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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

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
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
Clinical features and management of hereditary spastic paraplegia.
Faber I, Servelhere KR, Martinez AR, D'Abreu A, Lopes-Cendes I, França MC Jr
Arq Neuropsiquiatr 2014 Mar;72(3):219-26. doi: 10.1590/0004-282x20130248. PMID: 24676440

Recent clinical studies

Etiology

Expanding SPTAN1 monoallelic variant associated disorders: From epileptic encephalopathy to pure spastic paraplegia and ataxia.
Morsy H, Benkirane M, Cali E, Rocca C, Zhelcheska K, Cipriani V, Galanaki E, Maroofian R, Efthymiou S, Murphy D, O'Driscoll M, Suri M, Banka S, Clayton-Smith J, Wright T, Redman M, Bassetti JA, Nizon M, Cogne B, Jamra RA, Bartolomaeus T, Heruth M, Krey I, Gburek-Augustat J, Wieczorek D, Gattermann F, Mcentagart M, Goldenberg A, Guyant-Marechal L, Garcia-Moreno H, Giunti P, Chabrol B, Bacrot S, Buissonnière R, Magry V, Gowda VK, Srinivasan VM, Melegh B, Szabó A, Sümegi K, Cossée M, Ziff M, Butterfield R, Hunt D, Bird-Lieberman G, Hanna M, Koenig M, Stankewich M, Vandrovcova J, Houlden H; Genomics England Research Consortium
Genet Med 2023 Jan;25(1):76-89. Epub 2022 Nov 4 doi: 10.1016/j.gim.2022.09.013. PMID: 36331550Free PMC Article
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.
Blackstone C
Handb Clin Neurol 2018;148:633-652. doi: 10.1016/B978-0-444-64076-5.00041-7. PMID: 29478605
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

Diagnosis

Chediak-Higashi syndrome.
Talbert ML, Malicdan MCV, Introne WJ
Curr Opin Hematol 2023 Jul 1;30(4):144-151. Epub 2023 Apr 25 doi: 10.1097/MOH.0000000000000766. PMID: 37254856Free 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
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 clinical and molecular spectrum of ZFYVE26-associated hereditary spastic paraplegia: SPG15.
Saffari A, Kellner M, Jordan C, Rosengarten H, Mo A, Zhang B, Strelko O, Neuser S, Davis MY, Yoshikura N, Futamura N, Takeuchi T, Nabatame S, Ishiura H, Tsuji S, Aldeen HS, Cali E, Rocca C, Houlden H, Efthymiou S, Assmann B, Yoon G, Trombetta BA, Kivisäkk P, Eichler F, Nan H, Takiyama Y, Tessa A, Santorelli FM, Sahin M, Blackstone C, Yang E, Schüle R, Ebrahimi-Fakhari D
Brain 2023 May 2;146(5):2003-2015. doi: 10.1093/brain/awac391. PMID: 36315648Free 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
GCH1 mutations in hereditary spastic paraplegia.
Varghaei P, Yoon G, Estiar MA, Veyron S, Leveille E, Dupré N, Trempe JF, Rouleau GA, Gan-Or Z
Clin Genet 2021 Jul;100(1):51-58. Epub 2021 Mar 18 doi: 10.1111/cge.13955. PMID: 33713342
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

Prognosis

Hereditary spastic paraplegias proteome: common pathways and pathogenetic mechanisms.
Martinello C, Panza E, Orlacchio A
Expert Rev Proteomics 2023 Jul-Dec;20(7-9):171-188. Epub 2023 Oct 16 doi: 10.1080/14789450.2023.2260952. PMID: 37788157
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
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

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 clinical and molecular spectrum of ZFYVE26-associated hereditary spastic paraplegia: SPG15.
Saffari A, Kellner M, Jordan C, Rosengarten H, Mo A, Zhang B, Strelko O, Neuser S, Davis MY, Yoshikura N, Futamura N, Takeuchi T, Nabatame S, Ishiura H, Tsuji S, Aldeen HS, Cali E, Rocca C, Houlden H, Efthymiou S, Assmann B, Yoon G, Trombetta BA, Kivisäkk P, Eichler F, Nan H, Takiyama Y, Tessa A, Santorelli FM, Sahin M, Blackstone C, Yang E, Schüle R, Ebrahimi-Fakhari D
Brain 2023 May 2;146(5):2003-2015. doi: 10.1093/brain/awac391. PMID: 36315648Free PMC Article
Hereditary spastic paraplegia: Genetic heterogeneity and common pathways.
Panza E, Meyyazhagan A, Orlacchio A
Exp Neurol 2022 Nov;357:114203. Epub 2022 Aug 13 doi: 10.1016/j.expneurol.2022.114203. PMID: 35970204
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

Recent systematic reviews

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
Parkinsonian-Pyramidal syndromes: A systematic review.
Tranchant C, Koob M, Anheim M
Parkinsonism Relat Disord 2017 Jun;39:4-16. Epub 2017 Feb 22 doi: 10.1016/j.parkreldis.2017.02.025. PMID: 28256436
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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