What are the key clinical features that differentiate Neurofibromatosis Type 1 (NF1) from Neurofibromatosis Type 2 (NF2)?

Neurofibromatosis Type 1 (NF1) primarily presents with multiple café-au-lait macules, axillary or inguinal freckling, Lisch nodules (iris hamartomas), and cutaneous neurofibromas. It often manifests in childhood with these skin features and may include skeletal abnormalities and learning difficulties. NF1 is caused by mutations in the NF1 gene and is characterised by a wide phenotypic variability. Tumours in NF1 are typically benign neurofibromas arising from peripheral nerves.

Neurofibromatosis Type 2 (NF2), in contrast, is characterised by bilateral vestibular schwannomas (acoustic neuromas) leading to hearing loss, tinnitus, and balance problems, usually presenting in young adulthood. Other features include meningiomas, ependymomas, and cataracts. NF2 results from mutations in the NF2 gene and is primarily a disorder of the central nervous system tumours rather than cutaneous manifestations.

Key differentiating clinical features include the presence of multiple café-au-lait spots and cutaneous neurofibromas in NF1, which are absent in NF2. Conversely, bilateral vestibular schwannomas and central nervous system tumours are hallmark features of NF2 but not NF1. Lisch nodules are specific to NF1, while early-onset cataracts are more typical of NF2. The age of onset also differs, with NF1 often diagnosed in childhood and NF2 in adolescence or early adulthood.

Thus, the clinical diagnosis hinges on skin findings and peripheral nerve tumours for NF1, versus bilateral vestibular schwannomas and CNS tumours for NF2 ¹ (Gutmann et al., 2017; Evans, 2009; Kehrer-Sawatzki and Cooper, 2022).