schwannomatosis

Schwannomatosis is a rare form of neurofibromatosis characterized by the development of multiple schwannomas arising from peripheral nerves, typically without involvement of the vestibular nerve. It is distinguished from neurofibromatosis type 2 by the absence of bilateral vestibular schwannomas and other NF2-associated tumors.

Genetics and biology: most cases are inherited in an autosomal dominant pattern with variable penetrance. Recurrent mutations have been identified in SMARCB1 (INI1) and, in some families, in LZTR1. NF2 gene mutations are usually not present. Mosaicism may occur, contributing to phenotypic variability. Schwannomas originate from Schwann cells and are usually S-100 positive on pathology.

Clinical features: individuals develop two or more schwannomas along spinal, cranial, or peripheral nerves. Pain is a common and often prominent symptom, frequently neuropathic in quality; tumors may also cause numbness, weakness, or focal neurologic deficits. Cranial nerve involvement can occur but vestibular schwannomas are typically absent.

Diagnosis: the diagnosis relies on clinical criteria, imaging, and genetic testing. Magnetic resonance imaging reveals multiple schwannomas along nerves without evidence of vestibular nerve tumors. Genetic testing can identify SMARCB1 or LZTR1 mutations and helps distinguish schwannomatosis from NF2. Exclusion of NF2-related tumors and family history are considered in the evaluation.

Management and prognosis: there is no cure, and treatment focuses on symptom control and management of tumors. Options include surgical excision of symptomatic schwannomas with nerve-sparing techniques, and analgesic or neuropathic pain therapies. Regular imaging surveillance is common. The disease course is variable; pain can be disabling, but life expectancy is not necessarily reduced.

Epidemiology and research: schwannomatosis is much rarer than NF2, with ongoing research into genetic mechanisms and potential targeted therapies.