Phakomatoses or Neurocutaneous syndromes.pptx

Phakomatoses or Neurocutaneous syndromes

1. PHAKOMATOSeS Moderator : Dr. Sangeetha J Presenter : Dr. Sriraj Alapati

2. INTRODUCTION Neurocutaneous syndromes Van der Hoeve , a Dutch ophthalmologist. Group of congenital disorders with h amartomatous lesions of skin, CNS, PNS.

3. PATHOGENESIS

4. 1. NEUROFIBROMATOSIS (NF) NF-1 (Von Recklinghausen’s) NF-2 S chwannomatosis

5. Peripheral NF MC phakomatosis 1 in 3,000 Autosomal dominant NF1 gene ( Neurofibromin ) on chromosome 17 q11.2 is tumor suppressor gene. Loss of this tumor suppressor leads to uncontrolled cell proliferation. In schwann cells – neurofibromas (along course of nerves & internal organs except motor nerves). In melanocytes - café au lait macules & Lisch nodules NF-1 EPIDEMIOLOGY AND PATHOGENESIS

6. OCULAR MANIFESTATIONS I ris Lisch nodules Melanocytic hamartomas Small, dome-shaped, tan-dark brown pigmented. Inferior portion of iris Prevalence: 5 % in < 3 years age 42 % in 3-4 years age 55 % in 5-6 years age 100 % in >21 years age

7. congenital ectropion uveae Prominent corneal nerves Plexiform neurofibroma of upper eyelid ( S- shaped deformity, bag of worms ) Glaucoma ( Un common , u nilateral, congenital, angle anomoly , 50% have I/L upper li d neurofibroma & facial hemiatrophy )

8. Optic nerve gliomas Low-grade pilocytic astrocytoma U/L or B/L Fusiform enlargement of optic nerve Can affect optic chiasm Common features : DOV f/b axial proptosis, loss of colour vision, visual field defects, optic atrophy, strabismus. T2W MRI Proptosis

9. Retinal ‘corkscrew’ vessels OCT : Choroidal hyper-reflective nodules (sensitive & specific) Choroidal naevi ( drusen, halo) Choroidal melanoma : Elevated (>2mm) Orange pigment SRF/ERD Collar stud Drusen absent Halo absent

10. EXTRAOPHTHALMIC MANIFESTATIONS Café́-au-lait spots Axillary and inguinal freckling Meningiomas Cutaneous neurofibromas Plexiform neurofibromas Sphenoid bone dysplasia

11. DIAGNOSTIC CRITERIA ( At least 2 or more of 7 ) 6 or more 1 or more 2 or more ( Axillary / inguinal ) 2 or more

12. Lisch nodules do not require treatment Optic nerve glioma : Chemotherapy (vincristine or carboplastin ) Radiotherapy (not in younger children) Surgical removal (results in further visual morbidity) Plexiform neurofibromas : Surgical removal / Debulking Complete excision not possible due to infiltrative nature Recurrence TREATMENT

13. Central NF 1 in 25,000 Autosomal dominant Loss of NF 2 gene ( merlin ) on chromosome 22 q12.2 Affects schwann & leptomeningeal cells : schwannomas, meningiomas, ependymomas . NF-2 EPIDEMIOLOGY AND PATHOGENESIS OCULAR MANIFESTATIONS Axial proptosis f/b DOV OPTOCILIARY SHUNT Calcification, triple/tram track on CT PSCO ERM Retinal Hamartomas Optic nerve sheath meningioma

14. Confirmed : B/L vestibular schwannomas Probable : Family H/O of NF2 & U/L vestibular schwannoma, plus one of: Meningioma, Neurofibroma, Ependymoma, Glioma , PSCO DIAGNOSTIC CRITERIA EXTRAOPHTHALMIC MANIFESTATIONS B/L vestibular schwannomas sensorineural deafness 2. Spinal ependymoma (arise from ventricles)

15. 2. TUBEROUS SCLEROSIS (TS)

16. EPIDEMIOLOGY AND PATHOGENESIS Bourneville Disease / epiloia 1 in 10,000 Sporadic > Autosomal dominant Mutations of TSC1 ( hamartin ) on chromosome 9 q32-34 or TSC2 ( tuberin ) on chromosome 16 p13 Hamartoma of CNS, skin, retina OCULAR MANIFESTATIONS Palpebral angiofibroma Iris depigmentation

17. Retinal astrocytic hamartoma Benign lesion Don’t affect V/A (don’t involve macula/optic disc) Morphological types: Flat, smooth, translucent lesions without calcification. Opaque, elevated, multinodular, “ mulberry ” lesions with calcifications. transitional lesions OCT – moth eaten spaces FFA : prominent network of fine BV’s in superficial portion of mass during venous phase.

18. Vogt triad : epilepsy, mental retardation, adenoma sebaceum EXTRAOPHTHALMIC MANIFESTATIONS Adenoma sebaceum (facial angiofibroma) Ash leaf spots (hypopigmented macules) Shagreen patches Subungual hamartomas Paraventricular subependymal astrocytic hamartoma. Renal angiomyolipomas

19. DIAGNOSTIC CRITERIA

20. 3. VON HIPPEL–LINDAU SYNDROME (VHL)

21. EPIDEMIOLOGY AND PATHOGENESIS Retinal Angiomatosis 1 in 36,000 Autosomal dominant / sporadic Germline mutation of VHL tumor suppressor gene on chromosome 3 p 25-26 Vascular tumors (Hemangioblastomas)of retina, CNS (cerebellum). OCULAR MANIFESTATIONS Retinal capillary hemangioma (RCH) - Hemangioblastoma

22. Earliest manifestation Hallmark intraocular manifestation Round, red lesions between arteriole and venule with dilated, tortuous vessels (feeder). Peripheral / Juxtapapillary (temporal) complications : VH, ERD, TRD, NVG FA - early hyperfluorescence late leakage

23. EXTRAOPHTHALMIC MANIFESTATIONS Pheochromocytoma Pancreatic Cystadenoma RCC Cystic Cerebellar Hemangioblastoma Observation Laser photocoagulation Cryotherapy Plaque radiotherapy PPV and RD repair TREATMENT DIAGNOSTIC CRITERIA

24. 4. STURGE–WEBER SYNDROME ( sws )

25. EPIDEMIOLOGY AND PATHOGENESIS OCULAR MANIFESTATIONS Encephalotrigeminal angiomatosis 1 in 50,000 Sporadic Somatic mutation of GNAQ gene Trigeminal nerve territory (V1) “ Port-wine stain ” is associated with ipsilateral capillary-venous vascular malformation of leptomeninges. Telangiectasia of conjunctiva & episclera

26. Glaucoma: A/W I/L port-wine stain Early onset (congenital glaucoma) : Trabeculodysgenesis - Angle maldevelopment surgical : goniotomy / trabeculotomy, t rabeculectomy / glaucoma drainage device Late onset (Older patients) : Elevated episcleral pressure due to AV communication in episcleral hemanigioma ; premature aging of the trabecular meshwork Medical : aqueous suppressants, miotics

27. Choroidal hemangiomas: Diffuse or localized U/L and I/L to port-wine stain Involve posterior pole and fade into the periphery. No visual impairment Saturated red choroid - tomato ketchup appearance on fundus. B scan – diffuse highly echogenic thickening of choroid. Complications : retinal pigment atrophy, S/R haemorrhage, serous retinal detachment, CME.

28. 2 out of 3: Facial port wine birthmark Increased IOP Leptomeningeal Angiomatosis Glaucoma - medical and surgical management. PDT to treat symptomatic capillary hemangioma EXTRAOPHTHALMIC MANIFESTATIONS TREATMENT DIAGNOSTIC CRITERIA Port wine stain ( Facial nevus flammeus ) Leptomeningeal hemangioma Cerebral hemiatropy

29. 5. Ataxia Telangiectasia Louis Bar Syndrome 1 in 88,000 Autosomal recessive Mutation of ATM gene on chromosome 11 q 22-23. Conjunctival telangiectasis Abnormal eye movements: Saccadic intrusions, Oculomotor apraxia , Nystagmus, Convergence & accommodation abnormalities, Strabismus Cerebellar atrophy  with progressive ataxia Elevated levels of AFP, CA125 Absence of ATM protein on western blot.

30. Bloch Sulzberger syndrome X linked dominance Mutation of Nemo gene or IKBKG gene located on chromosome X q28 Ocular manifestations: Avascular peripheral retina Resemble ROP Absence of a foveal pit Optic nerve atrophy Retinal detachments Treatment : Photocoagulation (like ROP) 6. INCONTINENTIA PIGMENTI Stage 1:   Vesicular Stage 2:  Verrucous Stage 3:  Hyperpigmented Stage 4:  Hypopigmented 

31. 7. Wyburn Mason syndrome Racemose Angioma AVM of retina and brain 3 Groups- I : abnormal capillary plexus between artery & vein. II : direct AV anastomoses. III : dilated, tortuous vessels with no distinction between artery & vein. Complications- Intraocular Haemorrhage , NVG Skin involvement is rare

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