Chapter 65 Phakomatoses


The neurofibromatoses (NF) are diverse genetic conditions with a predisposition for tumor development. The two main types are neurofibromatosis type 1 (NF1) and type 2 (NF2).

Neurofibromatosis type 1

NF1 is a progressive disease and the final manifestations are extremely variable. Existing lesions tend to enlarge gradually and new lesions develop. The National Institutes of Health (NIH) diagnostic criteria are listed in Box 65.1.

Clinical presentation

Ocular findings are important in the NF1 diagnostic criteria (see Box 65.1), including Lisch nodules, orbital plexiform neurofibroma, sphenoid wing dysplasia, and optic nerve glioma.

Lisch nodules

Lisch nodules (melanocytic hamartomas) are dome-shaped, discrete lesions on the anterior surface of the iris or in the angle, usually bilateral. They are usually orange-brown (Fig. 65.1), appearing darker than blue irides but paler than brown irides (Fig. 65.2). Most are round and evenly distributed on the iris. Their size varies from a pinpoint to involvement of a segment of iris, sometimes confluent. In NF1, they are present in one-third of 2.5-year-olds, half of 5-year-olds, three-quarters of 15-year-olds, and almost all adults over 30.3 They occur earlier than neurofibromas and are, therefore, a useful marker for NF1. They need to be distinguished from iris nevi.

Anterior segment and uvea

Rarely, congenital glaucoma with buphthalmos occurs in NF1, often associated with an ipsilateral upper lid plexiform neurofibroma. Congenital ectropion uveae (Fig. 65.3), iris heterochromia, angle abnormalities, and posterior embryotoxon may predispose to later onset glaucoma. Cataract is not a feature of NF1. Pigmentary hamartomas (choroidal nevi) may involve the posterior uveal tract in up to 35%.

Skin, lids and orbits

Café-au-lait spots are hyperpigmented macular skin lesions, mostly present at birth and all appear by 1 year, enlarging at puberty. Common on the trunk, they are absent from the scalp, eyebrows, palms, and soles (Fig. 65.4). Histologically, there is melanocytic hyperplasia with increased pigmentation in the basal layer of the epidermis.

Neurofibromas are present in 30–50% of NF1 patients.4 They are network-like tumor growths involving multiple fascicles of nerve(s); four types are recognized (Table 65.1). The presence and growth pattern of neurofibromas is age related; in infancy and early childhood, diffuse plexiform neurofibromas are most active giving rise to cosmetic and visual problems within the orbit. Cutaneous or subcutaneous neurofibromas develop and grow fastest at puberty, the late teens, and during pregnancy. There is a lifelong risk of malignant transformation with poor prognosis for 5-year survival.5

Table 65.1 – Neurofibroma clinical features4

Neurofibroma types Location Clinical signs
Discrete cutaneous Epidermis and dermis Moves with skin, blueish tinge
Subcutaneous Deep to dermis Skin moves over, firm and rounded feel, located along peripheral nerves
Nodular plexiform Localized interdigitation with normal tissues “Bag of worms” feel (Figs 65.5, 65.6)
Diffuse plexiform Infiltrate widely and deeply Smooth, slightly irregular skin thickening

Complete surgical resection of plexiform neurofibromas is difficult due to their large size, location, local invasiveness, or involvement of critical peripheral nerves. Regrowth following subtotal resection is common. Chemotherapy is not effective. Promising clinical trials with biologic agents are underway.6

Neurofibromatosis type 2

Neurofibromatosis type 2 (NF2) affects 1 in 35 000 live births and is characterized by bilateral vestibular schwannomas, multiple central nervous system (CNS) tumors, cataracts, and retinal abnormalities. The diagnostic criteria for NF2 are shown in Box 65.2. Two patterns of presentation exist. Mild disease presents late (> 25 years), with few tumors other than bilateral vestibular schwannoma, and slow progression. Those with severe disease have onset before age 25, multiple CNS tumors (at least two of one type), and rapid progression, severe handicap or death before reproductive age. Treatment is multidisciplinary because of the complexities of the multiple and progressive lesions.7

Systemic findings

The hallmark of NF2 is bilateral vestibular schwannomas (“acoustic neuromas”) which may only be evident on gadolinium-enhanced MRI (see Fig. 65.11C ). The origin of the trigeminal nerve is another frequent intracranial site for schwannomas; they may occur on multiple cranial nerves. Anti-VEGF (vascular endothelial growth factor) therapy improves hearing and stabilizes tumor growth.8

Ocular findings

Most of the ophthalmic findings in NF2 (see Box 65.2) are congenital but may become more symptomatic over time.9 Visual loss increases morbidity since progressive bilateral hearing loss is so common in this condition.

Jun 4, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Phakomatoses

Full access? Get Clinical Tree

Get Clinical Tree app for offline access