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Spinocerebellar ataxia type 6(SCA6)

MedGen UID:
148458
Concept ID:
C0752124
Disease or Syndrome
Synonym: SCA6
SNOMED CT: Spinocerebellar ataxia type 6 (715752006)
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): CACNA1A (19p13.13)
 
Monarch Initiative: MONDO:0008457
OMIM®: 183086
Orphanet: ORPHA98758

Definition

Spinocerebellar ataxia type 6 (SCA6) is characterized by adult-onset, slowly progressive cerebellar ataxia, dysarthria, and nystagmus. The age of onset ranges from 19 to 73 years; mean age of onset is between 43 and 52 years. Initial symptoms are gait unsteadiness, stumbling, and imbalance (in ~90%) and dysarthria (in ~10%). Eventually all persons have gait ataxia, upper-limb incoordination, intention tremor, and dysarthria. Dysphagia and choking are common. Visual disturbances may result from diplopia, difficulty fixating on moving objects, horizontal gaze-evoked nystagmus, and vertical nystagmus. Hyperreflexia and extensor plantar responses occur in up to 40%-50%. Basal ganglia signs, including dystonia and blepharospasm, occur in up to 25%. Mentation is generally preserved. [from GeneReviews]

Additional description

From MedlinePlus Genetics
Spinocerebellar ataxia type 6 (SCA6) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other early signs and symptoms of SCA6 include speech difficulties, involuntary eye movements (nystagmus), and double vision. Over time, individuals with SCA6 may develop loss of coordination in their arms, tremors, and uncontrolled muscle tensing (dystonia).

Signs and symptoms of SCA6 typically begin in a person's forties or fifties but can appear anytime from childhood to late adulthood. People with this disorder may require walking or mobility assistance later in life.  https://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-6

Clinical features

From HPO
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Nausea and vomiting
MedGen UID:
45015
Concept ID:
C0027498
Sign or Symptom
Nausea is a commonly encountered symptom that has been defined as an unpleasant painless subjective feeling that one will imminently vomit. Vomiting has been defined as the forceful expulsion of the contents of the stomach, duodenum, or jejunum through the oral cavity. While nausea and vomiting are often thought to exist on a temporal continuum, this is not always the case. There are situations when severe nausea may be present without emesis and less frequently, when emesis may be present without preceding nausea.
Vertigo
MedGen UID:
53006
Concept ID:
C0042571
Sign or Symptom
An abnormal sensation of spinning while the body is actually stationary.
Abnormal vestibulo-ocular reflex
MedGen UID:
867213
Concept ID:
C4021571
Anatomical Abnormality
An abnormality of the vestibulo-ocular reflex (VOR). The VOR attempts to keep the image stable on the retina. Ideally passive or active head movements in one direction are compensated for by eye movements of equal magnitude.
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.
Sensory neuropathy
MedGen UID:
101791
Concept ID:
C0151313
Disease or Syndrome
Peripheral neuropathy affecting the sensory nerves.
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.
Slurred speech
MedGen UID:
65885
Concept ID:
C0234518
Finding
Abnormal coordination of muscles involved in speech.
Migraine without aura
MedGen UID:
137899
Concept ID:
C0338480
Disease or Syndrome
Repeated headache attacks lasting 4-72 h fulfilling at least two of the following criteria
Progressive cerebellar ataxia
MedGen UID:
140727
Concept ID:
C0393525
Disease or Syndrome
Truncal ataxia
MedGen UID:
96535
Concept ID:
C0427190
Sign or Symptom
Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting.
Incoordination
MedGen UID:
141714
Concept ID:
C0520966
Finding
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.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Intention tremor
MedGen UID:
1642960
Concept ID:
C4551520
Sign or Symptom
A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger).
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Frequent falls
MedGen UID:
163408
Concept ID:
C0850703
Finding
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.
Impaired smooth pursuit
MedGen UID:
325176
Concept ID:
C1837458
Finding
An impairment of the ability to track objects with the ocular smooth pursuit system, a class of rather slow eye movements that minimizes retinal target motion.
Gaze-evoked horizontal nystagmus
MedGen UID:
377895
Concept ID:
C1853394
Finding
Horizontal nystagmus made apparent by looking to the right or to the left.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSpinocerebellar ataxia type 6
Follow this link to review classifications for Spinocerebellar ataxia type 6 in Orphanet.

Professional guidelines

PubMed

Furuta M, Sato M, Tsukagoshi S, Tsushima Y, Ikeda Y
J Neurol Sci 2022 Jul 15;438:120281. Epub 2022 May 14 doi: 10.1016/j.jns.2022.120281. PMID: 35609364
Lowit A, Egan A, Hadjivassiliou M
Cerebellum 2020 Oct;19(5):701-714. doi: 10.1007/s12311-020-01153-3. PMID: 32588316Free PMC Article
Pastor PDH, Du X, Fazal S, Davies AN, Gomez CM
Cerebellum 2018 Feb;17(1):72-77. doi: 10.1007/s12311-018-0917-6. PMID: 29374372Free PMC Article

Recent clinical studies

Etiology

Rentiya Z, Hutnik R, Mekkam YQ, Bae J
Cerebellum 2020 Jun;19(3):459-464. doi: 10.1007/s12311-020-01120-y. PMID: 32125675
Den Dunnen WFA
Handb Clin Neurol 2017;145:383-391. doi: 10.1016/B978-0-12-802395-2.00027-4. PMID: 28987184
Rueda AD, Pedroso JL, Truksinas E, Do Prado GF, Coelho FM, Barsottini OG
J Sleep Res 2016 Dec;25(6):720-723. Epub 2016 Jul 5 doi: 10.1111/jsr.12439. PMID: 27377205
Solodkin A, Gomez CM
Handb Clin Neurol 2012;103:461-73. doi: 10.1016/B978-0-444-51892-7.00029-2. PMID: 21827907
Surtees R
Eur J Pediatr 2000 Dec;159 Suppl 3:S199-203. doi: 10.1007/pl00014403. PMID: 11216900

Diagnosis

Hommersom MP, van Prooije TH, Pennings M, Schouten MI, van Bokhoven H, Kamsteeg EJ, van de Warrenburg BPC
J Neurol 2022 Jun;269(6):3094-3108. Epub 2021 Nov 22 doi: 10.1007/s00415-021-10897-9. PMID: 34806130
Rentiya Z, Hutnik R, Mekkam YQ, Bae J
Cerebellum 2020 Jun;19(3):459-464. doi: 10.1007/s12311-020-01120-y. PMID: 32125675
Lieto M, Roca A, Santorelli FM, Fico T, De Michele G, Bellofatto M, Saccà F, De Michele G, Filla A
Neurol Sci 2019 Jul;40(7):1335-1342. Epub 2019 Mar 29 doi: 10.1007/s10072-019-03856-w. PMID: 30927137
Den Dunnen WFA
Handb Clin Neurol 2017;145:383-391. doi: 10.1016/B978-0-12-802395-2.00027-4. PMID: 28987184
Solodkin A, Gomez CM
Handb Clin Neurol 2012;103:461-73. doi: 10.1016/B978-0-444-51892-7.00029-2. PMID: 21827907

Therapy

Ikezawa J, Shimazaki R, Tobisawa S, Sugaya K, Takahashi K
Clin Neurol Neurosurg 2023 Jun;229:107721. Epub 2023 Apr 18 doi: 10.1016/j.clineuro.2023.107721. PMID: 37084651
Solodkin A, Gomez CM
Handb Clin Neurol 2012;103:461-73. doi: 10.1016/B978-0-444-51892-7.00029-2. PMID: 21827907
Nakamura K, Yoshida K, Miyazaki D, Morita H, Ikeda S
J Neurol Sci 2009 Mar 15;278(1-2):107-11. Epub 2009 Jan 21 doi: 10.1016/j.jns.2008.12.017. PMID: 19157422
Gazulla J, Tintoré M
Acta Neurol Scand 2007 May;115(5):356-63. doi: 10.1111/j.1600-0404.2006.00752.x. PMID: 17489948
Soong B, Liu R, Wu L, Lu Y, Lee H
Arch Neurol 2001 Feb;58(2):300-4. doi: 10.1001/archneur.58.2.300. PMID: 11176970

Prognosis

Pereira L, Airan RD, Fishman A, Pillai JJ, Kansal K, Onyike CU, Prince JL, Ying SH, Sair HI
Hum Brain Mapp 2017 Jun;38(6):3001-3010. Epub 2017 Mar 15 doi: 10.1002/hbm.23568. PMID: 28295805Free PMC Article
Isono C, Hirano M, Sakamoto H, Ueno S, Kusunoki S, Nakamura Y
Dysphagia 2017 Jun;32(3):420-426. Epub 2017 Jan 2 doi: 10.1007/s00455-016-9771-1. PMID: 28042641
Mark MD, Krause M, Boele HJ, Kruse W, Pollok S, Kuner T, Dalkara D, Koekkoek S, De Zeeuw CI, Herlitze S
J Neurosci 2015 Jun 10;35(23):8882-95. doi: 10.1523/JNEUROSCI.0891-15.2015. PMID: 26063920Free PMC Article
Yu-Wai-Man P, Gorman G, Bateman DE, Leigh RJ, Chinnery PF
J Neurol 2009 Jan;256(1):78-82. Epub 2009 Feb 9 doi: 10.1007/s00415-009-0068-2. PMID: 19224313
Geschwind DH, Perlman S, Figueroa KP, Karrim J, Baloh RW, Pulst SM
Neurology 1997 Nov;49(5):1247-51. doi: 10.1212/wnl.49.5.1247. PMID: 9371902

Clinical prediction guides

Den Dunnen WFA
Handb Clin Neurol 2017;145:383-391. doi: 10.1016/B978-0-12-802395-2.00027-4. PMID: 28987184
Isono C, Hirano M, Sakamoto H, Ueno S, Kusunoki S, Nakamura Y
Dysphagia 2017 Jun;32(3):420-426. Epub 2017 Jan 2 doi: 10.1007/s00455-016-9771-1. PMID: 28042641
Tamura I, Takei A, Hamada S, Nonaka M, Kurosaki Y, Moriwaka F
J Neurol 2017 Feb;264(2):260-267. Epub 2016 Nov 22 doi: 10.1007/s00415-016-8344-4. PMID: 27878440
Ishibashi K, Miura Y, Ishikawa K, Zhang MR, Toyohara J, Ishiwata K, Ishii K
J Neurol 2016 Nov;263(11):2179-2187. Epub 2016 Aug 8 doi: 10.1007/s00415-016-8248-3. PMID: 27502082
Mark MD, Krause M, Boele HJ, Kruse W, Pollok S, Kuner T, Dalkara D, Koekkoek S, De Zeeuw CI, Herlitze S
J Neurosci 2015 Jun 10;35(23):8882-95. doi: 10.1523/JNEUROSCI.0891-15.2015. PMID: 26063920Free PMC Article

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