In 2022, an international consensus recommendation revised the nomenclature for neurofibromatosis type 2 (NF2) and Schwannomatosis (SWN), now grouped under the umbrella term Schwannomatosis, and defined new diagnostic criteria.

This review describes the molecular criteria for diagnosis of schwannomatosis and the subsequent diagnosis strategy, while setting out the most recent advances in our understanding of the natural history, pathology, molecular biology and treatment of schwannomatosis-associated tumors, including schwannomas, meningiomas and ependymomas.

Somatic mutation screening should become a new standard for the diagnosis of NF2-, LTZTR1-, SMARCB1- and 22q-schwannomatosis to discriminate those conditions. Constitutional events in NF2-Schwannomatosis have a major influence on disease severity and justifiably motivate ongoing efforts on gene replacement therapy research. On the other hand, underlying mechanisms of disease severity and associated pain remain largely unknown in non-NF2-SWN and independent of germline mutation. Research efforts therefore focus on pain relief in ongoing trials and the discovery of new molecular mechanisms underlying schwannoma tumorigenesis/pain/neuropathies.