Neurofibromatosis

Neurofibromatosis refers to a group of genetic disorders characterized by tumor growth on nerves and various skin and systemic features. The major forms are neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis. All are inherited in an autosomal dominant pattern, though many cases arise from new mutations, and the clinical presentation can vary widely even within families.

NF1 is caused by mutations in the NF1 gene on chromosome 17, which encodes neurofibromin, a tumor suppressor that regulates cell growth. Common features include multiple café-au-lait macules, freckling in the armpits or groin, and cutaneous neurofibromas. Other findings may include plexiform neurofibromas, Lisch nodules in the iris, optic pathway gliomas, skeletal abnormalities, and learning difficulties. Diagnosis is based on clinical criteria, such as the presence of six or more café-au-lait spots, two or more neurofibromas (or one plexiform neurofibroma), axillary/inguinal freckling, Lisch nodules, optic glioma, distinctive bone lesions, or a first-degree relative with NF1. Regular monitoring for tumor development and vision, blood pressure, and learning issues is recommended.

NF2 results from mutations in the NF2 gene on chromosome 22, which encodes the merlin protein. It predominantly affects the nervous system, with bilateral vestibular schwannomas causing hearing loss and imbalance. Other tumors include meningiomas and ependymomas. Diagnosis relies on clinical features and MRI findings; management focuses on preserving function and controlling tumors, often through surgery or radiotherapy and regular surveillance.

Schwannomatosis is characterized by multiple non-vestibular schwannomas and the absence of vestibular schwannomas. Some families harbor mutations in SMARCB1 or LZTR1. Pain is a common symptom, and treatment is individualized, ranging from surgical removal of symptomatic tumors to pain management.

Prognosis and care require multidisciplinary genetic counseling and individualized surveillance, as disease course and complications vary by type.