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Phakomatoses

CHRONIC — Systemic

Symptoms

  • often asymptomatic in childhood; identified via routine skin or eye exams
  • vision loss: from optic gliomas (nf1), retinal hemangioblastomas (vhl), or macular fluid (sws)
  • strabismus or eyelid deformity (s-shaped lid from plexiform neurofibroma)
  • prominent birthmarks: café-au-lait spots, port-wine stains, or ash-leaf spots
  • hearing loss, tinnitus, or vertigo (classic for nf2)
  • systemic: seizures, intellectual disability, or motor deficits

Clinical Findings

Neurofibromatosis type 1 (NF1)

  • lisch nodules: tan-brown iris hamartomas (diagnostic in ~95% of adults)
  • optic pathway gliomas: pilocytic astrocytomas of the nerve/chiasm
  • plexiform neurofibroma: "bag of worms" texture; causes s-shaped ptosis

Neurofibromatosis type 2 (NF2)

  • juvenile cataracts: posterior subcapsular or wedge-shaped cortical opacities
  • combined hamartomas of the retina and rpe; notably lacks lisch nodules

Tuberous sclerosis complex (TSC)

  • astrocytic hamartomas: "mulberry-like" calcified or semi-transparent retinal lesions

Von Hippel-Lindau (VHL)

  • retinal capillary hemangioblastomas: orange-red lesions with large "feeder" vessels

Sturge-Weber syndrome (SWS)

  • "tomato-catsup fundus": diffuse choroidal hemangioma
  • ipsilateral glaucoma and episcleral vascular anomalies

Etiology

Genetic basis

  • nf1: autosomal dominant (17q11.2); neurofibromin mutation (ras-mapk pathway)
  • nf2: autosomal dominant (22q12); merlin/schwannomin mutation
  • tsc: autosomal dominant; tsc1 (hamartin) or tsc2 (tuberin) mutations
  • vhl: autosomal dominant (3p25.3); vhl tumor suppressor gene mutation
  • sws: sporadic somatic mutation (gnaq); mosaicism, not inherited

Red Flags

  • retinal capillary hemangioblastoma (vhl): heralds life-threatening renal cell carcinoma and pheochromocytoma
  • port-wine stain (v1 distribution): indicates high risk for ipsilateral glaucoma and brain angiomas
  • optic pathway glioma (opg): requires urgent neuro-oncology monitoring to save vision
  • hypertension in vhl: must rule out pheochromocytoma before any surgery

Investigations

Ocular assessment

  • slit-lamp (lisch nodules) and gonioscopy (angle anomalies/vascularity)
  • dilated fundoscopy: specifically looking for peripheral hemangiomas or calcified hamartomas

Neuro-imaging

  • mri brain/orbits with contrast: identify gliomas, schwannomas, or calcifications

Systemic screening

  • abdominal ct/mri: screen for renal tumors (vhl/tsc) and adrenal lesions
  • skin exam: wood lamp for "ash-leaf" spots in tuberous sclerosis

Treatment

Glaucoma (NF1/SWS)

  • topical medical therapy (beta-blockers/pgas); caution with surgery in sws (risk of choroidal effusion)

Retinal/choroidal lesions

  • vhl: laser photocoagulation or cryotherapy for capillary hemangioblastomas
  • sws: photodynamic therapy (pdt) or plaque radiotherapy for exudative hemangiomas

Optic glioma (NF1)

  • observation; chemotherapy (carboplatin) or mek inhibitors if vision or mri progresses

Systemic

  • surgical excision of neurofibromas; treatment of seizures in tsc/sws

Clinical Pearl

the "skin is a window to the eye and brain" in phakomatoses — café-au-lait spots, port-wine stains, adenoma sebaceum, and ash-leaf spots each point to a syndrome with predictable ocular and systemic complications.

Differential Diagnosis

  • • retinoblastoma (can mimic calcified hamartomas)
  • • coats disease (mimics exudative hemangiomas)
  • • familial exudative vitreoretinopathy (fevr)
  • • idiopathic choroidal hemangioma

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