Table 1.

Clinical manifestations of VCP MSP

Phenotype	System affected	Clinical features	Frequency in VCP patients
Inclusion body myopathy	Muscle	Axial and proximal weakness progressing distally is most common, although presentations resembling facioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, and distal myopathy have been described	~ 90%
Paget disease of bone (PDB)	Skeletal	Bone pain, bone deformities, pathological fractures, hearing loss	~ 40%
Frontotemporal dementia (FTD)	Cognitive	Rapidly progressive behavioral impairment, executive dysfunction, language impairment. Often associated with Parkinsonian features such as dystonia, tremor, gait disturbance	~ 30%
Respiratory dysfunction	Pulmonary	Recurrent respiratory infections, weak cough, aspiration, sleep disordered breathing, respiratory failure	40–50%
Amyotrophic lateral sclerosis (ALS)	Upper and lower motor neurons	Multifocal weakness, hyperreflexia and/or areflexia, atrophy, fasciculations, bulbar weakness, respiratory muscle involvement, weight loss	~ 10%
Parkinson disease (PD)	Central nervous system	Hypokinetic movement disorder, autonomic dysfunction, various non-motor features	4%
Alzheimer disease (AD)	Cognitive	Dementia with predominant amnestic and higher order cognitive dysfunction	2% [4]
Spastic paraplegia	Upper motor neurons	Length-dependent weakness, hyperreflexia, spasticity, clonus	Isolated cases
Sensorimotor neuropathy (axonal Charcot Marie Tooth disease (CMT))	Peripheral nerves	Length-dependent weakness, muscle atrophy and sensory loss. Trophic foot changes and distal areflexia	Isolated cases
Cardiomyopathy	Cardiac	Exertional shortness of breath, heart failure	Uncertain. Reported in case series
Dysphagia and dysarthria	Bulbar dysfunction	Impaired swallowing function, reduced speech volume and intelligibility	Uncertain
Urinary and anal incontinence	Genitourinary, gastrointestinal	Urinary incontinence, anal incontinence or dysfunction	Uncertain