Phakomatoses Ophtalmology

7/27/2019 Phakomatoses Ophtalmology

1/6

937

INTRODUCTION

The phakomatoses are a group o complex multisystem disorderslinked, at least in a historical sense, by various attributes o the compo-nent lesions, the organs involved, and the pattern o clinical inheritanceobserved in some cases. Although the term phakomatoses was coinedby van der Hoeve in 1923 in a paper concerned with the similarities be-tween von Recklinghausens neurobromatosis (NF) and Bournevillestuberous sclerosis (TS), this term has never been dened satisactorily.Absolute inclusion criteria were not presented by van der Hoeve, and aconsensus about such criteria has not been reached in the years since.Some authors dene the phakomatoses as neuro-oculo-cutaneous syn-dromes with autosomal dominant inheritance. Others believe that oneor more characteristic skin lesions must be present in a substantialnumber o patients who have a neuro-ocular syndrome to warrant its

classication as a phakomatosis. Still others believe that the essentialelement o a phakomatosis is the presence or development o multi-organ hamartomas.

For the purposes o this chapter, the authors dene the phakomatosesas a group o independent clinical syndromes characterized by multipletumors or tumor-like lesions, some o which are or can become malignantand arise in disparate organs o the body, including the eye in a substan-tial proportion o patients. Three syndromes are consistently classiedas phakomatoses by most authors and also meet our denitional criteria:NF, TS, and von Hippel-Lindau syndrome (VHLS). Two other syndromesare classied as phakomatoses by many authors but do not conormprecisely to our denition: Sturge-Weber syndrome (SWS) and Wyburn-

Mason syndrome (WMS). These ve syndromes are reviewed briefy inthis chapter. Other syndromes that are occasionally grouped with thephakomatoses by some authors (e.g., Louis-Bar syndrome (ataxia tel-angiectasia) and Weskamp-Cotlier syndrome (retinal-neuro-cutaneouscavernous hemangioma syndrome)) are not reviewed in this chapter.

NEUROFIBROMATOSIS

INTRODUCTION

The syndrome o NF consists o two distinct genetic diseases with con-siderable phenotypic overlap. Both are characterized by neuroectoder-mal tumors that arise within multiple organs and autosomal dominant

inheritance. These two orms o NF are termed NF-1 and NF-2.

EPIDEMIOLOGY AND PATHOGENESIS

Neurobromatosis is the most common phakomatosis, having arequency o approximately 1 case per 3500 persons in the generalpopulation.1 NF-1 is by ar the more common o the two types, aectingapproximately 1 person per 35004000 persons in the general popula-tion. In contrast, NF-2 aects no more than 1 person per 40 00050 000persons. Men and women appear to be aected with equal requency,and there is no racial predilection or either type o the disease.

Many eatures o these syndromes do not appear until late childhood

or early adulthood.2

The severity o the syndrome varies markedly rompatient to patient. Many patients who have limited orms o NF areprobably not identied.

The gene or NF-1 has been localized to chromosome 17q11,3 andthat or NF-2 has been localized to chromosome 22q12.4

EXTRAOPHTHALMIC MANIFESTATIONS

Neurobromatosis type 1 (peripheral NF, von Recklinghausens dis-ease) is characterized by cutaneous ca-au-lait spots, axillary andinguinal reckling, Lisch nodules o the iris, several types o cutane-ous neurobromas, optic nerve gliomas, and neurobromas or othersolid neoplasms o the central nervous system (CNS).1 Currently ac-cepted diagnostic criteria or NF-1 are listed in Box 8-13-1. The ca-au-lait spots in this syndrome tend to be multiple. Many are larger than0.5 cm in diameter in childhood and enlarge to 1.5 cm in diameter bythe postpubertal years. Six or more ca-au-lait spots larger than 1.5 cmin diameter in postpubertal individuals are generally considered diag-nostic o NF-1.5 Axillary reckling and inguinal reckling are present in9095% o aected individuals.6 Subcutaneous neurobromas in NF-1tend to arise multiocally and can be either pedunculated nodules ordiuse plexiorm lesions. CNS neurobromas can cause hemiparesis,hemiatrophy, and seizures in some aected individuals. Because o boneabnormalities related to the syndrome, some individuals develop severescoliosis. About one hal o the patients aected by NF-1 have some

sort o learning disability, but most are o normal intelligence. In olderpatients, systemic hypertension appears to be more requent than it isin the general population.

Neurobromatosis type 2 (central NF) is typied by bilateral vestibu-lar schwannomas (acoustic neuromas) and widely scattered neurobro-mas, meningiomas, gliomas, and schwannomas. Currently accepteddiagnostic criteria or NF-2 are listed in Box 8-13-2. The most consis-tent extraophthalmic problem suered by patients aected by NF-2 issensorineural deaness caused by the vestibular schwannomas.

OCULAR MANIFESTATIONS

Ophthalmologic ndings in NF-1 include Lisch nodules o the iris, subcu-taneous pedunculated and plexiorm neurobromas o the eyelids, opticnerve gliomas, multiocal choroidal nevi, and occasionally retinal tumorsindistinguishable rom the retinal astrocytic hamartomas ound in TS.7,8 Lisch nodules have been described as melanocytic hamartomas o the

PhakomatosesJames J. Augsburger and James P. Bolling

PART 8 INTRAOCULAR TUMORS

SECTION 3 phakomatoses

8.13

Denition: Grou o multisystem syndromes that have characteristicohthalmic maniestations:

n neuroibromatosis tye 1 (von Recklinghausens disease) and tye2 (central neuroibromatosis).

n tuberous sclerosis.

nn von Hiel-Lindau syndrome.

n Sturge-Weber syndrome.

nn Wyburn-Mason syndrome.

Key eatures

n Characteristic retinal or uveal lesions.

Associated eaturesn Characteristic cutaneous lesions in several o the syndromes.

n Characteristic central nervous system lesions in all o thesyndromes.

n Miscellaneous other systemic eatures seciic to syndrome.


2/6

8

938

INTRAOCULARTUMORS

iris stroma. These lesions appear as tan to light brown nodules that studthe iris surace (Fig. 8-13-1). They are rarely present at birth but tend todevelop by the second to third decade o lie in over 95% o persons whohave NF-1.9 Histopathologically, Lisch nodules consist o closely packeddendritic or spindle-shaped melanocytes within the anterior layers o irisstroma. Because these cells are normal uveal melanocytes and not nevuscells, these lesions are not true nevi. Neurobromas o the eyelids canbe either nodular or plexiorm in nature. They tend to develop early in

lie and can enlarge progressively. Gliomas o the optic nerve develop in1015% o aected patients.10 They can occur unilaterally or bilater-ally and requently involve the optic chiasm. Optic nerve gliomasin the orbit cause progressive proptosis and optic atrophy and re-quently result in unilateral or bilateral blindness. Those that arisewithin the brain and involve the chiasm can cause bilateral visual lossas well as intracranial mass eects. Some patients aected by NF-1have pulsating exophthalmos caused by anomalous developmento the sphenoid bone.7 Congenital and inantile glaucomas appearto be common in patients who have this syndrome.7 Some aectedpatients develop multiocal choroidal melanocytic nevi bilaterally,8 andthese patients appear to have an increased cumulative lietime risk or

the development o a uveal melanoma.11

Ophthalmologic ndings in NF-2 are relatively uncommon.12Lisch nodules o the iris, eyelid neurobromas, and optic nervegliomas occur occasionally but are not generally present. The mostconsistent ocular ndings in patients who have NF-2 are combined

hamartomas o the retina13 and juvenile posterior subcapsular orcortical lens opacities.5

SYSTEMIC EVALUATION

Detailed recommendations or systemic evaluation o patients whohave suspected NF-1 or NF-2 have been published.5 For patients whohave suspected NF-1, the basic diagnostic evaluation should con-sist o a complete history and comprehensive physical examination,including an ophthalmic examination. The history and physicalexamination should attempt to identiy the diagnostic criteria listedin Box 8-13-1. Ancillary studies such as computed tomography (CT)and magnetic resonance imaging (MRI) should be perormed in NF-1i the history or ndings revealed by physical examination suggestthat they might be helpul. For patients who have suspected NF-2,the basic diagnostic evaluation should consist o a complete history

and physical examination, including an ophthalmic examination,and high-resolution MRI or CT imaging o the brain and spinal cord.The history and physical examination should attempt to identiythe diagnostic criteria listed in Box 8-13-2, and the imaging studiesshould address the presence or absence o vestibular schwannomas.Other studies in suspected NF-2 are obtained as indicated by thendings detected during the basic evaluation.

TREATMENT

Treatment o optic nerve gliomas in NF is covered in Chapter 12.13.Treatment o neurobromas o the eyelids and conjunctiva is coveredin Chapter 12.9. Treatment o the intracranial lesions o NF-1 anNF-2 is beyond the scope o this book.

COURSE AND OUTCOME

Lie expectancy is reduced substantially in patients who have NF-1or NF-2.14, 15 The principal causes o early death in persons whohave NF-1 are complications o systemic hypertension, cancer, andexpansive growth o benign intracranial neoplasms. Several typeso cancer, including neurobrosarcoma, other sarcomas, leukemias,and lymphomas, occur with increased requency in patients whohave NF-1. In patients with NF-2, the main cause o early deathis expansion o a CNS neoplasm. Unilateral or bilateral blindness

occurs in some individuals aected by NF-1 or NF-2, usually be-cause o glioma o the optic nerves or chiasm (especially in NF-1) butoccasionally because o expansile intracranial growth o a vestibularschwannoma or an apoplectic episode (NF-2).

TUBEROUS SCLEROSIS

INTRODUCTION

TS is a multiorgan tumor syndrome that is characterized by multiocal,bilateral retinal astrocytic hamartomas, astrocytic tumors o the CNS,

several unusual cutaneous lesions, mental retardation, seizures, and avariety o cysts and tumors o other organs. The clinical spectrum isextremely broad and ranges rom minimal to marked in aectedindividuals. Many persons who have limited orms o the disease areprobably not recognized as TS suerers.

Fig. 8131 Lisch nodules in neurobromatosis type 1.

BOX 8-13-1 DIAGNOSTIC CRITERIA FORNEUROFIBROMATOSIS TYPE 1

THE PATIENT SHOULD HAVE TwO OR MORE OF THE FOLLOwING:

six or more ca-au-lait sots

each 1.5 cm or larger in ostubertal individuals

each 0.5 cm or larger in reubertal individuals

two or more neurobromas o any tye or one or more lexiorm

neurobroma

reckling in the axilla or groin

otic nerve glioma

two or more Lisch nodules o the iris

a distinctive bony lesion

dyslasia o shenoid bone

dyslasia or thinning o long bone cortex

a rst-degree relative with neurobromatosis tye 1

BOX 8-13-2 DIAGNOSTIC CRITERIA FOR

NEUROFIBROMATOSIS TYPE 2INDIVIDUALS wHO HAVE THE FOLLOwING CLINICAL FEATURES

SHOULD BE CONSIDERED TO HAVE DEFINITE NEUROFIBROMATOSIS

TYPE 2:

bilateral, vestibular schwannomas (acoustic neuromas)

or

a rst-degree relative with neurobromatosis tye 2

plus

unilateral, vestibular schwannoma aearing beore age 30 years

or any two o the ollowing: meningioma, glioma, schwannoma,

juvenile osterior subcasular lens oacities/juvenile cortical cataract,

and combined hamartoma o retina

INDIVIDUALS wHO HAVE THE FOLLOwING CLINICAL FEATURES

SHOULD BE REGARDED TO HAVE PROBABLE NEUROFIBROMATOSIS

TYPE 2:

unilateral, vestibular schwannoma aearing rior to age 30 years lus

at least one o the ollowing: meningioma, glioma, schwannoma,

juvenile, osterior, subcasular lens oacities/juvenile cortical cataract,

and combined hamartoma o retina

or

multile meningiomas (two or more) lus unilateral, vestibular

schwannoma aearing beore age 30 years or one o the ollowing:

glioma, schwannoma, juvenile, osterior, subcasular lens oacities/

juvenile cortical cataract, and combined hamartoma o retina


3/6

8.13

939

phakomatoses


The prevalence o TS in the general population has been estimated to beapproximately 1 case per 10 000 persons.16 About one third o cases areamilial and two thirds are sporadic. No recognized racial predilectionexists, and the sexes are aected equally. Signs and symptoms o TSusually begin by the time the patient is 6 years o age.

TS genes have been identied on loci on the long arm o chromo-some 9 (9q32-34), on the long arm o chromosome 11, on the shortarm o chromosome 16 (16p13), and on the long arm o chromosome12 (12q22-24).16 O these loci, the 9q32-34 locus has been the mostconsistent, being associated with between one third and one hal o allamilial cases.


Central nervous system tumors that occur in TS are generally low-gradeastrocytomas. These CNS lesions can become calcied and detectableon skull radiographs; however, they are revealed much more eectivelyby CT (Fig. 8-13-2) or MRI.17 Complications associated with suchlesions include mental deciency and seizures, both o which can rangerom mild to severe. Many individuals who have TS have normal intel-lectual abilities.

The cutaneous lesions characteristically associated with TS includeadenoma sebaceum, ash lea spots, shagreen patches, and subungualbromas.18 Adenoma sebaceum is an unusual acial dermatological

eruption characterized by pinhead to pea-sized yellowish to reddish-brown papules distributed in a butterfy ashion over the nose, cheeks,and nasolabial olds (Fig. 8-13-3). Histopathologically, the individualskin lesions are angiobromas. Ash lea spots are congenital white orhypomelanotic skin macules ranging in size rom about 1 mm to severalcentimeters in diameter and having a conguration that resembles anash lea. These lesions usually show up prominently when the skinis viewed under ultraviolet light. The shagreen patch is a thickenedpatch o skin with the texture o pigskin or sharkskin and usuallyoccurs over the lower back. Subungual bromas are benign broustumors that develop at the sides o the nail beds in some patients.

A variety o unusual tumors develop in the heart, kidney, lungs, thy-

roid, and other visceral organs in some patients who have TS. The mostcommon visceral tumor in TS appears to be the angiomyolipoma othe kidney.19 Probably the most distinctive visceral tumor in TS is thebenign cardiac rhabdomyoma. In some patients who have TS, an un-usual lung disease (pulmonary lymphangioleiomyomatosis) develops.19In addition, benign cysts develop multiocally in various visceral organs,including the kidneys, liver, and lungs, in many patients who have TS.


The classical ophthalmoscopic eature o TS is the retinal astrocytoma(astrocytic hamartoma).20 Lesions o this type are described in detail

and illustrated in Chapter 8.9. Approximately one hal o all patientsaected by TS develop at least one retinal astrocytoma in one eye.20 Inthe individuals who have TS and develop retinal astrocytomas, multiplelesions in both eyes occur in 4050% o cases.21 Malignant transorma-tion o retinal astrocytomas occurs in TS but is rare.

SYSTEMIC EVALUATION

Systemic evaluation o individuals or whom TS is suspected shouldinclude undus examination, dermatological evaluation to identiycharacteristic skin lesions, CT or MRI o the CNS, and CT or MRI othe abdominal viscera.21 Examination o amily members to look or a

amilial pattern is also appropriate.

TREATMENT

Treatment o aected individuals is purely symptomatic at present.Periodic physical examination and imaging o the CNS and abdominal-thoracic viscera by CT or MRI are appropriate to identiy potentiallytreatable problems such as cardiac rhabdomyomas, cysts and tumors othe kidney, and enlarging CNS astrocytomas.

COURSE AND OUTCOME

The lie expectancy o individuals who have TS is reduced substantiallycompared with that expected in the normal population.22 The mostcommon cause o early death in this syndrome is renal ailure secondaryto angiomyolipomas, cysts, or both. The second most common causeo death is obstructive hydrocephalus or other CNS problems caused byenlargement o one or more o the CNS astrocytomas. Other importantbut less requent causes o death are cardiac conduction deects andheart ailure rom cardiac rhabdomyoma and chronic pulmonary in-suciency associated with lymphangioleiomyomatosis o the lung. Inpatients who have proound mental retardation and severe seizures,death occurs requently as a result o status epilepticus or pneumonia.

VON HIPPEL-LINDAU SYNDROME

INTRODUCTION

VHLS is a multiorgan disorder characterized by retinal capillary hem-angiomas, CNS hemangioblastomas, various solid and cystic visceralhamartomas and hamartias, and malignant neoplasms, including renalcell carcinomas and pheochromocytomas. The ull-fedged syndromecommonly runs in amilies that have a clear autosomal dominantinheritance pattern. Aected individuals are at substantial risk o earlydeath, usually on the basis o their intracranial hemangiomatous lesionor renal cell carcinoma.


VHLS appears to be rare, but its precise incidence has not been deter-mined.23 In patients who have ull-fedged VHLS, one or more clinicallyidentiable maniestations o the disease are usually present by orbeore the third decade o lie. The median age at detection o the rstclinical eatures o VHLS is 2025 years.23 Capillary hemangiomaso the retina are usually the earliest detected maniestation o VHLS(probably because they are easiest to detect at a small size), whereasCNS hemangioblastomas typically appear slightly later and renal cellcarcinomas substantially later in lie. However, the timing o clini-

cal emergence o the various lesions in individual patients who haveVHLS varies greatly. The cumulative probability o developing retinalcapillary hemangiomas and CNS hemangioblastomas in a patientwho has VHLS is > 80%, and the probability o developing renal cellcarcinoma is > 60%.

Fig. 8132 Computed tomography oparaventricular astrocytomas in a patientho has tuberoussclerosis.

Fig. 8133 Adenomasebaceum o ace ina patient ho hastuberous sclerosis.


4/6

8

940

INTRAOCULARTUMORS

VHLS aects both sexes equally and occurs in all racial groups.Molecular biological studies have localized the VHLS gene to chromo-some 3p25-26.24


Important extraocular eatures o VHLS include hemangioblastomas(capillary hemangiomas) o the brain and spinal cord, renal cell carci-noma, pheochromocytoma, several other less common solid neoplasms

and related lesions, and cystic lesions o various visceral organs. Theclassical CNS lesions o VHLS are solid and cystic cerebellar heman-gioblastomas (Fig. 8-13-4),25 which occur in about 40% o aectedindividuals by the age o 30 years and in about 70% o them by theage o 60 years.23 The component cells in these tumors appear benignby histopathological criteria. Similar vascular lesions also occur in themedulla and spinal cord in 1015% o patients who have VHLS.

Renal cell carcinoma is an acquired malignant neoplasm o the kid-ney that occurs in about 5% o VHLS patients by the age o 30 years butin > 40% by the age o 60 years.23 The renal cell carcinomas that occurin VHLS are bilateral in approximately 75% o cases. 23 This tumor canmetastasize, so it must be recognized early and treated aggressively i a

atal outcome is to be avoided. Other visceral neoplasms that developin some patients who have VHLS include pheochromocytoma, isletcell carcinoma o the pancreas, and cyst-adenomas o the pancreas andepididymis.23 Also, those aected by VHLS have a strong tendency todevelop multiocal cysts in the kidneys, pancreas, and ovaries.23 UnlikeNF and TS, VHLS does not have dermatological lesions as part o thesyndrome.


The classic ocular lesion o VHLS is the retinal capillary hemangioma,which is described in detail in Chapter 8.10. Approximately 5060%o patients who have VHLS develop retinal capillary hemangiomatosisduring their lietimes, and about one hal o these individuals havemultiple retinal capillary hemangiomas in both eyes.26

SYSTEMIC EVALUATION

As a result o the requency and severity o the various multiorganlesions in VHLS, a comprehensive protocol o periodic re-examinationand ancillary testing o aected patients and at-risk relatives in identi-ed VHLS amilies has been developed (Box 8-13-3).

A challenging clinical situation occurs in patients who have asingle retinal capillary hemangioma, a single CNS hemangioblastoma,or renal cell carcinoma and no amily history o VHLS at the time o

initial diagnosis. More aggressive baseline evaluation and ollow-up areprobably appropriate or such patients who present with CNS or retinalvascular lesion or kidney tumor early in lie than or those who have alesion rst detected at age 40 years or older.

First- and second-degree relatives o patients with VHLS are at riskor VHLS. The only way to determine with certainty whether someone

has VHLS is through DNA testing. This testing is perormed on blood,which must be processed at a clinical testing laboratory that has thenecessary equipment and appropriate DNA probes. A list o clinicallaboratories that oer genetic testing or VHLS is currently available onthe Internet athttp://www.vhl.org/healthcare/dna-src.htm.

TREATMENT

Signs and symptoms o VHLS and the necessity or treatment depend

on the nature o the lesion, the location and size o the lesions, and thesymptoms that result. Treatment o retinal capillary hemangiomas iscovered in Chapter 8.10. Treatment o the CNS and visceral lesions othis disease is generally surgical and is beyond the scope o this book.

COURSE AND OUTCOME

Progression o retinal capillary hemangiomas in VHLS is highly vari-able, but tumor enlargement, intraretinal and intravitreal bleeding,exudation, gliosis, and retinal detachment may develop. These com-plications can result in proound visual loss or even phthisis bulbio one or both eyes. Fortunately, ophthalmic treatment is usually

able to preserve good vision in at least one eye. I the associatedrenal tumors and intracranial vascular tumors are not detected atan early stage or are not controlled by aggressive intervention, theycommonly prove atal to the aected individuals.23, 25 Consequently,the lie expectancy o patients who have VHLS is reduced consider-ably compared with that o unaected persons in the general popula-tion. The median age at death in patients who have VHLS is 4550years in most ser ies.23

STURGE-wEBER SYNDROME

INTRODUCTIONSWS is a dermato-oculo-neural syndrome characterized by cutaneousacial nevus fammeus in the distribution o the branches o the trigemi-nal nerve, ipsilateral diuse cavernous hemangioma o the choroid, andipsilateral meningeal hemangiomatosis. The lesions in the eye, skin,and brain are always present at birth (i.e., they are birthmarks or con-genital anomalies rather than acquired neoplasms such as those thatoccur in the three syndromes already covered in this chapter).


The requency o the complete SWS and its formes fruste is unknown.

Men and women appear to be aected equally. No recognized racialpredilection occurs. The vast majority o patients aected by SWS havesporadic nonamilial disease. Only a ew amilial clusters o the syn-drome have been reported, and most o these have not exhibited theclear-cut autosomal dominant inheritance pattern that typies NF, TS,and VHLS.

Fig. 8134 Computedtomography o cerebellar hemangioblastomain von HippelLindau

syndrome. Note cysticlesion in cerebellum andincreased intraocular den-sity isilaterally (related toadvanced retinal caillaryhemangiomatosis caus-ing hthisis bulbi).

BOX 8-13-3 SCREENING PROTOCOL FORVON HIPPEL-LINDAU SYNDROME

AFFECTED PATIENTS

Annual hysical examinationAnnual comrehensive undus examinationMagnetic resonance imaging o brain and sinal cord every 3 years to

age 50 years and every 5 years thereaterAnnual renal ultrasound scan, with comuted tomograhy scan every

3 years (more requently i multile renal cysts are resent)Annual 24-hour urine collection o vanillylmandelic acid

AT RISK RELATIVES

Annual hysical examinationAnnual comrehensive undus examination rom age 5 yearsMagnetic resonance imaging o brain and sinal cord every 3 years

rom age 15 to 50 years and then every 5 years until age 60 years

Annual renal ultrasound scan, with comuted tomograhy scan every3 years rom age 20 through 65 years

Annual 24-hour urine collection or vanillylmandelic acid
http://www.vhl.org/healthcare/dna-src.htmhttp://www.vhl.org/healthcare/dna-src.htm


5/6

8.13

941

phakomatoses


The classical cutaneous eature o SWS is the acial nevus fammeus (Fig.8-13-5), a fat to moderately thick zone o dilated telangiectatic cutane-ous capillaries lined by a single layer o endothelial cells in the dermis.27The lesion is usually unilateral and most requently involves the regionso the ace innervated by the rst, occasionally the rst and second, andrarely all three branches o the trigeminal nerve. The ipsilateral nasaland buccal mucosa is involved in some patients, and localized hyper-

trophy o the involved tissues may be present. The characteristic CNSmaniestation o SWS is ipsilateral leptomeningeal hemangiomatosis,which causes atrophy o the cortical parenchyma o the brain, seizures,and requently mental retardation.28 The CNS lesions are present atbirth and are detectable by MRI or CT.29 They tend to be progressivethroughout lie. In many patients, the aected meninges become irregu-larly calcied during lie, in which case the CNS vascular lesion can bedetected on routine skull radiographs.


The classical ocular maniestation o SWS is the diuse choroidal hem-

angioma, which is described in detail in Chapter 8.7. Other ocular ab-normalities that have been described in patients who have SWS includetelangiectasia o the conjunctiva and episclera (Fig. 8-13-6) and ipsilat-eral congenital, inantile, or juvenile glaucoma.27 These eatures andtheir potential sequelae are also discussed in Chapter 8.7.

SYSTEMIC EVALUATION

Because patients aected by SWS do not have any recognized propensityto develop benign or malignant neoplasms, they do not require periodicsystemic or CNS screening tests or such lesions. However, patientswho have SWS and develop seizures or progressive mental deteriorationprobably need periodic neurological evaluation and intermittent evalua-tion by CT or MRI o the brain to rule out treatable lesions or disorders.

Regular ophthalmological evaluations are appropriate in all patientswho have suspected or conrmed SWS to screen or treatable ocularcomplications such as glaucoma and exudative retinal detachment.

TREATMENT

Treatment o patients who have SWS is generally symptomatic and di-rected toward complications caused by the vascular lesions o the brainand eyes. Seizures are treated medically unless that therapy proves un-

successul. Intractable seizures and progressive mental deterioration aresometimes treated surgically by techniques such as subtotal hemispher-ectomy.30 The acial nevus fammeus can be treated by dermatologicallaser therapy. This treatment requently results in marked regression othe vascular birthmark and substantial cosmetic improvement. Treat-ment o the ophthalmic lesions and complications o SWS are discussedin Chapter 8.7.

COURSE AND OUTCOME

The lie expectancy o patients who have SWS appears to be reducedsubstantially compared with that o persons in the general popula-

tion.31

However, most early deaths occur in individuals who have pro-ound mental retardation and intractable seizures and not in those whohave a limited orm o the disease, normal intellectual ability, and noseizures.

wYBURN-MASON SYNDROME

INTRODUCTION

WMS is characterized by arteriovenous malormations (AVMs) othe retina and ipsilateral CNS. Because the abnormal lesions are notdistinct tumors but rather anomalous arteriovenous communications,this syndrome is not a true phakomatosis by the denition used herein.Furthermore, most patients who have WMS have unilateral, nonamil-ial disease. A hereditary pattern has not been identied.


This syndrome is very uncommon. The retinal and intracranial AVMso WMS are congenital. However, they are usually incompletely devel-oped at birth but progress during growth and aging.32, 33 Consequently,the vascular malormations in the retina and CNS are oten undetecteduntil the second through ourth decades o lie. The more extensivethe congenital vascular lesions, the earlier the presentation in most

patients. Men and women appear to be aected equally. No racial predi-lection occurs. No hereditary pattern has been identied.34


Complex AVMs occur in the orbit, in the periorbital sot tissues andbones, and in the midbrain ipsilateral to the retinal AVM. 33, 34 Notall patients who have a retinal AVM have or develop extraretinal

Fig. 8136 Episcleraltelangiectasis ipsilateralto acial nevus ammeusand difuse choroidalhemangioma in apatient ith Sturgeweber syndrome.

Fig. 8137 Complex arteriovenousmalormation o retinain a young omanith wyburnMasonsyndrome.

Fig. 8135 Facialnevus ammeus in apatient ith Sturgeweber syndrome.


6/6

8

942

INTRAOCU

LARTUMORS

AVMs, and only the patients who have both retinal and CNS AVMsshould be considered to have WMS. In general, the more complex theretinal vascular anomalies, the higher the likelihood o associatedCNS AVMs.34


The classic ophthalmic abnormality o WMS is the AVM o the retina(Fig. 8-13-7).

SYSTEMIC EVALUATION

Baseline assessment o patients who have a complex retinal AVMshould probably include MRI and possibly magnetic resonanceangiography o the ipsilateral orbit and brain.35 Such investigationis probably not indicated in patients who have small, limited reti-nal AVMs unless they have neurological symptoms. Currently, no

consensus exists about what constitutes appropriate ollow-up oaected patients.

TREATMENT

No eective treatment is currently available or retinal AVM. Complex,symptomatic intracranial AVMs can sometimes be managed eec-tively by intracranial resection, arterial ligation, arterial embolization,36stereotactic radiosurgery,37 or charged particle beam irradiation.

COURSE AND OUTCOME

Lie expectancy is reduced in patients who have WMS because o earlydeaths attributable to spontaneous bleeding rom the intracranialAVMs38 and strokes related to their treatment. In addition, the aectedeye is sometimes blinded as a result o spontaneous or post-therapeuticocclusion o the retinal AVM.

REFERENCES

1. Riccardi VM. Neurobromatosis: ast, resent, anduture. N Engl J Med. 1991;324:2835.

2. North K. Neurobromatosis tye 1: review o the rst200 atients in an Australian clinic. J Child Neurol.1993;8:395402.

3. OConnell p, Cawthon R, Xu GF, et al.The neurobro-matosis tye 1 (NF1) gene: identication and artialcharacterization o a utative tumor suressor gene.J Dermatol. 1992;19:8814.

4. MacCollin M, Mohney T, Troatter J, et al. DNA diagnosiso neurobromatosis 2. Altered coding sequence othe merlin tumor suressor in an extended edigree.

JAMA. 1993;170:231620.5. Guttmann DH, Aylsworth A, Carey JC,et al.The diag-nostic evaluation and multidiscilinary managemento neurobromatosis 1 and neurobromatosis 2. JAMA.1997;278:517.

6. Crowe FW. Axillary reckling as a diagnostic aid in neuro-bromatosis. Ann Intern Med. 1964;61:11423.

7. Huson S, Jones D, Beck L. Ohthalmic maniestations oneurobromatosis. Br J Ohthalmol. 1987;71:2358.

8. Destro M, DAmico DJ, Gragoudas ES, et al. Retinalmaniestations o neurobromatosis. Arch Ohthalmol.1991;109:6626.

9. Lewis RL, Riccardi VM. von Recklinghausen neurobro-matosis. Incidence o iris hamartomata. Ohthalmology.1981;88:34854.

10. Lewis RL, Gerson Lp, Axelson KA,et al. von Recklinghau-sen neurobromatosis. II. Incidence o otic gliomata.Ohthalmology. 1984;91:92935.

11. Wiznia RA, Freedman JK, Mancini AD, et al. Malignantmelanoma o choroid in neurobromatosis. Am J Oh-thalmol. 1978;86:6847.

12. Kaye LD, Rothner AD, Beaucham GR,et al. Ocularndings associated with neurobromatosis tye II.Ohthalmology. 1992;99:14249.

13. Sivalingam A, Augsburger JJ, perilongo G, et al. Com-bined hamartoma o the retina and retinal igmenteithelium in a atient with neurobromatosis tye 2.J pediatr Ohthalmol Strabismus. 1991;28:3202.

14. Zoller M, Rembeck B, Akesson HO, Angervall L. Lieexectancy, mortality and rognostic actors inneurobromatosis tye 1. A twelve-year ollow-uo an eidemiological study in Goteborg, Sweden.Acta Derm Venereol. 1995;75:13640.

15. Evans DG, Huson SM, Donnai D,et al. A clinical study otye 2 neurobromatosis. Q J Med. 1992;84:60318.

16. Northru H. Tuberous sclerosis comlex: geneticasects. J Dermatol. 1992;19:9149.

17. Truhan Ap, Filiek pA. Magnetic resonance imaging. Itsrole in the neuroradiologic evaluation o neurobroma-tosis, tuberous sclerosis, and Sturge-Weber syndrome.

Arch Dermatol. 1993;129:21926.18. Webb DW, Clarke A, Fryer A, Osborne Jp. The cutaneouseatures o tuberous sclerosis: a oulation study.Br J Ohthalmol. 1996;135:15.

19. Maziak DE, Kesten S, Raaort DC, Mauer J. Extratho-racic angiomyoliomas in lymhangioleiomyomatosis.Eur Res J. 1996;9:4025.

20. Nyboer JH, Robertson DM, Gomez MR. Retinal lesions intuberous sclerosis. Arch Ohthalmol. 1976;94:127780.

21. Roach ES, Smith M, Huttenlocher p, et al. Diagnosticcriteria: tuberous sclerosis comlex. Reort o theDiagnostic Criteria Committee o the National TuberousSclerosis Association. J Child Neurol. 1992;7:22134.

22. Sheherd CW, Gomez MR, Lie JT, Crowson CS. Causeso death in atients with tuberous sclerosis. Mayo Clinproc. 1991;66:7926.

23. Maher ER, Yates JR, Harries R, et al. Clinical eatures andnatural history o von Hiel-Lindau disease. Q J Med.1990;77:115163.

24. Glenn GM, Linehan WM, Hosoe S, et al. Screening or vonHiel-Lindau disease by DNA olymorhism analysis.JAMA. 1992;267:122636.

25. Neumann Hp, Eggert HR, Scheremet R, et al. Centralnervous system lesions in von Hiel-Lindau syndrome.J Neurol Neurosurg psychiatry. 1992;55:898901.

26. Hardwig p, Robertson DM. von Hiel-Lindau disease.A amilial, oten lethal, multi-system hakomatosis.Ohthalmology. 1984;91:26370.

27. Sullivan TJ, Clarke Mp, Morin JD. The ocular maniesta-tions o the Sturge-Weber syndrome. J pediatr Ohthal-mol Strabismus. 1992;29:34956.

28. pascual-Castroviejo I, Diaz-Gonzalez C, Garcia-MelianRM, et al. Sturge-Weber syndrome: study o 40 atients.pediatr Neurol. 1993;9:2838.

29. Marti-Bonmati L, Menor F, poyatos C, Cortina H. Diag-nosis o Sturge-Weber syndrome: comarison o theefcacy o CT and MR imaging in 14 cases. AJR AmJ Roentgenol. 1992;158:86771.

30. Ito M, Sato K, Ohnuki A, Uto A. Sturge-Weber disease:oerative indications and surgical results. Brain Dev.

1990;12:4737.31. Oakes WJ. The natural history o atients withthe Sturge-Weber syndrome. pediatr Neurosurg.1992;18:28790.

32. Augsburger JJ, Goldberg RE, Shields JA, et al. Chang-ing aearance o retinal arteriovenous malormation.Graees Arch Clin Ex Ohthalmol. 1980;215:6570.

33. Willinsky RA, Lasjaunias p, Terbrugge K, Burrows p.Multile cerebral ar teriovenous malormations (AVMs).Review o our exerience rom 203 atients with cere-bral vascular lesions. Neuroradiology. 1990;32:20710.

34. patel U, Guta SC. Wyburn-Mason syndrome. A casereort and review o the literature. Neuroradiology.1990;31:5446.

35. Nussel F, Wegmuller H, Huber p. Comarison o magnet-ic resonance angiograhy, magnetic resonance imagingand conventional angiograhy in cerebral arteriovenousmalormation. Neuroradiology. 1991;33:5661.

36. Morgan MK, Johnston IH, de Silva M. Treatment o oh-thalmoacial-hyothalamic ar teriovenous malormation(Bonnet-Dechaume-Blanc syndrome). Case reort.J Neurosurg. 1985;63:7946.

37. Lunsord LD, Kondziolka D, Flickinger JC, et al. Stereotac-tic radiosurgery or arteriovenous malormations o thebrain. J Neurosurg. 1991;75:51224.

38. Wilkins RH. Natural history o intracranial vascular mal-ormations: a review. Neurosurgery. 1985;16:42130.

Documents

Phakomatoses Ophtalmology