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Spinocerebellar ataxia 43(SCA43)

MedGen UID:
934730
Concept ID:
C4310763
Disease or Syndrome
Synonym: SCA43
SNOMED CT: Spinocerebellar ataxia type 43 (1208516002)
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): MME (3q25.2)
 
Monarch Initiative: MONDO:0014867
OMIM®: 617018
Orphanet: ORPHA497764

Definition

Spinocerebellar ataxia-43 is an autosomal dominant, slowly progressive neurologic disorder characterized by adult-onset gait and limb ataxia and often associated with peripheral neuropathy mainly affecting the motor system, although some patients may have distal sensory impairment (summary by Depondt et al., 2016). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400). [from OMIM]

Clinical features

From HPO
Lower limb pain
MedGen UID:
6033
Concept ID:
C0023222
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the leg.
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).
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
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.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Cerebellar vermis atrophy
MedGen UID:
149271
Concept ID:
C0742028
Disease or Syndrome
Wasting (atrophy) of the vermis of cerebellum.
Limb ataxia
MedGen UID:
196692
Concept ID:
C0750937
Finding
A kind of ataxia that affects movements of the extremities.
Palmomental reflex
MedGen UID:
155866
Concept ID:
C0751470
Finding
A type of primitive reflex characterized by an involuntary contraction of the mentalis muscle of the chin caused by stimulation of the thenar eminence of the palm.
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.
Sensorimotor neuropathy
MedGen UID:
207266
Concept ID:
C1112256
Disease or Syndrome
Postural instability
MedGen UID:
334529
Concept ID:
C1843921
Finding
A tendency to fall or the inability to keep oneself from falling; imbalance. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, Use of the retropulsion test includes a rapid balance perturbation in the backward direction, and the number of balance correcting steps (or total absence thereof) is used to rate the degree of postural instability. Healthy subjects correct such perturbations with either one or two large steps, or without taking any steps, hinging rapidly at the hips while swinging the arms forward as a counterweight. In patients with balance impairment, balance correcting steps are often too small, forcing patients to take more than two steps. Taking three or more steps is generally considered to be abnormal, and taking more than five steps is regarded as being clearly abnormal. Markedly affected patients continue to step backward without ever regaining their balance and must be caught by the examiner (this would be called true retropulsion). Even more severely affected patients fail to correct entirely, and fall backward like a pushed toy soldier, without taking any corrective steps.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
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.
Hypometric saccades
MedGen UID:
98065
Concept ID:
C0423082
Finding
Saccadic undershoot, i.e., a saccadic eye movement that has less than the magnitude that would be required to gain fixation of the object.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSpinocerebellar ataxia 43

Professional guidelines

PubMed

Du YC, Dong Y, Cheng HL, Li QF, Yang L, Shao YR, Ma Y, Ni W, Gan SR, Wu ZY
Parkinsonism Relat Disord 2020 Sep;78:116-121. Epub 2020 Aug 4 doi: 10.1016/j.parkreldis.2020.07.024. PMID: 32814229
Schon K, van Os NJH, Oscroft N, Baxendale H, Scoffings D, Ray J, Suri M, Whitehouse WP, Mehta PR, Everett N, Bottolo L, van de Warrenburg BP, Byrd PJ, Weemaes C, Willemsen MA, Tischkowitz M, Taylor AM, Hensiek AE
Ann Neurol 2019 Feb;85(2):170-180. doi: 10.1002/ana.25394. PMID: 30549301Free PMC Article
DaVee T, Coronel E, Papafragkakis C, Thaiudom S, Lanke G, Chakinala RC, Nogueras González GM, Bhutani MS, Ross WA, Weston BR, Lee JH
Gastrointest Endosc 2018 Jun;87(6):1443-1450. Epub 2018 Jan 5 doi: 10.1016/j.gie.2017.12.019. PMID: 29309780

Recent clinical studies

Etiology

Bremova-Ertl T, Ramaswami U, Brands M, Foltan T, Gautschi M, Gissen P, Gowing F, Hahn A, Jones S, Kay R, Kolnikova M, Arash-Kaps L, Marquardt T, Mengel E, Park JH, Reichmannová S, Schneider SA, Sivananthan S, Walterfang M, Wibawa P, Strupp M, Martakis K
N Engl J Med 2024 Feb 1;390(5):421-431. doi: 10.1056/NEJMoa2310151. PMID: 38294974
Zhou H, Nguyen H, Enriquez A, Morsy L, Curtis M, Piser T, Kenney C, Stephen CD, Gupta AS, Schmahmann JD, Vaziri A
Neurol Sci 2022 Apr;43(4):2589-2599. Epub 2021 Oct 19 doi: 10.1007/s10072-021-05657-6. PMID: 34664180
Schon K, van Os NJH, Oscroft N, Baxendale H, Scoffings D, Ray J, Suri M, Whitehouse WP, Mehta PR, Everett N, Bottolo L, van de Warrenburg BP, Byrd PJ, Weemaes C, Willemsen MA, Tischkowitz M, Taylor AM, Hensiek AE
Ann Neurol 2019 Feb;85(2):170-180. doi: 10.1002/ana.25394. PMID: 30549301Free PMC Article
Martin JJ
Handb Clin Neurol 2012;103:475-91. doi: 10.1016/B978-0-444-51892-7.00030-9. PMID: 21827908
Elden AC, Kim HJ, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, Armakola M, Geser F, Greene R, Lu MM, Padmanabhan A, Clay-Falcone D, McCluskey L, Elman L, Juhr D, Gruber PJ, Rüb U, Auburger G, Trojanowski JQ, Lee VM, Van Deerlin VM, Bonini NM, Gitler AD
Nature 2010 Aug 26;466(7310):1069-75. doi: 10.1038/nature09320. PMID: 20740007Free PMC Article

Diagnosis

Bremova-Ertl T, Ramaswami U, Brands M, Foltan T, Gautschi M, Gissen P, Gowing F, Hahn A, Jones S, Kay R, Kolnikova M, Arash-Kaps L, Marquardt T, Mengel E, Park JH, Reichmannová S, Schneider SA, Sivananthan S, Walterfang M, Wibawa P, Strupp M, Martakis K
N Engl J Med 2024 Feb 1;390(5):421-431. doi: 10.1056/NEJMoa2310151. PMID: 38294974
Paolini Paoletti F, Prontera P, Nigro P, Simoni S, Cappelletti G, Filidei M, Calabresi P, Parnetti L, Tambasco N
Neurol Sci 2021 Oct;42(10):4309-4315. Epub 2021 May 24 doi: 10.1007/s10072-021-05313-z. PMID: 34031796
Mei L, Zhang J, He K, Zhang J
J Hematol Oncol 2019 Apr 24;12(1):43. doi: 10.1186/s13045-019-0733-6. PMID: 31018854Free PMC Article
Schon K, van Os NJH, Oscroft N, Baxendale H, Scoffings D, Ray J, Suri M, Whitehouse WP, Mehta PR, Everett N, Bottolo L, van de Warrenburg BP, Byrd PJ, Weemaes C, Willemsen MA, Tischkowitz M, Taylor AM, Hensiek AE
Ann Neurol 2019 Feb;85(2):170-180. doi: 10.1002/ana.25394. PMID: 30549301Free PMC Article
Martin JJ
Handb Clin Neurol 2012;103:475-91. doi: 10.1016/B978-0-444-51892-7.00030-9. PMID: 21827908

Therapy

Bremova-Ertl T, Ramaswami U, Brands M, Foltan T, Gautschi M, Gissen P, Gowing F, Hahn A, Jones S, Kay R, Kolnikova M, Arash-Kaps L, Marquardt T, Mengel E, Park JH, Reichmannová S, Schneider SA, Sivananthan S, Walterfang M, Wibawa P, Strupp M, Martakis K
N Engl J Med 2024 Feb 1;390(5):421-431. doi: 10.1056/NEJMoa2310151. PMID: 38294974
Yap TA, Fontana E, Lee EK, Spigel DR, Højgaard M, Lheureux S, Mettu NB, Carneiro BA, Carter L, Plummer R, Cote GM, Meric-Bernstam F, O'Connell J, Schonhoft JD, Wainszelbaum M, Fretland AJ, Manley P, Xu Y, Ulanet D, Rimkunas V, Zinda M, Koehler M, Silverman IM, Reis-Filho JS, Rosen E
Nat Med 2023 Jun;29(6):1400-1411. Epub 2023 Jun 5 doi: 10.1038/s41591-023-02399-0. PMID: 37277454Free PMC Article
Moulaire P, Poulet PE, Petit E, Klockgether T, Durr A, Ashisawa T, Tezenas du Montcel S; READISCA Consortium
Mov Disord 2023 Jan;38(1):35-44. Epub 2022 Oct 23 doi: 10.1002/mds.29255. PMID: 36273394Free PMC Article
Kim G, Nakayama L, Blum JA, Akiyama T, Boeynaems S, Chakraborty M, Couthouis J, Tassoni-Tsuchida E, Rodriguez CM, Bassik MC, Gitler AD
Cell Rep 2022 Oct 25;41(4):111508. doi: 10.1016/j.celrep.2022.111508. PMID: 36288714Free PMC Article
Silva RC, Saute JA, Silva AC, Coutinho AC, Saraiva-Pereira ML, Jardim LB
Braz J Med Biol Res 2010 Jun;43(6):537-42. Epub 2010 Apr 16 doi: 10.1590/s0100-879x2010005000009. PMID: 20414586

Prognosis

Yap TA, Fontana E, Lee EK, Spigel DR, Højgaard M, Lheureux S, Mettu NB, Carneiro BA, Carter L, Plummer R, Cote GM, Meric-Bernstam F, O'Connell J, Schonhoft JD, Wainszelbaum M, Fretland AJ, Manley P, Xu Y, Ulanet D, Rimkunas V, Zinda M, Koehler M, Silverman IM, Reis-Filho JS, Rosen E
Nat Med 2023 Jun;29(6):1400-1411. Epub 2023 Jun 5 doi: 10.1038/s41591-023-02399-0. PMID: 37277454Free PMC Article
Moulaire P, Poulet PE, Petit E, Klockgether T, Durr A, Ashisawa T, Tezenas du Montcel S; READISCA Consortium
Mov Disord 2023 Jan;38(1):35-44. Epub 2022 Oct 23 doi: 10.1002/mds.29255. PMID: 36273394Free PMC Article
Alvarenga MP, Siciliani LC, Carvalho RS, Ganimi MC, Penna PS
Neurol Sci 2022 Aug;43(8):4997-5005. Epub 2022 Apr 25 doi: 10.1007/s10072-022-06084-x. PMID: 35469073
Gong Y, Chen Z, Liu M, Wan L, Wang C, Peng H, Shi Y, Peng Y, Xia K, Qiu R, Tang B, Jiang H
J Clin Neurosci 2021 Jun;88:39-46. Epub 2021 Mar 30 doi: 10.1016/j.jocn.2021.03.004. PMID: 33992201Free PMC Article
Faryniuk JH, Zeigelboim BS, Teive HAG, Fo VR, Liberalesso PBN, Marques JM
Int Tinnitus J 2017 Apr 19;20(2):93-101. doi: 10.5935/0946-5448.20160018. PMID: 28422031

Clinical prediction guides

Bremova-Ertl T, Ramaswami U, Brands M, Foltan T, Gautschi M, Gissen P, Gowing F, Hahn A, Jones S, Kay R, Kolnikova M, Arash-Kaps L, Marquardt T, Mengel E, Park JH, Reichmannová S, Schneider SA, Sivananthan S, Walterfang M, Wibawa P, Strupp M, Martakis K
N Engl J Med 2024 Feb 1;390(5):421-431. doi: 10.1056/NEJMoa2310151. PMID: 38294974
Yap TA, Fontana E, Lee EK, Spigel DR, Højgaard M, Lheureux S, Mettu NB, Carneiro BA, Carter L, Plummer R, Cote GM, Meric-Bernstam F, O'Connell J, Schonhoft JD, Wainszelbaum M, Fretland AJ, Manley P, Xu Y, Ulanet D, Rimkunas V, Zinda M, Koehler M, Silverman IM, Reis-Filho JS, Rosen E
Nat Med 2023 Jun;29(6):1400-1411. Epub 2023 Jun 5 doi: 10.1038/s41591-023-02399-0. PMID: 37277454Free PMC Article
Paul S, Dansithong W, Gandelman M, Figueroa KP, Zu T, Ranum LPW, Scoles DR, Pulst SM
Ann Neurol 2023 Feb;93(2):398-416. Epub 2022 Oct 27 doi: 10.1002/ana.26515. PMID: 36151701Free PMC Article
Alvarenga MP, Siciliani LC, Carvalho RS, Ganimi MC, Penna PS
Neurol Sci 2022 Aug;43(8):4997-5005. Epub 2022 Apr 25 doi: 10.1007/s10072-022-06084-x. PMID: 35469073
Zhou H, Nguyen H, Enriquez A, Morsy L, Curtis M, Piser T, Kenney C, Stephen CD, Gupta AS, Schmahmann JD, Vaziri A
Neurol Sci 2022 Apr;43(4):2589-2599. Epub 2021 Oct 19 doi: 10.1007/s10072-021-05657-6. PMID: 34664180

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