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Description
Spastic paraplegia type 8 belongs to a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and weakness. Hereditary spastic paraplegias are divided into two types: pure and complex. The pure (also called uncomplicated) types involve only the nerves and muscles that control the legs and bladder, whereas the complex (also called complicated) types also involve the nervous system in other parts of the body. Spastic paraplegia type 8 is a pure hereditary spastic paraplegia.
People with spastic paraplegia type 8 have spasticity and weakness of the leg muscles. Affected individuals may also experience exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, and reduced bladder control. The signs and symptoms of spastic paraplegia type 8 can begin in childhood, although they typically appear in early to mid-adulthood.
People with spastic paraplegia type 8 tend to be more severely affected than those with other types of hereditary spastic paraplegias; affected individuals typically require wheelchair assistance in adulthood. However, the signs and symptoms of spastic paraplegia type 8 can vary, even among members of the same family.
Frequency
The prevalence of all hereditary spastic paraplegias combined is estimated to be 1 to 18 in 100,000 people worldwide. Spastic paraplegia type 8 likely accounts for no more than 5 percent of all hereditary spastic paraplegia cases.
Causes
Variants (also called mutations) in the WASHC5 gene cause spastic paraplegia type 8. The WASHC5 gene provides instructions for making a protein called strumpellin. Strumpellin is active (expressed) throughout the body.
Strumpellin interacts with the structural framework inside cells (the cytoskeleton). Strumpellin also binds to other proteins to form a complex that helps regulate the activity of endosomes. Endosomes are structures inside the cell that are involved in sorting, transporting, and recycling proteins and other materials.
WASHC5 gene variants are thought to reduce the amount of functional strumpellin protein. Though it is not known exactly how this causes the characteristic features of spastic paraplegia type 8, it likely impairs the transport of important molecules inside the cell.
Inheritance
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 approximately 90 percent of cases, an affected person inherits the variant from an affected parent
. The remaining cases result from a new (de novo) variant
in the gene that occurs during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.
Other Names for This Condition
- Autosomal dominant spastic paraplegia 8
- Hereditary spastic paraplegia 8
- Spastic paraplegia 8
- SPG8
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Freeman C, Seaman MN, Reid E. The hereditary spastic paraplegia protein strumpellin: characterisation in neurons and of the effect of disease mutations on WASH complex assembly and function. Biochim Biophys Acta. 2013 Jan;1832(1):160-73. doi: 10.1016/j.bbadis.2012.10.011. Epub 2012 Oct 23. Citation on PubMed
- Hedera P, Rainier S, Alvarado D, Zhao X, Williamson J, Otterud B, Leppert M, Fink JK. Novel locus for autosomal dominant hereditary spastic paraplegia, on chromosome 8q. Am J Hum Genet. 1999 Feb;64(2):563-9. doi: 10.1086/302258. Citation on PubMed or Free article on PubMed Central
- Meijer IA, Valdmanis PN, Rouleau GA. Spastic Paraplegia 8. 2008 Aug 13 [updated 2020 May 21]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1827/ Citation on PubMed
- Rocco P, Vainzof M, Froehner SC, Peters MF, Marie SK, Passos-Bueno MR, Zatz M. Brazilian family with pure autosomal dominant spastic paraplegia maps to 8q: analysis of muscle beta 1 syntrophin. Am J Med Genet. 2000 May 15;92(2):122-7. doi: 10.1002/(sici)1096-8628(20000515)92:23.0.co;2-b. Citation on PubMed
- Valdmanis PN, Meijer IA, Reynolds A, Lei A, MacLeod P, Schlesinger D, Zatz M, Reid E, Dion PA, Drapeau P, Rouleau GA. Mutations in the KIAA0196 gene at the SPG8 locus cause hereditary spastic paraplegia. Am J Hum Genet. 2007 Jan;80(1):152-61. doi: 10.1086/510782. Epub 2006 Dec 1. Citation on PubMed or Free article on PubMed Central
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