Phakomatoses

Neurological, ocular and cutaneous features with tendency to develop tumours especially hamartomas

Neurofibromatosis

Type 1

Commonest: mutation in neurofibromin gene (Chr17q)

• Cafe au lait spots

• Axillary freckling

• Neurofibromas

  • Plexiform neurofibromas of the upper eyelid produce a classic S-shaped deformity and carry an increased risk of glaucoma

• Bony dysplasia: absent sphenoid

• Ocular

  • Optic nerve gliomas (>2): 30% of patient with optic nerve gliomas have NF-1
  • Lisch nodules (>2) aka iris hamartomas
  • Lid neurofibroma
  • Choroidal naevi
  • Retinal astrocytoma
  • Sphenoid dysplasia can cause pulsatile proptosis
  • Prominent corneal nerves
  • Ectropion uveae

Type 2

Autosomal dominant mutation in NF2 gene on chromosome 22

• Bilateral vestibular schwannomas (deafness, tinnitus)
• Meningiomas (including optic nerve sheath)
• Cranial nerve schwannomas (including optic nerve)
• Cataracts: cortical wedge cataracts and posterior subcapsular
• Retinal hamartomas
• Combined hamartomas of the retina and RPE
• ERM
• Morning Glory Anomaly

Tuberous sclerosis

Autosomal dominant mutation of tumour suppressor gene TSC1 (hamartin) on chromosome 9 Second most common phakomatosis (after NF-1)

Clinical features

• Cortical tubers (90%)
• Subependymal nodules (80%)
• Subependymal giant cell astrocytomas (10-15%)
• Epilepsy
• Learning disability
• Autism
• Skin: ash leaf spots (hypopigmented areas best seen under Wood’s UV light), facial angiofibromas (aka adenoma sebaceum, which appear as red papules), peri/sub-ungual fibromas, shagreen patches (localised rough skin thickening)
• Rhabdomyomas
• Renal angiomyolipomas
• Ocular:retinal astrocytic hamartomas: flat, indistinct margins. Arised from glial astrocytes in the NFL. Bilateral in 30%. Do not cause visual disability.

Sturge Weber syndrome

Differs from true phakomatoses since it occurssporadically (ie. is not genetically transmitted) Tumours are present from birth

Features

• Ocular

  • Episcleral haemangioma
  • Ciliary body/iris haemangioma
  • Choroidal haemangioma (tomato ketchup fundus)
  • Glaucoma: in early years due to angle malformation, in older years due to raised episcleral pressure. 50% risk of glaucoma

• Systemic

  • Naevus flammeus
  • CNS haemangioma
    • Leptomeningeal vascular malformation which can lead to dystrophic calcification
  • Seizures or stroke-like episodes (patients must avoid contact sports)

Wyburn-Mason syndrome

Rare, sporadic, neurocutaneous disorder causing AV malformations: arteries connect to veinswithout intervening capillariesfound in

• Midbrain
• Eyes
• Orbit
• Cutaneous naevi

Clinical features

• May be asymptomatic
• Proptosis
• Ptosis
• Nerve palsies
• Vitreous haemorrhage
• Visual loss is secondary to loss of the capillary bed

Always consider neuroimaging to exclude ipsilateral intracranial, orbital or mandibular AVMs. depending on location these can be surgically resected.

Ataxic telangiectasia

The only autosomal recessive phakomatosis. Aka Louis-Bar syndrome

• Ataxia
• Conjunctival telangiectasia
• Limitation of ocular versions
• Nystagmus