Phenotypic analysis of autosomal dominant hereditary spastic paraplegia linked to chromosome 8q

Objective: To describe clinical, electrophysiologic, neuroimaging, and musc le biopsy features in a hereditary spastic paraplegia (HSP) kindred linked to a new HSP locus on chromosome 8q. Background: HSP is a genetically diver se group of disorders characterized by insidiously progressive spastic weak ness in the legs. We recently analyzed a Caucasian kindred with autosomal d ominant HSP and identified tight linkage to a novel HSP locus on chromosome 8q23-24. Methods: Clinical analysis, nerve conduction studies, electromyog raphy, somatosensory evoked potentials, MRI of brain and spinal cord, and m uscle biopsy for mitochondrial analysis were performed in members of the fi rst HSP kindred linked to chromosome 8q. Results: Fifteen individuals showe d insidiously progressive spastic paraparesis beginning between ages 22 and 60 years (average, 37.2 years). Spinal cord MRI in 1 moderately affected s ubject showed significant atrophy of the thoracic spinal cord as determined by cross-sectional area measurements. Somatosensory evoked potential recor ding, electromyography, nerve conduction studies, and muscle biopsy, includ ing histochemical and biochemical analysis of mitochondrial function, were normal. Conclusions: The phenotype in this family is that of typical, but s evere, uncomplicated HSP. Other than apparently increased severity, there w ere no clinical features that distinguished this family from autosomal domi nant HSP linked to loci on chromosomes 2p, 14q, and 15q. This clinical simi larity between different genetic types of autosomal dominant HSP raises the possibility that genes responsible for these clinically indistinguishable disorders may participate in a common biochemical cascade. Normal results o f muscle histochemical and biochemical analysis suggest that mitochondrial disturbance, a feature of chromosome 16-linked autosomal recessive HSP due to paraplegin gene mutations, is not a feature of chromosome 8q-linked auto somal dominant HSP and may not be a common factor of HSP in general.