Neurofibromatosis type 1, also known as von Recklinghausen disease,1
is characterized by changes in pigmentation and the growth of tumours along nerves in the skin and other parts of the body. It is caused by a defect in a tumour-suppressing gene on chromosome 17q11.2. Normally the gene produces neurofibromin, a protein that regulates cellular proliferation.2
With the gene mutation, the lack of neurofibromin results in overgrowth of cells from neural crest areas in both the central nervous system (causing Schwann cell tumours on virtually every nerve) and the skin. All people who inherit a copy of the mutated gene are affected. As the pattern of inheritance is autosomal dominant, only 1 copy of the defective gene is needed to cause the condition. However, it is not necessary to have an affected parent. About 30%–50% of patients have a new mutation.
Neurofibromatosis type 2 is a much rarer form of neurofibromatosis caused by mutations in both alleles of a different tumour suppressor gene on chromosome 22q12.1.
About 1 in 3000–5000 individuals are affected by neurofibromatosis type 1, without differences related to ethnic background.3
Pigmented small macules and café-au-lait patches are often present shortly after birth, although neurofibromas are rare in early childhood. In later childhood and adolescence, both neurofibromas and pigmented lesions become common. Clinical manifestations are variable ().4
A diagnosis of neurofibromatosis type 1 is based on clinical findings. The patient should have 2 or more of the following: 6 or more café-au-lait spots of ≥ 1.5 cm in postpubertal individuals or ≥ 0.5 cm in prepubertal individuals; 2 or more neurofibromas of any type or 1 or more plexiform neurofibroma; and freckling in the underarms and groin.1
The differential diagnosis includes benign café-au-lait pigmentation (present in up to 10% of the general population), multiple lipomas, and sporadic schwannomas, gliomas and meningiomas in the central nervous system.
Most people with mild neurofibromatosis have little disability. People affected by more severe variants have a shortened life expectancy, especially if tumours of the central nervous system or other malignant neoplasms arise during the course of illness.1,3
The condition can have a serious psychological impact because the accumulation of skin nodules can be quite disfiguring.5
Surgical excision and laser treatment of the neurofibromas are possible, but neither treatment is universally effective.6
Transplantation with an allograft of composite tissue on the lower and middle parts of a patient's face was recently reported.7
Gliomas of the optic nerve are found in up to 15% of pediatric patients with neurofibromatosis type 1. Best detected using magnetic resonance imaging, these gliomas are symptomatic in about 50% of patients at diagnosis. A minority will progress to vision loss.8
The high prevalence of gliomas of the optic nerve that are asymptomatic may, however, be biased by referral patterns, Indeed, in patients with neurofibromatosis type 1, the threshold of risk for optic nerve glioma is low.9
Guidelines are available for the diagnosis and management of neurofibromatosis type 1.10,11
Physicians who identify patients with neurofibromatosis type 1 should refer them early to facilities where appropriate evaluation and monitoring of lesions can be carried out. Early detection and monitoring may help to prevent disability and death.