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Spastic Paraplegia 11

, PhD, , MD, PhD, and , MD.

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Initial Posting: ; Last Update: January 31, 2013.

Estimated reading time: 16 minutes


Clinical characteristics.

Spastic paraplegia 11 (SPG11) is characterized by progressive spasticity and weakness of the lower limbs frequently associated with the following: mild intellectual disability with learning difficulties in childhood and/or progressive cognitive decline; peripheral neuropathy; pseudobulbar involvement; and increased reflexes in the upper limbs. Less frequent findings include: cerebellar signs (ataxia, nystagmus, saccadic pursuit); retinal degeneration; pes cavus; scoliosis; and parkinsonism. Onset occurs mainly during infancy or adolescence (range: age 1-31 years). Most affected individuals become wheelchair bound one or two decades after disease onset.


Diagnosis is based on (1) clinical findings; (2) a characteristic brain MRI pattern including thinning of the corpus callosum (TCC) and in most cases periventricular white matter alterations; and, because the combination of TCC with white matter changes is not specific to SPG11 and may also be present in all affected individuals, (3) molecular genetic testing of SPG11.


Treatment of manifestations: Care by a multidisciplinary team; physiotherapy to stretch spastic muscles; anti-spastic drugs such as baclofen; botulin toxin and intrathecal baclofen for severe and disabling spasticity when oral drugs are ineffective. Urodynamic evaluation when bladder dysfunction is evident; anticholinergic drugs for urinary urgency. Treatment of psychiatric manifestations by standard protocols.

Prevention of secondary complications: Treatment of sphincter disturbances to prevent urinary tract infection secondary to bladder dysfunction.

Surveillance: Evaluation every six months to adjust physiotherapy and medications.

Genetic counseling.

SPG11 is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for at-risk pregnancies are possible once the pathogenic variants in a family are known.


Clinical Diagnosis

The basic phenotype of spastic paraplegia 11 (SPG11), caused by pathogenic variants in SPG11, is homogeneous and includes progressive spasticity and weakness of the lower limbs with the following associating signs [Shibasaki et al 2000, Casali et al 2004, Winner et al 2004, Lossos et al 2006, Olmez et al 2006, Stevanin et al 2006, Winner et al 2006, Del Bo et al 2007, Hehr et al 2007, Stevanin et al 2007b, Stevanin et al 2008, Denora et al 2009].

Frequent findings

  • Mild intellectual disability with learning difficulties in childhood and/or progressive cognitive decline
  • Axonal, motor, or sensorimotor peripheral neuropathy
  • Pseudobulbar involvement with dysarthria and/or dysphagia
  • Increased reflexes in the upper limbs

Less frequent findings

  • Cerebellar signs (ataxia or ocular signs including nystagmus and/or saccadic pursuit)
  • Retinal degeneration (Kjelling syndrome) [Puech et al 2011]
  • Pes cavus
  • Scoliosis
  • Extrapyramidal signs such as parkinsonism [Anheim et al 2009]


Brain and spinal cord MRI. The following MRI findings help distinguish SPG11 from other forms of hereditary spastic paraplegia (HSP), since 60% to 80% of individuals with pathogenic variants in SPG11 have these MRI findings [Del Bo et al 2007, Hehr et al 2007, Stevanin et al 2007b, Stevanin et al 2008, Denora et al 2009]:

Electromyography (EMG) and nerve conduction velocities (NCVs) frequently show signs of axonal sensorimotor neuropathy. These signs are more frequently observed when disease duration exceeds ten years. In a few cases, anterior horn cell abnormalities have been noted [Stevanin et al 2007b, Stevanin et al 2008].

Sural nerve biopsies have shown loss of unmyelinated nerve fibers and accumulation of pleomorphic membranous material in unmyelinated axons [Hehr et al 2007].

Molecular Genetic Testing

Gene. SPG11 (previously known as KIAA1840 or FLJ21439) is the only gene in which pathogenic variants are known to cause SPG11 [Stevanin et al 2007b].

Table 1.

Molecular Genetic Testing Used in Spastic Paraplegia 11

Gene 1Test MethodPathogenic Variants Detected 2Variant Detection Frequency by Test Method 3
SPG11Sequence analysis 4Sequence variants 5>90% 6
Sequence analysis of select exonsSequence variants in select exons 7Unknown
Deletion/duplication analysis 8Partial- and whole-gene deletions 9Unknown 9

See Molecular Genetics for information on allelic variants.


The ability of the test method used to detect a variant that is present in the indicated gene


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Small intragenic deletions/insertions and nonsense and splice site variants. A missense variant has also been reported as a possible pathogenic variant (c.4046T>A) but its consequence remains unknown [Denora et al 2009]. See Molecular Genetics, Pathogenic variants.


Failure to detect a pathogenic variant on sequence analysis does not definitely exclude the diagnosis because (a) the full spectrum of abnormalities in SPG11 has not yet been established and (b) other kinds of pathogenic variants (e.g., [multi]exon or whole-gene deletions and/or large genomic rearrangements) may be identified in the future and require other detection methods.


Exons sequenced may vary by laboratory.


Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; methods used may include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.


Crimella et al [2009] identified a 2.6-kb deletion of SPG11 as one of two pathogenic variants in affected individuals in one family. The deletion results from a large intragenic rearrangement. Bauer et al [2009] and Denora et al [2009] also identified individuals with large gene deletions of 8.2 and 9 kb, respectively. Stevanin et al [2010] reported that 11% of the pathogenic variants in SPG11 are rearrangements detectable by MLPA.

Testing Strategy

To confirm/establish of the diagnosis in a proband. Detection of pathogenic variants or rearrangements in SPG11 is the only way to confirm the diagnosis of SPG11. Sequence analysis should be performed first; if only one or no pathogenic variant is identified deletion/duplication analysis can be considered.

Note: The best clinical predictors of an SPG11 pathogenic variant are lower-limb spasticity, atrophy of the corpus callosum, and either intellectual disability or cognitive impairment in individuals with onset in the first to third decade. The presence of other features such as peripheral neuropathy and white matter hyperintensities on MRI increases the chance of finding an SPG11 pathogenic variant [Stevanin et al 2008].

Clinical Characteristics

Clinical Description

Onset of spastic paraplegia 11 (SPG11) occurs mainly during infancy or adolescence (age 1-31 years) and is characterized in most cases by gait disorders or less frequently by intellectual disability [Stevanin et al 2007b, Stevanin et al 2008].

Approximately ten years after onset, most affected individuals have the complete clinical picture of SPG11, including progressive lower-limb spasticity, atrophy of the corpus callosum with intellectual disability, and/or progressive cognitive decline. Most affected individuals become wheelchair bound one or two decades after disease onset [Stevanin et al 2008].

Cognitive decline with low Mini Mental State Evaluation (MMSE) scores, found in the majority of affected individuals, worsens with time and includes severe short-term memory impairment, emotional lability, childish behavior, reduced verbal fluency, and attention deficit indicative of executive dysfunction [Stevanin et al 2006, Hehr et al 2007, Stevanin et al 2008]. Psychiatric problems with behavioral disturbances are observed. Most individuals with SPG11 display little concern over the progression of their motor disease [Stevanin et al 2006]. All these findings correlate with the frontal atrophy detected on follow-up brain MRI.

Intellectual disability, found in all individuals with early onset, is characterized by learning difficulties in childhood and low IQ.

Eye findings can include the following:

  • Macular excavation or degeneration as reported in the Kjellin syndrome [Orlén et al 2009, Puech et al 2011]
  • Strabismus
  • Cerebellar ocular signs such as abnormal saccadic pursuit and nystagmus in individuals with the longest disease duration
  • Visual evoked potentials with increased latencies and decreased amplitudes [Del Bo et al 2007, Stevanin et al 2008]

Additional features are severe weakness, dysarthria, distal or generalized muscle wasting, and less frequently, pes cavus, scoliosis, parkinsonism, and orthostatic hypotension. Individuals with the longest disease duration may have swallowing difficulties [Stevanin et al 2008].

Genotype-Phenotype Correlations

No genotype-phenotype correlations have been identified to date.


SPG11 is one of several autosomal recessive disorders in which hereditary spastic paraplegia is associated with thin corpus callosum (HSP-TCC), a phenotype originally described in Japan [Nakamura et al 1995].

Based on the electromyography (EMG) and nerve conduction velocity (NCV) patterns present and on anterior horn cell abnormalities seen in some affected individuals (see Testing), several authors have characterized this clinical entity as upper and lower motor neuron disease [Stevanin et al 2008] or as juvenile amyotrophic lateral sclerosis with long disease duration [Orlacchio et al 2010].


The estimated prevalence for HSP of all types ranges from 1:100,000 to 10:100,000 depending on the country [Fink 2006]. A recent study estimated the prevalence for HSP in southern Tunisia to be 5.75:100,000 and 5.29:100,000 for autosomal recessive forms only [Boukhris et al 2009]. Since SPG11 was found to account for 18.9% of all recessive cases, a prevalence of 1:100,000 of this genetic entity can be estimated.

As expected in autosomal recessive diseases, most families with SPG11 originate from countries in which consanguinity is common particularly the Mediterranean basin or the Middle East [Casali et al 2004, Olmez et al 2006, Stevanin et al 2006, Winner et al 2006, Hehr et al 2007, Stevanin et al 2008, Denora et al 2009].

As previously suggested by linkage studies [Shibasaki et al 2000, Casali et al 2004, Lossos et al 2006, Olmez et al 2006, Stevanin et al 2006, Winner et al 2006], SPG11 pathogenic variants have also been found in families from Scandinavia, Asia, Africa, and South America [Del Bo et al 2007, Stevanin et al 2007b, Hehr et al 2007, Stevanin et al 2008, Boukhris et al 2008, Denora et al 2009, Southgate et al 2010, Rajakulendran et al 2011], indicating a worldwide distribution of SPG11. In populations with less consanguinity, most affected individuals represent simplex cases (i.e., a single occurrence in a family).

Differential Diagnosis

See Hereditary Spastic Paraplegia (HSP) Overview. The relative frequency of spastic paraplegia 11 (SPG11) varies according to phenotype. SPG11 accounts for:

Because the phenotype of progressive spasticity with mild intellectual disability and/or cognitive decline associated with TCC accounts for one third of autosomal recessive spastic paraplegia [França et al 2007] and because SPG11 is a common cause of this phenotype, SPG11 should account for approximately 21% of all autosomal recessive HSP [Stevanin et al 2008].

No instances of pure spastic paraplegia associated with an SPG11 pathogenic variant have been reported to date [personal data].

Lower motor neuron degeneration may mimic amyotrophic lateral sclerosis (ALS) when wasting is marked as reported by Stevanin et al [2008], Orlacchio et al [2010], and Daoud et al [2012]. Upper motor neuron degeneration with spasticity can be seen in a non-genetic disorder called primary lateral sclerosis.

Other spastic paraplegias in which TCC (referred to as AR-HSP-TCC) is observed:


Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with spastic paraplegia 11 (SPG11), the following evaluations are recommended:

  • Neuropsychological testing to assess the cognitive impairment and decline
  • Neuro-urologic examination for those with sphincter disturbance
  • Electrophysiologic investigations (e.g., ENMG, VEP, SEP)
  • Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

No specific drug treatment or cures exist for SPG11.

Care by a multidisciplinary team that may include a general practitioner, neurologist, medical geneticist, physiotherapist, physical therapist, social worker, and psychologist should be considered.

Symptomatic treatment to reduce pyramidal hyperactivity in the lower limbs includes the following:

  • Physiotherapy for stretching of the spastic muscles to prevent contractures
  • Anti-spastic drugs such as baclofen and tizanidine
  • Botulin toxin and intrathecal baclofen, which can be considered when oral drugs are ineffective and spasticity is severe and disabling

When sphincter disturbances become a problem, urodynamic evaluation should be performed in order to adapt treatment and monitor follow up. Anticholinergic drugs are indicated for urinary urgency.

Psychiatric manifestations should be treated in accordance with standard practice.

Prevention of Secondary Complications

Follow up of sphincter disturbances is important to prevent bladder dysfunction and infection.

Early regular physiotherapy helps to prevent contractures.


Specialized outpatient clinic evaluations are suggested every six months to adjust medication and physical rehabilitation.

Brain MRI can be used to follow the atrophy of the corpus callosum, cerebellum, and brain stem, and to monitor increases in the size and intensity of white matter hyperintensities.

Regular electrophysiologic investigations (e.g., ENMG, VEP, SEP) are recommended to follow the extent of the disease.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search in the US and in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Spastic paraplegia 11 (SPG11) is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

Sibs of a proband

  • At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
  • Once an at-risk sib is known to be unaffected, his/her risk of being a carrier is 2/3.
  • Heterozygotes (carriers) are asymptomatic.

Offspring of a proband. The offspring of an individual with SPG11 are obligate heterozygotes (carriers) for a pathogenic variant in SPG11.

Other family members of a proband. Each sib of the proband's parents is at a 50% risk of being a carrier.

Carrier (Heterozygote) Detection

Carrier testing for at-risk family members is possible once the causative pathogenic variants have been identified in the family.

Related Genetic Counseling Issues

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Diagnosis

Once the pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible.


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • HSP Research Foundation
    P.O. Box 4064
    Warrimoo New South Wales NSW 2774
  • National Institute of Neurological Disorders and Stroke (NINDS)
    PO Box 5801
    Bethesda MD 20824
    Phone: 800-352-9424 (toll-free); 301-496-5751; 301-468-5981 (TTY)
  • Spastic Paraplegia Foundation, Inc.
    7700 Leesburg Pike
    Ste 123
    Falls Church VA 22043
    Phone: 877-773-4483 (toll-free)
  • Tom Wahlig-Foundation
    Tom Wahlig Stiftung
    Büro Veghestrasse 22
    Phone: 49 (0) 251 - 20 07 91 20
  • A.I. Vi.P.S.
    Associazione Italiana Vivere la Paraparesi Spastica Onlus
    Via Tevere, 7
    20020 Lainate (MI)
    Phone: 39 392 9825622

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Spastic Paraplegia 11: Genes and Databases

Locus NameGeneChromosome LocusProteinLocus-Specific DatabasesHGMDClinVar
SPG11SPG1115q21​.1SpatacsinSPG11 databaseSPG11SPG11

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Spastic Paraplegia 11 (View All in OMIM)

610844SPG11 GENE; SPG11

Gene structure. See Table 2. Human SPG11 contains 40 exons spanning 101 kb of genomic DNA. For a detailed summary of gene and protein information, see Table A, Gene.

Table 2.

Selected SPG11 Benign Variants

Exon/ IntronDNA Nucleotide Change
(Alias 1)
Predicted Protein Change 2FrequencyReference Sequences
In Individuals with HSPIn Controls
Exon 4c.808G>Ap.Val270Ile1.5%2.3%NM_025137​.3
Exon 6c.1388T>Cp.Phe463Ser47%51%
Exon 19c.3420G>Ap.=2.3%3.3%
Exon 39c.7023C>Tp.=1.5%7.1%
Intron 37c.6843+62C>T
--ND 3ND
Intron 7c.1603-141A>C
Intron 7c.1603-139A>G

Note on variant classification: Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​ See Quick Reference for an explanation of nomenclature.


Variant designation that does not conform to current naming conventions


p.= indicates that no effect on protein level is expected.


ND = not done

Pathogenic variants. More than 100 different truncating variants have been identified to date [Del Bo et al 2007, Hehr et al 2007, Stevanin et al 2007b, Stevanin et al 2008, Bauer et al 2009, Boukhris et al 2009, Crimella et al 2009, Denora et al 2009, Stevanin et al 2010]. They are distributed throughout SPG11 from exon 1 to exon 39 (see Table 3 [pdf]).

A missense variant has also been reported as possibly causative (NM_025137.3:c.4046T>A; NP_079413.3:p.Phe1349Tyr); its effect remains unknown [Denora et al 2009]

Normal gene product. The full-length transcript encodes a predicted protein of 2443 amino acids of unknown function, called spatacsin (for spasticity with thin or atrophied corpus callosum syndrome protein) [Stevanin et al 2007b]. The sequence of spatacsin is strongly conserved through evolution with orthologs in mammals and other vertebrates: human spatacsin shares 85% identity with the homologous protein in dog, 76% and 73% with the mouse and rat homologs, and 59% with the chicken homolog, all of similar sizes. Neither the gene nor the predicted protein that it encodes in many species shows any significant sequence similarity to known cDNA or protein sequences. The spatacsin protein interacts with the SPG15 and SPG48 protein products [Słabicki et al 2010] and is an accessory protein of the adaptor protein 5 complex [Hirst et al 2011], consistent with its presence along microtubules [Murmu et al 2011].

Abnormal gene product. With the exception of one variant of uncertain clinical significance (c.4046T>A) [Denora et al 2009], all pathogenic variants identified to date in SPG11 predict truncation of the protein, suggesting that pathogenicity results from loss of function of the spatacsin protein. Indeed, reduced spg11 function in zebrafish led to abnormal development of motor neurons [Southgate et al 2010, Martin et al 2012].


Literature Cited

  • Al-Yahyaee S, Al-Gazali LI, De Jonghe P, Al-Barwany H, Al-Kindi M, De Vriendt E, Chand P, Koul R, Jacob PC, Gururaj A, Sztriha L, Parrado A, Van Broeckhoven C, Bayoumi RA. A novel locus for hereditary spastic paraplegia with thin corpus callosum and epilepsy. Neurology. 2006;66:1230–4. [PubMed: 16636240]
  • Anheim M, Lagier-Tourenne C, Stevanin G, Fleury M, Durr A, Namer IJ, Denora P, Brice A, Mandel JL, Koenig M, Tranchant C. SPG11 spastic paraplegia. A new cause of juvenile parkinsonism. J Neurol. 2009;256:104–8. [PubMed: 19224311]
  • Bauer P, Leshinsky-Silver E, Blumkin L, Schlipf N, Schröder C, Schicks J, Lev D, Riess O, Lerman-Sagie T, Schöls L. Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47) . Neurogenetics. 2012;13:73–6. [PubMed: 22290197]
  • Bauer P, Winner B, Schüle R, Bauer C, Häfele V, Hehr U, Bonin M, Walter M, Karle K, Ringer TM, Riess O, Winkler J, Schöls L. Identification of a heterozygous genomic deletion in the spatacsin gene in SPG11 patients using high-resolution comparative genomic hybridization. Neurogenetics. 2009;10:43–8. [PubMed: 18787847]
  • Boukhris A, Stevanin G, Feki I, Denis E, Elleuch N, Miladi MI, Truchetto J, Denora P, Belal S, Mhiri C, Brice A. Hereditary spastic paraplegia with mental impairment and thin corpus callosum in Tunisia: SPG11, SPG15, and further genetic heterogeneity. Arch Neurol. 2008;65:393–402. [PubMed: 18332254]
  • Boukhris A, Stevanin G, Feki I, Denora P, Elleuch N, Miladi MI, Goizet C, Truchetto J, Belal S, Brice A, Mhiri C. Tunisian hereditary spastic paraplegias: clinical variability supported by genetic heterogeneity. Clin Genet. 2009;75:527–36. [PubMed: 19438933]
  • Casali C, Valente EM, Bertini E, Montagna G, Criscuolo C, De Michele G, Villanova M, Damiano M, Pierallini A, Brancati F, Scarano V, Tessa A, Cricchi F, Grieco GS, Muglia M, Carella M, Martini B, Rossi A, Amabile GA, Nappi G, Filla A, Dallapiccola B, Santorelli FM. Clinical and genetic studies in hereditary spastic paraplegia with thin corpus callosum. Neurology. 2004;62:262–8. [PubMed: 14745065]
  • Coutinho P, Barros J, Zemmouri R, Guimaraes J, Alves C, Chorao R, Lourenco E, Ribeiro P, Loureiro JL, Santos JV, Hamri A, Paternotte C, Hazan J, Silva MC, Prud'homme JF, Grid D. Clinical heterogeneity of autosomal recessive spastic paraplegias: analysis of 106 patients in 46 families. Arch Neurol. 1999;56:943–9. [PubMed: 10448799]
  • Crimella C, Arnoldi A, Crippa F, Mostacciuolo ML, Boaretto F, Sironi M, D'Angelo MG, Manzoni S, Piccinini L, Turconi AC, Toscano A, Musumeci O, Benedetti S, Fazio R, Bresolin N, Daga A, Martinuzzi A, Bassi MT. Point mutations and a large intragenic deletion in SPG11 in complicated spastic paraplegia without thin corpus callosum. J Med Genet. 2009;46:345–51. [PubMed: 19196735]
  • Daoud H, Zhou S, Noreau A, Sabbagh M, Belzil V, Dionne-Laporte A, Tranchant C, Dion P, Rouleau GA. Exome sequencing reveals SPG11 mutations causing juvenile ALS. Neurobiol Aging. 2012;33:839.e5–9. [PubMed: 22154821]
  • Del Bo R, Di Fonzo A, Ghezzi S, Locatelli F, Stevanin G, Costa A, Corti S, Bresolin N, Comi GP. SPG11: a consistent clinical phenotype in a family with homozygous Spatacsin truncating mutation. Neurogenetics. 2007;8:301–5. [PubMed: 17717710]
  • Denora PS, Brockmann K, Ciccolella M, Truchetto J, Stevanin G, Santorelli FM. Identification of a de novo mutation in SPG11. Mov Disord. 2010;25:501–3. [PubMed: 20108361]
  • Denora PS, Schlesinger D, Casali C, Kok F, Tessa A, Boukhris A, Azzedine H, Dotti MT, Bruno C, Truchetto J, Biancheri R, Fedirko E, Di Rocco M, Bueno C, Malandrini A, Battini R, Sickl E, de Leva MF, Boespflug-Tanguy O, Silvestri G, Simonati A, Said E, Ferbert A, Criscuolo C, Heinimann K, Modoni A, Weber P, Palmeri S, Plasilova M, Pauri F, Cassandrini D, Battisti C, Pini A, Tosetti M, Hauser E, Masciullo M, Di Fabio R, Piccolo F, Denis E, Cioni G, Massa R, Della Giustina E, Calabrese O, Melone MA, De Michele G, Federico A, Bertini E, Durr A, Brockmann K, van der Knaap MS, Zatz M, Filla A, Brice A, Stevanin G, Santorelli FM. Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion. Hum Mutat. 2009;30:E500–19. [PubMed: 19105190]
  • Fink JK. Hereditary spastic paraplegia. Curr Neurol Neurosci Rep. 2006;6:65–76. [PubMed: 16469273]
  • França MC Jr, D'Abreu A, Maurer-Morelli CV, Seccolin R, Appenzeller S, Alessio A, Damasceno BP, Nucci A, Cendes F, Lopes-Cendes I. Prospective neuroimaging study in hereditary spastic paraplegia with thin corpus callosum. Mov Disord. 2007;22:1556–62. [PubMed: 17516453]
  • França MC Jr, Yasuda CL, Pereira FR, D'Abreu A, Lopes-Ramos CM, Rosa MV, Cendes F, Lopes-Cendes I. White and grey matter abnormalities in patients with SPG11 mutations. J Neurol Neurosurg Psychiatry. 2012;83:828–33. [PubMed: 22696581]
  • Goizet C, Boukhris A, Maltete D, Guyant-Maréchal L, Truchetto J, Mundwiller E, Hanein S, Jonveaux P, Roelens F, Loureiro J, Godet E, Forlani S, Melki J, Auer-Grumbach M, Fernandez JC, Martin-Hardy P, Sibon I, Sole G, Orignac I, Mhiri C, Coutinho P, Durr A, Brice A, Stevanin G. SPG15 is the second most common cause of hereditary spastic paraplegia with thin corpus callosum. Neurology. 2009;73:1111–9. [PubMed: 19805727]
  • Hanein S, Martin E, Boukhris A, Byrne P, Goizet C, Hamri A, Benomar A, Lossos A, Denora P, Fernandez J, Elleuch N, Forlani S, Durr A, Feki I, Hutchinson M, Santorelli FM, Mhiri C, Brice A, Stevanin G. Identification of the SPG15 gene, encoding spastizin, as a frequent cause of complicated autosomal-recessive spastic paraplegia, including Kjellin syndrome. Am J Hum Genet. 2008;82:992–1002. [PMC free article: PMC2427184] [PubMed: 18394578]
  • Hehr U, Bauer P, Winner B, Schule R, Olmez A, Koehler W, Uyanik G, Engel A, Lenz D, Seibel A, Hehr A, Ploetz S, Gamez J, Rolfs A, Weis J, Ringer TM, Bonin M, Schuierer G, Marienhagen J, Bogdahn U, Weber BH, Topaloglu H, Schols L, Riess O, Winkler J. Long-term course and mutational spectrum of spatacsin-linked spastic paraplegia. Ann Neurol. 2007;62:656–65. [PubMed: 18067136]
  • Hirst J, Barlow LD, Francisco GC, Sahlender DA, Seaman MN, Dacks JB, Robinson MS. The fifth adaptor protein complex. PLoS Biol. 2011;9:e1001170. [PMC free article: PMC3191125] [PubMed: 22022230]
  • Hughes CA, Byrne PC, Webb S, McMonagle P, Patterson V, Hutchinson M, Parfrey NA. SPG15, a new locus for autosomal recessive complicated HSP on chromosome 14q. Neurology. 2001;56:1230–3. [PubMed: 11342696]
  • Lossos A, Stevanin G, Meiner V, Argov Z, Bouslam N, Newman JP, Gomori JM, Klebe S, Lerer I, Elleuch N, Silverstein S, Durr A, Abramsky O, Ben-Nariah Z, Brice A. Hereditary spastic paraplegia with thin corpus callosum: reduction of the SPG11 interval and evidence for further genetic heterogeneity. Arch Neurol. 2006;63:756–60. [PubMed: 16682547]
  • Martin E, Yanicostas C, Rastetter A, Naini SM, Maouedj A, Kabashi E, Rivaud-Péchoux S, Brice A, Stevanin G, Soussi-Yanicostas N. Spatacsin and spastizin act in the same pathway required for proper spinal motor neuron axon outgrowth in zebrafish. Neurobiol Dis. 2012;48:299–308. [PubMed: 22801083]
  • Murmu RP, Martin E, Rastetter A, Esteves T, Muriel MP, El Hachimi KH, Denora PS, Dauphin A, Fernandez JC, Duyckaerts C, Brice A, Darios F, Stevanin G. Cellular distribution and subcellular localization of spatacsin and spastizin, two proteins involved in hereditary spastic paraplegia. Mol Cell Neurosci. 2011;47:191–202. [PubMed: 21545838]
  • Nakamura A, Izumi K, Umehara F, Kuriyama M, Hokezu Y, Nakagawa M, Shimmyozu K, Izumo S, Osame M. Familial spastic paraplegia with mental impairment and thin corpus callosum. J Neurol Sci. 1995;131:35–42. [PubMed: 7561945]
  • Olmez A, Uyanik G, Ozgül RK, Gross C, Cirak S, Elibol B, Anlar B, Winner B, Hehr U, Topaloglu H, Winkler J. Further clinical and genetic characterization of SPG11: hereditary spastic paraplegia with thin corpus callosum. Neuropediatrics. 2006;37:59–66. [PubMed: 16773502]
  • Orlacchio A, Babalini C, Borreca A, Patrono C, Massa R, Basaran S, Munhoz RP, Rogaeva EA, St George-Hyslop PH, Bernardi G, Kawarai T. SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis. Brain. 2010;133:591–8. [PMC free article: PMC2822627] [PubMed: 20110243]
  • Orlacchio A, Kawarai T, Totaro A, Errico A, St George-Hyslop PH, Rugarli EI, Bernardi G. Hereditary spastic paraplegia: clinical genetic study of 15 families. Arch Neurol. 2004;61:849–55. [PubMed: 15210521]
  • Orlén H, Melberg A, Raininko R, Kumlien E, Entesarian M, Söderberg P, Påhlman M, Darin N, Kyllerman M, Holmberg E, Engler H, Eriksson U, Dahl N. SPG11 mutations cause Kjellin syndrome, a hereditary spastic paraplegia with thin corpus callosum and central retinal degeneration. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:984–92. [PubMed: 19194956]
  • Puech B, Lacour A, Stevanin G, Sautiere BG, Devos D, Depienne C, Denis E, Mundwiller E, Ferriby D, Vermersch P, Defoort-Dhellemmes S. Kjellin syndrome: long-term neuro-ophthalmologic follow-up and novel mutations in the SPG11 gene. Ophthalmology. 2011;118:564–73. [PubMed: 21035867]
  • Rajakulendran S, Paisán-Ruiz C, Houlden H. Thinning of the corpus callosum and cerebellar atrophy is correlated with phenotypic severity in a family with spastic paraplegia type 11. J Clin Neurol. 2011;7:102–4. [PMC free article: PMC3131536] [PubMed: 21779300]
  • Schüle R, Schlipf N, Synofzik M, Klebe S, Klimpe S, Hehr U, Winner B, Lindig T, Dotzer A, Riess O, Winkler J, Schöls L, Bauer P. Frequency and phenotype of SPG11 and SPG15 in complicated hereditary spastic paraplegia. J Neurol Neurosurg Psychiatry. 2009;80:1402–4. [PubMed: 19917823]
  • Schuurs-Hoeijmakers JH, Geraghty MT, Kamsteeg EJ, Ben-Salem S, de Bot ST, Nijhof B, van de Vondervoort II, van der Graaf M, Nobau AC, Otte-Höller I, Vermeer S, Smith AC, Humphreys P, Schwartzentruber J., FORGE Canada Consortium. Ali BR, Al-Yahyaee SA, Tariq S, Pramathan T, Bayoumi R, Kremer HP, van de Warrenburg BP, van den Akker WM, Gilissen C, Veltman JA, Janssen IM, Vulto-van Silfhout AT, van der Velde-Visser S, Lefeber DJ, Diekstra A, Erasmus CE, Willemsen MA, Vissers LE, Lammens M, van Bokhoven H, Brunner HG, Wevers RA, Schenck A, Al-Gazali L, de Vries BB, de Brouwer AP. Mutations in DDHD2, encoding an intracellular phospholipase A(1), cause a recessive form of complex hereditary spastic paraplegia. Am J Hum Genet. 2012;91:1073–81. [PMC free article: PMC3516595] [PubMed: 23176823]
  • Shibasaki Y, Tanaka H, Iwabuchi K, Kawasaki S, Kondo H, Uekawa K, Ueda M, Kamiya T, Katayama Y, Nakamura A, Takashima H, Nakagawa M, Masuda M, Utsumi H, Nakamuro T, Tada K, Kurohara K, Inoue K, Koike F, Sakai T, Tsuji S, Kobayashi H. Linkage of autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum to chromosome 15A13-15. Ann Neurol. 2000;48:108–12. [PubMed: 10894224]
  • Simpson MA, Cross H, Proukakis C, Pryde A, Hershberger R, Chatonnet A, Patton MA, Crosby AH. Maspardin is mutated in mast syndrome, a complicated form of hereditary spastic paraplegia associated with dementia. Am J Hum Genet. 2003;73:1147–56. [PMC free article: PMC1180493] [PubMed: 14564668]
  • Southgate L, Dafou D, Hoyle J, Li N, Kinning E, Critchley P, Németh AH, Talbot K, Bindu PS, Sinha S, Taly AB, Raghavendra S, Müller F, Maher ER, Trembath RC. Novel SPG11 mutations in Asian kindreds and disruption of spatacsin function in the zebrafish. Neurogenetics. 2010;11:379–89. [PMC free article: PMC2944959] [PubMed: 20390432]
  • Słabicki M, Theis M, Krastev DB, Samsonov S, Mundwiller E, Junqueira M, Paszkowski-Rogacz M, Teyra J, Heninger AK, Poser I, Prieur F, Truchetto J, Confavreux C, Marelli C, Durr A, Camdessanche JP, Brice A, Shevchenko A, Pisabarro MT, Stevanin G, Buchholz F. A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. PLoS Biol. 2010;8:e1000408. [PMC free article: PMC2893954] [PubMed: 20613862]
  • Stevanin G, Azzedine H, Denora P, Boukhris A, Tazir M, Lossos A, Rosa AL, Lerer I, Hamri A, Alegria P, Loureiro J, Tada M, Hannequin D, Anheim M, Goizet C, Gonzalez-Martinez V, Le Ber I, Forlani S, Iwabuchi K, Meiner V, Uyanik G, Erichsen AK, Feki I, Pasquier F, Belarbi S, Cruz VT, Depienne C, Truchetto J, Garrigues G, Tallaksen C, Tranchant C, Nishizawa M, Vale J, Coutinho P, Santorelli FM, Mhiri C, Brice A, Durr A. Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration. Brain. 2008;131:772–84. [PubMed: 18079167]
  • Stevanin G, Denis E, Mundwiller E, Ferdiko E, Cazeneuve C, Leguern E, Durr A, Brice A, Depienne C. 31 novel mutations in SPG11/spatacsin identified using both direct sequencing and MLPA. Washington, DC: 60th Annual Meeting of the American Society of Human Genetics; 2010.
  • Stevanin G, Montagna G, Azzedine H, Valente EM, Durr A, Scarano V, Bouslam N, Cassandrini D, Denora PS, Criscuolo C, Belarbi S, Orlacchio A, Jonveaux P, Silvestri G, Hernandez AM, De Michele G, Tazir M, Mariotti C, Brockmann K, Malandrini A, van der Knapp MS, Neri M, Tonekaboni H, Melone MA, Tessa A, Dotti MT, Tosetti M, Pauri F, Federico A, Casali C, Cruz VT, Loureiro JL, Zara F, Forlani S, Bertini E, Coutinho P, Filla A, Brice A, Santorelli FM. Spastic paraplegia with thin corpus callosum: description of 20 new families, refinement of the SPG11 locus, candidate gene analysis and evidence of genetic heterogeneity. Neurogenetics. 2006;7:149–56. [PubMed: 16699786]
  • Stevanin G, Paternotte C, Coutinho P, Klebe S, Elleuch N, Loureiro JL, Denis E, Cruz VT, Durr A, Prud'homme JF, Weissenbach J, Brice A, Hazan J. A new locus for autosomal recessive spastic paraplegia (SPG32) on chromosome 14q12-q21. Neurology. 2007a;68:1837–40. [PubMed: 17515546]
  • Stevanin G, Santorelli FM, Azzedine H, Coutinho P, Chomilier J, Denora PS, Martin E, Ouvrard-Hernandez AM, Tessa A, Bouslam N, Lossos A, Charles P, Loureiro JL, Elleuch N, Confavreux C, Cruz VT, Ruberg M, Leguern E, Grid D, Tazir M, Fontaine B, Filla A, Bertini E, Durr A, Brice A. Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. Nat Genet. 2007b;39:366–72. [PubMed: 17322883]
  • Tesson C, Nawara M, Salih MA, Rossignol R, Zaki MS, Al Balwi M, Schule R, Mignot C, Obre E, Bouhouche A, Santorelli FM, Durand CM, Oteyza AC, El-Hachimi KH, Al Drees A, Bouslam N, Lamari F, Elmalik SA, Kabiraj MM, Seidahmed MZ, Esteves T, Gaussen M, Monin ML, Gyapay G, Lechner D, Gonzalez M, Depienne C, Mochel F, Lavie J, Schols L, Lacombe D, Yahyaoui M, Al Abdulkareem I, Zuchner S, Yamashita A, Benomar A, Goizet C, Durr A, Gleeson JG, Darios F, Brice A, Stevanin G. Alteration of Fatty-Acid-metabolizing enzymes affects mitochondrial form and function in hereditary spastic paraplegia. Am J Hum Genet. 2012;91:1051–64. [PMC free article: PMC3516610] [PubMed: 23176821]
  • Winner B, Gross C, Uyanik G, Schulte-Mattler W, Lürding R, Marienhagen J, Bogdahn U, Windpassinger C, Hehr U, Winkler J. Thin corpus callosum and amyotrophy in spastic paraplegia--case report and review of literature. Clin Neurol Neurosurg. 2006;108:692–8. [PubMed: 16102895]
  • Winner B, Uyanik G, Gross C, Lange M, Schulte-Mattler W, Schuierer G, Marienhagen J, Hehr U, Winkler J. Clinical progression and genetic analysis in hereditary spastic paraplegia with thin corpus callosum in spastic gait gene 11 (SPG11). Arch Neurol. 2004;61:117–21. [PubMed: 14732628]

Chapter Notes

Author Notes

Giovanni Stevanin, PhD is a molecular biologist with expertise in spinocerebellar degeneration. He is Director of Research at INSERM and Professor at the Ecole Pratique des Hautes Etudes University.

Alexandra Durr, MD, PhD is a neurologist with experience in the diagnosis and follow up of patients with hereditary spastic paraplegias at the National Reference Center for Neurogenetics, Pitié-Salpêtrière Hospital. She is also coordinator of the international SPATAX network.

Alexis Brice, MD is professor of medical genetics and coordinator of the National Reference Center for Neurogenetics, Pitié-Salpêtrière Hospital. He is also affiliated with Pitié-Salpêtrière Medical School and the Federation of Neurology. He is actually Director of the Brain and Spine Institute at the Pitié-Salpêtrière Hospital.


The authors' work is financially supported by the VERUM foundation, the French National Institute for Health and Medical Research (INSERM), the French Agency for Research (ANR) and the French Strümpell Lorrain Association (ASL).

Revision History

  • 31 January 2013 (me) Comprehensive update posted live
  • 3 September 2009 (cd) Revision: deletion/duplication analysis available clinically
  • 27 March 2008 (me) Review posted live
  • 26 November 2007 (gs) Original submission
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