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Complex hereditary spastic paraplegia

MedGen UID:
581446
•Concept ID:
C0393556
•
Disease or Syndrome
Synonyms: Complex familial spastic paraplegia; complex hereditary spastic paraplegia; Complex HSP; Complex SPG; Complicated familial spastic paraplegia; complicated familial spastic paraplegia; Complicated hereditary spastic paraplegia; complicated hereditary spastic paraplegia; Complicated HSP; complicated HSP; Complicated SPG; complicated SPG; syndrome associated with hereditary spastic paraplegia; syndromic hereditary spastic paraplegia
SNOMED CT: Complicated hereditary spastic paraplegia (230261006)
 
Monarch Initiative: MONDO:0015150
Orphanet: ORPHA102013

Definition

A hereditary spastic paraplegia that is part of a larger syndrome. [from MONDO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Complex hereditary spastic paraplegia

Professional guidelines

PubMed

Clinical heterogeneity and genotype-phenotype correlations in hereditary spastic paraplegia because of Spatacsin mutations (SPG11).
Paisan-Ruiz C, Nath P, Wood NW, Singleton A, Houlden H
Eur J Neurol 2008 Oct;15(10):1065-70. Epub 2008 Aug 20 doi: 10.1111/j.1468-1331.2008.02247.x. PMID: 18717728Free PMC Article

Recent clinical studies

Etiology

A homozygous variant in CHMP3 is associated with complex hereditary spastic paraplegia.
Cohen-Barak E, Danial-Farran N, Chervinsky E, Alimi-Kasem O, Zagairy F, Livneh I, Mawassi B, Hreish M, Khayat M, Lossos A, Meiner V, Ehilevitch N, Weiss K, Shalev S
J Med Genet 2023 Mar;60(3):233-240. Epub 2022 Jun 16 doi: 10.1136/jmedgenet-2022-108508. PMID: 35710109
Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia.
Ebrahimi-Fakhari D, Teinert J, Behne R, Wimmer M, D'Amore A, Eberhardt K, Brechmann B, Ziegler M, Jensen DM, Nagabhyrava P, Geisel G, Carmody E, Shamshad U, Dies KA, Yuskaitis CJ, Salussolia CL, Ebrahimi-Fakhari D, Pearson TS, Saffari A, Ziegler A, Kölker S, Volkmann J, Wiesener A, Bearden DR, Lakhani S, Segal D, Udwadia-Hegde A, Martinuzzi A, Hirst J, Perlman S, Takiyama Y, Xiromerisiou G, Vill K, Walker WO, Shukla A, Dubey Gupta R, Dahl N, Aksoy A, Verhelst H, Delgado MR, Kremlikova Pourova R, Sadek AA, Elkhateeb NM, Blumkin L, Brea-Fernández AJ, Dacruz-Álvarez D, Smol T, Ghoumid J, Miguel D, Heine C, Schlump JU, Langen H, Baets J, Bulk S, Darvish H, Bakhtiari S, Kruer MC, Lim-Melia E, Aydinli N, Alanay Y, El-Rashidy O, Nampoothiri S, Patel C, Beetz C, Bauer P, Yoon G, Guillot M, Miller SP, Bourinaris T, Houlden H, Robelin L, Anheim M, Alamri AS, Mahmoud AAH, Inaloo S, Habibzadeh P, Faghihi MA, Jansen AC, Brock S, Roubertie A, Darras BT, Agrawal PB, Santorelli FM, Gleeson J, Zaki MS, Sheikh SI, Bennett JT, Sahin M
Brain 2020 Oct 1;143(10):2929-2944. doi: 10.1093/brain/awz307. PMID: 32979048Free PMC Article
Genetic and phenotypic characterization of complex hereditary spastic paraplegia.
Kara E, Tucci A, Manzoni C, Lynch DS, Elpidorou M, Bettencourt C, Chelban V, Manole A, Hamed SA, Haridy NA, Federoff M, Preza E, Hughes D, Pittman A, Jaunmuktane Z, Brandner S, Xiromerisiou G, Wiethoff S, Schottlaender L, Proukakis C, Morris H, Warner T, Bhatia KP, Korlipara LV, Singleton AB, Hardy J, Wood NW, Lewis PA, Houlden H
Brain 2016 Jul;139(Pt 7):1904-18. Epub 2016 May 23 doi: 10.1093/brain/aww111. PMID: 27217339Free PMC Article
Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia.
Boukhris A, Schule R, Loureiro JL, Lourenço CM, Mundwiller E, Gonzalez MA, Charles P, Gauthier J, Rekik I, Acosta Lebrigio RF, Gaussen M, Speziani F, Ferbert A, Feki I, Caballero-Oteyza A, Dionne-Laporte A, Amri M, Noreau A, Forlani S, Cruz VT, Mochel F, Coutinho P, Dion P, Mhiri C, Schols L, Pouget J, Darios F, Rouleau GA, Marques W Jr, Brice A, Durr A, Zuchner S, Stevanin G
Am J Hum Genet 2013 Jul 11;93(1):118-23. Epub 2013 Jun 6 doi: 10.1016/j.ajhg.2013.05.006. PMID: 23746551Free PMC Article
NIPA1 mutation in complex hereditary spastic paraplegia with epilepsy.
Svenstrup K, Møller RS, Christensen J, Budtz-Jørgensen E, Gilling M, Nielsen JE
Eur J Neurol 2011 Sep;18(9):1197-9. Epub 2011 Feb 22 doi: 10.1111/j.1468-1331.2011.03359.x. PMID: 21599812

Diagnosis

Cation leak through the ATP1A3 pump causes spasticity and intellectual disability.
Calame DG, Moreno Vadillo C, Berger S, Lotze T, Shinawi M, Poupak J, Heller C, Cohen J, Person R, Telegrafi A, Phitsanuwong C, Fiala K, Thiffault I, Del Viso F, Zhou D, Fleming EA, Pastinen T, Fatemi A, Thomas S, Pascual SI, Torres RJ, Prior C, Gómez-González C, Biskup S, Lupski JR, Maric D, Holmgren M, Regier D, Yano ST
Brain 2023 Aug 1;146(8):3162-3171. doi: 10.1093/brain/awad124. PMID: 37043503Free PMC Article
Early-Onset and Severe Complex Hereditary Spastic Paraplegia Caused by De Novo Variants in SPAST.
Mo A, Saffari A, Kellner M, Döbler-Neumann M, Jordan C, Srivastava S, Zhang B, Sahin M, Fink JK, Smith L, Posey JE, Alter KE, Toro C, Blackstone C, Soldatos AG, Christie M, Schüle R, Ebrahimi-Fakhari D
Mov Disord 2022 Dec;37(12):2440-2446. Epub 2022 Sep 14 doi: 10.1002/mds.29225. PMID: 36103453Free PMC Article
Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia.
Ebrahimi-Fakhari D, Teinert J, Behne R, Wimmer M, D'Amore A, Eberhardt K, Brechmann B, Ziegler M, Jensen DM, Nagabhyrava P, Geisel G, Carmody E, Shamshad U, Dies KA, Yuskaitis CJ, Salussolia CL, Ebrahimi-Fakhari D, Pearson TS, Saffari A, Ziegler A, Kölker S, Volkmann J, Wiesener A, Bearden DR, Lakhani S, Segal D, Udwadia-Hegde A, Martinuzzi A, Hirst J, Perlman S, Takiyama Y, Xiromerisiou G, Vill K, Walker WO, Shukla A, Dubey Gupta R, Dahl N, Aksoy A, Verhelst H, Delgado MR, Kremlikova Pourova R, Sadek AA, Elkhateeb NM, Blumkin L, Brea-Fernández AJ, Dacruz-Álvarez D, Smol T, Ghoumid J, Miguel D, Heine C, Schlump JU, Langen H, Baets J, Bulk S, Darvish H, Bakhtiari S, Kruer MC, Lim-Melia E, Aydinli N, Alanay Y, El-Rashidy O, Nampoothiri S, Patel C, Beetz C, Bauer P, Yoon G, Guillot M, Miller SP, Bourinaris T, Houlden H, Robelin L, Anheim M, Alamri AS, Mahmoud AAH, Inaloo S, Habibzadeh P, Faghihi MA, Jansen AC, Brock S, Roubertie A, Darras BT, Agrawal PB, Santorelli FM, Gleeson J, Zaki MS, Sheikh SI, Bennett JT, Sahin M
Brain 2020 Oct 1;143(10):2929-2944. doi: 10.1093/brain/awz307. PMID: 32979048Free PMC Article
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
Genetic and phenotypic characterization of complex hereditary spastic paraplegia.
Kara E, Tucci A, Manzoni C, Lynch DS, Elpidorou M, Bettencourt C, Chelban V, Manole A, Hamed SA, Haridy NA, Federoff M, Preza E, Hughes D, Pittman A, Jaunmuktane Z, Brandner S, Xiromerisiou G, Wiethoff S, Schottlaender L, Proukakis C, Morris H, Warner T, Bhatia KP, Korlipara LV, Singleton AB, Hardy J, Wood NW, Lewis PA, Houlden H
Brain 2016 Jul;139(Pt 7):1904-18. Epub 2016 May 23 doi: 10.1093/brain/aww111. PMID: 27217339Free PMC Article

Prognosis

Novel CAPN1 missense variants in complex hereditary spastic paraplegia with early-onset psychosis.
Alecu JE, Saffari A, Jumo H, Ziegler M, Strelko O, Brownstein CA, Gonzalez-Heydrich J, Rodan LH, Gorman MP, Sahin M, Ebrahimi-Fakhari D
Ann Clin Transl Neurol 2022 Apr;9(4):570-576. Epub 2022 Mar 16 doi: 10.1002/acn3.51531. PMID: 35297214Free PMC Article
Is NIPA1-associated hereditary spastic paraplegia always 'pure'? Further evidence of motor neurone disease and epilepsy as rare manifestations.
Tanti M, Cairns D, Mirza N, McCann E, Young C
Neurogenetics 2020 Oct;21(4):305-308. Epub 2020 Jun 5 doi: 10.1007/s10048-020-00619-0. PMID: 32500351
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
Three cases of Troyer syndrome in two families of Filipino descent.
Butler S, Helbig KL, Alcaraz W, Seaver LH, Hsieh DT, Rohena L
Am J Med Genet A 2016 Jul;170(7):1780-5. Epub 2016 Apr 26 doi: 10.1002/ajmg.a.37658. PMID: 27112432
SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia.
Paisan-Ruiz C, Dogu O, Yilmaz A, Houlden H, Singleton A
Neurology 2008 Apr 15;70(16 Pt 2):1384-9. Epub 2008 Mar 12 doi: 10.1212/01.wnl.0000294327.66106.3d. PMID: 18337587Free PMC Article

Clinical prediction guides

Early-Onset and Severe Complex Hereditary Spastic Paraplegia Caused by De Novo Variants in SPAST.
Mo A, Saffari A, Kellner M, Döbler-Neumann M, Jordan C, Srivastava S, Zhang B, Sahin M, Fink JK, Smith L, Posey JE, Alter KE, Toro C, Blackstone C, Soldatos AG, Christie M, Schüle R, Ebrahimi-Fakhari D
Mov Disord 2022 Dec;37(12):2440-2446. Epub 2022 Sep 14 doi: 10.1002/mds.29225. PMID: 36103453Free PMC Article
Novel CAPN1 missense variants in complex hereditary spastic paraplegia with early-onset psychosis.
Alecu JE, Saffari A, Jumo H, Ziegler M, Strelko O, Brownstein CA, Gonzalez-Heydrich J, Rodan LH, Gorman MP, Sahin M, Ebrahimi-Fakhari D
Ann Clin Transl Neurol 2022 Apr;9(4):570-576. Epub 2022 Mar 16 doi: 10.1002/acn3.51531. PMID: 35297214Free PMC Article
Homozygous TFG gene variants expanding the mutational and clinical spectrum of hereditary spastic paraplegia 57 and a review of literature.
Khorrami M, Tabatabaiefar MA, Khorram E, Yaghini O, Rezaei M, Hejazifar A, Riahinezhad M, Kheirollahi M
J Hum Genet 2021 Oct;66(10):973-981. Epub 2021 Mar 25 doi: 10.1038/s10038-021-00919-9. PMID: 33767317
Genetic and phenotypic characterization of complex hereditary spastic paraplegia.
Kara E, Tucci A, Manzoni C, Lynch DS, Elpidorou M, Bettencourt C, Chelban V, Manole A, Hamed SA, Haridy NA, Federoff M, Preza E, Hughes D, Pittman A, Jaunmuktane Z, Brandner S, Xiromerisiou G, Wiethoff S, Schottlaender L, Proukakis C, Morris H, Warner T, Bhatia KP, Korlipara LV, Singleton AB, Hardy J, Wood NW, Lewis PA, Houlden H
Brain 2016 Jul;139(Pt 7):1904-18. Epub 2016 May 23 doi: 10.1093/brain/aww111. PMID: 27217339Free PMC Article
SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia.
Paisan-Ruiz C, Dogu O, Yilmaz A, Houlden H, Singleton A
Neurology 2008 Apr 15;70(16 Pt 2):1384-9. Epub 2008 Mar 12 doi: 10.1212/01.wnl.0000294327.66106.3d. PMID: 18337587Free PMC Article

Recent systematic reviews

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

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