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Spinocerebellar ataxia type 28(SCA28)

MedGen UID:
339941
Concept ID:
C1853249
Disease or Syndrome
Synonym: SCA28
SNOMED CT: Spinocerebellar ataxia type 28 (715824008)
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.
 
Gene (location): AFG3L2 (18p11.21)
 
Monarch Initiative: MONDO:0012450
OMIM®: 610246
Orphanet: ORPHA101109

Definition

Spinocerebellar ataxia type 28 (SCA28) is characterized by young-adult onset, very slowly progressive gait and limb ataxia resulting in coordination and balance problems, dysarthria, ptosis, nystagmus, and ophthalmoparesis. In most individuals, SCA28 presents as a loss of coordination of lower limbs (unsteadiness, gait ataxia). Less frequently, ptosis/ophthalmoplegia, dysarthria, or upper-limb incoordination may occur as the initial finding. The course of the disease is slowly progressive without impairment of functional autonomy even decades after onset. [from GeneReviews]

Clinical features

From HPO
Lower limb hypertonia
MedGen UID:
375612
Concept ID:
C1845245
Finding
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.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
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.
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.
Parkinsonian disorder
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Limb ataxia
MedGen UID:
196692
Concept ID:
C0750937
Finding
A kind of ataxia that affects movements of the extremities.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Lower limb hyperreflexia
MedGen UID:
322973
Concept ID:
C1836696
Finding
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.
Ragged-red muscle fibers
MedGen UID:
477048
Concept ID:
C3275417
Finding
An abnormal appearance of muscle fibers observed on muscle biopsy. Ragged red fibers can be visualized with Gomori trichrome staining as irregular and intensely red subsarcolemmal zones, whereas the normal myofibrils are green. The margins of affect fibers appear red and ragged. The ragged-red is due to the accumulation of abnormal mitochondria below the plasma membrane of the muscle fiber, leading to the appearance of a red rim and speckled sarcoplasm.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Ophthalmoparesis
MedGen UID:
155551
Concept ID:
C0751401
Sign or Symptom
Ophthalmoplegia is a paralysis or weakness of one or more of the muscles that control eye movement.
Slow saccadic eye movements
MedGen UID:
232942
Concept ID:
C1321329
Finding
An abnormally slow velocity of the saccadic eye movements.
Dysmetric saccades
MedGen UID:
322908
Concept ID:
C1836392
Finding
The controller signal for saccadic eye movements has two components
Gaze-evoked nystagmus
MedGen UID:
1808161
Concept ID:
C5574666
Disease or Syndrome
Nystagmus made apparent by looking to the right or to the left.
Abnormal activity of mitochondrial respiratory chain
MedGen UID:
868721
Concept ID:
C4023126
Finding
An increased or decreased activity of the mitochondrial respiratory chain.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSpinocerebellar ataxia type 28
Follow this link to review classifications for Spinocerebellar ataxia type 28 in Orphanet.

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

Eskandrani A, AlHashem A, Ali ES, AlShahwan S, Tlili K, Hundallah K, Tabarki B
Pediatr Neurol 2017 Jun;71:24-28. Epub 2017 Apr 5 doi: 10.1016/j.pediatrneurol.2017.03.019. PMID: 28449981
Svenstrup K, Nielsen TT, Aidt F, Rostgaard N, Duno M, Wibrand F, Vinther-Jensen T, Law I, Vissing J, Roos P, Hjermind LE, Nielsen JE
Cerebellum 2017 Feb;16(1):62-67. doi: 10.1007/s12311-016-0765-1. PMID: 26868664
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
Jia D, Tang B, Chen Z, Shi Y, Sun Z, Zhang L, Wang J, Xia K, Jiang H
Int J Neurosci 2012 Oct;122(10):560-2. Epub 2012 Jun 22 doi: 10.3109/00207454.2012.690796. PMID: 22563911

Diagnosis

Liu X, Wang L, Chen J, Kang C, Li J
Medicine (Baltimore) 2021 Dec 17;100(50):e28008. doi: 10.1097/MD.0000000000028008. PMID: 34918652Free PMC Article
Dosi C, Galatolo D, Rubegni A, Doccini S, Pasquariello R, Nesti C, Sicca F, Barghigiani M, Battini R, Tessa A, Santorelli FM
Ann Clin Transl Neurol 2020 Apr;7(4):595-601. Epub 2020 Apr 1 doi: 10.1002/acn3.51024. PMID: 32237276Free PMC Article
Tunc S, Dulovic-Mahlow M, Baumann H, Baaske MK, Jahn M, Junker J, Münchau A, Brüggemann N, Lohmann K
Cerebellum 2019 Aug;18(4):817-822. doi: 10.1007/s12311-019-01036-2. PMID: 31111429
Musova Z, Kaiserova M, Kriegova E, Fillerova R, Vasovcak P, Santava A, Mensikova K, Zumrova A, Krepelova A, Sedlacek Z, Kanovsky P
Cerebellum 2014 Jun;13(3):331-7. doi: 10.1007/s12311-013-0538-z. PMID: 24272953
Pierson TM, Adams D, Bonn F, Martinelli P, Cherukuri PF, Teer JK, Hansen NF, Cruz P, Mullikin For The Nisc Comparative Sequencing Program JC, Blakesley RW, Golas G, Kwan J, Sandler A, Fuentes Fajardo K, Markello T, Tifft C, Blackstone C, Rugarli EI, Langer T, Gahl WA, Toro C
PLoS Genet 2011 Oct;7(10):e1002325. Epub 2011 Oct 13 doi: 10.1371/journal.pgen.1002325. PMID: 22022284Free PMC Article

Therapy

Maltecca F, Baseggio E, Consolato F, Mazza D, Podini P, Young SM Jr, Drago I, Bahr BA, Puliti A, Codazzi F, Quattrini A, Casari G
J Clin Invest 2015 Jan;125(1):263-74. Epub 2014 Dec 8 doi: 10.1172/JCI74770. PMID: 25485680Free PMC Article

Prognosis

Dosi C, Galatolo D, Rubegni A, Doccini S, Pasquariello R, Nesti C, Sicca F, Barghigiani M, Battini R, Tessa A, Santorelli FM
Ann Clin Transl Neurol 2020 Apr;7(4):595-601. Epub 2020 Apr 1 doi: 10.1002/acn3.51024. PMID: 32237276Free PMC Article
Eskandrani A, AlHashem A, Ali ES, AlShahwan S, Tlili K, Hundallah K, Tabarki B
Pediatr Neurol 2017 Jun;71:24-28. Epub 2017 Apr 5 doi: 10.1016/j.pediatrneurol.2017.03.019. PMID: 28449981

Clinical prediction guides

Gorman GS, Pfeffer G, Griffin H, Blakely EL, Kurzawa-Akanbi M, Gabriel J, Sitarz K, Roberts M, Schoser B, Pyle A, Schaefer AM, McFarland R, Turnbull DM, Horvath R, Chinnery PF, Taylor RW
JAMA Neurol 2015 Jan;72(1):106-11. doi: 10.1001/jamaneurol.2014.1753. PMID: 25420100
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
Mariotti C, Bella DD, Di Donato S, Taroni F
Handb Clin Neurol 2012;103:575-9. doi: 10.1016/B978-0-444-51892-7.00039-5. PMID: 21827917
Mariotti C, Brusco A, Di Bella D, Cagnoli C, Seri M, Gellera C, Di Donato S, Taroni F
Cerebellum 2008;7(2):184-8. doi: 10.1007/s12311-008-0053-9. PMID: 18769991

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