Description

The phakomatoses are syndromes involving hamartomas and neoplasms throughout the body, particularly of the nervous system and skin. The neurofibromatoses are the most common of these syndromes. There are two main types, Type 1 (von Recklinghausen’s disease, NF1) being the most common. The affected gene, on chromosome 17, encodes neurofibromin, which is heavily expressed in neural tissue. Inheritance is autosomal dominant.

Symptoms

Skin changes may be of cosmetic concern. Neurofibromas may cause itch or pain.

Signs – General

  • Dermatological signs include abnormal pigmentation with café-au-lait (‘milk-coffee’) spots and axillary freckling: Café-au-lait patches are benign, flat, light-brown patches up to several centimeters in size. Axillary freckles, when present, are pathognomonic of NF1.
  • Cutaneous or subcutaneous neurofibromas are well-delineated nerve sheath tumors. They may become large and pedunculated (fibroma molluscum). Plexiform neurofibromas are less well-defined lesions that often merge with surrounding tissues and can become malignant. A neurofibroma or plexiform neuroma of the eyelid may be associated with glaucoma.
  • Skeletal growth abnormalities include bone dysplasia, scoliosis and facial hemiatrophy. Cognitive impairment and epilepsy are common.
  • Phaeochromocytoma, gastrointestinal and genitourinary malignancies are also possible.

Signs – Ocular

  • Lisch nodules occur in over 95 percent of NF1 patients, and are a highly sensitive and specific sign. The nodules are pigmented iris hamartomas that appear as light-brown, smooth, dome-shaped nodules on the surface of the iris. They are important diagnostically, since they usually appear during childhood, before the development of cutaneous neurofibromas.
  • Gliomas of the optic nerve or optic chiasm may develop. These neoplasms are usually non-progressive, but may cause proptosis or visual impairment. Retinal astrocytomas occur rarely (images: see Neurofibromatosis type 2).
  • Proptosis or diplopia may also be caused by orbital tumors or by a bony defect in the orbit. The latter condition characteristically produces a pulsating enophthalmos.
  • Choroidal nevi are common.
  • Glaucoma is rare, and usually unilateral and congenital. It appears to result from abnormal development of aqueous drainage channels, or from obstruction by neurofibromas and is associated with an ipsilateral neurofibroma of the upper eyelid or facial hemiatrophy.

Incidence

One of the more common genetic disorders (prevalence of 1 in 3000).

Significance

Clinicians must bear in mind the diverse range of potential malignancies when these patients present with new symptoms or signs in any organ system.

Differential Diagnosis

Tuberous sclerosis

See Also

Neurofibromatosis Type 2, Glaucoma – classification, Choroidal Nevus

Management

Genetics

On average, patients will transmit the disease to half of their children. The manifestations and severity of disease cannot be predicted.

Referral

The patient may require neurological, dermatological, surgical and ophthalmological input. Thorough neurological examination at regular intervals is appropriate.

Additional investigations

Suspected central nervous system tumors are investigated with computed tomography (CT) or magnetic resonance imaging (MRI). Some clinicians advocate cerebral and orbital MRI of all children with NF1 in order to identify a possibly quiescent optic nerve glioma. Assessment of visual evoked potentials is useful in assessing optic nerve function.

Surgery

The treatment of optic nerve gliomas is controversial. Lesions are usually observed if there is little or no visual loss. The surgical management of plexiform neurofibromas is often difficult. Their tendency to infiltrate important adjacent tissues, including major nerve trunks, often precludes complete removal.

Review

Skin and eye lesions are best reviewed every 6 to 12 months. Infants with plexiform neurofibroma of the eyelid require more frequent review, as 50 percent develop early-onset glaucoma. eye may become involved at any time, even decades after the initial episode

Figure 1.

Lisch nodules

Figure 2.

Eyelid plexiform neurofibroma

Neurofibromatosis Type 1