Hereditary spastic paraplegia: Clinicogenetic lessons from 608 patients

  title={Hereditary spastic paraplegia: Clinicogenetic lessons from 608 patients},
  author={Rebecca Sch{\"u}le and Sarah Wiethoff and Peter Martus and Kathrin N. Karle and Susanne Otto and Stephan Klebe and Sven Klimpe and Constanze Gallenm{\"u}ller and Delia Kurzwelly and Dorothea Henkel and Florian Rimmele and Henning Stolze and Zacharias Kohl and Jan Kassubek and Thomas Klockgether and Stefan Vielhaber and Christoph Kamm and Thomas Klopstock and Peter Bauer and Stephan Z{\"u}chner and Inga Liepelt-Scarfone and Ludger Sch{\"o}ls},
  journal={Annals of Neurology},
OBJECTIVE Hereditary spastic paraplegias (HSPs) are genetically driven disorders with the hallmark of progressive spastic gait disturbance. [] Key MethodMETHODS We recruited 608 HSP cases from 519 families of mostly German origin. Clinical severity was assessed by the Spastic Paraplegia Rating Scale. Complicating symptoms were recorded by a standardized inventory. RESULTS Family history indicated dominant (43%), recessive (10%), and simplex (47%) disease.
Hereditary spastic paraplegia from 1880 to 2017: an historical review.
The authors have constructed a brief timeline of major clinical research related to hereditary spastic paraplegia research, from the first clinical descriptions by Adolf von Strümpell in 1880 to the present day, with the transformation of these diseases into a rapidly-growing and heterogeneous group of neurogenetic diseases.
Paediatric‐onset hereditary spastic paraplegias: a retrospective cohort study
To describe the clinical and neurogenetic spectrum of paediatric‐onset hereditary spastic paraplegias (HSPs) diagnosed in our unit.
Hereditary spastic paraplegia
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Movement disorders: Are umbrella terms for rare genetic diseases still useful?
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Spastic Paraplegia with Paget's Disease of Bone due to a VCP Gene Mutation
A 50-year-old Japanese woman who presented with slowly progressing spastic paraplegia and a history of Paget's disease of bone was reported, and genetic testing revealed a mutation of the Valosin-containing protein (VCP) gene (p.436C>T).
Randomized Trial of Botulinum Toxin Type A in Hereditary Spastic Paraplegia — The SPASTOX Trial
The objective of the current study was to evaluate the efficacy and safety of BoNT‐A in patients with hereditary spastic paraplegias.
[Common forms of hereditary spastic paraplegias].
Clinical and genetic characteristics of common autosomal dominant and autosomal recessive spastic paraplegia forms and methods of next generation sequencing are presented.
Chinese patients with hereditary spastic paraplegias (HSPs): a protocol for a hospital-based cohort study
This study will observe clinical manifestations and disease severity based on different molecular mechanisms, including oxidative stress, cholesterol metabolism and microtubule dynamics, all of which have been proposed as potential treatment targets or modalities.


Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms
Long‐term course and mutational spectrum of spatacsin‐linked spastic paraplegia
The long‐term course and the mutational spectrum of spatacsin‐associated ARHSP with TCC was assessed and one form of autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) was linked to chromosomal region 15q13‐21 (SPG11) and associated with mutations in the spatacsIn gene.
Leukodystrophies underlying cryptic spastic paraparesis: frequency and phenotype in 76 patients
To determine the frequency of leukodystrophies and the phenotypic spectrum patients with cryptic spasticity of the legs were screened for underlying neurometabolic abnormalities.
SPG3A is the most frequent cause of hereditary spastic paraplegia with onset before age 10 years
Seven families with six different SPG3A mutations were identified among 106 with autosomal dominant hereditary spastic paraplegia (HSP). Two mutations were novel (T162P, C375R). SPG3A was twice as
Genotype-phenotype correlations in spastic paraplegia type 7: a study in a large Dutch cohort.
In this large Dutch cohort, the first genotype-phenotype correlation in spastic paraplegia type 7 seems to have been identified by observing an association between the cerebellar phenotype ofSPG7 type 7 and SPG7 null alleles.
Genetics of hereditary spastic paraplegias.
An overview on clinical, neurophysiologic, and neuroradiologic characteristics of the more common HSP subtypes is provided, and a genetic testing strategy is proposed.
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.
Spastin mutations are frequent in sporadic spastic paraparesis and their spectrum is different from that observed in familial cases
The unexpected presence of SPG4 gene mutations in patients with sporadic spastic paraplegia suggests that gene testing should be done in individuals with pure or complicated spastic wheelchair without family histories.
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.
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.