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Spinocerebellar ataxia 46(SCA46)

MedGen UID:
1624251
Concept ID:
C4540404
Disease or Syndrome
Synonym: SPINOCEREBELLAR ATAXIA, 46, AUTOSOMAL DOMINANT, WITH SENSORY AXONAL NEUROPATHY
SNOMED CT: SCA46 - spinocerebellar ataxia type 46 (1279839002); Spinocerebellar ataxia type 46 (1279839002)
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): PLD3 (19q13.2)
 
Monarch Initiative: MONDO:0033481
OMIM®: 617770
Orphanet: ORPHA589522

Definition

A rare autosomal dominant cerebellar ataxia with characteristics of slowly progressive late-onset cerebellar ataxia variably combined with sensory axonal neuropathy. Patients may present gait and limb ataxia, dysarthria, abnormal oculomotor function and distal sensory impairment. Cerebellar atrophy is typically mild or absent. [from SNOMEDCT_US]

Clinical features

From HPO
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.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Positive Romberg sign
MedGen UID:
66017
Concept ID:
C0240914
Finding
The patient stands with the feet placed together and balance and is asked to close his or her eyes. A loss of balance upon eye closure is a positive Romberg sign and is interpreted as indicating a deficit in proprioception.
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.
Sensory axonal neuropathy
MedGen UID:
334116
Concept ID:
C1842587
Finding
An axonal neuropathy of peripheral sensory nerves.
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.
Slow saccadic eye movements
MedGen UID:
232942
Concept ID:
C1321329
Finding
An abnormally slow velocity of the saccadic eye movements.
Jerky ocular pursuit movements
MedGen UID:
342908
Concept ID:
C1853558
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSpinocerebellar ataxia 46

Professional guidelines

PubMed

Rossi M, Hamed M, Rodríguez-Antigüedad J, Cornejo-Olivas M, Breza M, Lohmann K, Klein C, Rajalingam R, Marras C, van de Warrenburg BP
Mov Disord 2023 Mar;38(3):368-377. Epub 2022 Nov 14 doi: 10.1002/mds.29278. PMID: 36374860
Yoshida K, Kuwabara S, Nakamura K, Abe R, Matsushima A, Beppu M, Yamanaka Y, Takahashi Y, Sasaki H, Mizusawa H; Research Group on Ataxic Disorders
J Neurol Sci 2018 Jan 15;384:30-35. Epub 2017 Nov 7 doi: 10.1016/j.jns.2017.11.008. PMID: 29249373
Bhatt JM, Bush A, van Gerven M, Nissenkorn A, Renke M, Yarlett L, Taylor M, Tonia T, Warris A, Zielen S, Zinna S, Merkus PJ; European Respiratory Society
Eur Respir Rev 2015 Dec;24(138):565-81. doi: 10.1183/16000617.0066-2015. PMID: 26621971Free PMC Article

Recent clinical studies

Etiology

Nanetti L, Magri S, Fichera M, Castaldo A, Nigri A, Pinardi C, Mongelli A, Sarro L, Pareyson D, Grisoli M, Gellera C, Di Bella D, Mariotti C, Taroni F
Mov Disord 2023 Apr;38(4):665-675. Epub 2023 Feb 17 doi: 10.1002/mds.29352. PMID: 36799493
Rossi M, Hamed M, Rodríguez-Antigüedad J, Cornejo-Olivas M, Breza M, Lohmann K, Klein C, Rajalingam R, Marras C, van de Warrenburg BP
Mov Disord 2023 Mar;38(3):368-377. Epub 2022 Nov 14 doi: 10.1002/mds.29278. PMID: 36374860
Liang L, Chen T, Wu Y
Neurophysiol Clin 2016 Feb;46(1):27-34. Epub 2016 Mar 2 doi: 10.1016/j.neucli.2015.12.006. PMID: 26947625
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320
Sandoval N, Platzer M, Rosenthal A, Dörk T, Bendix R, Skawran B, Stuhrmann M, Wegner RD, Sperling K, Banin S, Shiloh Y, Baumer A, Bernthaler U, Sennefelder H, Brohm M, Weber BH, Schindler D
Hum Mol Genet 1999 Jan;8(1):69-79. doi: 10.1093/hmg/8.1.69. PMID: 9887333

Diagnosis

Nanetti L, Magri S, Fichera M, Castaldo A, Nigri A, Pinardi C, Mongelli A, Sarro L, Pareyson D, Grisoli M, Gellera C, Di Bella D, Mariotti C, Taroni F
Mov Disord 2023 Apr;38(4):665-675. Epub 2023 Feb 17 doi: 10.1002/mds.29352. PMID: 36799493
Rossi M, Hamed M, Rodríguez-Antigüedad J, Cornejo-Olivas M, Breza M, Lohmann K, Klein C, Rajalingam R, Marras C, van de Warrenburg BP
Mov Disord 2023 Mar;38(3):368-377. Epub 2022 Nov 14 doi: 10.1002/mds.29278. PMID: 36374860
Alyasin S, Esmaeilzadeh H, Ebrahimi N, Nabavizadeh SH, Nemati H
Arch Iran Med 2019 Dec 1;22(12):682-686. PMID: 31823618
Liang L, Chen T, Wu Y
Neurophysiol Clin 2016 Feb;46(1):27-34. Epub 2016 Mar 2 doi: 10.1016/j.neucli.2015.12.006. PMID: 26947625
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

Coarelli G, Dubec-Fleury C, Petit E, Sayah S, Fischer C, Nassisi M, Gatignol P, Dorgham K, Daghsen L, Daye P, Cunha P, Kacher R, Hilab R, Hurmic H, Lamazière A, Lamy JC, Welter ML, Chupin M, Mangin JF, Lane R, Gaymard B, Pouget P, Audo I, Brice A, Tezenas du Montcel S, Durr A
Neurology 2024 Sep 10;103(5):e209749. Epub 2024 Aug 12 doi: 10.1212/WNL.0000000000209749. PMID: 39133883Free PMC Article
Rossi M, Hamed M, Rodríguez-Antigüedad J, Cornejo-Olivas M, Breza M, Lohmann K, Klein C, Rajalingam R, Marras C, van de Warrenburg BP
Mov Disord 2023 Mar;38(3):368-377. Epub 2022 Nov 14 doi: 10.1002/mds.29278. PMID: 36374860
Adin-Cinar S, Gelmez MY, Akdeniz N, Ozcit-Gurel G, Kiykim A, Karakoc-Aydiner E, Barlan I, Deniz G
Immunol Lett 2021 Dec;240:46-55. Epub 2021 Sep 30 doi: 10.1016/j.imlet.2021.09.008. PMID: 34599947
Diallo A, Jacobi H, Tezenas du Montcel S, Klockgether T
J Neurol 2021 Aug;268(8):2749-2756. Epub 2020 Apr 7 doi: 10.1007/s00415-020-09815-2. PMID: 32266540
Jacobi H, du Montcel ST, Romanzetti S, Harmuth F, Mariotti C, Nanetti L, Rakowicz M, Makowicz G, Durr A, Monin ML, Filla A, Roca A, Schöls L, Hengel H, Infante J, Kang JS, Timmann D, Casali C, Masciullo M, Baliko L, Melegh B, Nachbauer W, Bürk-Gergs K, Schulz JB, Riess O, Reetz K, Klockgether T
Lancet Neurol 2020 Sep;19(9):738-747. doi: 10.1016/S1474-4422(20)30235-0. PMID: 32822634

Prognosis

Nanetti L, Magri S, Fichera M, Castaldo A, Nigri A, Pinardi C, Mongelli A, Sarro L, Pareyson D, Grisoli M, Gellera C, Di Bella D, Mariotti C, Taroni F
Mov Disord 2023 Apr;38(4):665-675. Epub 2023 Feb 17 doi: 10.1002/mds.29352. PMID: 36799493
Faber J, Schaprian T, Berkan K, Reetz K, França MC Jr, de Rezende TJR, Hong J, Liao W, van de Warrenburg B, van Gaalen J, Durr A, Mochel F, Giunti P, Garcia-Moreno H, Schoels L, Hengel H, Synofzik M, Bender B, Oz G, Joers J, de Vries JJ, Kang JS, Timmann-Braun D, Jacobi H, Infante J, Joules R, Romanzetti S, Diedrichsen J, Schmid M, Wolz R, Klockgether T
Mov Disord 2021 Oct;36(10):2273-2281. Epub 2021 May 5 doi: 10.1002/mds.28610. PMID: 33951232Free PMC Article
Stezin A, Venkatesh SD, Thennarasu K, Purushottam M, Jain S, Yadav R, Pal PK
J Neurol Sci 2018 Nov 15;394:14-18. Epub 2018 Sep 1 doi: 10.1016/j.jns.2018.08.024. PMID: 30196130
Bhatt JM, Bush A, van Gerven M, Nissenkorn A, Renke M, Yarlett L, Taylor M, Tonia T, Warris A, Zielen S, Zinna S, Merkus PJ; European Respiratory Society
Eur Respir Rev 2015 Dec;24(138):565-81. doi: 10.1183/16000617.0066-2015. PMID: 26621971Free PMC Article
Schmitz-Hübsch T, Coudert M, Bauer P, Giunti P, Globas C, Baliko L, Filla A, Mariotti C, Rakowicz M, Charles P, Ribai P, Szymanski S, Infante J, van de Warrenburg BP, Dürr A, Timmann D, Boesch S, Fancellu R, Rola R, Depondt C, Schöls L, Zdienicka E, Kang JS, Döhlinger S, Kremer B, Stephenson DA, Melegh B, Pandolfo M, di Donato S, du Montcel ST, Klockgether T
Neurology 2008 Sep 23;71(13):982-9. Epub 2008 Aug 6 doi: 10.1212/01.wnl.0000325057.33666.72. PMID: 18685131

Clinical prediction guides

Nanetti L, Magri S, Fichera M, Castaldo A, Nigri A, Pinardi C, Mongelli A, Sarro L, Pareyson D, Grisoli M, Gellera C, Di Bella D, Mariotti C, Taroni F
Mov Disord 2023 Apr;38(4):665-675. Epub 2023 Feb 17 doi: 10.1002/mds.29352. PMID: 36799493
Alyasin S, Esmaeilzadeh H, Ebrahimi N, Nabavizadeh SH, Nemati H
Arch Iran Med 2019 Dec 1;22(12):682-686. PMID: 31823618
Zhou Y, Yuan Y, Liu Z, Zeng S, Chen Z, Shen L, Jiang H, Xia K, Tang B, Wang J
J Neurol 2019 Dec;266(12):2979-2986. Epub 2019 Aug 30 doi: 10.1007/s00415-019-09519-2. PMID: 31471687
Teive HAG, Camargo CHF, Munhoz RP
Parkinsonism Relat Disord 2018 Jan;46:3-8. Epub 2017 Dec 12 doi: 10.1016/j.parkreldis.2017.12.009. PMID: 29249681
Sandoval N, Platzer M, Rosenthal A, Dörk T, Bendix R, Skawran B, Stuhrmann M, Wegner RD, Sperling K, Banin S, Shiloh Y, Baumer A, Bernthaler U, Sennefelder H, Brohm M, Weber BH, Schindler D
Hum Mol Genet 1999 Jan;8(1):69-79. doi: 10.1093/hmg/8.1.69. PMID: 9887333

Recent systematic reviews

Tenorio RB, Camargo CHF, Donis KC, Almeida CCB, Teive HAG
Cerebellum 2024 Aug;23(4):1552-1565. Epub 2023 Nov 11 doi: 10.1007/s12311-023-01629-y. PMID: 37950147
Rossi M, Hamed M, Rodríguez-Antigüedad J, Cornejo-Olivas M, Breza M, Lohmann K, Klein C, Rajalingam R, Marras C, van de Warrenburg BP
Mov Disord 2023 Mar;38(3):368-377. Epub 2022 Nov 14 doi: 10.1002/mds.29278. PMID: 36374860
Winser S, Chan HK, Chen WK, Hau CY, Leung SH, Leung YH, Bello UM
Physiother Theory Pract 2023 Jul 3;39(7):1355-1375. Epub 2022 Feb 25 doi: 10.1080/09593985.2022.2037115. PMID: 35212247
Diallo A, Jacobi H, Tezenas du Montcel S, Klockgether T
J Neurol 2021 Aug;268(8):2749-2756. Epub 2020 Apr 7 doi: 10.1007/s00415-020-09815-2. PMID: 32266540
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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