Which cytogenic findings are characteristic of hereditary spastic paraparesis (HSP)?

Updated: Apr 28, 2014
  • Author: Hidehiro Takei, MD; Chief Editor: Adekunle M Adesina, MD, PhD  more...
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Answer

Hereditary spastic paraparesis (HSP) comprises a large clinically and genetically heterogeneous group of inherited neurologic disorders and is transmitted as an autosomal dominant, autosomal recessive, or (rarely) X-linked recessive trait. Autosomal dominant inheritance accounts for 70-80% of all HSP cases and is most commonly associated with pure forms of HSP. Autosomal recessive HSPs are less common but exhibit greater phenotypic variability.

Of the 45 known gene loci, 20 have been identified as causative. [57] About 40% of autosomal dominant HSP cases are linked to the spastic paraplegia 4 (SPG4) locus on chromosome 2p21-p22. More than 150 mutations are scattered along the coding regions of the gene SPAST, encoding spastin, [57] and have been implicated in causing various types of DNA modification. [58, 59] About 10% are due to mutations in ATL1, encoding for atlastin, with an early-onset pure phenotype (SPG3A). [57, 59]

Of autosomal recessive HSP cases, SPG11 (SPG11, spatacsin) reportedly is the most common form, followed by SPG15 (ZFYVE26, spastizin). [60] Clinically, both forms are characterized by complicated HSP, cognitive deficits, a thin corpus callosum (seemingly the best phenotypic predictor for these 2 forms of HSP), peripheral neuropathy, and mild cerebellar ataxia. [61]


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