The hereditary spastic paraplegias - Classification and molecular genetics

The hereditary spastic paraplegias are a genetically defined group of disor ders characterized by slowly progressive spastic paraparesis. Depending on the clinical presentation they are classified as "pure" or "complicated". T he "pure" form shows spastic paraplegia in isolation, while the complicated form is characterized by additional major clinical features. The different ial diagnosis includes inflammatory, degenerative and metabolic disorders a s well as structural abnormalities of brain and spinal cord. The HSP are ge netically complex. Autosomal dominant (70-80% of all families), autosomal r ecessive and X-linked inheritance patterns have been described. For autosom al dominant HSP, genetic loci on chromosome 2, 8, 10, 12, 14, 15 and 19 hav e been found. A gene on chromosome 2 has been cloned, the gene product is a protein called spastin. For autosomal recessive HSP, the protein paraplegi n could be identified as a candidate gene on chromosome 16. In addition to this, there are genetic loci on chromosome 3, 8 and 15. In X-linked HSP, mu tations in the L1 CAM gene and the proteolipid proteine gene have been desc ribed. The pathogenetic role of the genes known so far is not clear. In the near future, a new classification of HSP based on genetic and metabolic de fects can be expected.