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Hereditary spastic paraplegia 43(SPG43)

MedGen UID:
760531
Concept ID:
C2680446
Disease or Syndrome
Synonym: Spastic paraplegia 43, autosomal recessive
SNOMED CT: Autosomal recessive spastic paraplegia type 43 (764736001)
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).
 
Gene (location): C19orf12 (19q12)
 
Monarch Initiative: MONDO:0014024
OMIM®: 615043
Orphanet: ORPHA320370

Definition

Spastic paraplegia-43 (SPG43) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive spasticity affecting the lower and upper limbs (summary by Meilleur et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800. [from OMIM]

Clinical features

From HPO
Knee flexion contracture
MedGen UID:
98042
Concept ID:
C0409355
Finding
A type of knee joint contracture in which the knee is in a fixed bent (flexed) configuration such that it cannot be straightened actively or passively.
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).
Ankle flexion contracture
MedGen UID:
332440
Concept ID:
C1837407
Anatomical Abnormality
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
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.
Spastic paraplegia
MedGen UID:
20882
Concept ID:
C0037772
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 43
Follow this link to review classifications for Hereditary spastic paraplegia 43 in Orphanet.

Recent clinical studies

Etiology

Xing F, Du J
Neurol Sci 2022 Aug;43(8):4989-4996. Epub 2022 Mar 28 doi: 10.1007/s10072-022-05921-3. PMID: 35348942
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
Teinert J, Behne R, Wimmer M, Ebrahimi-Fakhari D
J Inherit Metab Dis 2020 Jan;43(1):51-62. Epub 2019 Apr 8 doi: 10.1002/jimd.12084. PMID: 30854657
Schüle R, Wiethoff S, Martus P, Karle KN, Otto S, Klebe S, Klimpe S, Gallenmüller C, Kurzwelly D, Henkel D, Rimmele F, Stolze H, Kohl Z, Kassubek J, Klockgether T, Vielhaber S, Kamm C, Klopstock T, Bauer P, Züchner S, Liepelt-Scarfone I, Schöls L
Ann Neurol 2016 Apr;79(4):646-58. Epub 2016 Mar 11 doi: 10.1002/ana.24611. PMID: 26856398
Roşulescu E, Stănoiu C, Buteică E, Stănoiu B, Burada F, Zăvăleanu M
Rom J Morphol Embryol 2009;50(2):299-303. PMID: 19434327

Diagnosis

Iannibelli E, Gibertini S, Cheli M, Blasevich F, Cavaliere A, Riolo G, Ruggieri A, Maggi L
Acta Myol 2023;42(1):2-13. Epub 2023 Mar 31 doi: 10.36185/2532-1900-244. PMID: 37091525Free PMC Article
Xing F, Du J
Neurol Sci 2022 Aug;43(8):4989-4996. Epub 2022 Mar 28 doi: 10.1007/s10072-022-05921-3. PMID: 35348942
Schüle R, Wiethoff S, Martus P, Karle KN, Otto S, Klebe S, Klimpe S, Gallenmüller C, Kurzwelly D, Henkel D, Rimmele F, Stolze H, Kohl Z, Kassubek J, Klockgether T, Vielhaber S, Kamm C, Klopstock T, Bauer P, Züchner S, Liepelt-Scarfone I, Schöls L
Ann Neurol 2016 Apr;79(4):646-58. Epub 2016 Mar 11 doi: 10.1002/ana.24611. PMID: 26856398
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
Roşulescu E, Stănoiu C, Buteică E, Stănoiu B, Burada F, Zăvăleanu M
Rom J Morphol Embryol 2009;50(2):299-303. PMID: 19434327

Therapy

Diella E, D'Angelo MG, Stefan C, Girardi G, Morganti R, Martinuzzi A, Biffi E
PLoS One 2024;19(4):e0301452. Epub 2024 Apr 1 doi: 10.1371/journal.pone.0301452. PMID: 38557877Free PMC Article
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
van de Venis L, van de Warrenburg BPC, Weerdesteyn V, van Lith BJH, Geurts ACH, Nonnekes J
Trials 2021 Jan 7;22(1):32. doi: 10.1186/s13063-020-04932-9. PMID: 33413555Free PMC Article
Antczak J, Pera J, Dąbroś M, Koźmiński W, Czyżycki M, Wężyk K, Dwojak M, Banach M, Slowik A
Neural Plast 2019;2019:7638675. Epub 2019 May 12 doi: 10.1155/2019/7638675. PMID: 31214256Free PMC Article
Margetis K, Korfias S, Boutos N, Gatzonis S, Themistocleous M, Siatouni A, Dalivigka Z, Flaskas T, Stranjalis G, Boviatsis E, Sakas D
Clin Neurol Neurosurg 2014 Aug;123:142-5. Epub 2014 Jun 4 doi: 10.1016/j.clineuro.2014.05.024. PMID: 24973568

Prognosis

Xing F, Du J
Neurol Sci 2022 Aug;43(8):4989-4996. Epub 2022 Mar 28 doi: 10.1007/s10072-022-05921-3. PMID: 35348942
Zucchi E, Bedin R, Fasano A, Fini N, Gessani A, Vinceti M, Mandrioli J
Neurodegener Dis 2018;18(5-6):255-261. Epub 2018 Nov 14 doi: 10.1159/000493986. PMID: 30428468
Tian X, Wang M, Zhang K, Zhang X
Can J Neurol Sci 2016 Nov;43(6):833-840. Epub 2016 Mar 28 doi: 10.1017/cjn.2016.17. PMID: 27018819
Schüle R, Wiethoff S, Martus P, Karle KN, Otto S, Klebe S, Klimpe S, Gallenmüller C, Kurzwelly D, Henkel D, Rimmele F, Stolze H, Kohl Z, Kassubek J, Klockgether T, Vielhaber S, Kamm C, Klopstock T, Bauer P, Züchner S, Liepelt-Scarfone I, Schöls L
Ann Neurol 2016 Apr;79(4):646-58. Epub 2016 Mar 11 doi: 10.1002/ana.24611. PMID: 26856398
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

Clinical prediction guides

Xing F, Du J
Neurol Sci 2022 Aug;43(8):4989-4996. Epub 2022 Mar 28 doi: 10.1007/s10072-022-05921-3. PMID: 35348942
Di Donato I, Gallo A, Ricca I, Fini N, Silvestri G, Gurrieri F, Cirillo M, Cerase A, Natale G, Matrone F, Riso V, Melone MAB, Tessa A, De Michele G, Federico A, Filla A, Dotti MT, Santorelli FM
Neurol Sci 2022 Feb;43(2):1071-1077. Epub 2021 Jul 23 doi: 10.1007/s10072-021-05462-1. PMID: 34296356Free PMC Article
Schüle R, Wiethoff S, Martus P, Karle KN, Otto S, Klebe S, Klimpe S, Gallenmüller C, Kurzwelly D, Henkel D, Rimmele F, Stolze H, Kohl Z, Kassubek J, Klockgether T, Vielhaber S, Kamm C, Klopstock T, Bauer P, Züchner S, Liepelt-Scarfone I, Schöls L
Ann Neurol 2016 Apr;79(4):646-58. Epub 2016 Mar 11 doi: 10.1002/ana.24611. PMID: 26856398
Servelhere KR, Faber I, Saute JA, Moscovich M, D'Abreu A, Jardim LB, Teive HA, Lopes-Cendes I, Franca MC Jr
Eur J Neurol 2016 Feb;23(2):408-11. doi: 10.1111/ene.12839. PMID: 26806216
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

Recent systematic reviews

Giannoccaro MP, Matteo E, Bartiromo F, Tonon C, Santorelli FM, Liguori R, Rizzo G
Neurol Sci 2022 Sep;43(9):5501-5511. Epub 2022 May 21 doi: 10.1007/s10072-022-06145-1. PMID: 35595875

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