Question 1

Diagnosis and treatment of VCP disease

Accepted Answer

Diagnosis: Pursuing a diagnosis of VCP disease, also known as multisystem proteinopathy (MSP1), should be considered in patients and families with one or more of the MSP phenotypes: inclusion body myopathy, Paget's disease of bone, frontotemporal dementia, ALS, axonal CMT, Parkinson's, and/or spastic paraplegia. Genetic testing is considered the golden standard for diagnosis of VCP disease. Single-gene testing is sufficient in the case of a known familial VCP variant, and multi-gene panel sequencing in undifferentiated cases.

Surveillance and management: Regular and ongoing multidisciplinary team follow-up is essential for proactive screening and management of secondary complications.

The table below summarizes the published disease management recommendations according to the VCP clinician consortium.

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Reference: Development of a standard of care for patients with valosin-containing protein associated multisystem proteinopathy | Orphanet Journal of Rare Diseases | Full Text (biomedcentral.com) (https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02172-5)

Question 2

What is VCP disease?

Accepted Answer

VCP disease is a rare and heterogeneous disorder caused by a pathogenic variant of the valosin-containing protein (VCP/p97) gene. The VCP protein is involved in a wide variety of cellular functions. When VCP is not functioning properly, multiple body systems can be affected, including muscle, skeletal, cognitive, pulmonary, motor neurons, cardiac, peripheral nerves, and the central nervous system. VCP disease is progressive, causing the majority of patients to lose the ability to walk and care for themselves in adulthood. The average age of onset of VCP disease is in a person's mid-forties; however, some patients present with symptoms as late as in their mid-sixties and as early as in their twenties. Recently, cases of new and different VCP pathogenic variants have been reported in children. Frequent medical surveillance by a multi-disciplinary care team is recommended to assist with the multitude of symptoms that develop over the course of the disease.

Other names for VCP disease: VCP disease is referred to as multisystem proteinopathy-1 (MSP1) in recent publications. In disease ontology databases, VCP disease is categorized as inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1 (IBMPFD1), using codes OMIM #167320, ICD-11 Code 4A41.21, and ORPHA: 52430 (https://www.orpha.net/consor/cgi-bin/Disease_HPOTerms.php?lng=EN&data_id=10698&Typ=Pat&diseaseType=Pat&from=rightMenu)

Reference: Development of a standard of care for patients with valosin-containing protein associated multisystem proteinopathy | Orphanet Journal of Rare Diseases | Full Text (biomedcentral.com)(https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02172-5)

Question 3

What are the symptoms of VCP disease?

Accepted Answer

Symptoms of VCP disease are progressive, heterogeneous, and new phenotypes may manifest over the course of the disease.  A patient may develop one or any combination of the following phenotypes: inclusion body myopathy, Paget disease of bone, frontotemporal dementia, respiratory dysfunction, amyotrophic lateral sclerosis, Parkinson disease, Alzheimer disease, Charcot-Marie Tooth 2Y, spastic paraplegia, and autism.

Other symptoms to monitor:  VCP patients may also experience pain, depression, balance issues, neuropathy, urinary incontinence, and anal dysfunction.

Below is a summary of clinical manifestations for adult on-set diseases caused by VCP mutations:

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Reference: Development of a standard of care for patients with valosin-containing protein associated multisystem proteinopathy | Orphanet Journal of Rare Diseases | Full Text (biomedcentral.com)(https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02172-5)

For clinical manifestations of childhood disorders due to VCP mutations, you can refer to 
An autosomal-dominant childhood-onset disorder associated with pathogenic variants in VCP: The American Journal of Human Genetics (cell.com)(https://www.cell.com/ajhg/fulltext/S0002-9297(23)00360-9)

Question 4

What is VCP Myopathy?

Accepted Answer

VCP Myopathy, a term used by the MDA,(https://www.mda.org/disease/distal-myopathies/types) refers to the inclusion body myopathy phenotype caused by a pathogenic variant of the VCP gene. VCP myopathy can present proximally and distally and is commonly misdiagnosed as limb-girdle muscular dystrophy and inclusion body myositis.

A consortium of clinical experts published a provisional practice guideline to aid in the diagnosis and monitoring of patients with VCP myopathy.

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Reference: Provisional practice recommendation for the management of myopathy in VCP-associated multisystem proteinopathy - PubMed (nih.gov)(https://pubmed.ncbi.nlm.nih.gov/37026610/)

Question 5

Which healthcare professionals should be on a VCP clinical care team?

Accepted Answer

A patient with VCP disease will need coordinated care with a multidisciplinary team of healthcare professionals. The exact composition of the team will differ depending on each patient's unique and evolving needs; however, the following healthcare professionals should be considered:

• Physicians: Primary care physician, Neurologist (specialties: neuromuscular, movement disorders, and memory care), Endocrinologist, Pulmonologist, Cardiologist, Geneticist, Psychiatrist

• Support Team: Physical Therapist, Occupational Therapist, Speech Language Pathologist, Respiratory Therapist, Genetic Counselor, Social Worker, Caregiver/Family Support

Reference: Development of a standard of care for patients with valosin-containing protein associated multisystem proteinopathy | Orphanet Journal of Rare Diseases | Full Text (biomedcentral.com)(https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02172-5)

Question 6

Inheritance and genetics of VCP disease

Accepted Answer

VCP disease is primarily an adult-onset, autosomal dominant disorder. Approximately 80% of affected individuals also have an affected parent; 20% of reported cases occur de novo or without recognized family history. Expression is variable between families as well as within the same family. Penetrance is almost complete, but age of onset is highly variable. 
Reference: Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia - GeneReviews® - NCBI Bookshelf (nih.gov) (https://www.ncbi.nlm.nih.gov/books/NBK1476/)

It has recently been discovered that disorders from pathogenic variants in VCP present in children. Thirteen children (12 de novo) were reported with disorders including autism, muscle weakness, and developmental delays. published in October 2023.
​Reference:  An autosomal-dominant childhood-onset disorder associated with pathogenic variants in VCP: The American Journal of Human Genetics (cell.com) (https://www.cell.com/ajhg/fulltext/S0002-9297(23)00360-9)

The VCP/p97 gene is located on chromosome 9p13 - p12.  Over 50 VCP pathogenic variants have been identified.
Reference: Genes | Free Full-Text | Multisystem Proteinopathy Due to VCP Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis (mdpi.com)(https://www.mdpi.com/2073-4425/13/6/963)

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Clinical Care

Clinical Information and Publications

Additional Information

The contents of this page were reviewed by the Chief Scientific Officer of Cure VCP Disease based on information published in peer-reviewed medical journals.

If you are a clinician interested in joining our VCP Medical Network, please contact us.

Stay Up To Date

Clinical Care

Clinical Information and Publications

Additional Information

The contents of this page were reviewed by the Chief Scientific Officer of Cure VCP Disease based on information published in peer-reviewed medical journals. If you are a clinician interested in joining our VCP Medical Network, please contact us.

Stay Up To Date

The contents of this page were reviewed by the Chief Scientific Officer of Cure VCP Disease based on information published in peer-reviewed medical journals.

If you are a clinician interested in joining our VCP Medical Network, please contact us.