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Hereditary spastic paraplegia 57(SPG57)

MedGen UID:
811490
Concept ID:
C3714897
Disease or Syndrome
Synonym: Spastic paraplegia 57, autosomal recessive
SNOMED CT: Autosomal recessive spastic paraplegia type 57 (723826007); Spastic paraplegia due to partial TFG deficiency (723826007)
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): TFG (3q12.2)
 
Monarch Initiative: MONDO:0014295
OMIM®: 615658
Orphanet: ORPHA431329

Definition

An extremely rare, complex type of hereditary spastic paraplegia, with onset in infancy of pronounced leg spasticity (leading to the inability to walk independently), reduced visual acuity due to optic atrophy and distal wasting of the hands and feet due to an axonal demyelinating sensorimotor neuropathy. Caused by mutations in the TFG gene (3q12.2) encoding protein TFG, which is thought to play a role in ER microtubular architecture and function. [from SNOMEDCT_US]

Clinical features

From HPO
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.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
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.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Demyelinating motor neuropathy
MedGen UID:
409836
Concept ID:
C1969462
Finding
Demyelination of peripheral motor nerves.
Somatic sensory dysfunction
MedGen UID:
1790456
Concept ID:
C5551413
Finding
An abnormality of the primary sensation that is mediated by peripheral nerves (pain, temperature, touch, vibration, joint position). The word hypoesthesia (or hypesthesia) refers to a reduction in cutaneous sensation to a specific type of testing.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Hand muscle atrophy
MedGen UID:
116091
Concept ID:
C0239830
Finding
Muscular atrophy involving the muscles of the hand.
Lower limb amyotrophy
MedGen UID:
870475
Concept ID:
C4024921
Finding
Muscular atrophy affecting the lower limb.
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.
Visual loss
MedGen UID:
784038
Concept ID:
C3665386
Finding
Loss of visual acuity (implying that vision was better at a certain time point in life). Otherwise the term reduced visual acuity should be used (or a subclass of that).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 57

Professional guidelines

PubMed

van Gassen KL, van der Heijden CD, de Bot ST, den Dunnen WF, van den Berg LH, Verschuuren-Bemelmans CC, Kremer HP, Veldink JH, Kamsteeg EJ, Scheffer H, van de Warrenburg BP
Brain 2012 Oct;135(Pt 10):2994-3004. Epub 2012 Sep 10 doi: 10.1093/brain/aws224. PMID: 22964162

Recent clinical studies

Etiology

Fussiger H, Pereira BLDS, Padilha JPD, Donis KC; Rare-Genomes Project Consortium, Siebert M, Brusius-Facchin AC, Baldo G, Saute JAM
Clin Genet 2023 May;103(5):580-584. Epub 2023 Jan 15 doi: 10.1111/cge.14280. PMID: 36537231
Narendiran S, Debnath M, Shivaram S, Kannan R, Sharma S, Christopher R, Seshagiri DV, Jain S, Purushottam M, Mangalore S, Bharath RD, Bindu PS, Sinha S, Taly AB, Nagappa M
J Neurogenet 2022 Mar;36(1):21-31. Epub 2022 May 2 doi: 10.1080/01677063.2022.2064463. PMID: 35499206
Joussain C, Levy J, Charlanes A, Even A, Falcou L, Chartier Kastler E, Denys P
Neurourol Urodyn 2019 Apr;38(4):1081-1085. Epub 2019 Mar 8 doi: 10.1002/nau.23957. PMID: 30848841
Kanavin ØJ, Fjermestad KW
Orphanet J Rare Dis 2018 Apr 16;13(1):58. doi: 10.1186/s13023-018-0804-8. PMID: 29661209Free PMC Article
Ormerod IE, Harding AE, Miller DH, Johnson G, MacManus D, du Boulay EP, Kendall BE, Moseley IF, McDonald WI
J Neurol Neurosurg Psychiatry 1994 Jan;57(1):51-7. doi: 10.1136/jnnp.57.1.51. PMID: 8301305Free PMC Article

Diagnosis

Fussiger H, Pereira BLDS, Padilha JPD, Donis KC; Rare-Genomes Project Consortium, Siebert M, Brusius-Facchin AC, Baldo G, Saute JAM
Clin Genet 2023 May;103(5):580-584. Epub 2023 Jan 15 doi: 10.1111/cge.14280. PMID: 36537231
Sainio MT, Aaltio J, Hyttinen V, Kortelainen M, Ojanen S, Paetau A, Tienari P, Ylikallio E, Auranen M, Tyynismaa H
Acta Neurol Scand 2022 Jan;145(1):63-72. Epub 2021 Aug 21 doi: 10.1111/ane.13522. PMID: 34418069
Joussain C, Levy J, Charlanes A, Even A, Falcou L, Chartier Kastler E, Denys P
Neurourol Urodyn 2019 Apr;38(4):1081-1085. Epub 2019 Mar 8 doi: 10.1002/nau.23957. PMID: 30848841
Ormerod IE, Harding AE, Miller DH, Johnson G, MacManus D, du Boulay EP, Kendall BE, Moseley IF, McDonald WI
J Neurol Neurosurg Psychiatry 1994 Jan;57(1):51-7. doi: 10.1136/jnnp.57.1.51. PMID: 8301305Free PMC Article
Schady W, Smith CM
J Neurol Neurosurg Psychiatry 1994 Jun;57(6):693-8. doi: 10.1136/jnnp.57.6.693. PMID: 8006649Free PMC Article

Therapy

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
Hecht MJ, Stolze H, Auf dem Brinke M, Giess R, Treig T, Winterholler M, Wissel J; German Spasticity Education Group
Mov Disord 2008 Jan 30;23(2):228-33. doi: 10.1002/mds.21809. PMID: 17999430

Prognosis

GBD 2016 Motor Neuron Disease Collaborators
Lancet Neurol 2018 Dec;17(12):1083-1097. Epub 2018 Nov 5 doi: 10.1016/S1474-4422(18)30404-6. PMID: 30409709Free PMC Article
Jia X, Madireddy L, Caillier S, Santaniello A, Esposito F, Comi G, Stuve O, Zhou Y, Taylor B, Kilpatrick T, Martinelli-Boneschi F, Cree BAC, Oksenberg JR, Hauser SL, Baranzini SE
Ann Neurol 2018 Jul;84(1):51-63. Epub 2018 Jul 3 doi: 10.1002/ana.25263. PMID: 29908077Free PMC Article
Morita M, Ho M, Hosler BA, McKenna-Yasek D, Brown RH Jr
Neurosci Lett 2002 May 31;325(1):57-61. doi: 10.1016/s0304-3940(02)00239-2. PMID: 12023066
Landau WM, Schmidt RE, McGlennen RC, Reich SG
Arch Neurol 2000 May;57(5):733-9. doi: 10.1001/archneur.57.5.733. PMID: 10815141
Schady W, Smith CM
J Neurol Neurosurg Psychiatry 1994 Jun;57(6):693-8. doi: 10.1136/jnnp.57.6.693. PMID: 8006649Free PMC Article

Clinical prediction guides

Malina J, Huessler EM, Jöckel KH, Boog-Whiteside E, Jeschonneck N, Schröder B, Schüle R, Kühl T, Klebe S
Orphanet J Rare Dis 2024 Jan 2;19(1):2. doi: 10.1186/s13023-023-03012-w. PMID: 38167479Free PMC Article
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
Shin S, Park J, Hong J, Park JH
BMJ Support Palliat Care 2020 Dec;10(4):e41. Epub 2019 Jun 14 doi: 10.1136/bmjspcare-2018-001738. PMID: 31201153
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
Ormerod IE, Harding AE, Miller DH, Johnson G, MacManus D, du Boulay EP, Kendall BE, Moseley IF, McDonald WI
J Neurol Neurosurg Psychiatry 1994 Jan;57(1):51-7. doi: 10.1136/jnnp.57.1.51. PMID: 8301305Free PMC Article

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