Hereditary spastic paraplegia
- Puneet Opal, MD, PhD
Puneet Opal, MD, PhD
- Associate Professor of Neurology
- Feinberg School of Medicine, Northwestern University
- Senda Ajroud-Driss, MD
Senda Ajroud-Driss, MD
- Instructor in Neurology
- Northwestern University
Hereditary spastic paraplegia (HSP) refers to a group of familial diseases that are characterized by progressive degeneration of the corticospinal tracts. Clinically, they present with lower limb spasticity and weakness.
HSP, also called familial spastic paraplegia, was initially referred to as Strumpell-Lorrain disease, a name given for the two physicians who in the late 19th century independently described key features of spastic paraplegia. It has become evident that HSP is not one disease but a mixed group of genetically heterogeneous conditions that result in broadly overlapping clinical features.
HSPs are clinically differentiated into "pure" forms if spastic paraplegia with bladder involvement is the only clinical finding, and "complicated" (or complex) forms if there are additional neurologic or systemic abnormalities. In the pre-genetic era, attempts were made to further classify HSP based upon age of onset, degree of spasticity, and rate of progression . Today, however, the classification of HSP is increasingly based upon genetics, especially given the phenotypic heterogeneity of HSP within the same family harboring the same genetic defect.
The genetic classification of HSP is based upon mode of inheritance, chromosomal locus, and causative mutation (if known) . Hereditary spastic paraplegias include autosomal dominant, autosomal recessive, and X-linked forms. The genetic loci are designated as SPG (for SPastic parapleGia) and are numbered sequentially as SPG1, SPG2, SPG3, and so on (table 1). The numbering of the SPGs is based upon the order of locus discovery and not on the mechanism of genetic transmission. The number of loci now exceeds 55 and continues to expand (see http://omim.org/phenotypicSeries/PS303350) .
The correlation of clinical classification (pure or complicated) with genetic classification (SPG type) is imperfect, and some genetic types of HSP are associated with both pure and complicated phenotypes .
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