Hereditary spastic paraplegia (HSP) is usually inherited in an autosomal dominant manner (although recessive and even X-linked inheritance have been described)
Autosomal dominant familial spastic parapleiga (AD-FSP) may be simple or complicated by, for example dementia or epilepsy.
Notes:
- HSPs are a heterogeneous group of neurodegenerative disorders commonly characterized by the degeneration of long axons of the cortico-spinal tract and dorsal columns
- at present, genetic mapping and exome sequencing have identified at least 71 HSP gene loci, designated SPG 1-71, and up to date 54 genes causing an autosomal-dominant, -recessive (AR-HSP) or X-linked inheritance (2)
- mutations in SPG11 are the most frequent cause of AR-HSP
- mutations in SPG11 were first described by screening patients with AR-HSP, thin corpus callosum (TCC) and cognitive impairment (3)
- additional symptoms including pseudobulbar symptoms such as dysarthria and dysphagia, neuropathy and amyotrophy are also present in some patients with SPG11 mutations
Reference:
- 1) Heinzlef O, Paternotte C, Mahieux F, et al. Mapping of a complicated familial spastic paraplegia to locus SPG4 on chromosome 2p. Journal of Medical Genetics 1998;35(2):89-93
- 2) Bettencourt C., Lopez-Sendon J., Garcia-Caldentey J., Rizzu P., Bakker I., Shomroni O., Quintans B., Davila J., Bevova M., Sobrido M.J., et al . Exome sequencing is a useful diagnostic tool for complicated forms of hereditary spastic paraplegia. Clin. Genet 2013;85:154-158
- 3) Stevanin G., Santorelli F.M., Azzedine H., Coutinho P., Chomilier J., Denora P.S., Martin E., Ouvrard-Hernandez A.M., Tessa A., Bouslam N., et al . Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. Nat. Genet. 2007;39:366-372.