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Hereditary spastic paraplegia 55(SPG55)

MedGen UID:
761342
Concept ID:
C3539506
Disease or Syndrome
Synonym: Spastic paraplegia 55, autosomal recessive
SNOMED CT: Autosomal recessive spastic paraplegia type 55 (723825006)
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): MTRFR (12q24.31)
 
Monarch Initiative: MONDO:0014020
OMIM®: 615035
Orphanet: ORPHA320375

Definition

A rare complex type of hereditary spastic paraplegia with characteristics of childhood onset of progressive spastic paraplegia associated with optic atrophy (with reduced visual acuity and central scotoma), ophthalmoplegia, reduced upper-extremity strength and dexterity, muscular atrophy in the lower extremities and sensorimotor neuropathy. Caused by mutations in the C12ORF65 gene (12q24.31) encoding probable peptide chain release factor C12ORF65, mitochondrial. [from SNOMEDCT_US]

Clinical features

From HPO
Talipes equinovarus
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
Foot dorsiflexor weakness
MedGen UID:
356163
Concept ID:
C1866141
Finding
Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.
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.
Cognitive impairment
MedGen UID:
90932
Concept ID:
C0338656
Mental or Behavioral Dysfunction
Abnormal cognition with deficits in thinking, reasoning, or remembering.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Steppage gait
MedGen UID:
98105
Concept ID:
C0427149
Finding
An abnormal gait pattern that arises from weakness of the pretibial and peroneal muscles due to a lower motor neuron lesion. Affected patients have footdrop and are unable to dorsiflex and evert the foot. The leg is lifted high on walking so that the toes clear the ground, and there may be a slapping noise when the foot strikes the ground again.
Knee clonus
MedGen UID:
488908
Concept ID:
C0520823
Finding
Clonus is an involuntary tendon reflex that causes repeated flexion and extension of the foot. Knee clonus can be tested by rapidly pushing the patella towards the toes.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
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
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Onion bulb formation
MedGen UID:
376237
Concept ID:
C1847906
Finding
Repeated episodes of segmental demyelination and remyelination lead to the accumulation of supernumerary Schwann cells around axons, which is referred to as onion bulb formation. This finding affects peripheral nerves.
Impaired distal vibration sensation
MedGen UID:
381262
Concept ID:
C1853767
Finding
A decrease in the ability to perceive vibration in the distal portions of the limbs.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Impaired distal tactile sensation
MedGen UID:
867225
Concept ID:
C4021583
Finding
A reduced sense of touch (tactile sensation) on the skin of the distal limbs. This is usually tested with a wisp of cotton or a fine camel's hair brush, by asking patients to say 'now' each time they feel the stimulus.
Difficulty walking
MedGen UID:
86319
Concept ID:
C0311394
Finding
Reduced ability to walk (ambulate).
Tibialis anterior muscle atrophy
MedGen UID:
868961
Concept ID:
C4023375
Finding
Wasting of the tibialis anterior muscle.
Lower limb amyotrophy
MedGen UID:
870475
Concept ID:
C4024921
Finding
Muscular atrophy affecting the lower limb.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
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.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Central scotoma
MedGen UID:
57750
Concept ID:
C0152191
Finding
An area of depressed vision located at the point of fixation and that interferes with central vision.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 55
Follow this link to review classifications for Hereditary spastic paraplegia 55 in Orphanet.

Professional guidelines

PubMed

Kerstens HCJW, Nijkrake MJ, De Swart BJM, Nijhuis-van der Sanden RWG, Vos-van de Hulst M, Bos GJ, Geurts ACH, Van der Wees PJ
J Rehabil Med 2023 Apr 19;55:jrm00383. doi: 10.2340/jrm.v55.6572. PMID: 37073790Free PMC Article
Kerstens HCJW, Van Lith BJH, Nijkrake MJ, De Swart BJM, Van den Bemd LAC, Smeets RJEM, Klemens F, Van de Warrenburg BPC, Van der Wees PJ, Geurts ACH
Orphanet J Rare Dis 2021 Jun 24;16(1):283. doi: 10.1186/s13023-021-01915-0. PMID: 34167574Free PMC Article

Recent clinical studies

Etiology

Cui F, Sun L, Qiao J, Li J, Li M, Chen S, Sun B, Huang X
Medicine (Baltimore) 2020 Jun 5;99(23):e20193. doi: 10.1097/MD.0000000000020193. PMID: 32501971Free PMC Article
Cui F, Sun L, Qiao J, Xiong J, Zhao Y, Li J, Li M, Chen S, Huang X
Neurol Res 2018 Dec;40(12):1088-1093. doi: 10.1080/01616412.2018.1522412. PMID: 30352018
Lo Giudice T, Lombardi F, Santorelli FM, Kawarai T, Orlacchio A
Exp Neurol 2014 Nov;261:518-39. Epub 2014 Jun 20 doi: 10.1016/j.expneurol.2014.06.011. PMID: 24954637
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320
Fourtassi M, Jacquin-Courtois S, Scheiber-Nogueira MC, Hajjioui A, Luaute J, Charvier K, Maucort-Boulch D, Rode G
Spinal Cord 2012 Jul;50(7):558-62. Epub 2012 Jan 31 doi: 10.1038/sc.2011.193. PMID: 22289900

Diagnosis

Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Cui F, Sun L, Qiao J, Li J, Li M, Chen S, Sun B, Huang X
Medicine (Baltimore) 2020 Jun 5;99(23):e20193. doi: 10.1097/MD.0000000000020193. PMID: 32501971Free PMC Article
Cui F, Sun L, Qiao J, Xiong J, Zhao Y, Li J, Li M, Chen S, Huang X
Neurol Res 2018 Dec;40(12):1088-1093. doi: 10.1080/01616412.2018.1522412. PMID: 30352018
Lu C, Li LX, Dong HL, Wei Q, Liu ZJ, Ni W, Gitler AD, Wu ZY
J Mol Med (Berl) 2018 Jul;96(7):701-712. Epub 2018 Jun 11 doi: 10.1007/s00109-018-1655-4. PMID: 29934652
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320

Therapy

Kerstens HCJW, Nijkrake MJ, De Swart BJM, Nijhuis-van der Sanden RWG, Vos-van de Hulst M, Bos GJ, Geurts ACH, Van der Wees PJ
J Rehabil Med 2023 Apr 19;55:jrm00383. doi: 10.2340/jrm.v55.6572. PMID: 37073790Free 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
Bensmail D, Quera Salva MA, Roche N, Benyahia S, Bohic M, Denys P, Bussel B, Lofaso F
Neurology 2006 Oct 24;67(8):1432-6. doi: 10.1212/01.wnl.0000239827.38036.23. PMID: 17060570

Prognosis

Zhu ZY, Li ZY, Zhang C, Liu XL, Tian WT, Cao L
Eur J Med Genet 2022 Nov;65(11):104608. Epub 2022 Sep 12 doi: 10.1016/j.ejmg.2022.104608. PMID: 36100157
Rosello M, Caro-Llopis A, Orellana C, Oltra S, Alemany-Albert M, Marco-Hernandez AV, Monfort S, Pedrola L, Martinez F, Tomás M
Pediatr Res 2021 Aug;90(2):284-288. Epub 2020 Nov 11 doi: 10.1038/s41390-020-01250-3. PMID: 33177673
Galvão CRC, Cavalcante PMA, Olinda R, Graciani Z, Zatz M, Kok F, Santos S, Lancman S
BMC Neurol 2019 Oct 27;19(1):256. doi: 10.1186/s12883-019-1465-5. PMID: 31656170Free PMC Article
Arnoldi A, Crimella C, Tenderini E, Martinuzzi A, D'Angelo MG, Musumeci O, Toscano A, Scarlato M, Fantin M, Bresolin N, Bassi MT
Clin Genet 2012 Feb;81(2):150-7. Epub 2011 Jan 31 doi: 10.1111/j.1399-0004.2011.01624.x. PMID: 21214876
Pearce DA
Hum Genet 1999 Jun;104(6):443-8. doi: 10.1007/s004390050985. PMID: 10453730

Clinical prediction guides

Zhu ZY, Li ZY, Zhang C, Liu XL, Tian WT, Cao L
Eur J Med Genet 2022 Nov;65(11):104608. Epub 2022 Sep 12 doi: 10.1016/j.ejmg.2022.104608. PMID: 36100157
Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Cui F, Sun L, Qiao J, Xiong J, Zhao Y, Li J, Li M, Chen S, Huang X
Neurol Res 2018 Dec;40(12):1088-1093. doi: 10.1080/01616412.2018.1522412. PMID: 30352018
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
Pearce DA
Hum Genet 1999 Jun;104(6):443-8. doi: 10.1007/s004390050985. PMID: 10453730

Recent systematic reviews

Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320

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