial lesions; eg, spinal-cord ----OpticMeningiomas glioma? (intracranial) schwannomas, intracranial meningiomas, ----ProminentEpendymomas corneal nerves? and ependymomas What is an ependymoma? NF2 is also known as MISME syndrome. MISME is an acronym. A glioma consisting of ependymal cells What does it stand for? --Multiple OK smart guy, what are ependymal cells? -- Inherited The epithelial-like glial cells that form the inner lining of the --Schwannomas cerebral ventricles and the central canal of the spinal cord --Meningiomas, and --Ependymomas 275 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules Neuroglial lesions Do NF2 pts get peripheral-nerveMelanocytic lesions tumors --Nodular neurofibromas like NF1 pts? --Café au lait spots Neuroglial--Plexiform neurofibromas lesions --Axillary/inguinal freckles --Optic glioma Yes, but at much --Lischlower nodules rates --Choroidal lesions --Nodular neurofibromas? OK then, other than acoustic neuromas, --Prominent corneal nerves what sorts of neuroglial lesions occur in NF2? --Schwannomas--Plexiform neurofibromas? of the SC CNS neuroglial lesions; eg, spinal-cord --Meningiomas--Optic glioma? (intracranial) schwannomas, intracranial meningiomas, --Ependymomas--Prominent corneal nerves? and ependymomas What is an ependymoma? Do the neuroglial NF2lesions is also in knownNF2 carry as MISME a risk syndrome of malignant. MISME transformation? is an acronym. A glioma consisting of ependymal cells No. Unlike in NF1,What malignant does it stand transformation for? of benign lesions in NF2 is --Multiple almost OKunheard smart guy,of what are ependymal cells? -- Inherited The epithelial-like glial cells that form the inner lining of the --Schwannomas cerebral ventricles and the central canal of the spinal cord --Meningiomas, and --Ependymomas 276 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules Neuroglial lesions Do NF2 pts get peripheral-nerveMelanocytic lesions tumors --Nodular neurofibromas like NF1 pts? --Café au lait spots Neuroglial--Plexiform neurofibromas lesions --Axillary/inguinal freckles --Optic glioma Yes, but at much --Lischlower nodules rates --Choroidal lesions --Nodular neurofibromas? OK then, other than acoustic neuromas, --Prominent corneal nerves what sorts of neuroglial lesions occur in NF2? --Schwannomas--Plexiform neurofibromas? of the SC CNS neuroglial lesions; eg, spinal-cord --Meningiomas--Optic glioma? (intracranial) schwannomas, intracranial meningiomas, --Ependymomas--Prominent corneal nerves? and ependymomas What is an ependymoma? Do the neuroglial NF2lesions is also in knownNF2 carry as MISME a risk syndrome of malignant. MISME transformation? is an acronym. A glioma consisting of ependymal cells No. Unlike in NF1,What malignant does it stand transformation for? of benign lesions in NF2 is --Multiple almost OKunheard smart guy,of. what are ependymal cells? -- Inherited The epithelial-like glial cells that form the inner lining of the --Schwannomas cerebral ventricles and the central canal of the spinal cord --Meningiomas, and --Ependymomas 277 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

By way of a refresher: What is a hamartoma? 278 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

By way of a refresher: What is a hamartoma? clinical state opposite A tumor composed of histologically abnormal cells found in their normalclinical state location 279 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

By way of a refresher: What is a hamartoma? A tumor composed of histologically abnormal cells found in their normal location 280 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --EyeAgain, findings: a refresher: Common: What is tPSC/corticalhe name of the cataracts; reverse clinical Rare:entity, Combined ie, one with normalhamartomacells found of retinain an abnormal and RPElocation?; Rarer: Lisch nodules A choristoma

? By way of a refresher: What is a hamartoma? an abnormal A tumor composed of histologically abnormalnormal cells found in their normal location 281 Phakomatoses

choristoma By way of a refresher: What is a hamartoma? an abnormal A tumor composed of histologically abnormalnormal cells found in their normal location 282 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

By way of a refresher: What is a hamartoma? A tumor composed of histologically abnormal cells found in their normal location

So, what combination of hamartomatous cells of the retina and RPE are involved in a combined hamartoma of the retina and RPE? 283 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

By way of a refresher: What is a hamartoma? A tumor composed of histologically abnormal cells found in their normal location

So, what combination of hamartomatous cells of the retina and RPE are involved in a combined hamartoma of the retina and RPE? RPE cells (duh) and retinal glial cells 284 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

By way of a refresher: What is a hamartoma? A tumor composed of histologically abnormal cells found in their normal location

So, what combination of hamartomatous cells of the retina and RPE are involved in a combined hamartoma of the retina and RPE? RPE cells (duh) and retinal glial cells

How does it present clinically? 285 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

By way of a refresher: What is a hamartoma? A tumor composed of histologically abnormal cells found in their normal location

So, what combination of hamartomatous cells of the retina and RPE are involved in a combined hamartoma of the retina and RPE? RPE cells (duh) and retinal glial cells

How does it present clinically? As a variably pigmented, slightly elevated retinal mass of the peripapillarylocation retina 286 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

By way of a refresher: What is a hamartoma? A tumor composed of histologically abnormal cells found in their normal location

So, what combination of hamartomatous cells of the retina and RPE are involved in a combined hamartoma of the retina and RPE? RPE cells (duh) and retinal glial cells

How does it present clinically? As a variably pigmented, slightly elevated retinal mass of the peripapillary retina 287 Phakomatoses

Combined hamartoma of retina and RPE 288 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

By way of a refresher: What is a hamartoma? A tumor composed of histologically abnormal cells found in their normal location

So, what combination of hamartomatous cells of the retina and RPE are involved in a combined hamartoma of the retina and RPE? RPE cells (duh) and retinal glial cells

How does it present clinically? As a variably pigmented, slightly elevated retinal mass of the peripapillary retina

With what more sinister dz entity is it often confused? 289 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

By way of a refresher: What is a hamartoma? A tumor composed of histologically abnormal cells found in their normal location

So, what combination of hamartomatous cells of the retina and RPE are involved in a combined hamartoma of the retina and RPE? RPE cells (duh) and retinal glial cells

How does it present clinically? As a variably pigmented, slightly elevated retinal mass of the peripapillary retina

With what more sinister dz entity is it often confused? Choroidal melanoma--eyes have been enucleated because of this misdiagnosis 290 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

By way of a refresher: What is a hamartoma? A tumor composed of histologically abnormal cells found in their normal location

So, what combination of hamartomatous cells of the retina and RPE are involved in a combined hamartoma of the retina and RPE? RPE cells (duh) and retinal glial cells

How does it present clinically? As a variably pigmented, slightly elevated retinal mass of the peripapillary retina

With what more sinister dz entityHow can is itone often avoid confused? making such a disastrous mistake? By taking pains to carefully determine the anatomic location of the tumor Choroidal melanoma--eyes have been enucleated because of this misdiagnosis in question--choroidal melanomas originate behind Bruch’s membrane, whereas combined hamartomas of the retina and RPE are located wholly in front of it 291 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

By way of a refresher: What is a hamartoma? A tumor composed of histologically abnormal cells found in their normal location

So, what combination of hamartomatous cells of the retina and RPE are involved in a combined hamartoma of the retina and RPE? RPE cells (duh) and retinal glial cells

How does it present clinically? As a variably pigmented, slightly elevated retinal mass of the peripapillary retina

Combined hamartoma of retina and RPE. Note the entire lesion is above Bruchs 293 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Acoustic neuroma

? ? Another eye finding associated with acoustic neuroma is corneal decompensation. By what two mechanisms might this occur? ? ?

Corneal decompensation 294 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Acoustic neuroma

Bag CN V1 Bag CN VII Another eye finding associated with acoustic neuroma is corneal decompensation. By what two mechanisms might this occur? ??

Corneal decompensation 295 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Acoustic neuroma

Bag CN V1 Bag CN VII Another eye finding associated with acoustic neuroma is corneal decompensation. By what two mechanisms might this occur? Decreased corneal Lagophthalmos sensation

Corneal decompensation 296 Phakomatoses

NF2: Acoustic neuroma 297 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber --Classic stigmata is the port-winethree words stain --Ipsilateral meningeal AVM  seizures --Classic tomato catsup fundus appearance is due to a diffuse choroidal hemangioma --Another classic finding on DFE: Glaucomatous cupping in the ipsilateral ONH only --Glaucoma surgery: ↑ risk of massive choroidal effusion due to abnormal choroidal vasculature 298 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber --Classic stigmata is the port-wine stain --Ipsilateral meningeal AVM  seizures --Classic tomato catsup fundus appearance is due to a diffuse choroidal hemangioma --Another classic finding on DFE: Glaucomatous cupping in the ipsilateral ONH only --Glaucoma surgery: ↑ risk of massive choroidal effusion due to abnormal choroidal vasculature 299 Phakomatoses

Sturge-Weber: Port-wine stain 300

Phakomatoses In one word, what sort of lesion is the port-wine stain? An angioma NF2 --Central NF By what ‘official’ name is it known? --Classic finding: bilateral acoustic neuromas Nevus flammeus --Eye findings: Common: PSC/cortical cataracts; Occasional: Lisch nodules When does it present? Rare: Combined hamartoma of retina and RPEAt birth

Sturge-Weber What is the typical pattern of distribution? It comports to the distribution of one or more divisions of --Classic stigmata is the port-wine stain CN5 --Ipsilateral meningeal AVM  seizures --Classic tomato catsup fundus appearance isDoes due it to always a diffuse present choroidal in this manner? hemangioma --Another classic finding on DFE: GlaucomatousNo. Somecupping cases in thewill crossipsilateral the midline ONH of only the face --Glaucoma surgery: ↑ risk of massive choroidal effusion due to abnormal choroidal vasculature All infants with SWS have a port-wine stain. Do all infants with a port-wine stain have SWS? No

If the port-wine stain involves the eyelid, what adjacent structure is commonly affected as well? The conjunctiva. It will have increased vascularity and hyperemia, producing a false impression of ‘pink eye’ 301

Sturge-Weber: Port-wine stain 307

Sturge-Weber What is the typical pattern of distribution? It comports to the distribution of one or more divisions of --Classic stigmata is the port-wine stain CN5CN#? --Ipsilateral meningeal AVM  seizures --Classic tomato catsup fundus appearance isDoes due it to always a diffuse present choroidal in this manner? hemangioma --Another classic finding on DFE: GlaucomatousNo. Somecupping cases in thewill crossipsilateral the midline ONH of only the face --Glaucoma surgery: ↑ risk of massive choroidal effusion due to abnormal choroidal vasculature All infants with SWS have a port-wine stain. Do all infants with a port-wine stain have SWS? No

Sturge-Weber: Conjunctival hyperemia 317 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber --Classic stigmata is the port-wine stain --Ipsilateral meningeal AVM  seizuressymptom/sign --Classic tomato catsup fundus appearance is due to a diffuse choroidal hemangioma --Another classic finding on DFE: Glaucomatous cupping in the ipsilateral ONH only --Glaucoma surgery: ↑ risk of massive choroidal effusion due to abnormal choroidal vasculature 318 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber --Classic stigmata is the port-wine stain --Ipsilateral meningeal AVM  seizures --Classic tomato catsup fundus appearance is due to a diffuse choroidal hemangioma Is the meningeal AVM prone to bleeding? Noa--Anotherses classic finding on DFE: Glaucomatous cupping in the ipsilateral ONH only --Glaucoma surgery: ↑ risk of massive choroidal effusion due to abnormal choroidal vasculature 320 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber --Classic stigmata is the port-wine stain --Ipsilateral meningeal AVM  seizures --Classic tomato catsup fundus appearance is due to a diffuse choroidal hemangioma Is the meningeal AVM prone to bleeding? No--Anotherases classic finding on DFE: Glaucomatous cupping in the ipsilateral ONH only --Glaucoma surgery: ↑ risk of massive choroidal effusion due to abnormal choroidal vasculature 321 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber --Classic stigmata is the port-wine stain --Ipsilateral meningeal AVM  seizures How prevalent is seizure activity in SWS? Very--estimates run as high as 90% of cases --Classic tomato catsup fundus appearance is due to a diffuse choroidal hemangioma --Another classic finding on DFE: Glaucomatous cupping in the ipsilateral ONH only --Glaucoma surgery: ↑ risk of massive choroidal effusion due to abnormal choroidal vasculature 322 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber --Classic stigmata is the port-wine stain --Ipsilateral meningeal AVM  seizures --Classic tomatommm… catsup fundus appearance is due to a diffuselesion choroidal (something something hemangioma something) --Another classic finding on DFE: Glaucomatous cupping in the ipsilateral ONH only --Glaucoma surgery: ↑ risk of massive choroidal effusion due to abnormal choroidal vasculature 324 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber: Tomato catsup fundus OD 326 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber --Classic stigmata is the port-wine stain --Ipsilateral meningeal AVM  seizures --Classic tomato catsup fundus appearance is due to a diffuse choroidal hemangioma --Another classic finding on DFE: Glaucomatous cupping in the ipsilateral ONH only --Glaucoma surgery: ↑ risk ofDiffuse massive choroidal choroidal hemangioma effusion is presentdue to inabnormal what percent choroidal of SWS? vasculature About 50%

Can the choroidal hemangioma be present bilaterally? Yes, but it’s uncommon

Does the choroidal hemangioma have malignant potential? No 327 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber --Classic stigmata is the port-wine stain --Ipsilateral meningeal AVM  seizures --Classic tomato catsup fundus appearance is due to a diffuse choroidal hemangioma --Another classic finding on DFE: Glaucomatous cupping in the ipsilateral ONH only --Glaucoma surgery: ↑ risk ofDiffuse massive choroidal choroidal hemangioma effusion is presentdue to inabnormal what percent choroidal of SWS? vasculature About 50%

Can the choroidal hemangioma be present bilaterally? Yes, but it’s uncommon

Does the choroidal hemangioma have malignant potential? No 328 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber --Classic stigmata is the port-wine stain --Ipsilateral meningeal AVM  seizures --Classic tomato catsup fundus appearance is due to a diffuse choroidal hemangioma --Another classic finding on DFE: Glaucomatous cupping in the ipsilateral ONH only --Glaucoma surgery: ↑ risk ofDiffuse massive choroidal choroidal hemangioma effusion is presentdue to inabnormal what percent choroidal of SWS? vasculature About 50%

Can the choroidal hemangioma be present bilaterally? Yes, but it’s uncommon

Does the choroidal hemangioma have malignant potential? No 329 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber --Classic stigmata is the port-wine stain --Ipsilateral meningeal AVM  seizures --Classic tomato catsup fundus appearance is due to a diffuse choroidal hemangioma --Another classic finding on DFE: Glaucomatous cupping in the ipsilateral ONH only --Glaucoma surgery: ↑ risk ofDiffuse massive choroidal choroidal hemangioma effusion is presentdue to inabnormal what percent choroidal of SWS? vasculature About 50%

Can the choroidal hemangioma be present bilaterally? Yes, but it’s uncommon

Does the choroidal hemangioma have malignant potential? No 330 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber --Classic stigmata is the port-wine stain --Ipsilateral meningeal AVM  seizures --Classic tomato catsup fundus appearance is due to a diffuse choroidal hemangioma --Another classic finding on DFE: Glaucomatous cupping in the ipsilateral ONH only --Glaucoma surgery: ↑ risk ofDiffuse massive choroidal choroidal hemangioma effusion is presentdue to inabnormal what percent choroidal of SWS? vasculature About 50%

Can the choroidal hemangioma be present bilaterally? Yes, but it’s uncommon

Does the choroidal hemangioma have malignant potential? No 331 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber --Classic stigmata is the port-wine stain --Ipsilateral meningeal AVM  seizures --Classic tomato catsup fundus appearance is due to a diffuse choroidal hemangioma --Another classic finding on DFE: Glaucomatous cupping in the ipsilateral ONH only --Glaucoma surgery: ↑ risk ofDiffuse massive choroidal choroidal hemangioma effusion is presentdue to inabnormal what percent choroidal of SWS? vasculature About 50%

Can the choroidal hemangioma be present bilaterally? Yes, but it’s uncommon

Does the choroidal hemangioma have malignant potential? No 332 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber --Classic stigmata is the port-wine stain --Ipsilateral meningeal AVM  seizures --Classic tomato catsup fundus appearance is due to a diffuse choroidal hemangioma --Another classic finding on DFE: Glaucomatous cuppingnon-retinal in pathology the ipsilateral ONH only --Glaucoma surgery: ↑ risk of massive choroidal effusion due to abnormal choroidal vasculature 333 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

Sturge-Weber: Note the glaucomatous cupping on the affected side 335 Phakomatoses

Sturge-Weber: Note the subtle PWS; also the buphthalmos, and enlarged cornea typical of congenital glaucoma 336 Phakomatoses

NF2 --Central NF --Classic finding: bilateral acoustic neuromas --Eye findings: Common: PSC/cortical cataracts; Rare: Combined hamartoma of retina and RPE; Rarer: Lisch nodules

What percent of SWS pts develop glaucoma? Estimates run as high as 70

Is there a relationship between the port-wine stain and risk of glaucoma? Yes. If the port-wine stain involves the eyelid , the risk is increased

Elevated IOP in SWS stems from three different mechanisms. What are they? --Increased episcleral venous pressure (EVP) --Increased ciliary-body perfusionaqueous hyperproduction --Developmental anomalies of the drainage angle 337 Phakomatoses