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Hereditary spastic paraplegia

MedGen UID:
20844
•Concept ID:
C0037773
•
Disease or Syndrome
Synonym: Familial spastic paraparesis
SNOMED CT: HSP - Hereditary spastic paraplegia (39912006); Spastic congenital paraplegia (39912006); Hereditary spastic paraplegia (39912006); Strumpell-Lorrain disease (39912006); Familial spastic paraplegia syndrome (39912006)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
X-linked recessive inheritance
MedGen UID:
375779
•Concept ID:
C1845977
•
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
See: This record
Autosomal recessive inheritance (Orphanet)
Autosomal dominant inheritance (Orphanet)
X-linked recessive inheritance (Orphanet)
 
Monarch Initiative: MONDO:0019064
OMIM® Phenotypic series: PS303350
Orphanet: ORPHA685

Definition

A genetically and clinically heterogeneous group of slowly progressive neurological disorders which in the pure form is characterized by pyramidal signs (weakness, spasticity, brisk tendon reflexes, and extensor plantar responses) predominantly affecting the lower limbs and with possible association of sphincter disturbances and deep sensory loss; and in the complex form by the addition of variable neurological or non-neurological features. [from ORDO]

Professional guidelines

PubMed

Hereditary spastic paraplegia: Manifestations and treatment challenges.
Dong L, Zhuo X, Jiang Z
Asian J Surg 2024 Sep;47(9):4078-4079. Epub 2024 May 14 doi: 10.1016/j.asjsur.2024.05.034. PMID: 38749834
Non-pharmacological treatment of hereditary spastic paraplegia: a systematic review.
Maccora S, Torrente A, Di Stefano V, Lupica A, Iacono S, Pilati L, Pignolo A, Brighina F
Neurol Sci 2024 Mar;45(3):963-976. Epub 2023 Nov 16 doi: 10.1007/s10072-023-07200-1. PMID: 37968432Free PMC Article
Importance of genetic testing for childhood-onset hereditary spastic paraplegia.
Blackstone C
Dev Med Child Neurol 2023 Mar;65(3):307-308. Epub 2022 Sep 27 doi: 10.1111/dmcn.15416. PMID: 36168202

Recent clinical studies

Etiology

Distal hereditary motor neuropathies.
Tazir M, Nouioua S
Rev Neurol (Paris) 2024 Dec;180(10):1031-1036. Epub 2024 May 3 doi: 10.1016/j.neurol.2023.09.005. PMID: 38702287
Hereditary spastic paraplegia.
Murala S, Nagarajan E, Bollu PC
Neurol Sci 2021 Mar;42(3):883-894. Epub 2021 Jan 13 doi: 10.1007/s10072-020-04981-7. PMID: 33439395
Hereditary spastic paraplegia: from diagnosis to emerging therapeutic approaches.
Shribman S, Reid E, Crosby AH, Houlden H, Warner TT
Lancet Neurol 2019 Dec;18(12):1136-1146. Epub 2019 Jul 31 doi: 10.1016/S1474-4422(19)30235-2. PMID: 31377012
Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms.
Fink JK
Acta Neuropathol 2013 Sep;126(3):307-28. Epub 2013 Jul 30 doi: 10.1007/s00401-013-1115-8. PMID: 23897027Free PMC Article
Pure hereditary spastic paraplegia.
Reid E
J Med Genet 1997 Jun;34(6):499-503. doi: 10.1136/jmg.34.6.499. PMID: 9192272Free PMC Article

Diagnosis

Distal hereditary motor neuropathies.
Tazir M, Nouioua S
Rev Neurol (Paris) 2024 Dec;180(10):1031-1036. Epub 2024 May 3 doi: 10.1016/j.neurol.2023.09.005. PMID: 38702287
Hereditary Spastic Paraplegia: An Update.
Meyyazhagan A, Orlacchio A
Int J Mol Sci 2022 Feb 1;23(3) doi: 10.3390/ijms23031697. PMID: 35163618Free PMC Article
A Diagnostic Approach to Spastic ataxia Syndromes.
Pedroso JL, Vale TC, França Junior MC, Kauffman MA, Teive H, Barsottini OGP, Munhoz RP
Cerebellum 2022 Dec;21(6):1073-1084. Epub 2021 Nov 15 doi: 10.1007/s12311-021-01345-5. PMID: 34782953
Hereditary spastic paraplegia.
Murala S, Nagarajan E, Bollu PC
Neurol Sci 2021 Mar;42(3):883-894. Epub 2021 Jan 13 doi: 10.1007/s10072-020-04981-7. PMID: 33439395
Hereditary spastic paraplegia: from diagnosis to emerging therapeutic approaches.
Shribman S, Reid E, Crosby AH, Houlden H, Warner TT
Lancet Neurol 2019 Dec;18(12):1136-1146. Epub 2019 Jul 31 doi: 10.1016/S1474-4422(19)30235-2. PMID: 31377012

Therapy

Intrathecal AAV9/AP4M1 gene therapy for hereditary spastic paraplegia 50 shows safety and efficacy in preclinical studies.
Chen X, Dong T, Hu Y, De Pace R, Mattera R, Eberhardt K, Ziegler M, Pirovolakis T, Sahin M, Bonifacino JS, Ebrahimi-Fakhari D, Gray SJ
J Clin Invest 2023 May 15;133(10) doi: 10.1172/JCI164575. PMID: 36951961Free PMC Article
The Puzzle of Hereditary Spastic Paraplegia: From Epidemiology to Treatment.
Meyyazhagan A, Kuchi Bhotla H, Pappuswamy M, Orlacchio A
Int J Mol Sci 2022 Jul 11;23(14) doi: 10.3390/ijms23147665. PMID: 35887006Free PMC Article
Clinical and genetic update of hereditary spastic paraparesis.
Lallemant-Dudek P, Durr A
Rev Neurol (Paris) 2021 May;177(5):550-556. Epub 2020 Aug 15 doi: 10.1016/j.neurol.2020.07.001. PMID: 32807405
Visual inspection methods for cervical cancer prevention.
Sankaranarayanan R, Nessa A, Esmy PO, Dangou JM
Best Pract Res Clin Obstet Gynaecol 2012 Apr;26(2):221-32. Epub 2011 Nov 9 doi: 10.1016/j.bpobgyn.2011.08.003. PMID: 22075441
The genetics of hereditary spastic paraplegia and implications for drug therapy.
Züchner S
Expert Opin Pharmacother 2007 Jul;8(10):1433-9. doi: 10.1517/14656566.8.10.1433. PMID: 17661726

Prognosis

Clinical and genetic spectra of 1550 index patients with hereditary spastic paraplegia.
Méreaux JL, Banneau G, Papin M, Coarelli G, Valter R, Raymond L, Kol B, Ariste O, Parodi L, Tissier L, Mairey M, Ait Said S, Gautier C, Guillaud-Bataille M; French SPATAX clinical network, Forlani S, de la Grange P, Brice A, Vazza G, Durr A, Leguern E, Stevanin G
Brain 2022 Apr 29;145(3):1029-1037. doi: 10.1093/brain/awab386. PMID: 34983064
Genetics in hereditary spastic paraplegias: Essential but not enough.
Darios F, Coarelli G, Durr A
Curr Opin Neurobiol 2022 Feb;72:8-14. Epub 2021 Aug 14 doi: 10.1016/j.conb.2021.07.005. PMID: 34403957
Genetic mimics of cerebral palsy.
Pearson TS, Pons R, Ghaoui R, Sue CM
Mov Disord 2019 May;34(5):625-636. Epub 2019 Mar 26 doi: 10.1002/mds.27655. PMID: 30913345
Hereditary spastic paraplegia.
Fink JK
Curr Neurol Neurosci Rep 2006 Jan;6(1):65-76. doi: 10.1007/s11910-996-0011-1. PMID: 16469273
Hereditary spastic paraplegia.
Fink JK
Neurol Clin 2002 Aug;20(3):711-26. doi: 10.1016/s0733-8619(02)00007-5. PMID: 12432827

Clinical prediction guides

Distal hereditary motor neuropathies.
Tazir M, Nouioua S
Rev Neurol (Paris) 2024 Dec;180(10):1031-1036. Epub 2024 May 3 doi: 10.1016/j.neurol.2023.09.005. PMID: 38702287
Intrathecal AAV9/AP4M1 gene therapy for hereditary spastic paraplegia 50 shows safety and efficacy in preclinical studies.
Chen X, Dong T, Hu Y, De Pace R, Mattera R, Eberhardt K, Ziegler M, Pirovolakis T, Sahin M, Bonifacino JS, Ebrahimi-Fakhari D, Gray SJ
J Clin Invest 2023 May 15;133(10) doi: 10.1172/JCI164575. PMID: 36951961Free PMC Article
Hereditary Spastic Paraplegia: An Update.
Meyyazhagan A, Orlacchio A
Int J Mol Sci 2022 Feb 1;23(3) doi: 10.3390/ijms23031697. PMID: 35163618Free PMC Article
Clinical and genetic spectra of 1550 index patients with hereditary spastic paraplegia.
Méreaux JL, Banneau G, Papin M, Coarelli G, Valter R, Raymond L, Kol B, Ariste O, Parodi L, Tissier L, Mairey M, Ait Said S, Gautier C, Guillaud-Bataille M; French SPATAX clinical network, Forlani S, de la Grange P, Brice A, Vazza G, Durr A, Leguern E, Stevanin G
Brain 2022 Apr 29;145(3):1029-1037. doi: 10.1093/brain/awab386. PMID: 34983064
Genetics in hereditary spastic paraplegias: Essential but not enough.
Darios F, Coarelli G, Durr A
Curr Opin Neurobiol 2022 Feb;72:8-14. Epub 2021 Aug 14 doi: 10.1016/j.conb.2021.07.005. PMID: 34403957

Recent systematic reviews

Non-pharmacological treatment of hereditary spastic paraplegia: a systematic review.
Maccora S, Torrente A, Di Stefano V, Lupica A, Iacono S, Pilati L, Pignolo A, Brighina F
Neurol Sci 2024 Mar;45(3):963-976. Epub 2023 Nov 16 doi: 10.1007/s10072-023-07200-1. PMID: 37968432Free PMC Article
Movement disorders in hereditary spastic paraplegia (HSP): a systematic review and individual participant data meta-analysis.
Fereshtehnejad SM, Saleh PA, Oliveira LM, Patel N, Bhowmick S, Saranza G, Kalia LV
Neurol Sci 2023 Mar;44(3):947-959. Epub 2022 Nov 28 doi: 10.1007/s10072-022-06516-8. PMID: 36441344Free PMC Article
Hereditary spastic paraplegia type 11: Clinicogenetic lessons from 339 patients.
Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Genotype-phenotype associations in hereditary spastic paraplegia: a systematic review and meta-analysis on 13,570 patients.
Erfanian Omidvar M, Torkamandi S, Rezaei S, Alipoor B, Omrani MD, Darvish H, Ghaedi H
J Neurol 2021 Jun;268(6):2065-2082. Epub 2019 Nov 19 doi: 10.1007/s00415-019-09633-1. PMID: 31745725
The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies.
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320

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