Complicated autosomal recessive hereditary spastic paraplegia

Abstract

Listen

Translate article

Hereditary spastic paraplegia (HSP) has emerged as one of the most genetically heterogeneous neurodegenerative disorders. Almost 40 genetic loci have been implicated as a cause of HSP and this number is likely to further increase in the near future.1 The genetic diversity of HSP represents a significant challenge for molecular diagnosis. The selection of genetic tests primarily depends on the mode of inheritance. The most significant progress has been achieved for autosomal dominant HSP with routine clinical testing presently available for five genes: spastin, atlastin, NIPA1, strumpellin (KIAA0196) , and REEP1 (Athena Diagnostics). Direct genetic testing in patients with dominant inheritance reveals a causative genetic defect in approximately 2/3 of US patients.1 Spastin mutations are more common (approximately 40% of all autosomal dominant HSP) than any other HSP gene defects.2 Mutations in these genes, in particular spastin mutations, may also be detected in patients with apparently sporadic HSP due to either de novo mutations or reduced penetrance (not everybody carrying the pathogenic mutation will develop the disease), even though further studies are necessary to determine the frequency of spontaneous mutations in these genes.3,4 Autosomal recessive …