Neurofibromatosis

ICD-11

LD2D.1Z

Synonyms

Von Recklinghausen disease.

Epidemiology

Neurofibromatosis Type 1 (NF1): Prevalence 1:2,000–3,500, incidence 1:2,000-3,000 – Male:female ratio approx. 1:1.

Neurofibromatosis Type 2 (NF2): Prevalence 1:100,000, incidence 1:33,000-40,000.

Definition

Genetic disease, autosomal dominant inheritance, sporadic appearance in 43%. Neurocutaneous disease with multiple benign neurofibromas and potentially multi-organ involvement.

Aetiology & Pathogenesis

Mutations in suppressor genes.

NF1: Neurofibromin (chromosome 17q11.2).
NF2: Merlin (schwannomin) (chromosome 22q12).

Signs & Symptoms

NF1:

- Skin: café-au-lait macules (>5, larger than 1.5 cm, 86%), axillary and inguinal freckling (84%), cutaneous neurofibromas (localised, buttonhole phenomenon, 75-99%), plexiform neurofibromas (large nodular or diffuse tumors, 30%).
- Eyes: pigmented iris hamartomas (Lisch nodules) (40%)
- Skeletal system: kyphoscoliosis (25%)
- CNS: optic pathway glioma (13%)
- Other organs: hydrocephalus (3%)

NF2:
- Vestibular schwannomas (usually bilateral; 95%)
- Schwannomas on other intracranial nerves and in the spinal compartment
- Meningiomas, ependymomas, and gliomas

Localisation

Generalized.

Classification

Molecular classification
• NF1: skin findings (+/-), neurofibromas, Lisch nodules.
• NF2: bilateral acoustic schwannomas

Laboratory & other workups

Genetic analysis.

Examinations via radiological and other imaging techniques for detection of organ involvement and complications.

Dermatopathology

Cutaneous neurofibroma: Non-encapsulated proliferation of all elements of peripheral nerves.

Plexiform neurofibroma: Tumour growth within and beyond a nerve bundle.

Course

The course of the disease is not predictable. Cutaneous neurofibromas and café-au-lait macules can increase with progressing age (always benign). Plexiform neurofibromas have a potential for malignant transformation. Half of the patients with optic pathway glioma will develop visual symptoms. Long-bone dysplasia can result in pseudarthrosis.

NF1 life time risk for malignant nerve sheath tumor-associated mortality 8-13%.

Complications

Osteoporosis, learning disability, pregnancy and delivery complications, cardiovascular abnormalities, speech defects and malignant peripheral nerve sheath tumor (6%).

Diagnosis

Clinical findings, family history, genetic analysis.

Differential diagnosis

Clinical: lentigines, phakomatoses, neurofibrosarcoma.

Histopathological: Schwannoma, perineuroma, dermatofibrosarcoma protuberans.

Prevention & Therapy

Genetic counselling, excision of disturbing or painful neurofibromas.

Special

Belongs to rare diseases.

6.1.1 Neurofibromatosis