Neurofibromatosis

Neurofibromatosis 1:

• Due to a defect in the NF1 gene on chromosome 17q11 damaging neurofibromin 1

• For a diagnosis to be made, it must possess 2 of the 7 following criteria:

  • Six or more cafe-au-lait spots

    • >5mm in pre-pubertal children

    • >15mm in post-pubertal children

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  • 2 or more Lisch Nodules of the iris.

    • Seen typically from the 2nd or 3rd decade as translucent or pigmented nodules (<3mm)

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  • 2 or more neurofibromas of any type, or one plexiform neurofibroma

    • Neurofibromas appear at puberty as pedunculated and flabby nodules

      • Increases number with life, often widely distributed, internally and externally

      • Cutaneous neurofibromas are soft skin-coloured to purple nodules that may become pedunculated as they grow

      • Usually develop in late adolescence and found in vast majority of Px with NF1

      • Can have few lesions to thousands. They are benign with no risk of malignancy, but are very uncomfortable and have cosmetic disfigurement

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    • Plexiform neurofibromas present in 30% of NF1, affecting the more complex nerve plexuses and can lead to eyelid neurofibromas which can cause mechanical ptosis.

      

      • Associated with glaucoma

      • Neurofibromas infiltrate the anterior angle, leading to secondary angle closure, since the neurofibromas cause ciliary body and choroidal thickening, along with ectropion uveae and endothelialisation of angle

      • Fibrovascularisation can cause synechial angle closure and neovascular glaucoma.

      • Developmental angle abnormalities

  • Freckling in the axilla or groin

  • Optic pathway glioma

    • Represents ~70% of all ON sheath tumours; can arise within optic pathways, ON, optic tract and brainstem.

    • ~15-20% of children with NF-1 will develop an optic pathway glioma

    • A benign slow growing tumour.

    • ~30% of optic pathway glioma Px have NF1 and bilateral optic pathway gliomas are diagnostic for NF1

      

    • Children aged <6y with NF1 are most at risk

  • Distinct bony lesion

    • Bone defect in orbital wall (sphenoid), or bowing of long bones in legs. etc.

  • A 1st degree relative with NF1 with above criteria

• Choroidal Nodules

Neurofibromatosis 2:

Associated with certain clinical features:

• hearing loss/tinitius/imbalance

• Bilateral acoustic neuromas (schwannomas) from schwann cells around nerves)

• 1st degree relative with NF2 with unilateral acoustic neuroma + any 2 of the following:

  • Meningioma

  • Glioma

  • Schwannomas of other nerves

  • Early onset cataracts

  • Combined hamartoma of retina/RPE

• Ophthalmic Features:

  • Cataracts before age 30

  • Fundus lesions like hamartomas, perifoveal epiretinal membrane

  • Ocular motor problems (~10%)

  • Others like optic pathway glioma, ON sheath meningioma

Schwannomatosis (NF3):

• Benign tumour composed of Schwann cells.

• Unlike NF2, doesn't develop vestibular tumours

• Growth of multiple Schwannomas throughout body causes chronic intense pain

• Can have unilateral vestibular schwannomas sometimes, but not bilateral (NF2)