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The revered Anita E. Harding died in 1995 at age 43. Among her numerous pioneering achievements in neurogenetics,1 she was the one who classified hereditary spastic paraplegia (HSP) as “pure” or “complicated” forms.2 In the uncomplicated HSPs, the clinical manifestations are dominated by upper motor neuron signs in the legs, allowing pes cavus and some loss of vibration sense as well. In complicated HSP, on the other hand, the more serious neurologic manifestations include ataxia, deafness, cataracts, epilepsy, dementia, or other signs.3
Genetic heterogeneity is prominent in the HSPs; inheritance may be autosomal dominant, autosomal recessive, or X-linked. Among the autosomal dominant forms, 40% are attributed to mutations in the gene for spastin (SPG4) and 10% for atlastin (SPG3). In contrast, some mutations are so rare they account for less than 1% each. With the two families reported in this issue of Neurology® by Orlacchio et al.,4 the number of …
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