Posted - June 2012 in Research Highlights
Described by mode of inheritance
22 genes and 52 different forms of HSP (SPG1-52) have now been discovered and described. This is 4 more forms than reported here last quarter in the Autumn edition of Research Highlights.
Hereditary spastic paraplegia (SPG) is a clinically and genetically heterogeneous group of neurodegenerative disorders that are clinically characterised by progressive spasticity and weakness of the lower-limbs (pure SPG) and, majoritorian, additional more extensive neurological or non-neurological manifestations (complex or complicated SPG). Pure SPG is characterised by progressive spasticity and weakness of the lower-limbs, and occasionally sensory disturbances or bladder dysfunction. Complex SPGs additionally include cognitive impairment, dementia, epilepsy, extrapyramidal disturbances, cerebellar involvement, retinopathy, optic atrophy, deafness, polyneuropathy, or skin lesions in the absence of coexisting disorders.
SPGs are due to mutations in genes encoding for proteins involved in the maintenance of corticospinal tract neurons, the nerve cells of the brain and spinal cord with a long axon or arm.
HSP classification by trait of inheritance:
19 SPGs are autosomal-dominant (AD-SPG)
27 autosomal-recessive (AR-SPG)
5 X-linked (XL-SPG) and
1 a maternal trait of inheritance.
SPGs are due to mutations in genes encoding for proteins involved in the maintenance of corticospinal tract neurons.
Among the AD-SPGs, 40-45% of patients carry mutations in the SPAST-gene (SPG4) and 10% in the ATL1-gene (SPG3), while the other 9 genes are more rarely involved (NIPA1 (SPG6), KIAA0196 (SPG8), KIF5A (SPG10), RNT2 (SPG12), SPGD1 (SPG13), BSCL2 (SPG17), REEP1 (SPG31), ZFYVE27 (SPG33, debated), and SLC33A1 (SPG42, debated)).
Among the AR-SPGs, ~20% of the patients carry mutations in the KIAA1840 (SPG11) gene whereas the 15 other genes are rarely mutated and account for SPGs in single families yet (CYP7B1 (SPG5), SPG7 (SPG7), ZFYVE26 (SPG15), ERLIN2 (SPG18), SPG20 (SPG20), ACP33 (SPG21), KIF1A (SPG30), FA2H (SPG35), NTE (SPG39), GJA12/GJC2 (SPG44), KIAA0415 (SPG48) and 4 genes encoding for the AP4-complex (SPG47)).
Among the XL-SPGs, 3 causative genes have been identified (L1CAM (SPG1), PLP1 (SPG2), and SLC16A2 (SPG22)).
The diagnosis of SPGs is based on clinical, instrumental and genetic investigations. Treatment is exclusively symptomatic.
SOURCE: J Neurol Sci. 2012 May 1. [Epub ahead of print]
Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance.
Finsterer J, Löscher W, Quasthoff S, Wanschitz J, Auer-Grumbach M, Stevanin G.
Krankenanstalt Rudolfstiftung, Wien, Austria; Danube University Krems, Krems, Austria.