J Clin Neurol.  2014 Apr;10(2):166-170. 10.3988/jcn.2014.10.2.166.

Involvement of Peripheral and Central Nervous Systems in a Valosin-Containing Protein Mutation

• Segers K
• Glibert G
• Callebaut
• Kevers L
• Alcan I
• Dachy B

• KMID: 2287536
• DOI: http://doi.org/10.3988/jcn.2014.10.2.166

Abstract

BACKGROUND
Inclusion-body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD) is a rare, late-onset autosomal disorder arising from missense mutations in a gene coding for valosin-containing protein.
CASE REPORT
We report the case of a man carrying the previously described p.Arg159His mutation, who had an unusual axonal sensorimotor neuropathy as the first clinical manifestation of IBMPFD, and for whom diagnosis only became clear 8 years later when the patient developed frontotemporal dementia.
CONCLUSIONS
Peripheral neuropathy is a rare manifestation of IBMPFD. This underdiagnosed disorder should be considered when a patient develops dementia or has signs of Paget's disease.

Keyword

sensorimotor neuropathy; valosin-containing protein; IBMPFD; frontotemporal dementia; Paget's disease

MeSH Terms

Axons
Central Nervous System*
Clinical Coding
Dementia
Diagnosis
Frontotemporal Dementia
Genes, vif
Humans
Muscular Diseases
Mutation, Missense
Peripheral Nervous System Diseases

Figure

• 

  Fig. 1 Selected transversal slides from MRI of the patient's brain. Note the prominent atrophy of the pole of the left temporal lobe (white arrow) on a T2-weighted image (A) and the bilateral frontotemporal atrophy on a T1-weighted image (B).

• 

  Fig. 2 Selected transversal slide from computed tomography of the pelvis. Note the prominent atrophy of the left quadriceps (white arrow) compared to the right side.

Reference

1. Watts GD, Wymer J, Kovach MJ, Mehta SG, Mumm S, Darvish D, et al. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat Genet. 2004; 36:377–381.

2. Yamanaka K, Sasagawa Y, Ogura T. Recent advances in p97/VCP/Cdc48 cellular functions. Biochim Biophys Acta. 2012; 1823:130–137.

3. Nalbandian A, Donkervoort S, Dec E, Badadani M, Katheria V, Rana P, et al. The multiple faces of valosin-containing protein-associated diseases: inclusion body myopathy with Paget's disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis. J Mol Neurosci. 2011; 45:522–531.

4. Kimonis VE, Mehta SG, Fulchiero EC, Thomasova D, Pasquali M, Boycott K, et al. Clinical studies in familial VCP myopathy associated with Paget disease of bone and frontotemporal dementia. Am J Med Genet A. 2008; 146A:745–757.

5. Sieben A, Van Langenhove T, Engelborghs S, Martin JJ, Boon P, Cras P, et al. The genetics and neuropathology of frontotemporal lobar degeneration. Acta Neuropathol. 2012; 124:353–372.

6. Djamshidian A, Schaefer J, Haubenberger D, Stogmann E, Zimprich F, Auff E, et al. A novel mutation in the VCP gene (G157R) in a German family with inclusion-body myopathy with Paget disease of bone and frontotemporal dementia. Muscle Nerve. 2009; 39:389–391.

7. Kovach MJ, Waggoner B, Leal SM, Gelber D, Khardori R, Levenstien MA, et al. Clinical delineation and localization to chromosome 9p13.3-p12 of a unique dominant disorder in four families: hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementia. Mol Genet Metab. 2001; 74:458–475.

8. de Bot ST, Schelhaas HJ, Kamsteeg EJ, van de Warrenburg BP. Hereditary spastic paraplegia caused by a mutation in the VCP gene. Brain. 2012; 135(Pt 12):e223. author reply e224.

9. Spina S, Van Laar AD, Murrell JR, Hamilton RL, Kofler JK, Epperson F, et al. Phenotypic variability in three families with valosin-containing protein mutation. Eur J Neurol. 2013; 20:251–258.

10. Miller TD, Jackson AP, Barresi R, Smart CM, Eugenicos M, Summers D, et al. Inclusion body myopathy with Paget disease and frontotemporal dementia (IBMPFD): clinical features including sphincter disturbance in a large pedigree. J Neurol Neurosurg Psychiatry. 2009; 80:583–584.

11. van der Zee J, Pirici D, Van Langenhove T, Engelborghs S, Vandenberghe R, Hoffmann M, et al. Clinical heterogeneity in 3 unrelated families linked to VCP p.Arg159His. Neurology. 2009; 73:626–632.

12. Haubenberger D, Bittner RE, Rauch-Shorny S, Zimprich F, Mannhalter C, Wagner L, et al. Inclusion body myopathy and Paget disease is linked to a novel mutation in the VCP gene. Neurology. 2005; 65:1304–1305.

13. Stojkovic T, Hammouda el H, Richard P, López de Munain A, Ruiz-Martinez J, Camaño P, et al. Clinical outcome in 19 French and Spanish patients with valosin-containing protein myopathy associated with Paget's disease of bone and frontotemporal dementia. Neuromuscul Disord. 2009; 19:316–323.

14. Kumar KR, Liang C, Needham M, Burke D, Sue CM, Ng K. Axonal hyperpolarization in inclusion-body myopathy, Paget disease of the bone, and frontotemporal dementia (IBMPFD). Muscle Nerve. 2011; 44:191–196.

15. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998; 51:1546–1554.