The hereditary spastic paraplegias

doi:10.1017/CBO9780511544873.054

53 - The hereditary spastic paraplegias

from Part IX - Motor neuron diseases

Published online by Cambridge University Press: 04 August 2010

Anthony E. Lang and

M. Flint Beal: Affiliation:
Cornell University, New York
Anthony E. Lang: Affiliation:
University of Toronto
Albert C. Ludolph: Affiliation:
Universität Ulm, Germany
John K. Fink: Affiliation:
Department of Neurology, University of Michigan and Geriatric Research Education and Care Center, Ann Arbor Veterans Affairs Medical Center, MI, USA

Book contents

Get access

Summary

Introduction and classification

Inherited disorders in which the predominant clinical syndrome is gait disturbance due to lower extremity spastic weakness are referred to collectively as the hereditary spastic paraplegias (HSPs). The various types of HSP are classified clinically according to the mode of inheritance (dominant, recessive, and X-linked); and whether lower extremity spasticity and weakness and often urinary urgency and subtle dorsal column impairment occur alone (“uncomplicated HSP”), or are accompanied by additional neurologic or systemic symptoms for which alternative causes are excluded (“complicated HSP”) (Harding, 1983).

There are at least 20 genetically distinct types of HSP (Table 53.1) including ten dominant, seven recessive, and three X-linked HSP syndromes. Eight of these HSP syndromes are “uncomplicated;” eight of these are “complicated” by the presence of additional neurologic signs; and four of these may present as either “uncomplicated” or “complicated” HSP syndromes. For some of these latter syndromes, both “uncomplicated” and “complicated” HSP phenotypes may coexist even in the same family (Table 53.1).

It is important to recognize that the HSPs are classified clinically, rather than on the basis of subclinical involvement or neuropathologic findings. Certainly, lower extremity spastic weakness may be an important feature of many other disorders, both inherited and apparently sporadic including such diverse disorders as amyotrophic lateral sclerosis, Friedreich's ataxia (Berciano et al., 2002; Ragno et al., 1977), Machado Joseph disease (spinocerebellar ataxia type 3), Charlevoix–Sanguenay syndrome (Engert et al., 2000), primary lateral sclerosis, and familial Alzheimer's disease due to presenilin 1 mutation (Brooks et al., 2003; Assini et al., 2003; Tabira et al., 2002).

Type: Chapter
Information: Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
, pp. 794 - 802

DOI: https://doi.org/10.1017/CBO9780511544873.054 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Alvarado, D. M., Ming, L., Hedera, P.et al. (2001). Atlastin gene analysis in early onset hereditary spastic paraplegia. Am. J. Hum. Genet., 69, 597(Abstract)Google Scholar

Assini, A., Terreni, L., Borghi, R.et al. (2003). Pure spastic paraparesis associated with a novel presenilin 1 R278K mutation. Neurology, 60, 150CrossRef Google Scholar PubMed

Azim, A. C., Hentati, A., Haque, M. F. U., Hirano, M., Ouachi, K. & Siddique, T. (2000). Spastin, a new AAA protein, binds to α and β tubulins. Am. J. Hum. Genet. (Suppl.), 67, 197Google Scholar

Behan, W. & Maia, M. (1974). Strumpell's familial spastic paraplegia: genetics and neuropathology. J. Neurol. Neurosurg. Psychiatr., 37, 8–20CrossRef Google Scholar PubMed

Berciano, J., Mateo, I., DePablos, C., Polo, J. M. & Combarros, O. (2002). Friedreich ataxia with minimal GAA expression presenting as adult-onset spastic ataxia. J. Neurol. Sci., 194, 75–82CrossRef Google Scholar

Brooks, W. S., Kwok, J. B., Kril, J. J.et al. (2003). Alzheimer's disease with spastic paraparesis and “cotton wool” plaques: two pedigrees with PS-1 exon 9 deletions. Brain, 126, 783–91CrossRef Google Scholar

Byrne, P. C., Webb, S., McSweeney, F., Burke, T., Hutchinson, M., & Parfrey, N. (1998). Linkage of AD HSP and cognitive impairment to chromosome 2p: haplotype and phenotype analysis indicates variable expression and low or delayed penetrance. Eur. J. Hum. Genet., 6, 275–82CrossRef Google Scholar PubMed

Cambi, F., Tartaglino, L., Lublin, F. D. & McCarren, D. (1995). X-linked pure familial spastic paraparesis: characterization of a large kindred with magnetic resonance imaging studies. Arch. Neurol., 52, 665–9CrossRef Google Scholar PubMed

Casari, G., Fusco, M., Ciarmatori, S.et al. (1998). Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell, 93, 973–83CrossRef Google Scholar PubMed

Charvin, D., Fonknechten, N., Cifuentes-Diaz, C.et al. (2002). Mutations in SPG4 are responsible for a loss of function of spastin, an abundant neuronal protein localized to the nucleus. Am. J. Hum. Genet., 71, 516 (Abstract)Google Scholar

Claus, D. & Jaspert, A. (1995). Central motor conduction in hereditary spastic paraparesis (Strumpell's disease) and tropical spastic paraparesis. Neurol. Croatic., 44, 23–31Google Scholar

Claus, D., Waddy, H. M. & Harding, A. E. (1990). Hereditary motor and sensory neuropathies and hereditary spastic paraplegia: a magnetic stimulation study. Ann. Neurol., 28, 43–9CrossRef Google Scholar PubMed

Crosby, A. H. & Proukakis, C. (2002). Is the transportation highway the right road for hereditary spastic paraplegia?Am. J. Hum. Genet., 71, 1009–16CrossRef Google Scholar PubMed

Cross, H. E. & McKusick, V. A. (1967). The Troyer syndrome. A recessive form of spastic paraplegia with distal muscle wasting. Arch. Neurol. 16, 473–85CrossRef Google Scholar PubMed

DeMichele, G., DeFusco, M., Cavalcanti, F.et al. (1998). A new locus for autosomal recessive hereditary spastic paraplegia maps to chromosome 16q24.3. Am. J. Hum. Genet., 63, 135–9CrossRef Google Scholar

Dube, M.-P., Boutros, M., Figlewicz, D. A. & Rouleau, G. A. (1997). A new pure hereditary spastic paraplegia kindred maps to the proteolipid protein gene locus. Am. J. Hum. Genet., 61, A169 (Abstract)Google Scholar

Engert, J. C., Berube, P., Mercier, J.et al. (2000). ARSACS, a spastic ataxia common in northeastern Quebec, is caused by mutations in a new gene encoding an 11.5-kb ORF. Nat. Genet., 24, 120–5CrossRef Google Scholar

Errico, A., Ballabio, A. & Rugarli, E. (2002). Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics. Hum. Mol. Genet., 15, 153–63CrossRef Google Scholar

Farag, T. I., El-badramany, M. H. & Al-Sharkawy, S. (1994). Troyer Syndrome: report of the first “non-Amish” sibship and review. Am. J. Med. Genet., 52, 383–5CrossRef Google Scholar

Fink, J. K. (2001). Progressive spastic paraparesis: hereditary spastic paraplegia and its relation to primary and amyotrophic lateral sclerosis. Semin. Neurol., 21, 199–208CrossRef Google Scholar PubMed

Fink, J. K. & Hedera, P. (1999). Hereditary spastic paraplegia: genetic heterogeneity and genotype–phenotype correlation. Semin. Neurol., 19, 301–10CrossRef Google Scholar PubMed

Fink, J. K., Heiman-Patterson, T., Bird, T.et al. (1996). Hereditary spastic paraplegia: advances in genetic research. Neurology, 46, 1507–14CrossRef Google Scholar PubMed

Fonknecten, N., Mavel, D., Byrne, P.et al. (2000). Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia. Hum. Mol. Genet., 9, 637–44CrossRef Google Scholar

Fransen, E., Vits, L., VanCamp, G. & Willems, P. J. (1996). The clinical spectrum of mutations in L1, a neuronal cell adhesion molecule. Am. J. Med. Genet., 64, 73–73.0.CO;2-P>CrossRef Google Scholar PubMed

Hansen, J. J., Durr, A., Cournu-Rebeix, I.et al. (2002). Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. Am. J. Hum. Genet., 70, 000–000CrossRef Google Scholar PubMed

Harding, A. E. (1983). Classification of the hereditary ataxias and paraplegias. Lancet, 1, 1151–5CrossRef Google Scholar PubMed

Harding, A. E. (1993). Hereditary spastic paraplegias. Semin. Neurol., 13, 333–6CrossRef Google Scholar PubMed

Hazan, J., Fonknechten, N., Mavel, D.et al. (1999). Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. Nat. Genet., 23, 296–303CrossRef Google Scholar PubMed

Hedera, P., DiMauro, S., Bonilla, E., Wald, J. J. & Fink, J. K. (2000). Mitochondrial analysis in autosomal dominant hereditary spastic paraplegia. Neurology, 55, 1591–2CrossRef Google Scholar PubMed

Heinzlef, O., Paternotte, C., Mahieux, F.et al. (1998). Mapping of a complicated familial spastic paraplegia to locus SPG4 on chromosome 2p. J. Med. Genet., 35, 89–93CrossRef Google Scholar PubMed

Hentati, A., Deng, H. X., Zhai, B. A.et al. (2000). Novel mutations in spastin gene and absence of correlation with age at onset of symptoms. Neurology, 55, 1388–90CrossRef Google Scholar PubMed

Hodgkinson, C. A., Bohlega, S., Abu-Amero, S. N.et al. (2002). A novel form of autosomal recessive pure hereditary spastic paraplegia maps to chromosome 13q14. Neurology, 59, 1905–9CrossRef Google Scholar PubMed

Kenwrick, S., Watkins, A. & Angelis, E.et al. (2000). Neural cell recognition molecule L1: relating biological complexity to human disease mutations. Hum. Mol. Genet., 9, 879–86CrossRef Google Scholar PubMed

Lindsey, J. C., Lusher, M. E., McDermott, C. J.et al. (2000). Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis. J. Med. Genet., 37, 759–65CrossRef Google Scholar PubMed

Lizcano-Gil, L. A., Garcia-Cruz, D., Bernal-Beltran, M. D. P. & Hernandez, A. (1997). Association of late onset spastic paraparesis and dementia: probably an autosomal dominant form of complicated paraplegia. Am. J. Med. Genet. 68, 1–63.0.CO;2-V>CrossRef Google Scholar PubMed

McLeod, J. G., Morgan, J. A. & Reye, C. (1993). Electrophysiological studies in familial spastic paraplegia. Neurol. Neurosurg. Psychiatr., 40, 611–15CrossRef Google Scholar

Martinez-Murillo, F. M., Kobayashi, H., Pegoraro, E.et al. (1999). Genetic localization of a new locus for recessive familial spastic paraparesis to 15q13–15. Neurology, 53, 50–6CrossRef Google Scholar PubMed

Muglia, M., Magariello, A., Nicoletti, G. et al. (2002). Further evidence that SPG3A gene mutations cause autosomal dominant hereditary spastic paraplegia. Ann. Neurol., in press

Nakamura, A., Izumi, K., Umehara, F.et al. (1995). Familial spastic paraplegia with mental impairment and thin corpus callosum. J. Neurol. Sci., 131, 35–42CrossRef Google Scholar PubMed

Ohnishi, J., Tomoda, Y. & Yokoyama, K. (2001). Neuroradiological findings in hereditary spastic paraplegia with a thin corpus callosum. Acta. Neurol. Scand., 104, 191–2CrossRef Google Scholar PubMed

Patel, H., Cross, H., Proukakis, C.et al. (2002). SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. Nat. Genet., 31, 347–8CrossRef Google Scholar PubMed

Pedersen, L. & Trojaborg, W. (1981). Visual, auditory and somatosensory pathway involvement in hereditary cerebellar ataxia, Friedreich's ataxia and familial spastic paraplegia. Electroencephalogr. Clin. Neurophys., 52, 283–97CrossRef Google Scholar PubMed

Pelosi, L., Lanzillo, B. & Perretti, A. (1991). Motor and somatosensory evoked potentials in hereditary spastic paraplegia. J. Neurol. Neurosurg. Psychiatr., 54, 1099–102CrossRef Google Scholar PubMed

Pericak-Vance, M. A., Kloos, M. T., Reid, E.et al. (2002). A kinesin heavy chain (K1F5A) mutation in Hereditary Spastic Paraplegia (SPG10). Am. J. Hum. Genet., 71, 165 (Abstract)Google Scholar

Polo, J. M., Calleja, J., Combarris, O. & Berciano, J. (1993). Hereditary “pure” spastic paraplegia: a study of nine families. J. Neurol. Neurosurg. Psychiatr., 56, 175–81CrossRef Google Scholar PubMed

Ragno, M., DeMichele, G., Cavalcanti, F.et al. (1997). Broadened Friedreich's ataxia phenotype after gene cloning. Neurology, 49, 1617–20CrossRef Google Scholar PubMed

Rainier, S., Chai, J.-H., Tokarz, D., Nicholls, R. D. & Fink, J. K. (2003). NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6). Nat. Genet., submitted:CrossRef

Reid, E., Grayson, C., Rubinsztein, D. C., Rogers, M. T. & Rubinsztein, J. S. (1999). Subclinical cognitive impairment in autosomal dominant ‘pure’ hereditary spastic paraplegia. J. Med. Genet., 36, 797–8CrossRef Google Scholar PubMed

Schady, W., Dick, J. P., Sheard, A. & Crampton, S. (1991). Central motor conduction studies in hereditary spastic paraplegia. J. Neurol. Neurosurg. Psychiatr., 54, 775–9CrossRef Google Scholar PubMed

Schwarz, G. A. (1952). Hereditary (familial) spastic paraplegia. AMA Arch. Neurol. Psychiatry, 68, 655–82CrossRef Google Scholar PubMed

Schwarz, G. A. & Liu, C.-N. (1956). Hereditary (familial) spastic paraplegia. Further clinical and pathologic observations. Arch. Neurol. Psychiatr., 75, 144–62CrossRef Google Scholar PubMed

Shibaski, Y., Tanaka, H., Iwabuchi, K.et al. (2000). Linkage of autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum to chromosome 15q13–15. Ann. Neurol., 48, 108–123.0.CO;2-A>CrossRef Google Scholar

Silver, J. R. (1966). Familial spastic paraplegia with amyotrophy of the hands. Ann. Hum. Genet., 30, 69–73CrossRef Google Scholar PubMed

Svenson, I. K., Ashley-Koch, A. E., Gaskell, P. C.et al. (2000). Mutation analysis of the spastin gene in hereditary spastic paraplegia type 4 – evidence of aberrant transcript splicing caused by mutations in concanonical splice site sequences. Am. J. Hum. Genet., 67 (suppl. 2), 375Google Scholar

Tabira, T., Chui, D., Nakayama, H., Kuroda, S. & Shibuya, M. (2002). Alzheimer's disease with spastic paresis and cotton wool type plaques. J. Neurosci. Res., 70, 367–72CrossRef Google Scholar PubMed

Tedeschi, G., Allocca, S., DiCostanzo, A.et al. (1991). Multisystem involvement of the central nervous system in Strumpell's disease. A neurophysiological and neuropsychological study. J. Neurol. Sci., 103, 55–60CrossRef Google Scholar PubMed

Wang, J., Hennigan, A. N., Morini, A., Ananth, U. & Seltzer, W. K. (2002). Molecular diagnostic testing for autosomal dominant hereditary spastic paraplegia: identification of novel mutations in the SPG4 gene. Am. J. Hum. Genet., 71, 386 (Abstract)Google Scholar

Webb, S., Coleman, D., Byrne, P.et al. (1998). Autosomal dominant hereditary spastic paraparesis with cognitive loss linked to chromosome 2p. Brain, 121, 601–9CrossRef Google Scholar PubMed

Zhao, X., Alvarado, D., Rainier, S.et al. (2001). Mutations in a novel GTPase cause autosomal dominant hereditary spastic paraplegia. Nat. Genet., 29, 326–31CrossRef Google Scholar