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Hereditary spastic paraplegia 74(SPG74)

MedGen UID:
1800260
Concept ID:
C5568837
Disease or Syndrome
Synonym: Spastic paraplegia 74, autosomal recessive
SNOMED CT: Autosomal recessive spastic paraplegia type 74 (1187191003)
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): IBA57 (1q42.13)
 
Monarch Initiative: MONDO:0014644
OMIM®: 616451
Orphanet: ORPHA468661

Definition

Spastic paraplegia-74 (SPG74) is an autosomal recessive neurologic disorder characterized by onset of slowly progressive lower limb spasticity, optic atrophy, and peripheral neuropathy in the first decade (summary by Lossos et al., 2015). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800). [from OMIM]

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.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation 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.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.
Visual field defect
MedGen UID:
854603
Concept ID:
C3887875
Finding
An absolute or relative reduction in the extent of the normal field of vision.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 74

Recent clinical studies

Etiology

Ollenschläger M, Höfner P, Ullrich M, Kluge F, Greinwalder T, Loris E, Regensburger M, Eskofier BM, Winkler J, Gaßner H
Orphanet J Rare Dis 2023 Aug 29;18(1):249. doi: 10.1186/s13023-023-02854-8. PMID: 37644478Free PMC Article
Perić S, Marković V, Candayan A, De Vriendt E, Momčilović N, Savić A, Dragašević-Mišković N, Svetel M, Stević Z, Božović I, Mesaroš Š, Drulović J, Basta I, Petrović I, Tamaš O, Mijajlović M, Novaković I, Sokić D, Jordanova A
Cells 2022 Sep 8;11(18) doi: 10.3390/cells11182804. PMID: 36139378Free PMC Article
Simonsen CS, Celius EG, Brunborg C, Tallaksen C, Eriksen EF, Holmøy T, Moen SM
BMC Neurol 2016 Dec 5;16(1):252. doi: 10.1186/s12883-016-0771-4. PMID: 27919248Free 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
Erichsen AK, Koht J, Stray-Pedersen A, Abdelnoor M, Tallaksen CM
Brain 2009 Jun;132(Pt 6):1577-88. Epub 2009 Mar 31 doi: 10.1093/brain/awp056. PMID: 19339254

Diagnosis

Perić S, Marković V, Candayan A, De Vriendt E, Momčilović N, Savić A, Dragašević-Mišković N, Svetel M, Stević Z, Božović I, Mesaroš Š, Drulović J, Basta I, Petrović I, Tamaš O, Mijajlović M, Novaković I, Sokić D, Jordanova A
Cells 2022 Sep 8;11(18) doi: 10.3390/cells11182804. PMID: 36139378Free PMC Article
Panwala TF, Garcia-Santibanez R, Vizcarra JA, Garcia AG, Verma S
Pediatr Neurol 2022 May;130:7-13. Epub 2022 Mar 3 doi: 10.1016/j.pediatrneurol.2022.02.007. PMID: 35303589
Wassenberg T, Schouten MI, Helmich RC, Willemsen MAAP, Kamsteeg EJ, van de Warrenburg BPC
Parkinsonism Relat Disord 2020 May;74:12-15. Epub 2020 Apr 1 doi: 10.1016/j.parkreldis.2020.03.019. PMID: 32278297
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
Erichsen AK, Koht J, Stray-Pedersen A, Abdelnoor M, Tallaksen CM
Brain 2009 Jun;132(Pt 6):1577-88. Epub 2009 Mar 31 doi: 10.1093/brain/awp056. PMID: 19339254

Therapy

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

Mahungu AC, Monnakgotla N, Nel M, Heckmann JM
Orphanet J Rare Dis 2022 Mar 24;17(1):133. doi: 10.1186/s13023-022-02280-2. PMID: 35331287Free PMC Article
Wassenberg T, Schouten MI, Helmich RC, Willemsen MAAP, Kamsteeg EJ, van de Warrenburg BPC
Parkinsonism Relat Disord 2020 May;74:12-15. Epub 2020 Apr 1 doi: 10.1016/j.parkreldis.2020.03.019. PMID: 32278297

Clinical prediction guides

Simonsen CS, Celius EG, Brunborg C, Tallaksen C, Eriksen EF, Holmøy T, Moen SM
BMC Neurol 2016 Dec 5;16(1):252. doi: 10.1186/s12883-016-0771-4. PMID: 27919248Free PMC Article
Elsayed LEO, Mohammed IN, Hamed AAA, Elseed MA, Johnson A, Mairey M, Mohamed HESA, Idris MN, Salih MAM, El-Sadig SM, Koko ME, Mohamed AYO, Raymond L, Coutelier M, Darios F, Siddig RA, Ahmed AKMA, Babai AMA, Malik HMO, Omer ZMBM, Mohamed EOE, Eltahir HB, Magboul NAA, Bushara EE, Elnour A, Rahim SMA, Alattaya A, Elbashir MI, Ibrahim ME, Durr A, Audhya A, Brice A, Ahmed AE, Stevanin G
Eur J Hum Genet 2016 Jan;25(1):100-110. Epub 2016 Sep 7 doi: 10.1038/ejhg.2016.108. PMID: 27601211Free PMC Article
Mishra V, Guo X, Delgado MR, Huang H
Magn Reson Med 2015 Dec;74(6):1768-79. Epub 2014 Dec 1 doi: 10.1002/mrm.25548. PMID: 25447208Free PMC Article
Erichsen AK, Koht J, Stray-Pedersen A, Abdelnoor M, Tallaksen CM
Brain 2009 Jun;132(Pt 6):1577-88. Epub 2009 Mar 31 doi: 10.1093/brain/awp056. PMID: 19339254
De Michele G, De Fusco M, Cavalcanti F, Filla A, Marconi R, Volpe G, Monticelli A, Ballabio A, Casari G, Cocozza S
Am J Hum Genet 1998 Jul;63(1):135-9. doi: 10.1086/301930. PMID: 9634528Free PMC Article

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