The document defines phakomatoses as multisystem disorders that affect the central nervous system, eyes, and skin with characteristic lesions and hamartomas. Common phakomatoses include neurofibromatosis types 1 and 2, tuberous sclerosis, Von Hippel-Lindau syndrome, Sturge-Weber syndrome, and Wyburn-Mason syndrome. Neurofibromatosis type 1 is characterized by café au lait spots and Lisch nodules on the iris. Tuberous sclerosis causes retinal astrocytic hamartomas and adenoma sebaceum skin lesions. Von Hippel-Lindau syndrome features retinal capillary hemangioblastomas and central

1. DavudAhmadzada220I1-a
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