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Distal hereditary motor neuropathy, type V

Reviewed August 2009

What is distal hereditary motor neuropathy, type V?

Distal hereditary motor neuropathy, type V is a progressive disorder that affects nerve cells in the spinal cord. It results in muscle weakness and affects movement of the hands and feet.

Symptoms of distal hereditary motor neuropathy, type V usually begin during adolescence, but onset varies from infancy to the mid-thirties. Cramps in the hand brought on by exposure to cold temperatures are often the initial symptom.

The characteristic features of distal hereditary motor neuropathy, type V are weakness and wasting (atrophy) of muscles of the hand, specifically on the thumb side of the index finger and in the palm at the base of the thumb. Foot abnormalities, such as a high arch (pes cavus), are also common, and some affected individuals eventually develop problems with walking (gait disturbance). People with this disorder have normal life expectancies.

How common is distal hereditary motor neuropathy, type V?

The incidence of distal hereditary motor neuropathy, type V is unknown. Only a small number of cases have been reported.

What genes are related to distal hereditary motor neuropathy, type V?

Mutations in the BSCL2 and GARS genes cause distal hereditary motor neuropathy, type V.

The BSCL2 gene provides instructions for making a protein called seipin, whose function is unknown. Mutations in the BSCL2 gene likely alter the structure of seipin, causing it to fold into an incorrect 3-dimensional shape. Research findings indicate that misfolded seipin proteins accumulate in the endoplasmic reticulum, which is a structure inside the cell that is involved in protein processing and transport. This accumulation likely damages and kills motor neurons (specialized nerve cells in the brain and spinal cord that control muscle movement), leading to muscle weakness in the hands and feet.

The GARS gene provides instructions for making an enzyme called glycyl-tRNA synthetase, which is involved in the production (synthesis) of proteins. It is unclear how GARS gene mutations lead to distal hereditary motor neuropathy, type V. The mutations probably reduce the activity of glycyl-tRNA synthetase. A reduction in the activity of this enzyme may impair transmission of nerve impulses. As a result, nerve cells slowly lose the ability to communicate with muscles in the hands and feet.

Related Gene(s)

Changes in these genes are associated with distal hereditary motor neuropathy, type V.

  • BSCL2
  • GARS

How do people inherit distal hereditary motor neuropathy, type V?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Where can I find information about diagnosis or management of distal hereditary motor neuropathy, type V?

These resources address the diagnosis or management of distal hereditary motor neuropathy, type V, and may include treatment providers.

  • Gene Review: BSCL2-Related Neurologic Disorders/Seipinopathy (http://www.ncbi.nlm.nih.gov/books/NBK1307/)
  • Gene Review: GARS-Associated Axonal Neuropathy (http://www.ncbi.nlm.nih.gov/books/NBK1242/)
  • Genetic Testing Registry: Distal hereditary motor neuronopathy type 5 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1833308)
  • MedlinePlus Encyclopedia: High-Arched Foot (http://www.nlm.nih.gov/medlineplus/ency/article/001261.htm)

You might also find information on the diagnosis or management of distal hereditary motor neuropathy, type V, in Educational resources (http://www.ghr.nlm.nih.gov/condition/distal-hereditary-motor-neuropathy-type-v/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/distal-hereditary-motor-neuropathy-type-v/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about distal hereditary motor neuropathy, type V?

You may find the following resources about distal hereditary motor neuropathy, type V, helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for distal hereditary motor neuropathy, type V?

  • DHMN-V
  • distal hereditary motor neuronopathy type 5
  • distal hereditary motor neuronopathy, type V
  • distal spinal muscular atrophy, type V
  • DSMAV
  • HMN V
  • spinal muscular atrophy, distal type V
  • spinal muscular atrophy, distal, with upper limb predominance

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about distal hereditary motor neuropathy, type V?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding distal hereditary motor neuropathy, type V?

atrophy ; autosomal ; autosomal dominant ; cell ; distal ; endoplasmic reticulum ; enzyme ; gait ; gene ; hereditary ; incidence ; inherited ; motor ; neuropathy ; pes cavus ; protein ; symptom ; synthesis ; tRNA ; wasting

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Antonellis A, Ellsworth RE, Sambuughin N, Puls I, Abel A, Lee-Lin SQ, Jordanova A, Kremensky I, Christodoulou K, Middleton LT, Sivakumar K, Ionasescu V, Funalot B, Vance JM, Goldfarb LG, Fischbeck KH, Green ED. Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V. Am J Hum Genet. 2003 May;72(5):1293-9. Epub 2003 Apr 10. (http://www.ncbi.nlm.nih.gov/pubmed/12690580?dopt=Abstract)
  • Antonellis A, Lee-Lin SQ, Wasterlain A, Leo P, Quezado M, Goldfarb LG, Myung K, Burgess S, Fischbeck KH, Green ED. Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for tRNA-charging enzymes in peripheral axons. J Neurosci. 2006 Oct 11;26(41):10397-406. (http://www.ncbi.nlm.nih.gov/pubmed/17035524?dopt=Abstract)
  • Auer-Grumbach M, Löscher WN, Wagner K, Petek E, Körner E, Offenbacher H, Hartung HP. Phenotypic and genotypic heterogeneity in hereditary motor neuronopathy type V: a clinical, electrophysiological and genetic study. Brain. 2000 Aug;123 ( Pt 8):1612-23. (http://www.ncbi.nlm.nih.gov/pubmed/10908191?dopt=Abstract)
  • Dubourg O, Azzedine H, Yaou RB, Pouget J, Barois A, Meininger V, Bouteiller D, Ruberg M, Brice A, LeGuern E. The G526R glycyl-tRNA synthetase gene mutation in distal hereditary motor neuropathy type V. Neurology. 2006 Jun 13;66(11):1721-6. Erratum in: Neurology. 2006 Aug 22;67(4):727. (http://www.ncbi.nlm.nih.gov/pubmed/16769947?dopt=Abstract)
  • Irobi J, De Jonghe P, Timmerman V. Molecular genetics of distal hereditary motor neuropathies. Hum Mol Genet. 2004 Oct 1;13 Spec No 2:R195-202. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15358725?dopt=Abstract)
  • Ito D, Suzuki N. Molecular pathogenesis of seipin/BSCL2-related motor neuron diseases. Ann Neurol. 2007 Mar;61(3):237-50. (http://www.ncbi.nlm.nih.gov/pubmed/17387721?dopt=Abstract)
  • Ito D, Suzuki N. Seipinopathy: a novel endoplasmic reticulum stress-associated disease. Brain. 2009 Jan;132(Pt 1):8-15. doi: 10.1093/brain/awn216. Epub 2008 Sep 12. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18790819?dopt=Abstract)
  • Rohkamm B, Reilly MM, Lochmüller H, Schlotter-Weigel B, Barisic N, Schöls L, Nicholson G, Pareyson D, Laurà M, Janecke AR, Miltenberger-Miltenyi G, John E, Fischer C, Grill F, Wakeling W, Davis M, Pieber TR, Auer-Grumbach M. Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with predominant hand involvement and Silver syndrome. J Neurol Sci. 2007 Dec 15;263(1-2):100-6. Epub 2007 Jul 30. (http://www.ncbi.nlm.nih.gov/pubmed/17663003?dopt=Abstract)
  • Sivakumar K, Kyriakides T, Puls I, Nicholson GA, Funalot B, Antonellis A, Sambuughin N, Christodoulou K, Beggs JL, Zamba-Papanicolaou E, Ionasescu V, Dalakas MC, Green ED, Fischbeck KH, Goldfarb LG. Phenotypic spectrum of disorders associated with glycyl-tRNA synthetase mutations. Brain. 2005 Oct;128(Pt 10):2304-14. Epub 2005 Jul 13. (http://www.ncbi.nlm.nih.gov/pubmed/16014653?dopt=Abstract)
  • Windpassinger C, Auer-Grumbach M, Irobi J, Patel H, Petek E, Hörl G, Malli R, Reed JA, Dierick I, Verpoorten N, Warner TT, Proukakis C, Van den Bergh P, Verellen C, Van Maldergem L, Merlini L, De Jonghe P, Timmerman V, Crosby AH, Wagner K. Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome. Nat Genet. 2004 Mar;36(3):271-6. Epub 2004 Feb 22. (http://www.ncbi.nlm.nih.gov/pubmed/14981520?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2009
Published: July 21, 2014