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Hereditary spastic paraplegia 36(SPG36)

MedGen UID:
422457
•Concept ID:
C2936879
•
Disease or Syndrome
Synonym: Spastic paraplegia 36, autosomal dominant
SNOMED CT: Autosomal dominant spastic paraplegia type 36 (723819007)
Modes of inheritance:
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.
Autosomal dominant inheritance (Orphanet)
 
Monarch Initiative: MONDO:0013132
OMIM®: 613096
Orphanet: ORPHA320365

Definition

A complex form of hereditary spastic paraplegia, with onset in childhood or adulthood of progressive spastic paraplegia (with spastic gait, spasticity, lower limb weakness, pes cavus and urinary urgency) associated with the additional manifestation of peripheral sensorimotor neuropathy. The SPG36 phenotype has been mapped to a locus on chromosome 12q23-q24. [from SNOMEDCT_US]

Clinical features

From HPO
Urinary incontinence
MedGen UID:
22579
•Concept ID:
C0042024
•
Finding
Loss of the ability to control the urinary bladder leading to involuntary urination.
See: Feature record | Search on this feature
Urinary urgency
MedGen UID:
39315
•Concept ID:
C0085606
•
Finding
Urge incontinence is the strong, sudden need to urinate.
See: Feature record | Search on this feature
Pes cavus
MedGen UID:
675590
•Concept ID:
C0728829
•
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
See: Feature record | Search on this feature
Lower limb muscle weakness
MedGen UID:
324478
•Concept ID:
C1836296
•
Finding
Weakness of the muscles of the legs.
See: Feature record | Search on this feature
Babinski sign
MedGen UID:
19708
•Concept ID:
C0034935
•
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
See: Feature record | Search on this feature
Spastic paraplegia
MedGen UID:
20882
•Concept ID:
C0037772
•
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
See: Feature record | Search on this feature
Sensory neuropathy
MedGen UID:
101791
•Concept ID:
C0151313
•
Disease or Syndrome
Peripheral neuropathy affecting the sensory nerves.
See: Feature record | Search on this feature
Hyperreflexia
MedGen UID:
57738
•Concept ID:
C0151889
•
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
See: Feature record | Search on this feature
Spastic gait
MedGen UID:
115907
•Concept ID:
C0231687
•
Finding
Spasticity is manifested by increased stretch reflex which is intensified with movement velocity. This results in excessive and inappropriate muscle activation which can contribute to muscle hypertonia. Spastic gait is characterized by manifestations such as muscle hypertonia, stiff knee, and circumduction of the leg.
See: Feature record | Search on this feature
Lower limb spasticity
MedGen UID:
220865
•Concept ID:
C1271100
•
Finding
Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis.
See: Feature record | Search on this feature
Impaired vibration sensation in the lower limbs
MedGen UID:
338617
•Concept ID:
C1849134
•
Finding
A decrease in the ability to perceive vibration in the legs.
See: Feature record | Search on this feature
Demyelinating motor neuropathy
MedGen UID:
409836
•Concept ID:
C1969462
•
Finding
Demyelination of peripheral motor nerves.
See: Feature record | Search on this feature
Demyelinating sensory neuropathy
MedGen UID:
868959
•Concept ID:
C4023373
•
Disease or Syndrome
Demyelination of peripheral sensory nerves.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 36
Follow this link to review classifications for Hereditary spastic paraplegia 36 in Orphanet.

Professional guidelines

PubMed

Infantile onset of hereditary spastic paraplegia poorly predicts the genotype.
Blair MA, Riddle ME, Wells JF, Breviu BA, Hedera P
Pediatr Neurol 2007 Jun;36(6):382-6. doi: 10.1016/j.pediatrneurol.2007.02.003. PMID: 17560499

Recent clinical studies

Etiology

Gait-Adaptability Training in People With Hereditary Spastic Paraplegia: A Randomized Clinical Trial.
van de Venis L, van de Warrenburg B, Weerdesteyn V, Geurts ACH, Nonnekes J
Neurorehabil Neural Repair 2023 Jan;37(1):27-36. Epub 2023 Jan 25 doi: 10.1177/15459683221147839. PMID: 36695288Free PMC Article
Brain Damage and Gene Expression Across Hereditary Spastic Paraplegia Subtypes.
Servelhere KR, Rezende TJR, de Lima FD, de Brito MR, de França Nunes RF, Casseb RF, Pedroso JL, Barsottini OGP, Cendes F, França MC Jr
Mov Disord 2021 Jul;36(7):1644-1653. Epub 2021 Feb 11 doi: 10.1002/mds.28519. PMID: 33576112
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
Clinical spectrum and genetic landscape for hereditary spastic paraplegias in China.
Dong EL, Wang C, Wu S, Lu YQ, Lin XH, Su HZ, Zhao M, He J, Ma LX, Wang N, Chen WJ, Lin X
Mol Neurodegener 2018 Jul 6;13(1):36. doi: 10.1186/s13024-018-0269-1. PMID: 29980238Free PMC Article
Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia.
McCorquodale DS 3rd, Ozomaro U, Huang J, Montenegro G, Kushman A, Citrigno L, Price J, Speziani F, Pericak-Vance MA, Züchner S
Clin Genet 2011 Jun;79(6):523-30. doi: 10.1111/j.1399-0004.2010.01501.x. PMID: 20718791Free PMC Article

Diagnosis

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
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
Homozygosity mapping and next generation sequencing for the genetic diagnosis of hereditary ataxia and spastic paraplegia in consanguineous families.
Jiao B, Zhou Z, Hu Z, Du J, Liao X, Luo Y, Wang J, Yan X, Jiang H, Tang B, Shen L
Parkinsonism Relat Disord 2020 Nov;80:65-72. Epub 2020 Sep 14 doi: 10.1016/j.parkreldis.2020.09.013. PMID: 32961396
Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia.
McCorquodale DS 3rd, Ozomaro U, Huang J, Montenegro G, Kushman A, Citrigno L, Price J, Speziani F, Pericak-Vance MA, Züchner S
Clin Genet 2011 Jun;79(6):523-30. doi: 10.1111/j.1399-0004.2010.01501.x. PMID: 20718791Free PMC Article
Clinical mitochondrial genetics.
Chinnery PF, Howell N, Andrews RM, Turnbull DM
J Med Genet 1999 Jun;36(6):425-36. PMID: 10874629Free PMC Article

Therapy

Emerging therapies for childhood-onset movement disorders.
Vogt L, Quiroz V, Ebrahimi-Fakhari D
Curr Opin Pediatr 2024 Jun 1;36(3):331-341. Epub 2024 Apr 4 doi: 10.1097/MOP.0000000000001354. PMID: 38655812Free PMC Article
Gait-Adaptability Training in People With Hereditary Spastic Paraplegia: A Randomized Clinical Trial.
van de Venis L, van de Warrenburg B, Weerdesteyn V, Geurts ACH, Nonnekes J
Neurorehabil Neural Repair 2023 Jan;37(1):27-36. Epub 2023 Jan 25 doi: 10.1177/15459683221147839. PMID: 36695288Free 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
Randomized Trial of Botulinum Toxin Type A in Hereditary Spastic Paraplegia - The SPASTOX Trial.
Diniz de Lima F, Faber I, Servelhere KR, Bittar MFR, Martinez ARM, Piovesana LG, Martins MP, Martins CR Jr, Benaglia T, de Sá Carvalho B, Nucci A, França MC Jr
Mov Disord 2021 Jul;36(7):1654-1663. Epub 2021 Feb 17 doi: 10.1002/mds.28523. PMID: 33595142
Factors influencing disease progression in autosomal dominant cerebellar ataxia and spastic paraplegia.
Tezenas du Montcel S, Charles P, Goizet C, Marelli C, Ribai P, Vincitorio C, Anheim M, Guyant-Maréchal L, Le Bayon A, Vandenberghe N, Tchikviladzé M, Devos D, Le Ber I, N'Guyen K, Cazeneuve C, Tallaksen C, Brice A, Durr A
Arch Neurol 2012 Apr;69(4):500-8. doi: 10.1001/archneurol.2011.2713. PMID: 22491195

Prognosis

Robotic gait training improves motor skills and quality of life in hereditary spastic paraplegia.
Bertolucci F, Di Martino S, Orsucci D, Ienco EC, Siciliano G, Rossi B, Mancuso M, Chisari C
NeuroRehabilitation 2015;36(1):93-9. doi: 10.3233/NRE-141196. PMID: 25547770
Hereditary spastic paraparesis in adults. A clinical and genetic perspective from Tuscany.
Orsucci D, Petrucci L, Ienco EC, Chico L, Simi P, Fogli A, Baldinotti F, Simoncini C, LoGerfo A, Carlesi C, Arnoldi A, Bassi MT, Siciliano G, Bonuccelli U, Mancuso M
Clin Neurol Neurosurg 2014 May;120:14-9. Epub 2014 Feb 17 doi: 10.1016/j.clineuro.2014.02.002. PMID: 24731568
Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot-Marie-Tooth type 2.
Crimella C, Baschirotto C, Arnoldi A, Tonelli A, Tenderini E, Airoldi G, Martinuzzi A, Trabacca A, Losito L, Scarlato M, Benedetti S, Scarpini E, Spinicci G, Bresolin N, Bassi MT
Clin Genet 2012 Aug;82(2):157-64. Epub 2011 Jun 21 doi: 10.1111/j.1399-0004.2011.01717.x. PMID: 21623771
Frequency and phenotype of SPG11 and SPG15 in complicated hereditary spastic paraplegia.
Schüle R, Schlipf N, Synofzik M, Klebe S, Klimpe S, Hehr U, Winner B, Lindig T, Dotzer A, Riess O, Winkler J, Schöls L, Bauer P
J Neurol Neurosurg Psychiatry 2009 Dec;80(12):1402-4. doi: 10.1136/jnnp.2008.167528. PMID: 19917823
Infantile onset of hereditary spastic paraplegia poorly predicts the genotype.
Blair MA, Riddle ME, Wells JF, Breviu BA, Hedera P
Pediatr Neurol 2007 Jun;36(6):382-6. doi: 10.1016/j.pediatrneurol.2007.02.003. PMID: 17560499

Clinical prediction guides

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
Selective dorsal rhizotomy for spasticity of genetic etiology.
Lohkamp LN, Coulter I, Ibrahim GM
Childs Nerv Syst 2020 Jul;36(7):1357-1365. Epub 2020 Apr 16 doi: 10.1007/s00381-020-04601-x. PMID: 32300873
Clinical spectrum and genetic landscape for hereditary spastic paraplegias in China.
Dong EL, Wang C, Wu S, Lu YQ, Lin XH, Su HZ, Zhao M, He J, Ma LX, Wang N, Chen WJ, Lin X
Mol Neurodegener 2018 Jul 6;13(1):36. doi: 10.1186/s13024-018-0269-1. PMID: 29980238Free PMC Article
Hereditary spastic paraparesis in adults. A clinical and genetic perspective from Tuscany.
Orsucci D, Petrucci L, Ienco EC, Chico L, Simi P, Fogli A, Baldinotti F, Simoncini C, LoGerfo A, Carlesi C, Arnoldi A, Bassi MT, Siciliano G, Bonuccelli U, Mancuso M
Clin Neurol Neurosurg 2014 May;120:14-9. Epub 2014 Feb 17 doi: 10.1016/j.clineuro.2014.02.002. PMID: 24731568
Disease severity affects quality of life of hereditary spastic paraplegia patients.
Klimpe S, Schüle R, Kassubek J, Otto S, Kohl Z, Klebe S, Klopstock T, Ratzka S, Karle K, Schöls L
Eur J Neurol 2012 Jan;19(1):168-71. Epub 2011 Jun 1 doi: 10.1111/j.1468-1331.2011.03443.x. PMID: 21631647

Recent systematic reviews

Monoallelic KIF1A-related disorders: a multicenter cross sectional study and systematic literature review.
Vecchia SD, Tessa A, Dosi C, Baldacci J, Pasquariello R, Antenora A, Astrea G, Bassi MT, Battini R, Casali C, Cioffi E, Conti G, De Michele G, Ferrari AR, Filla A, Fiorillo C, Fusco C, Gallone S, Germiniasi C, Guerrini R, Haggiag S, Lopergolo D, Martinuzzi A, Melani F, Mignarri A, Panzeri E, Pini A, Pinto AM, Pochiero F, Primiano G, Procopio E, Renieri A, Romaniello R, Sancricca C, Servidei S, Spagnoli C, Ticci C, Rubegni A, Santorelli FM
J Neurol 2022 Jan;269(1):437-450. Epub 2021 Sep 6 doi: 10.1007/s00415-021-10792-3. PMID: 34487232
Selective dorsal rhizotomy for spasticity of genetic etiology.
Lohkamp LN, Coulter I, Ibrahim GM
Childs Nerv Syst 2020 Jul;36(7):1357-1365. Epub 2020 Apr 16 doi: 10.1007/s00381-020-04601-x. PMID: 32300873

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