Table 5 Neurodegenerative conditions that can be caused by VCP mutations. Clinical attributes were collected from GeneReviews® [283]; they may overlap for some of the VCP diseases. For most neurodegenerative diseases listed in the table, different VCP variants can serve as trigger. (See Table 4 for details on the link between individual VCP mutants and the diagnosed type of neurodegeneration.) Not determined, consistent datasets are not available
Disease; prevalence | Proportion attributed to pathogenic variants of VCP gene | Clinical features | Affected parts of the nervous system; functions impaired |
|---|---|---|---|
MSP1 (IBMPFD); prevalence approximately 1 per 300,000 [283], | > 99% | early-onset Paget disease of the bone; adult-onset proximal and distal muscle weakness; premature frontotemporal dementia; cause of death includes respiratory and cardiac failure[276, 284] | degeneration of the frontal and anterior temporal lobes; control of reasoning, personality, movement, speech, social behavior, language; marginal impact on episodic memory |
ALS; prevalence approximately ~ 2–9 per 100,000 [285] | 1–2% of familial ALS [241] (5–10% of ALS cases are familial) | upper and lower motor neuron dysfunction; rapid and progressive paralysis; disease presentation, progression, and survival highly variable; death mostly due to respiratory failure | affects brain and spinal cord; motor neurons and potentially additional areas in frontal and temporal lobes; systems outside the nervous system (bone, muscle); cognitive and/or behavioral symptoms possible |
PD; global prevalence 200 per 100,000 [286] | postural instability, tremor, rigidity, bradykinesia [286]; falls and pneumonia as major causes of death | loss of dopaminergic neurons in the substantia nigra, motor dysfunction | |
CMT2Y; prevalence < 1 per 1,000,000 [287] | peripheral neuropathy; distal muscle weakness and atrophy; distal sensory loss [289] | axonal neuropathy, non-demyelinating | |
Hereditary spastic paraplegia, SPG8; global prevalence 1 per 1,000,000 [287] | not determined | progressive lower-limb spasticity; SPG8 generally more severe than other forms of HSP [290] | not determined |
Behavioral FTD | not determined | early-onset progressive cognitive impairment; apathy; irritability; progressive speech–language impairment, culminating in mutism; bulimia; epileptic seizures | not determined |
Vacuolar tauopathy (VCPD395G) [119] | not determined | frontotemporal lobar degeneration accompanied by tau inclusions (FTLD-tau); no muscle or bone disease comorbidity [119] | tau aggregates in degenerating frontal neocortex; vacuolization in non-degenerating brain regions (i.e. visual cortex) |