My Colleague Dr.Sindhuja murugesan's presentation PG resident MS ophthalmology .

1. D R . S I N D H U J A M U R U G E S A N
PHAKOMATOSES

2. DEFINITION
 Coined by van der Hoeve.
 No satisfactory definition present.
 Phakomatoses (or neuro-oculo-cutaneous
syndromes, neurocutaneous disorders) are multisystem
disorders that have characteristic CNS, ocular, and cutaneous
lesions/hamartomas of variable severity.

3. Common syndromes
 Neurofibromatosis type 1
 Neurofibromatosis type 2
 Tuberous sclerosis
 Von Hippel-Lindau syndrome
 Sturge Weber syndrome
 Wyburn-Mason syndrome

4. Uncommon syndromes
 Klipple trenaunay Weber syndrome
 Louis bar syndrome
 Diffuse congenital hemangiomatosis
 Oculodermal melanocytosis
 Basal cell naevus syndrome

5. NEUROFIBROMATOSIS TYPE 1
 Also known as peripheral NF, von Recklinghausen’s disease.
 Neuroectodermal tumors with autosomal dominant
inheritance.
 1 person per 3500–4000 persons in the general population.
 Men and women equally affected.
 No racial predilection.
 The gene for NF-1 has been localized to chromosome 17q11.

7. OCULAR MANIFESTATIONS
 Lignes grises – intrastromal hyperplastic nerves.
 Subcutaneous pedunculated and plexiform neurofibromas
of the eyelids

8.  Lisch nodules : melanocytic hamartomas of the iris stroma.
 Tan to light brown nodules that stud the iris surface.
 Histopathologically - closely packed dendritic or spindle-
shaped melanocytes within the anterior layers of iris stroma.
These cells are normal uveal melanocytes and not nevus cells.

9.  Optic nerve gliomas : 10-15% cases.
 Unilateral or bilateral
 Frequently involves optic chiasma
 In the orbit cause progressive proptosis and optic atrophy.

10.  Choroidal naevi : Increased risk of developing
choroidal melanoma
 Retinal astrocytic hamartomas are common.

11.  Glaucoma :

12. EXTRAOCULAR MANIFESTATIONS
 Café au lait spots - Six or more café-au-lait spots
larger than 1.5cm in diameter in postpubertal
individuals are generally considered diagnostic of
NF-1.

13.  Axillary or inguinal freckling – 90-95% of the cases.
 Subcutaneous or neurological plexiform
neurofibromas.
 Sphenoid wing dysplasia, Lamboid suture defects.

14. NEUROFIBROMATOSIS TYPE 2
 1 person per 40000–50000 persons
 localized to chromosome 22q12.
 bilateral vestibular schwannomas (acoustic neuromas) and
widely scattered neurofibromas, meningiomas, gliomas, and
schwannomas.

15.  Ophthalmologic findings in NF-2 are relatively
uncommon.
 Combined hamartomas of the retina and juvenile
posterior subcapsular or cortical lens opacities.

17. TUBEROUS SCLEROSIS
 Multiorgan tumor syndrome
 Multifocal, bilateral retinal astrocytic hamartomas,
astrocytic tumors of the CNS, several unusual
cutaneous lesions, mental retardation, seizures, and
a variety of cysts and tumors of other organs.

18.  1 case per 10000 persons
 one third of cases are familial and two thirds are sporadic.
 No racial predilection
 Sexes are affected equally.
 Signs and symptoms begin by the time the patient is 6 years of
age.
 Loci on the long arm of chromosome 9 (9q32-34), on the long
arm of chromosome 11, on the short arm of chromosome 16
(16p13), and on the long arm of chromosome 12 (12q22-24).

19. OCULAR MANIFESTATIONS
 Astrocytic hamartomas : 50% of the patients develop retinal
astrocytoma in atleast one eye.
 Histologically – composed of felt-like network of atypical
astrocytes and small blood vessels located in the superficial layers.
 Vision loss occurs when the papillomacular bundle is affected.

20. CUTANEOUS LESIONS
 Adenoma sebaceum : unusual facial dermatological
eruption characterized by pinhead to pea-sized yellowish
to reddish-brown papules distributed in a butterfly
fashion over the nose, cheeks, and nasolabial folds.

21.  Ash leaf spots – hypopigmented macula better seen under UV
light.
 Shagreen patch - thickened patch of skin with the texture of
pigskin or sharkskin and usually occurs over the lower back.

22.  Common visceral tumor in TS appears to be the
angiomyolipoma of the kidney.
 Probably the most distinctive visceral tumor-
rhabdomyoma.

23. STURGE WEBER SYNDROME
 Dermato-oculo-neural syndrome.
 Cutaneous facial nevus flammeus in the distribution of
the branches of the trigeminal nerve
 Ipsilateral diffuse cavernous hemangioma of the choroid
 Ipsilateral meningeal hemangiomatosis.
 The lesions in the eye, skin, and brain are always present
at birth

24.  Sporadic nonfamilial disease.
 No racial prediliction
 Men and female affected equally.

25. OCULAR MANIFESTATIONS
 Telangiectasia of the conjunctiva and episclera.
 Diffuse choroidal hemangioma – occurs in 50% of
patients. Associated with choroidal thickening and
retinal detachment.

26.  Glaucoma : Occurs in 30 to 70 % Bilateral glaucoma can occur in the
presence of bilateral facial hemangiomas.
 Mechanisms of glaucoma - Developmental anomaly of the
anterior chamber angle and elevated episcleral venous pressure,
each of which leads to aqueous outflow obstruction.
 Clinical and histopathological features of the drainage angle in SWS
are similar to those seen in primary congenital glaucoma.
 On gonioscopy, the angle structures appear indistinct, with a high
iris insertion. An anteriorly displaced iris root, poorly developed
scleral spur, and thickened uveal meshwork have been observed.

27. CUTANEOUS MANIESTATIONS
 Facial nevus flammeus, a flat to moderately thick zone of dilated
telangiectatic cutaneous capillaries lined by a single layer of endothelial
cells in the dermis.
 Unilateral.
 Involves the regions of the face innervated by the first branch of the
trigeminal nerve.

28. CNS MANIFESTATTIONS
 Ipsilateral leptomeningeal hemangiomatosis, which
causes atrophy of the cortical parenchyma of the
brain, seizures, and frequently mental retardation.
 Present at birth and are detectable by MRI or CT.
 Progressive throughout life.

29. VON HIPPLE LINDAU DISEASE
 Characterized by :
 Retinal capillary hemangiomas,
 CNS hemangioblastomas,
 Solid and cystic visceral hamartomas
 Renal cell carcinomas
 Pheochromocytomas.

30.  Capillary hemangiomas of the retina-earliest detected
manifestation
 The cumulative probability of developing retinal capillary
hemangiomas and CNS hemangioblastomas in a patient who
has VHLS is >80%, and the probability of developing renal
cell carcinoma is >60%.
 Autosomal dominant inheritance pattern
 The median age at detection is 20–25 years
 VHLS gene to chromosome 3p25-26

31. OCULAR MANIFESTATTIONS
 Retinal capillary hemangioblastoma
commonly seen in 60% patients
 Peripheral lesions hav subtle red hue
and are no larger than a few hundred
microns.
 As the proliferation continues, acquire
a more nodular appearance with
marked dilated and engorged afferent
and efferent blood vessels.
 Retinal edema and hard exudates.

32.  Juxtapapillary lesions,11-15% of cases, can cause
pseudopapilledema from elevation and exudation around
the optic nerve .

33.  A classic diagnostic finding - dilated, tortuous vessels
leading to and away of the vascular tumor.
 FFA - shows early leakage and marked hyperfluorescence.

34. EXTRAOCULAR MANIFESTATIONS
 Solid and cystic cerebellar hemangioblastomas.
 CNS hemangioblastomas,
 Solid and cystic visceral hamartomas
 Renal cell carcinomas( 5% by age of 30 years but >40% by age of
60 years)
 Pheochromocytomas.

36.  Differential diagnosis for retinal capillary
hemangioblastomas :
 Coat's disease
 Retinal Cavernous Hemangioma
 Retinal Macroaneurysm

37.  Visual loss due to RCH:
 Exudation : increase in capillary tumor vasopermeablity leading to
macular edema or exudative retinal detachment.
 Tractional effects : glial proliferation on the surface of the tumor
may induce retinal striae & distortion or even tractional retinal
detachment
 Vitreous Hemorrhage : from rupture and bleeding of the RCH into
the vitreous cavity
 Neovascular glaucoma : leaking of angiogenic factors, such as
VEGF, to the anterior chamber causing neovascularization of the angle.

38. WYBURN MASON SYNDROME
 Arteriovenous malformations (AVMs) of the retina and
ipsilateral CNS.
 Abnormal lesions are not distinct tumors but anomalous
arteriovenous communications, hence not a true
phakomatoses.
 The retinal and intracranial AVMs are congenital.
 Incompletely developed at birth but progress during growth
and aging.

40.  Occur in the orbit, in the periorbital soft tissues and
bones, and in the midbrain ipsilateral to the retinal AVM.
 More complex the retinal vascular anomalies, the higher
the likelihood of associated CNS AVMs.

41. Klipple - trenaunay Weber syndrome
 Triad of cutaneous hemangioma, varicosities in the
lower limb, hypertrophy of the bone and soft tissue.
 Ocular findings :
 Enophthalmos
 Cojunctival telangiectasia
 Heterochromia iridis
 Iris coloboma
 Choroidal angiomas

42. LOUIS BAR SYNDROME
 Recessive inherited multisystem
 Ocular findings : Bulbar conjunctival telangiectesia,
strabismus, nystagmus
 Progressive ataxia of childhood.

43. OCULODERMAL MELANOCYTOSIS