Neuropathies in the setting of Neurofibromatosis tumor syndromes: Complexities and opportunities

Care of adults with neurofibromatosis type 1: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

“…It is painless in the majority of patients 109 and may arise from nerve microlesions. 110 Glomus tumors are small, benign, but painful tumors of the glomus body, a thermoregulatory shunt in the fingertips, and are part of the NF1 phenotype. 111 These tumors should not be confused with paragangliomas, which have also been called glomus tumors in the older literature.…”

Genetic Counseling for Neurofibromatosis 1, Neurofibromatosis 2, and Schwannomatosis—Practice Resource of the National Society of Genetic Counselors

“…Progressive severe pain in individuals with NF1 is less common but may be an important indicator for malignancy (MPNST) (Evans et al., 2002). Itching is also a common complaint associated with pain among those with NF1 (Schulz et al., 2018). Pain associated with NF2 is primarily neuropathic and can be independent of a tumor.…”

Dorsal root ganglia volume differentiates schwannomatosis and neurofibromatosis 2

“…Because primary sensory neuronal somata are an integral part of the afferent segment of the sensory system, alterations in DRG structure, metabolism, and function may play a crucial role in the development of areflexia and sensory loss in NF2. This hypothesis is supported by studies reporting that NF2‐related neuropathy typically involves several nerves (polyneuropathy) and affects extremities in a distal and symmetric fashion, suggesting a systemic rather than a local tumor‐dependent pathogenesis …”

“…Additional intrafascicular microlesions along peripheral nerves are considered responsible for the underlying neuropathy and appear indistinguishable between these entities, both histologically and on magnetic resonance imaging (MRI) . Therefore, there is considerable pathomorphological overlap between both diseases although genetic origins and clinical symptoms vary greatly . Whereas NF2 is mainly characterized by weakness, areflexia, and sensory loss, the most common and dominant symptom of schwannomatosis is a severe and chronic pain syndrome .…”