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Spinocerebellar ataxia 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
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: OMIM, Orphanet
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
Genetic anticipation with paternal anticipation bias
MedGen UID:
892380
Concept ID:
C4025574
Finding
Source: HPO
Autosomal dominant inheritance
MedGen UID:
892334
Concept ID:
CN000007
Functional Concept
Source: HPO
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)
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 over 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 GHR
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://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-1

Clinical features

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.
Optic disc pallor
MedGen UID:
482636
Concept ID:
C3281006
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.
Supranuclear ophthalmoplegia
MedGen UID:
504529
Concept ID:
CN000585
Finding
A vertical gaze palsy with inability to direct the gaze of the eyes downwards.
Gaze-evoked nystagmus
MedGen UID:
504533
Concept ID:
CN000601
Finding
Nystagmus made apparent by looking to the right or to the left.
Optic atrophy
MedGen UID:
504537
Concept ID:
CN000609
Finding
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.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
If you have a swallowing disorder, you may have difficulty or pain when swallowing. Some people cannot swallow at all. Others may have trouble swallowing liquids, foods, or saliva. This makes it hard to eat. Often, it can be difficult to take in enough calories and fluids to nourish your body. Anyone can have a swallowing disorder, but it is more likely in the elderly. It often happens because of other conditions, including. - Nervous system disorders, such as Parkinson's disease and cerebral palsy. - Problems with your esophagus, including GERD (gastroesophageal reflux disease). - Stroke. - Head or spinal cord injury. - Cancer of the head, neck, or esophagus. Medicines can help some people, while others may need surgery. Swallowing treatment with a speech-language pathologist can help. You may find it helpful to change your diet or hold your head or neck in a certain way when you eat. In very serious cases, people may need feeding tubes. NIH: National Institute on Deafness and Other Communication Disorders.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
If you have a swallowing disorder, you may have difficulty or pain when swallowing. Some people cannot swallow at all. Others may have trouble swallowing liquids, foods, or saliva. This makes it hard to eat. Often, it can be difficult to take in enough calories and fluids to nourish your body. Anyone can have a swallowing disorder, but it is more likely in the elderly. It often happens because of other conditions, including. - Nervous system disorders, such as Parkinson's disease and cerebral palsy. - Problems with your esophagus, including GERD (gastroesophageal reflux disease). - Stroke. - Head or spinal cord injury. - Cancer of the head, neck, or esophagus. Medicines can help some people, while others may need surgery. Swallowing treatment with a speech-language pathologist can help. You may find it helpful to change your diet or hold your head or neck in a certain way when you eat. In very serious cases, people may need feeding tubes. NIH: National Institute on Deafness and Other Communication Disorders.
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.
Extrapyramidal disease
MedGen UID:
41927
Concept ID:
C0015371
Disease or Syndrome
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).
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 rhythmically tapping the fingers on the knee.
Absent tendon reflex
MedGen UID:
548673
Concept ID:
C0278124
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Decreased 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.
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.
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
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.
Bulbar palsy
MedGen UID:
504786
Concept ID:
CN001175
Finding
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.
Chorea
MedGen UID:
505081
Concept ID:
CN001874
Finding
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.
Scanning speech
MedGen UID:
505136
Concept ID:
CN001965
Finding
Dorsal column degeneration
MedGen UID:
506015
Concept ID:
CN006114
Finding
Spinocerebellar atrophy
MedGen UID:
506046
Concept ID:
CN006352
Finding
Atrophy affecting the cerebellum and the spinocerebellar tracts of the spinal cord.
Cognitive impairment
MedGen UID:
451875
Concept ID:
CN117436
Finding
Abnormality in the process of thought including the ability to process information.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
If you have a swallowing disorder, you may have difficulty or pain when swallowing. Some people cannot swallow at all. Others may have trouble swallowing liquids, foods, or saliva. This makes it hard to eat. Often, it can be difficult to take in enough calories and fluids to nourish your body. Anyone can have a swallowing disorder, but it is more likely in the elderly. It often happens because of other conditions, including. - Nervous system disorders, such as Parkinson's disease and cerebral palsy. - Problems with your esophagus, including GERD (gastroesophageal reflux disease). - Stroke. - Head or spinal cord injury. - Cancer of the head, neck, or esophagus. Medicines can help some people, while others may need surgery. Swallowing treatment with a speech-language pathologist can help. You may find it helpful to change your diet or hold your head or neck in a certain way when you eat. In very serious cases, people may need feeding tubes. NIH: National Institute on Deafness and Other Communication Disorders.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
A diminution of the skeletal muscle tone marked by a diminished resistance to passive stretching.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Finding
Muscular atrophy affecting muscles in the distal portions of the extremities.
Bulbar palsy
MedGen UID:
504786
Concept ID:
CN001175
Finding
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.

Term Hierarchy

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

Professional guidelines

PubMed

van de Warrenburg BP, van Gaalen J, Boesch S, Burgunder JM, Dürr A, Giunti P, Klockgether T, Mariotti C, Pandolfo M, Riess O
Eur J Neurol 2014 Apr;21(4):552-62. Epub 2014 Jan 13 doi: 10.1111/ene.12341. [Epub ahead of print] PMID: 24418350
Gasser T, Finsterer J, Baets J, Van Broeckhoven C, Di Donato S, Fontaine B, De Jonghe P, Lossos A, Lynch T, Mariotti C, Schöls L, Spinazzola A, Szolnoki Z, Tabrizi SJ, Tallaksen CM, Zeviani M, Burgunder JM, Harbo HF; EFNS
Eur J Neurol 2010 Feb;17(2):179-88. Epub 2009 Dec 28 doi: 10.1111/j.1468-1331.2009.02873.x. [Epub ahead of print] PMID: 20050888

Recent clinical studies

Etiology

Öz G, Kittelson E, Demirgöz D, Rainwater O, Eberly LE, Orr HT, Clark HB
Neurobiol Dis 2015 Feb;74:158-66. Epub 2014 Nov 29 doi: 10.1016/j.nbd.2014.11.011. [Epub ahead of print] PMID: 25446943Free PMC Article
Kumaran D, Balagopal K, Tharmaraj RG, Aaron S, George K, Muliyil J, Sivadasan A, Danda S, Alexander M, Hasan G
BMC Med Genet 2014 Oct 25;15:114. doi: 10.1186/s12881-014-0114-5. [Epub ahead of print] PMID: 25344417Free PMC Article
Reetz K, Costa AS, Mirzazade S, Lehmann A, Juzek A, Rakowicz M, Boguslawska R, Schöls L, Linnemann C, Mariotti C, Grisoli M, Dürr A, van de Warrenburg BP, Timmann D, Pandolfo M, Bauer P, Jacobi H, Hauser TK, Klockgether T, Schulz JB; axia Study Group Investigators
Brain 2013 Mar;136(Pt 3):905-17. Epub 2013 Feb 18 doi: 10.1093/brain/aws369. [Epub ahead of print] PMID: 23423669
Prakash N, Hageman N, Hua X, Toga AW, Perlman SL, Salamon N
Neuroimage 2009 Aug;47 Suppl 2:T72-81. Epub 2009 May 14 doi: 10.1016/j.neuroimage.2009.05.013. [Epub ahead of print] PMID: 19446636
Frontali M, Sabbadini G, Novelletto A, Jodice C, Naso F, Spadaro M, Giunti P, Jacopini AG, Veneziano L, Mantuano E, Malaspina P, Ulizzi L, Brice A, Durr A, Terrenato L
Ann Hum Genet 1996 Sep;60(Pt 5):423-35. PMID: 8912795

Diagnosis

Öz G, Kittelson E, Demirgöz D, Rainwater O, Eberly LE, Orr HT, Clark HB
Neurobiol Dis 2015 Feb;74:158-66. Epub 2014 Nov 29 doi: 10.1016/j.nbd.2014.11.011. [Epub ahead of print] PMID: 25446943Free PMC Article
Kumaran D, Balagopal K, Tharmaraj RG, Aaron S, George K, Muliyil J, Sivadasan A, Danda S, Alexander M, Hasan G
BMC Med Genet 2014 Oct 25;15:114. doi: 10.1186/s12881-014-0114-5. [Epub ahead of print] PMID: 25344417Free PMC Article
Németh AH, Kwasniewska AC, Lise S, Parolin Schnekenberg R, Becker EB, Bera KD, Shanks ME, Gregory L, Buck D, Zameel Cader M, Talbot K, de Silva R, Fletcher N, Hastings R, Jayawant S, Morrison PJ, Worth P, Taylor M, Tolmie J, O'Regan M; UK Ataxia Consortium, Valentine R, Packham E, Evans J, Seller A, Ragoussis J
Brain 2013 Oct;136(Pt 10):3106-18. Epub 2013 Sep 11 doi: 10.1093/brain/awt236. [Epub ahead of print] PMID: 24030952Free PMC Article
Reetz K, Costa AS, Mirzazade S, Lehmann A, Juzek A, Rakowicz M, Boguslawska R, Schöls L, Linnemann C, Mariotti C, Grisoli M, Dürr A, van de Warrenburg BP, Timmann D, Pandolfo M, Bauer P, Jacobi H, Hauser TK, Klockgether T, Schulz JB; axia Study Group Investigators
Brain 2013 Mar;136(Pt 3):905-17. Epub 2013 Feb 18 doi: 10.1093/brain/aws369. [Epub ahead of print] PMID: 23423669
Prakash N, Hageman N, Hua X, Toga AW, Perlman SL, Salamon N
Neuroimage 2009 Aug;47 Suppl 2:T72-81. Epub 2009 May 14 doi: 10.1016/j.neuroimage.2009.05.013. [Epub ahead of print] PMID: 19446636

Therapy

Hearst SM, Shao Q, Lopez M, Raucher D, Vig PJ
J Neurochem 2014 Oct;131(1):101-14. Epub 2014 Jun 23 doi: 10.1111/jnc.12782. [Epub ahead of print] PMID: 24903464
Tanaka M, Machida Y, Nukina N
J Mol Med (Berl) 2005 May;83(5):343-52. Epub 2005 Mar 10 doi: 10.1007/s00109-004-0632-2. [Epub ahead of print] PMID: 15759103

Prognosis

Németh AH, Kwasniewska AC, Lise S, Parolin Schnekenberg R, Becker EB, Bera KD, Shanks ME, Gregory L, Buck D, Zameel Cader M, Talbot K, de Silva R, Fletcher N, Hastings R, Jayawant S, Morrison PJ, Worth P, Taylor M, Tolmie J, O'Regan M; UK Ataxia Consortium, Valentine R, Packham E, Evans J, Seller A, Ragoussis J
Brain 2013 Oct;136(Pt 10):3106-18. Epub 2013 Sep 11 doi: 10.1093/brain/awt236. [Epub ahead of print] PMID: 24030952Free PMC Article
Frontali M, Sabbadini G, Novelletto A, Jodice C, Naso F, Spadaro M, Giunti P, Jacopini AG, Veneziano L, Mantuano E, Malaspina P, Ulizzi L, Brice A, Durr A, Terrenato L
Ann Hum Genet 1996 Sep;60(Pt 5):423-35. PMID: 8912795

Clinical prediction guides

Kumaran D, Balagopal K, Tharmaraj RG, Aaron S, George K, Muliyil J, Sivadasan A, Danda S, Alexander M, Hasan G
BMC Med Genet 2014 Oct 25;15:114. doi: 10.1186/s12881-014-0114-5. [Epub ahead of print] PMID: 25344417Free PMC Article
Hearst SM, Shao Q, Lopez M, Raucher D, Vig PJ
J Neurochem 2014 Oct;131(1):101-14. Epub 2014 Jun 23 doi: 10.1111/jnc.12782. [Epub ahead of print] PMID: 24903464
Németh AH, Kwasniewska AC, Lise S, Parolin Schnekenberg R, Becker EB, Bera KD, Shanks ME, Gregory L, Buck D, Zameel Cader M, Talbot K, de Silva R, Fletcher N, Hastings R, Jayawant S, Morrison PJ, Worth P, Taylor M, Tolmie J, O'Regan M; UK Ataxia Consortium, Valentine R, Packham E, Evans J, Seller A, Ragoussis J
Brain 2013 Oct;136(Pt 10):3106-18. Epub 2013 Sep 11 doi: 10.1093/brain/awt236. [Epub ahead of print] PMID: 24030952Free PMC Article
Reetz K, Costa AS, Mirzazade S, Lehmann A, Juzek A, Rakowicz M, Boguslawska R, Schöls L, Linnemann C, Mariotti C, Grisoli M, Dürr A, van de Warrenburg BP, Timmann D, Pandolfo M, Bauer P, Jacobi H, Hauser TK, Klockgether T, Schulz JB; axia Study Group Investigators
Brain 2013 Mar;136(Pt 3):905-17. Epub 2013 Feb 18 doi: 10.1093/brain/aws369. [Epub ahead of print] PMID: 23423669
Frontali M, Sabbadini G, Novelletto A, Jodice C, Naso F, Spadaro M, Giunti P, Jacopini AG, Veneziano L, Mantuano E, Malaspina P, Ulizzi L, Brice A, Durr A, Terrenato L
Ann Hum Genet 1996 Sep;60(Pt 5):423-35. PMID: 8912795

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