Phakomatoses ppt

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

1. Dr. Sindhuja murugesan 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.

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

7. 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.

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

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

10. Glaucoma :

11. 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.

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

13. 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 .

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

15. 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.

16. 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).

17. 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.

18. 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.

19. 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.

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

21. 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

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

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

24. Glaucoma : Occurs in 30 to 70 % Bilateral glaucoma can occur in the presence of bilateral facial hemangiomas . Mechanisms of glaucoma - D evelopmental 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.

25. 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.

26. 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.

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

28. 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

29. 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.

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

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

32. 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 .

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

34. 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.

35. 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.

36. 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.

37. 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

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

39. OCULODERMAL MELANOCYTOSIS