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Spastic Paraplegia 11

Includes: SPG11-Related Hereditary Spastic Paraplegia with Thin Corpus Callosum (SPG11-Related HSP-TCC)

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

Author Information
, PhD
INSERM U975, Centre de Recherche de l’Institut du Cerveau et de la Moelle Epinière
AP-HP Fédération de Génétique
Laboratoire de Neurogénétique de l’Ecole Pratique des Hautes Etudes
Hôpital Pitié-Salpêtrière
Paris, France
, MD, PhD
INSERM U975, AP-HP Fédération de Génétique
Institut du Cerveau et de la Moelle Epinière
Hôpital Pitié-Salpêtrière
Paris, France
, MD
INSERM U975, Centre de Recherche de l’Institut du Cerveau et de la Moelle Epinière
AP-HP Fédération de Génétique
Hôpital Pitié-Salpêtrière
Paris, France

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

Summary

Disease 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/testing. 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.

Management. 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 when the disease-causing mutations in a family are known.

Diagnosis

Clinical Diagnosis

The basic phenotype of spastic paraplegia 11 (SPG11), caused by mutations 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]

Testing

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 mutations 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 mutations are known to cause SPG11 [Stevanin et al 2007b].

Clinical testing

Table 1. Summary of Molecular Genetic Testing Used in Spastic Paraplegia 11

Gene 1Test MethodMutations Detected 2Mutation Detection Frequency by Test Method 3
SPG11 Sequence analysis Sequence variants 4,5>90% 6
Sequence analysis of select exonsSequence variants in select exons 7Unknown
Deletion / duplication analysis 8Partial- and whole-gene deletions 9Unknown 9

1. See Table A. Genes and Databases for chromosome locus and protein name.

2. See Molecular Genetics for information on allelic variants.

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

4. Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations; typically, exonic or whole gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

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

6. Failure to detect a mutation 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 mutations (e.g., exonic, multiexonic, or whole-gene deletions and/or large genomic rearrangements) may be identified in the future and require other detection methods.

7. Exons sequenced may vary by laboratory.

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

9. Crimella et al [2009] identified a 2.6-kb deletion of SPG11 as one of two mutations 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 mutations in SPG11 are rearrangements detectable by MLPA.

Testing Strategy

To confirm/establish of the diagnosis in a proband. Detection of mutations 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 mutations are identified deletion/duplication analysis can be considered.

Note: The best clinical predictors of an SPG11 mutation 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 mutation [Stevanin et al 2008].

Carrier testing for at-risk relatives requires prior identification of the disease-causing mutations in the family.

Note: Carriers are heterozygotes for this autosomal recessive disorder and are not at risk of developing the disorder.

Prenatal diagnosis for at-risk pregnancies requires prior identification of the disease-causing mutations in the family.

Clinical Description

Natural History

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.

Nomenclature

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].

Prevalence

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 mutations 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:

  • 4.5% of persons with spastic paraplegia and cognitive impairment without TCC but with white matter hyperintensities (one family reported by Stevanin et al [2008]);
  • Up to 59% of persons with simplex or autosomal recessive early-onset progressive spasticity with mild intellectual disability and/or cognitive decline associated with TCC [Stevanin et al 2008, Denora et al 2009].

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 mutation 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:

Note to clinicians: For a patient-specific ‘simultaneous consult’ related to this disorder, go to Image SimulConsult.jpg, an interactive diagnostic decision support software tool that provides differential diagnoses based on patient findings (registration or institutional access required).

Management

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)
  • Medical genetics consultation

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.

Surveillance

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 ClinicalTrials.gov 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

  • In almost all cases, the parents of an affected child are heterozygotes, and therefore each carries one mutant allele.
  • In one rare case, a de novo mutation in one parental allele and a mutant allele inherited from the other parent were identified in the proband [Denora et al 2010].
  • Heterozygotes (carriers) are asymptomatic but abnormal ocular fundus may occasionally be observed [Puech et al 2011].

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 disease-causing mutation 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 Detection

Carrier testing for at-risk family members is possible once the causative mutations 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, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

If the disease-causing mutations have been identified in the family, prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis (usually performed at ~15-18 weeks’ gestation) or chorionic villus sampling (usually performed at ~10-12 weeks’ gestation).

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Preimplantation genetic diagnosis (PGD) may be an option for some families in which the disease-causing mutations have been identified.

Resources

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.

  • Association Strumpell-Lorrain (ASL)
    France
    Email: asl-secretariat@orange.fr
  • 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.
    PO Box 1208
    Fortson GA 31808-1208
    Phone: 877-773-4483 (toll-free)
    Email: information@sp-foundation.org
  • National Ataxia Foundation
    2600 Fernbrook Lane
    Suite 119
    Minneapolis MN 55447
    Phone: 763-553-0020
    Email: naf@ataxia.org

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 NameGene SymbolChromosomal LocusProtein NameLocus SpecificHGMD
SPG11SPG1115q21​.1SpatacsinSPG11 homepage - Mendelian genesSPG11

Data are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B. OMIM Entries for Spastic Paraplegia 11 (View All in OMIM)

604360SPASTIC PARAPLEGIA 11, AUTOSOMAL RECESSIVE; SPG11
610844SPG11 GENE; SPG11

Normal allelic variants. See Table 2. Human SPG11 contains 40 exons spanning 101 kb of genomic DNA.

Table 2. Selected SPG11 Normal Allelic Variants

Exon/ IntronDNA Nucleotide Change
(Alias 1)
Protein Amino Acid Change 2 Frequency Reference Sequences
In Individuals with HSPIn Controls
Exon 4c.808G>Ap.Val270Ile1.5%2.3%NM_025137​.3
NP_079413​.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
(IV37+62C>T)
--ND 3 ND
Intron 7c.1603-141A>C
(IV7-141A>C)
--NDND
Intron 7c.1603-139A>G
(IV7-139A>G)
--NDND

Stevanin et al [2008]

Note on variant classification: Variants listed in the table have been provided by the author(s). 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 (www​.hgvs.org). See Quick Reference for an explanation of nomenclature.

1. Variant designation that does not conform to current naming conventions

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

3. ND = not done

Pathologic allelic variants. More than 100 different truncating mutations 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 a possible mutation (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 orthologues in mammalians and other vertebrates: human spatacsin shares 85% identity with the homologous protein in dog, 76% and 73% with the mouse and rat homologues, and 59% with the chicken homologue, 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 pathologic allelic 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].

References

Literature Cited

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Suggested Reading

  1. Brockmann K, Simpson MA, Faber A, Bonnemann C, Crosby AH, Gartner J. Complicated hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) and childhood onset. Neuropediatrics. 2005;36:274–8. [PubMed: 16138254]
  2. Depienne C, Stevanin G, Brice A, Durr A. Hereditary spastic paraplegias: an update. Curr Opin Neurol. 2007;20:674–80. [PubMed: 17992088]
  3. Finsterer J, Löscher W, Quasthoff S, Wanschitz J, Auer-Grumbach M, Stevanin G. Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance. J Neurol Sci. 2012;318:1–18. [PubMed: 22554690]
  4. Martinez Murillo F, Kobayashi H, Pegoraro E, Galluzzi G, Creel G, Mariani C, Farina E, Ricci E, Alfonso G, Pauli RM, Hoffman EP. Genetic localization of a new locus for recessive familial spastic paraparesis to 15q13-15. Neurology. 1999;53:50–6. [PubMed: 10408536]
  5. Sperfeld AD, Kassubek J, Crosby AH, Winner B, Ludolph AC, Uttner I, Hanemann CO. Complicated hereditary spastic paraplegia with thin corpus callosum: variation of phenotypic expression over time. J Neurol. 2004;251:1285–7. [PubMed: 15503116]
  6. Stevanin G, Ruberg M, Brice A. Recent advances in the genetics of spastic paraplegias. Curr Neurol Neurosci Rep. 2008;8:198–210. [PubMed: 18541115]
  7. Tang BS, Chen X, Zhao GH, Shen L, Yan XX, Jiang H, Luo W. Clinical features of hereditary spastic paraplegia with thin corpus callosum: report of 5 Chinese cases. Chin Med J (Engl). 2004;117:1002–5. [PubMed: 15265372]
  8. Teive HA, Iwamoto FM, Della Coletta MV, Camargo CH, Bezerra RD, Minguetti G, Werneck LC. Hereditary spastic paraplegia associated with thin corpus callosum. Arq Neuropsiquiatr. 2001;59:790–2. [PubMed: 11593284]

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 Dürr, 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.

Acknowledgments

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 to live Web site
  • 26 November 2007 (gs) Original submission
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