Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance.
Journal of the Neurological Sciences. 2012-07-01; 318(1-2): 1-18
DOI: 10.1016/j.jns.2012.03.025
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1. J Neurol Sci. 2012 Jul 15;318(1-2):1-18. doi: 10.1016/j.jns.2012.03.025. Epub
2012 May 1.
Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or
maternal trait of inheritance.
Finsterer J(1), Löscher W, Quasthoff S, Wanschitz J, Auer-Grumbach M, Stevanin G.
Author information:
(1)Krankenanstalt Rudolfstiftung, Wien, Austria.
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. Nineteen SPGs follow an
autosomal-dominant (AD-SPG), 27 an autosomal-recessive (AR-SPG), 5 X-linked
(XL-SPG), and one 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.
Copyright © 2012 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.jns.2012.03.025
PMID: 22554690 [Indexed for MEDLINE]