Spastic paraplegia type 4

Reviewed January 2008

What is spastic paraplegia type 4?

Spastic paraplegia type 4 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve only the lower limbs, whereas the complex types also involve the upper limbs (to a lesser degree) and the nervous system. Spastic paraplegia type 4 is a pure hereditary spastic paraplegia.

Like all hereditary spastic paraplegias, spastic paraplegia type 4 involves spasticity of the leg muscles and muscle weakness. People with this condition can also experience exaggerated reflexes (hyperreflexia), ankle spasms, high-arched feet (pes cavus), and reduced bladder control. Spastic paraplegia type 4 generally affects nerve and muscle function in the lower half of the body only.

How common is spastic paraplegia type 4?

The prevalence of spastic paraplegia type 4 is estimated to be 2 to 6 in 100,000 people worldwide.

What genes are related to spastic paraplegia type 4?

Mutations in the SPAST gene cause spastic paraplegia type 4. The SPAST gene provides instructions for producing a protein called spastin. Spastin is found throughout the body, particularly in certain nerve cells (neurons). The spastin protein plays a role in the function of microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules are also involved in transporting cell components and facilitating cell division. Spastin likely helps restrict microtubule length and disassemble microtubule structures when they are no longer needed. Mutations in spastin impair the microtubules' ability to transport cell components, especially in nerve cells; researchers believe this contributes to the major signs and symptoms of spastic paraplegia type 4.

Related Gene(s)

Changes in this gene are associated with spastic paraplegia type 4.

SPAST

How do people inherit spastic paraplegia type 4?

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.

In most cases, an affected person inherits the mutation from one affected parent. The remaining cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of spastic paraplegia type 4?

These resources address the diagnosis or management of spastic paraplegia type 4 and may include treatment providers.

Gene Review: Hereditary Spastic Paraplegia (http://www.ncbi.nlm.nih.gov/books/NBK1509/)
Gene Review: Spastic Paraplegia 4 (http://www.ncbi.nlm.nih.gov/books/NBK1160/)
Genetic Alliance (http://www.geneticalliance.org/site-search/results/paraplegia+spastic+hereditary+taxonomy%3A13)
Genetic Testing Registry: Spastic paraplegia 4, autosomal dominant (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1866855)

You might also find information on the diagnosis or management of spastic paraplegia type 4 in Educational resources (http://www.ghr.nlm.nih.gov/condition/spastic-paraplegia-type-4/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/spastic-paraplegia-type-4/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 spastic paraplegia type 4?

You may find the following resources about spastic paraplegia type 4 helpful. These materials are written for the general public.

MedlinePlus - Health information
- Health Topic: Neurologic Diseases (http://www.nlm.nih.gov/medlineplus/neurologicdiseases.html)
- Health Topic: Neuromuscular Disorders (http://www.nlm.nih.gov/medlineplus/neuromusculardisorders.html)
- Health Topic: Paralysis (http://www.nlm.nih.gov/medlineplus/paralysis.html)
Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/6637/resources/resources/1)
Additional NIH Resources - National Institutes of Health
National Institute of Neurological Disorders and Stroke: Hereditary Spastic Paraplegia (http://www.ninds.nih.gov/disorders/hereditary_spastic_paraplegia/hereditary_spastic_paraplegia.htm)
Educational resources - Information pages
- Merck Manual of Medical Information, Second Home Edition (http://www.merckmanuals.com/home/brain_spinal_cord_and_nerve_disorders/spinal_cord_disorders/hereditary_spastic_paraparesis.html)
- Orphanet: Spastic paraplegia, familial (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=685)
Patient support - For patients and families
- National Ataxia Foundation (http://www.ataxia.org/)
- National Organization for Rare Disorders (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/398/viewAbstract)
- RareConnect (https://www.rareconnect.org/en/community/hereditary-spastic-paraplegia)

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

Gene Reviews - Clinical summary
- Gene Review: Hereditary Spastic Paraplegia (http://www.ncbi.nlm.nih.gov/books/NBK1509/)
- Gene Review: Spastic Paraplegia 4 (http://www.ncbi.nlm.nih.gov/books/NBK1160/)
Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Spastic paraplegia 4, autosomal dominant (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1866855)
ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22spastic%20paraplegia%204%22%20OR%20%22Paraplegia%2C%20Spastic%22%20OR%20%22Spastic%20Paraplegia%22)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(SPG4%5BTIAB%5D)%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20720%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/182601)

What other names do people use for spastic paraplegia type 4?

Autosomal Dominant Hereditary Spastic Paraplegia
Hereditary Autosomal Dominant Spastic Paraplegia
Hereditary Spastic Paraplegia
spastic paraplegia 4

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 spastic paraplegia type 4?

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

What glossary definitions help with understanding spastic paraplegia type 4?

autosomal ; autosomal dominant ; cell ; cell division ; cytoskeleton ; gene ; microtubule ; mutation ; nervous system ; paraplegia ; pes cavus ; prevalence ; protein ; spasticity

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

References

Depienne C, Fedirko E, Forlani S, Cazeneuve C, Ribaï P, Feki I, Tallaksen C, Nguyen K, Stankoff B, Ruberg M, Stevanin G, Durr A, Brice A. Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia. J Med Genet. 2007 Apr;44(4):281-4. Epub 2006 Nov 10. (http://www.ncbi.nlm.nih.gov/pubmed/17098887?dopt=Abstract)
McDermott CJ, Burness CE, Kirby J, Cox LE, Rao DG, Hewamadduma C, Sharrack B, Hadjivassiliou M, Chinnery PF, Dalton A, Shaw PJ; UK and Irish HSP Consortium. Clinical features of hereditary spastic paraplegia due to spastin mutation. Neurology. 2006 Jul 11;67(1):45-51. Erratum in: Neurology. 2009 Apr 28;72(17):1534. (http://www.ncbi.nlm.nih.gov/pubmed/16832076?dopt=Abstract)
Reid E. Science in motion: common molecular pathological themes emerge in the hereditary spastic paraplegias. J Med Genet. 2003 Feb;40(2):81-6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12566514?dopt=Abstract)
Roll-Mecak A, Vale RD. Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin. Nature. 2008 Jan 17;451(7176):363-7. doi: 10.1038/nature06482. (http://www.ncbi.nlm.nih.gov/pubmed/18202664?dopt=Abstract)
Salinas S, Carazo-Salas RE, Proukakis C, Schiavo G, Warner TT. Spastin and microtubules: Functions in health and disease. J Neurosci Res. 2007 Sep;85(12):2778-82. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17348041?dopt=Abstract)
Soderblom C, Blackstone C. Traffic accidents: molecular genetic insights into the pathogenesis of the hereditary spastic paraplegias. Pharmacol Ther. 2006 Jan;109(1-2):42-56. Epub 2005 Jul 7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16005518?dopt=Abstract)
Yip AG, Dürr A, Marchuk DA, Ashley-Koch A, Hentati A, Rubinsztein DC, Reid E. Meta-analysis of age at onset in spastin-associated hereditary spastic paraplegia provides no evidence for a correlation with mutational class. J Med Genet. 2003 Sep;40(9):e106. (http://www.ncbi.nlm.nih.gov/pubmed/12960222?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.