Phacomatoses
Dr Shylesh B Dabke
Resident
Dept of ophthalmology
KMC Mangalore
• Syndromes characterized by hamartomas of the skin, eye, central
nervous system (CNS), and other viscera are collectively called
phacomatoses.
• These disorders produce significant visual and neurologic
disturbances.
• Although most of these syndromes arise from mutations in single
genes inherited in a Mendelian pattern, some have no apparent
hereditary basis.
Includes:
Common:
 NF 1
 NF 2
 Tuberous sclerosis
 Sturge-Weber Syndrome
 Von Hipple Lindau disease
 Wyburn Mayson syndrome
Uncommon
Klipple trenaunay Weber syndrome
Louis bar syndrome
Diffuse congenital hemangiomatosis
Oculodermal melanocytosis
Basal cell nevus syndrome
Neurofibromatoses
 Neuroectodermal tumors arising within multiple organs.
 Autosomal dominant inheritance.
 Two types :1.NF1 (Von Recklinghausen’s neurofibromatosis or Peripheral
Neurofibromatoses)
2.NF2 (central or bilateral acoustic neurofibromatosis)
Neurofibromatoses 1
 The most common type of the two and the most common
autosomal dominant disorder.
 Characterized by:
* Cafe´-au-lait spots.
* Peripheral neurofibromas.
* Lisch nodules.
Ocular Findings
 Lisch nodules.
 Neurofibroma or plexiform neurofibroma of eyelid.
 Congenital glaucoma.
 Optic nerve or chiasmal gliomas.
Orbital involvement.
 Strabismus.
 Retinal abnormalities.
Uveal tract.
 Lignes grises – Hyperplastic intrastromal
nerves.
 Conjunctival hamartomas.
Neurofibromatoses 2
 CNS tumors are the major feature in NF2.
 Meningiomas, gliomas, and schwannomas are common, but
bilateral vestibular schwannomas are nearly always present.
 Ocular findings may predate the onset of symptoms.
* Characteristic: PSCO or Wedge cortical cataract
* less common findings are retinal hamartoma and combined
hamartomas of the retina and retinal pigment epithelium
Tuberous Scleroses
 Also known as Bourneville disease.
 Vogt triad: Mental retardation
Seizures
Facial angiofibromas
 Primary features of this disorder:
* Facial angiofibroma
* Ungual fibromas (multiple)
* Cortical tuber
* Subependymal nodule (giant cell astrocytoma)
* Multiple retinal astrocytomas
 Hypopigmented lesions analogous to white spots of the skin
are occasionally seen in the iris or choroid.
 Characteristic ocular manifestation of TS is the retinal
astrocytic hamartoma or Retinal Phakoma.
* Phakomas can develop anywhere in the fundus.
* Arise from astrocytes of sensory retina.
* vary in size from about half to twice the DD.
* Vision is rarely affected Significantly.
 Three types
* Type1 :Flat, soft and semitransparent lesions
Usually at posterior pole
Boundaries are grey or faint yellow
* Type 2:Elevated,nodular and solid apparing masses
Usually near disc margin and also at midperiphery
* Type 3:Border is flat, soft and transparent
Centrally elevated and nodular
Von Hippel Lindau Disease
 Autosomal dominantly inherited disorder of incomplete
penetrance manifesting both benign and malignant tumors of
many organ systems.
 Most common abnormalities are vascular tumors
(hemangioblastomas) of the retina and CNS, most often the
cerebellum.
 Retinal lesions usually become visible ophthalmoscopically
between ages 10 and 35 years, about a decade before the
peak clinical incidence of cerebellar disease.
 Tumors are multiple in the same eye in about one-third of
cases and bilateral in as many as one-half of cases.
Tumors typically occur in the peripheral fundus, but lesions
adjacent to the optic disc have also been described.
 The incipient retinal lesion appears as a minor, nonspecific
vascular anomaly or a small reddish dot in the fundus.
The lesion ultimately acquires the fully developed
appearance of a pink globular mass 1 to 3 or more disc
diameters in size.
 The hallmark of the mature tumor is a pair of markedly
dilated vessels (artery and vein) running between the lesion
and the optic disc, indicating Significant arteriovenous
shunting.
 Histopathologically, retinal angiomas - relatively well
formed capillaries - fluorescein angiography shows these
vessels to be leaky.
 Transudation of fluid into the subretinal space - lipid
accumulation, retinal detachment - loss of vision.
 Secondary degenerative changes including cataract and
glaucoma.
 Management and prognosis
* cryotherapy or laser photocoagulation(Small lesions)
* Multiple treatment sessions may be necessary
* Early diagnosis increases the likelihood of successful
treatment.
 Ocular lesions of VHL are asymptomatic prior to retinal
detachment - children known to be at risk for the disease
should undergo periodic ophthalmologic evaluation.
Cutaneous Lesions
Adenoma sebaceum
Ash leaf spots
Shagreen patch
Confetti lesions
Periangual fibroma
Sturge-Weber Syndrome
 Encephalotrigeminal angiomatosis.
 Characterstic lesions:* Cutaneous facial nevus flammeus ( in distribution of
branches of trigeminal nerve )
* Ipsilateral diffuse cavernous hemangioma choroid
* Ipsilateral meningeal hemangiomatosis
These lesions are always present at birth in affected patients
 Unique among the 4 major neurocutaneous syndromes not a genetically transmitted.
 Cutaneous Manifestations:
* Facial nevus flammeus/port wine stain
* zone of dilated telangiectatic cutaneous capillaries
* usually unilateral
 CNS Manifestations:
* Ipsilateral leptomeningeal hemangiomatosis
* Atrophy of cortical parenchyma
* Lesions present at birth, detected by MRI or CT
* Meninges become irregularly calcified, detected by
Skull radiographs
Ocular Manifestations
* Increased conjunctival vascularity commonly
produces a pinkish discoloration.
* An abnormal plexus of episcleral vessels.
 choroid is the site of the most significance - increased
numbers of well-formed choroidal vessels - bright red or
redorange color.
 Glaucoma is the most common and serious ocular
complication(70% Cases).
 Cause of elevated lOP is uncertain but is likely secondary to:
* Elevated episcleral venous pressure.
* Hyperemia of the Ciliary body with hypersecretion of
aqueous
* Or developmental anomaly of the anterior chamber
angle.
Management
 SWS glaucoma is difficult to treat, and there is no universally
accepted treatment scheme.
 Initial therapy with topical drops can be effective
 Surgery is indicated when medical treatment is inadequate.
 Adequate long-term pressure control can frequently be
achieved, although multiple operations are typically necessary.
 A particular risk of glaucoma surgery - massive intraoperative
or postoperative exudation or hemorrhage - anomalous
choroidal vessels - rapid ocular decompression.
Wyburn-Mason
Syndrome
 racemose angioma.
 noninhereditary arteriovenous malformation of the eye and
brain.
 Typically involving the optic disc or retina and the midbrain.
 Ocular manifest - unilateral and congenital.
 Lesions are not distinct tumors - Not a true phakomatoses.
 Most patients have unilateral lesions.
 Vision ranges from normal to markedly reduced in the
involved eye.
 Intraocular hemorrhage and secondary neovascular
glaucoma are possible complications.
 No treatment is indicated for primary ocular lesions.
Klippel – TrenaunayWeber syndrome
 Triad of:
* Cutaneous hemangiomas extending over the limbs.
* Varicosities in the affected limb
* Hypertrophy of bone and soft tissue.
 Ocular findings:
* Enophthalmos
* Conjunctival telangiectasia.
* Heterochromia iridis
* Iris coloboma
* Retinal varicosities
* Choroidal angiomas
Louis Bar Syndrome/Ataxia
Telangiectasia
 Recessive inherited multisystem disease
 Ocular lesions – * Bulbar conjunctival telangiectasia
* Oculomotor apraxia with Supranuclear
palsies, Nystagmus & Strabismus
 CNS – progressive ataxia in childhood
Oculodermal Melanocytosis
Aka Nevus of Ota
 Deep dermal pigmentation in distribution of first and
second divisions of Trigeminal nerve
 Ocular findings :* Hyper pigmentation of sclera,conjunctiva,cornea and iris
* Increased incidence of uveal and orbital melanomas
* Glaucoma is also reported
Diffuse congenital
hemangiomatosis
 Multiple small cutaneous hemangiomas.
 Ocular findings
* Hemangiomas of iris,conjunctiva & lid.
* Abnormal chorioretinal vasculature
* Microphthalmos
* Galucoma
* Central system hemangiomas - cortical blindness.
Basal cell nevus syndrome
Multiple skin tumors
Autosomal dominant inheritance
Most lesions are benign
Ocular findings:* Congenital cataract
* Coloboma of choroid and optic disc
* Corneal leucomata