Diagnosis, investigation and management of hereditary spastic paraplegias in the era of next-generation sequencing

@article{Hensiek2014DiagnosisIA,
  title={Diagnosis, investigation and management of hereditary spastic paraplegias in the era of next-generation sequencing},
  author={Anke E. Hensiek and Stephen Kirker and Evan Reid},
  journal={Journal of Neurology},
  year={2014},
  volume={262},
  pages={1601 - 1612}
}
The hereditary spastic paraplegias (HSPs) are a group of genetic conditions in which spastic paralysis of the legs is the principal clinical feature. This is caused by a relatively selective distal axonal degeneration involving the longest axons of the corticospinal tracts. Consequently, these conditions provide an opportunity to identify genes, proteins and cellular pathways that are critical for axonal health. In this review, we will provide a brief overview of the classification, clinical… 

Hereditary Spastic Paraplegia: An Update

The present review assimilates the available data on HSP and lists down the chromosomes involved in its pathophysiology and the mutations observed in the respective genes on the chromosomes and sheds light on the treatment available along with the oral/intrathecal medications, physical therapies, and surgical interventions.

Update on the Genetics of Spastic Paraplegias

Major advances in understanding the molecular basis of neurodegenerative diseases have revealed unifying pathogenic models that could be targeted in the much-needed development of new treatments.

Hereditary spastic paraplegia

The target of this review article is to provide a comprehensive overview of the HSP classification, neuropathology, and differential diagnosis.

The Puzzle of Hereditary Spastic Paraplegia: From Epidemiology to Treatment

The current work briefly explains the causative genes, epidemiology, underlying mechanism, and the management approach undertaken to date for hereditary spastic paraplegia, and mentioned the latest approved drugs to summarise the available knowledge on therapeutic strategies.

Clinical application of next generation sequencing in hereditary spinocerebellar ataxia: increasing the diagnostic yield and broadening the ataxia-spasticity spectrum. A retrospective analysis

Different NGS methods applied in heterogeneous cohorts of patients with suspected HA are reviewed and exome sequencing should be considered the first-tier genetic approach in this setting and lends support to the hypothesis of HA and HSP as two extremes of a continuous spectrum.

Molecular Genetic Diversity and DNA Diagnostics of Hereditary Spastic Paraplegia

Hereditary spastic paraplegia is a heterogeneous group of neurodegenerative disorders predominantly characterized by damage to the pyramidal tract, and the discovery of the pathogenic action of different genes requires the development of new therapeutic approaches.

Clinical Features and Genetic Spectrum of Patients With Clinically Suspected Hereditary Progressive Spastic Paraplegia

Causative genetic mutations were identified in 51.9% of patients with clinically suspected HSPs by NGS and triplet repeat primed PCR and dynamic mutations should be screened in patients with clinical suspected Hsps, especially in those with phenotypes of complex form of H SPs.

References

SHOWING 1-10 OF 92 REFERENCES

Child Neurology: Hereditary spastic paraplegia in children

A 4-year-old boy presented with progressive walking difficulties from the time he started walking at the age of 12 to 13 months and Diagnostic genetic testing in both the patient and his mother revealed a pathogenic mutation in REEP1 (SPG31) which causes a pure HSP.

Hereditary spastic paraplegia: advances in genetic research. Hereditary Spastic Paraplegia Working group.

Clinical, genetic, and pathologic features of HSP are reviewed and differential diagnosis and diagnostic criteria of this important group of disorders are presented.

Complicated forms of autosomal dominant hereditary spastic paraplegia are frequent in SPG10

The largest series of SPG10 families described so far is reported, which extends both the mutational spectrum of the disease and its phenotype, which now includes complicated forms of HSP.

The Global Epidemiology of Hereditary Ataxia and Spastic Paraplegia: A Systematic Review of Prevalence Studies

Assessing the global distribution and prevalence of HCA and HSP by a systematic review and meta-analysis of prevalence studies found highly variable prevalence values are reported across the world, reflecting the different genetic make-up of the populations, but also methodological heterogeneity.

SPG10 is a rare cause of spastic paraplegia in European families

SPG10 accounts for approximately 3% of European autosomal dominant HSP families, and all mutations affect the motor domain of kinesin and thus most likely impair axonal transport.

Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration.

The study reveals the high frequency of SPG11 mutations in patients with HSP, a TCC and cognitive impairment, including in isolated patients, and extends the associated phenotype.

The Prevalence of Hereditary Spastic Paraplegia and the Occurrence of SPG4 Mutations in Estonia

The epidemiological data are comparable with the results from epidemiological studies performed elsewhere, indicating that the clinical diagnostic management of HSP patients in Estonia is adequate and the chosen methodological approach for data collection was reliable.

Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum

Ten mutations in a previously unidentified gene expressed ubiquitously in the nervous system but most prominently in the cerebellum, cerebral cortex, hippocampus and pineal gland are identified, suggesting a loss-of-function mechanism in ARHSP.

Screening of hereditary spastic paraplegia patients for alterations at NIPA1 mutational hotspots

Early onset autosomal dominant spastic paraplegia caused by novel mutations in SPG3A

The comparison of the clinical data for all SPG3A-HSP families reported to date failed to reveal any genotype/phenotype correlation as demonstrated for other forms of AD-H SP, but it confirmed the early onset of this form of HSP, which was observed in almost all affected individuals with a mutation in the atlastin gene.
...