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Spinocerebellar ataxia type 1(SCA1)

MedGen UID:
155703
Concept ID:
C0752120
Disease or Syndrome
Synonyms: Cerebelloparenchymal disorder 1; CEREBELLOPARENCHYMAL DISORDER I; Olivopontocerebellar atrophy 1; Olivopontocerebellar atrophy 4; OLIVOPONTOCEREBELLAR ATROPHY I; OLIVOPONTOCEREBELLAR ATROPHY IV; SCA1; Spinocerebellar atrophy 1; SPINOCEREBELLAR ATROPHY I
SNOMED CT: Spinocerebellar ataxia type 1 (715748006)
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): ATXN1 (6p22.3)
 
Monarch Initiative: MONDO:0008119
OMIM®: 164400
Orphanet: ORPHA98755

Definition

Spinocerebellar ataxia type 1 (SCA1) is characterized by progressive cerebellar ataxia, dysarthria, and eventual deterioration of bulbar functions. Early in the disease, affected individuals may have gait disturbance, slurred speech, difficulty with balance, brisk deep tendon reflexes, hypermetric saccades, nystagmus, and mild dysphagia. Later signs include slowing of saccadic velocity, development of up-gaze palsy, dysmetria, dysdiadochokinesia, and hypotonia. In advanced stages, muscle atrophy, decreased deep tendon reflexes, loss of proprioception, cognitive impairment (e.g., frontal executive dysfunction, impaired verbal memory), chorea, dystonia, and bulbar dysfunction are seen. Onset is typically in the third or fourth decade, although childhood onset and late-adult onset have been reported. Those with onset after age 60 years may manifest a pure cerebellar phenotype. Interval from onset to death varies from ten to 30 years; individuals with juvenile onset show more rapid progression and more severe disease. Anticipation is observed. An axonal sensory neuropathy detected by electrophysiologic testing is common; brain imaging typically shows cerebellar and brain stem atrophy. [from GeneReviews]

Additional descriptions

From OMIM
The autosomal dominant cerebellar degenerative disorders are generally referred to as 'spinocerebellar ataxias,' (SCAs) even though 'spinocerebellar' is a hybrid term, referring to both clinical signs and neuroanatomical regions (Margolis, 2003). Neuropathologists have defined SCAs as cerebellar ataxias with variable involvement of the brainstem and spinal cord, and the clinical features of the disorders are caused by degeneration of the cerebellum and its afferent and efferent connections, which involve the brainstem and spinal cord (Schols et al., 2004; Taroni and DiDonato, 2004). Historically, Harding (1982) proposed a clinical classification for autosomal dominant cerebellar ataxias (ADCAs). ADCA I was characterized by cerebellar ataxia in combination with various associated neurologic features, such as ophthalmoplegia, pyramidal and extrapyramidal signs, peripheral neuropathy, and dementia, among others. ADCA II was characterized by the cerebellar ataxia, associated neurologic features, and the additional findings of macular and retinal degeneration. ADCA III was a pure form of late-onset cerebellar ataxia without additional features. SCA1, SCA2 (183090), and SCA3, or Machado-Joseph disease (109150), are considered to be forms of ADCA I. These 3 disorders are characterized at the molecular level by CAG repeat expansions on 6p24-p23, 12q24.1, and 14q32.1, respectively. SCA7 (607640), caused by a CAG repeat expansion in the ATXN7 gene (607640) on chromosome 3p13-p12, is a form of ADCA II. SCA5 (600224), SCA31 (117210), SCA6 (183086), and SCA11 (600432) are associated with phenotypes most suggestive of ADCA III. However, Schelhaas et al. (2000) noted that there is significant phenotypic overlap between different forms of SCA as well as significant phenotypic variability within each subtype. Classic reviews of olivopontocerebellar atrophies and of inherited ataxias in general include those of Konigsmark and Weiner (1970), who identified 5 types of olivopontocerebellar atrophy, Berciano (1982), Harding (1993), Schelhaas et al. (2000), and Margolis (2003).  http://www.omim.org/entry/164400
From MedlinePlus Genetics
Spinocerebellar ataxia type 1 (SCA1) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other signs and symptoms of SCA1 include speech and swallowing difficulties, muscle stiffness (spasticity), and weakness in the muscles that control eye movement (ophthalmoplegia). Eye muscle weakness leads to rapid, involuntary eye movements (nystagmus). Individuals with SCA1 may have difficulty processing, learning, and remembering information (cognitive impairment).

Over time, individuals with SCA1 may develop numbness, tingling, or pain in the arms and legs (sensory neuropathy); uncontrolled muscle tensing (dystonia); muscle wasting (atrophy); and muscle twitches (fasciculations). Rarely, rigidity, tremors, and involuntary jerking movements (chorea) have been reported in people who have been affected for many years.

Signs and symptoms of the disorder typically begin in early adulthood but can appear anytime from childhood to late adulthood. People with SCA1 typically survive 10 to 20 years after symptoms first appear.  https://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-1

Clinical features

From HPO
Urinary bladder sphincter dysfunction
MedGen UID:
334804
Concept ID:
C1843663
Finding
Abnormal function of a sphincter of the urinary bladder.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Chorea
MedGen UID:
3420
Concept ID:
C0008489
Disease or Syndrome
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities.
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.
Fasciculations
MedGen UID:
5124
Concept ID:
C0015644
Sign or Symptom
Fasciculations are observed as small, local, involuntary muscle contractions (twitching) visible under the skin. Fasciculations result from increased irritability of an axon (which in turn is often a manifestation of disease of a motor neuron). This leads to sporadic discharges of all the muscle fibers controlled by the axon in isolation from other motor units.
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.
Olivopontocerebellar atrophy
MedGen UID:
10435
Concept ID:
C0028968
Disease or Syndrome
Neuronal degeneration in the cerebellum, pontine nuclei, and inferior olivary nucleus.
Paresthesia
MedGen UID:
14619
Concept ID:
C0030554
Disease or Syndrome
Abnormal sensations such as tingling, pricking, or numbness of the skin with no apparent physical cause.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
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.
Spinocerebellar atrophy
MedGen UID:
39733
Concept ID:
C0087012
Disease or Syndrome
Atrophy affecting the cerebellum and the spinocerebellar tracts of the spinal cord.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Abnormality of extrapyramidal motor function
MedGen UID:
115941
Concept ID:
C0234133
Sign or Symptom
A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless).
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
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.
Dysdiadochokinesis
MedGen UID:
115975
Concept ID:
C0234979
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to perform rapidly alternating movements, such as pronating and supinating his or her hand on the dorsum of the other hand as rapidly as possible.
Scanning speech
MedGen UID:
116113
Concept ID:
C0240952
Mental or Behavioral Dysfunction
An abnormal pattern of speech in which the words are as if measured or scanned; there is a pause after every syllable, and the syllables themselves are pronounced slowly.
Cognitive impairment
MedGen UID:
90932
Concept ID:
C0338656
Mental or Behavioral Dysfunction
Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.
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.
Limb ataxia
MedGen UID:
196692
Concept ID:
C0750937
Finding
A kind of ataxia that affects movements of the extremities.
Impaired vibratory sensation
MedGen UID:
220959
Concept ID:
C1295585
Finding
A decrease in the ability to perceive vibration. Clinically, this is usually tested with a tuning fork which vibrates at 128 Hz and is applied to bony prominences such as the malleoli at the ankles or the metacarpal-phalangeal joints. There is a slow decay of vibration from the tuning fork. The degree of vibratory sense loss can be crudely estimated by counting the number of seconds that the examiner can perceive the vibration longer than the patient.
Impaired pain sensation
MedGen UID:
373348
Concept ID:
C1837522
Finding
Reduced ability to perceive painful stimuli.
Dilated fourth ventricle
MedGen UID:
376050
Concept ID:
C1847117
Finding
An abnormal dilatation of the fourth cerebral ventricle.
Decreased sensory nerve conduction velocity
MedGen UID:
336512
Concept ID:
C1849148
Finding
Reduced speed of conduction of the action potential along a sensory nerve.
Impaired proprioception
MedGen UID:
346424
Concept ID:
C1856691
Finding
A loss or impairment of the sensation of the relative position of parts of the body and joint position.
Decreased motor nerve conduction velocity
MedGen UID:
388130
Concept ID:
C1858729
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Spinocerebellar tract degeneration
MedGen UID:
401075
Concept ID:
C1866751
Disease or Syndrome
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.
Decreased amplitude of sensory action potentials
MedGen UID:
870496
Concept ID:
C4024943
Finding
A reduction in the amplitude of sensory nerve action potential. This feature is measured by nerve conduction studies.
Dorsal column degeneration
MedGen UID:
870506
Concept ID:
C4024953
Pathologic Function
Bulbar palsy
MedGen UID:
898626
Concept ID:
C4082299
Disease or Syndrome
Bulbar weakness (or bulbar palsy) refers to bilateral impairment of function of the lower cranial nerves IX, X, XI and XII, which occurs due to lower motor neuron lesion either at nuclear or fascicular level in the medulla or from bilateral lesions of the lower cranial nerves outside the brain-stem. Bulbar weakness is often associated with difficulty in chewing, weakness of the facial muscles, dysarthria, palatal weakness and regurgitation of fluids, dysphagia, and dysphonia.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Muscle spasm
MedGen UID:
52431
Concept ID:
C0037763
Sign or Symptom
Sudden and involuntary contractions of one or more muscles.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
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.
Optic disc pallor
MedGen UID:
108218
Concept ID:
C0554970
Finding
A pale yellow discoloration of the optic disk (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression.
Slow saccadic eye movements
MedGen UID:
232942
Concept ID:
C1321329
Finding
An abnormally slow velocity of the saccadic eye movements.
Supranuclear ophthalmoplegia
MedGen UID:
235616
Concept ID:
C1408507
Disease or Syndrome
A vertical gaze palsy with inability to direct the gaze of the eyes downwards.
Dysmetric saccades
MedGen UID:
322908
Concept ID:
C1836392
Finding
The controller signal for saccadic eye movements has two components
Impaired horizontal smooth pursuit
MedGen UID:
355793
Concept ID:
C1866753
Finding
An abnormality of ocular smooth pursuit characterized by an impairment of the ability to track horizontally moving objects.
Gaze-evoked nystagmus
MedGen UID:
1808161
Concept ID:
C5574666
Disease or Syndrome
Nystagmus made apparent by looking to the right or to the left.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSpinocerebellar ataxia type 1
Follow this link to review classifications for Spinocerebellar ataxia type 1 in Orphanet.

Professional guidelines

PubMed

Bauer PO, Matoska V, Zumrova A, Boday A, Doi H, Marikova T, Goetz P
J Appl Genet 2005;46(3):325-8. PMID: 16110192
Zühlke C, Dalski A, Hellenbroich Y, Bubel S, Schwinger E, Bürk K
Eur J Hum Genet 2002 Mar;10(3):204-9. doi: 10.1038/sj.ejhg.5200788. PMID: 11973625
Zhou YX, Qiao WH, Gu WH, Xie H, Tang BS, Zhou LS, Yang BX, Takiyama Y, Tsuji S, He HY, Deng CX, Goldfarb LG, Wang GX
Arch Neurol 2001 May;58(5):789-94. doi: 10.1001/archneur.58.5.789. PMID: 11346374

Recent clinical studies

Etiology

Tejwani L, Lim J
Cell Mol Life Sci 2020 Oct;77(20):4015-4029. Epub 2020 Apr 18 doi: 10.1007/s00018-020-03520-z. PMID: 32306062Free PMC Article
Lee Y
Exp Mol Med 2020 Apr;52(4):531-537. Epub 2020 Apr 1 doi: 10.1038/s12276-020-0411-3. PMID: 32238859Free PMC Article
Martins CR Jr, Martinez ARM, de Rezende TJR, Branco LMT, Pedroso JL, Barsottini OGP, Lopes-Cendes I, França MC Jr
Cerebellum 2017 Aug;16(4):792-796. doi: 10.1007/s12311-017-0854-9. PMID: 28386793
Donato SD, Mariotti C, Taroni F
Handb Clin Neurol 2012;103:399-421. doi: 10.1016/B978-0-444-51892-7.00025-5. PMID: 21827903
Umahara T, Uchihara T
Cerebellum 2010 Jun;9(2):183-9. doi: 10.1007/s12311-010-0158-9. PMID: 20155408

Diagnosis

Tamuli D, Kaur M, Jaryal AK, Srivastava AK, Deepak KK
J Clin Neurosci 2023 Jul;113:114-120. Epub 2023 May 30 doi: 10.1016/j.jocn.2023.05.019. PMID: 37257217
Tezenas du Montcel S, Petit E, Olubajo T, Faber J, Lallemant-Dudek P, Bushara K, Perlman S, Subramony SH, Morgan D, Jackman B, Paulson HL, Öz G, Klockgether T, Durr A, Ashizawa T; READISCA Consortium Collaborators
Neurology 2023 Apr 25;100(17):e1836-e1848. Epub 2023 Feb 16 doi: 10.1212/WNL.0000000000207088. PMID: 36797067Free PMC Article
Wilke C, Mengel D, Schöls L, Hengel H, Rakowicz M, Klockgether T, Durr A, Filla A, Melegh B, Schüle R, Reetz K, Jacobi H, Synofzik M
Neurology 2022 May 17;98(20):e1985-e1996. Epub 2022 Mar 9 doi: 10.1212/WNL.0000000000200257. PMID: 35264424Free PMC Article
Donato SD, Mariotti C, Taroni F
Handb Clin Neurol 2012;103:399-421. doi: 10.1016/B978-0-444-51892-7.00025-5. PMID: 21827903
Subramony SH
Curr Opin Neurol 1994 Aug;7(4):316-22. doi: 10.1097/00019052-199408000-00007. PMID: 7952239

Therapy

Tezenas du Montcel S, Petit E, Olubajo T, Faber J, Lallemant-Dudek P, Bushara K, Perlman S, Subramony SH, Morgan D, Jackman B, Paulson HL, Öz G, Klockgether T, Durr A, Ashizawa T; READISCA Consortium Collaborators
Neurology 2023 Apr 25;100(17):e1836-e1848. Epub 2023 Feb 16 doi: 10.1212/WNL.0000000000207088. PMID: 36797067Free PMC Article
Chandrasekaran J, Petit E, Park YW, du Montcel ST, Joers JM, Deelchand DK, Považan M, Banan G, Valabregue R, Ehses P, Faber J, Coupé P, Onyike CU, Barker PB, Schmahmann JD, Ratai EM, Subramony SH, Mareci TH, Bushara KO, Paulson H, Durr A, Klockgether T, Ashizawa T, Lenglet C, Öz G; READISCA Consortium
Ann Neurol 2023 Apr;93(4):686-701. Epub 2022 Dec 29 doi: 10.1002/ana.26573. PMID: 36511514Free PMC Article
Wilke C, Mengel D, Schöls L, Hengel H, Rakowicz M, Klockgether T, Durr A, Filla A, Melegh B, Schüle R, Reetz K, Jacobi H, Synofzik M
Neurology 2022 May 17;98(20):e1985-e1996. Epub 2022 Mar 9 doi: 10.1212/WNL.0000000000200257. PMID: 35264424Free PMC Article
Sheeler C, Rosa JG, Borgenheimer E, Mellesmoen A, Rainwater O, Cvetanovic M
Cerebellum 2021 Jun;20(3):420-429. Epub 2021 Jan 4 doi: 10.1007/s12311-020-01226-3. PMID: 33394333Free PMC Article
King MK, Pardo M, Cheng Y, Downey K, Jope RS, Beurel E
Pharmacol Ther 2014 Jan;141(1):1-12. Epub 2013 Jul 31 doi: 10.1016/j.pharmthera.2013.07.010. PMID: 23916593Free PMC Article

Prognosis

Tejwani L, Ravindra NG, Lee C, Cheng Y, Nguyen B, Luttik K, Ni L, Zhang S, Morrison LM, Gionco J, Xiang Y, Yoon J, Ro H, Haidery F, Grijalva RM, Bae E, Kim K, Martuscello RT, Orr HT, Zoghbi HY, McLoughlin HS, Ranum LPW, Shakkottai VG, Faust PL, Wang S, van Dijk D, Lim J
Neuron 2024 Feb 7;112(3):362-383.e15. Epub 2023 Nov 27 doi: 10.1016/j.neuron.2023.10.039. PMID: 38016472
Iwabuchi K, Koyano S, Yagishita S
Neuropathology 2022 Oct;42(5):379-393. Epub 2022 Jul 20 doi: 10.1111/neup.12823. PMID: 35859519
Wilke C, Mengel D, Schöls L, Hengel H, Rakowicz M, Klockgether T, Durr A, Filla A, Melegh B, Schüle R, Reetz K, Jacobi H, Synofzik M
Neurology 2022 May 17;98(20):e1985-e1996. Epub 2022 Mar 9 doi: 10.1212/WNL.0000000000200257. PMID: 35264424Free PMC Article
Mähler A, Steiniger J, Endres M, Paul F, Boschmann M, Doss S
Cerebellum 2014 Aug;13(4):440-6. doi: 10.1007/s12311-014-0555-6. PMID: 24604678
Zoghbi HY, Orr HT
Semin Cell Biol 1995 Feb;6(1):29-35. doi: 10.1016/1043-4682(95)90012-8. PMID: 7620119

Clinical prediction guides

Tamuli D, Kaur M, Jaryal AK, Srivastava AK, Deepak KK
J Clin Neurosci 2023 Jul;113:114-120. Epub 2023 May 30 doi: 10.1016/j.jocn.2023.05.019. PMID: 37257217
Iwabuchi K, Koyano S, Yagishita S
Neuropathology 2022 Oct;42(5):379-393. Epub 2022 Jul 20 doi: 10.1111/neup.12823. PMID: 35859519
Tejwani L, Lim J
Cell Mol Life Sci 2020 Oct;77(20):4015-4029. Epub 2020 Apr 18 doi: 10.1007/s00018-020-03520-z. PMID: 32306062Free PMC Article
Martins CR Jr, Martinez ARM, de Rezende TJR, Branco LMT, Pedroso JL, Barsottini OGP, Lopes-Cendes I, França MC Jr
Cerebellum 2017 Aug;16(4):792-796. doi: 10.1007/s12311-017-0854-9. PMID: 28386793
Zoghbi HY, Orr HT
Semin Cell Biol 1995 Feb;6(1):29-35. doi: 10.1016/1043-4682(95)90012-8. PMID: 7620119

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