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Spinocerebellar ataxia type 17(SCA17)

MedGen UID:
337637
Concept ID:
C1846707
Disease or Syndrome
Synonyms: Cerebelloparenchymal disorder II; HUNTINGTON DISEASE-LIKE 4; Olivopontocerebellar atrophy 5; Olivopontocerebellar atrophy V; SCA 17; SCA17; Spinocerebellar Ataxia Type17
SNOMED CT: Spinocerebellar ataxia type 17 (719249005); Huntington disease-like 4 (719249005)
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): TBP (6q27)
 
Monarch Initiative: MONDO:0011781
OMIM®: 607136
Orphanet: ORPHA98759

Definition

Spinocerebellar ataxia type 17 (SCA17) is characterized by ataxia, dementia, and involuntary movements, including chorea and dystonia. Psychiatric symptoms, pyramidal signs, and rigidity are common. The age of onset ranges from three to 55 years. Individuals with full-penetrance alleles develop neurologic and/or psychiatric symptoms by age 50 years. Ataxia and psychiatric abnormalities are frequently the initial findings, followed by involuntary movement, parkinsonism, dementia, and pyramidal signs. Brain MRI shows variable atrophy of the cerebrum, brain stem, and cerebellum. The clinical features correlate with the length of the polyglutamine expansion but are not absolutely predictive of the clinical course. [from GeneReviews]

Additional descriptions

From OMIM
SCA17 is a neurologic disorder characterized by cerebellar ataxia, pyramidal and extrapyramidal signs, cognitive impairment, psychosis, and seizures. Most patients have onset of symptoms after age 30, although earlier onset has been reported. The clinical phenotype and inheritance pattern are similar to Huntington disease (HD; 143100) (Gao et al., 2008). SCA17 shows a complex pattern of inheritance, including autosomal dominant, autosomal dominant with incomplete penetrance, and digenic (see MOLECULAR GENETICS) depending on the size of the TBP repeat expansion. Unaffected individuals have between 25 and 41 CAG/CAA repeats in the TBP gene. Alleles with 47 or more CAG/CAA repeats are fully penetrant for SCA17. Alleles with 'intermediate expansions' between 41 and 46 repeats show incomplete penetrance. However, patients with intermediate TBP expanded alleles in combination with heterozygous mutations in the STUB1 gene (607207) demonstrate full penetrance of the disease, suggesting that intermediate SCA17 is actually a digenic disease and may represent the same entity as SCA48 (618093), which has a similar phenotype (Magri et al., 2022). Rarely, SCA17 has been found to be caused by homozygous or compound heterozygous TBP repeat expansions, consistent with autosomal recessive inheritance. For a general discussion of autosomal dominant of spinocerebellar ataxia, see SCA1 (164400).  http://www.omim.org/entry/607136
From MedlinePlus Genetics
As its name suggests, a Huntington's disease-like (HDL) syndrome is a condition that resembles Huntington's disease. Researchers have described four HDL syndromes, designated Huntington's disease-like 1 (HDL1) through Huntington's disease-like 4 (HDL4). These progressive brain disorders are characterized by uncontrolled movements, emotional problems, and loss of thinking ability. HDL syndromes occur in people with the characteristic features of Huntington's disease who do not have a variant (also called mutation) in the gene typically associated with that disorder.

HDL1, HDL2, and HDL4 usually appear in early to mid-adulthood, although they can begin earlier in life. The first signs and symptoms of these conditions often include irritability, emotional problems, small involuntary movements, poor coordination, and trouble learning new information or making decisions. Many affected people develop involuntary jerking or twitching movements known as chorea. As the disease progresses, these abnormal movements become more pronounced. Affected individuals may develop problems with walking, speaking, and swallowing. People with these disorders also experience changes in personality and a decline in thinking and reasoning abilities. Individuals with an HDL syndrome can live for a few years to more than a decade after signs and symptoms begin.

HDL3 begins much earlier in life than most of the other HDL syndromes (usually around age 3 or 4). Affected children experience a decline in thinking ability, difficulties with movement and speech, and seizures. Because HDL3 has a somewhat different pattern of signs and symptoms and a different pattern of inheritance, researchers are unsure whether it belongs in the same category as the other HDL syndromes.  https://medlineplus.gov/genetics/condition/huntingtons-disease-like-syndrome

Clinical features

From HPO
Urinary incontinence
MedGen UID:
22579
Concept ID:
C0042024
Finding
Loss of the ability to control the urinary bladder leading to involuntary urination.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Apraxia
MedGen UID:
8166
Concept ID:
C0003635
Mental or Behavioral Dysfunction
A defect in the understanding of complex motor commands and in the execution of certain learned movements, i.e., deficits in the cognitive components of learned movements.
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).
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.
Confusion
MedGen UID:
3587
Concept ID:
C0009676
Mental or Behavioral Dysfunction
Lack of clarity and coherence of thought, perception, understanding, or action.
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
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.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
Gliosis is the focal proliferation of glial cells in the central nervous system.
Hallucinations
MedGen UID:
6709
Concept ID:
C0018524
Mental or Behavioral Dysfunction
Perceptions in a conscious and awake state that, in the absence of external stimuli, have qualities of real perception. These perceptions are vivid, substantial, and located in external objective space.
Mutism
MedGen UID:
6476
Concept ID:
C0026884
Disease or Syndrome
Inability to speak or communicate verbally past the age of typical language development.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Bradykinesia
MedGen UID:
115925
Concept ID:
C0233565
Sign or Symptom
Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement).
Lack of insight
MedGen UID:
65855
Concept ID:
C0233824
Mental or Behavioral Dysfunction
Lack of insight (Anosognosia) is a neurological condition in which an individual is unaware of his or her own neurological deficit or psychiatric condition. Anosognosia can be associated with mental illness, dementia, and structural brain lesions and can affect an indviduals's conscious awareness of deficits involving judgment, emotions, memory, executive function, language skills, and motor ability.
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.
Parkinsonian disorder
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
Frontal lobe dementia
MedGen UID:
572577
Concept ID:
C0338455
Disease or Syndrome
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Diffuse cerebral atrophy
MedGen UID:
108958
Concept ID:
C0598275
Finding
Diffuse unlocalised atrophy affecting the cerebrum.
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.
Broad-based gait
MedGen UID:
167799
Concept ID:
C0856863
Finding
An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia.
Paranoia
MedGen UID:
306130
Concept ID:
C1456784
Mental or Behavioral Dysfunction
An inappropriate feeling of being persecuted or being the subject of hostility from others.
Frontal release signs
MedGen UID:
318834
Concept ID:
C1833297
Finding
Primitive reflexes traditionally held to be a sign of disorders that affect the frontal lobes.
Neuronal loss in central nervous system
MedGen UID:
342515
Concept ID:
C1850496
Finding
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).
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.
Impaired pursuit initiation and maintenance
MedGen UID:
370086
Concept ID:
C1969722
Finding
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 17
Follow this link to review classifications for Spinocerebellar ataxia type 17 in Orphanet.

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
Huang DS, Lin HY, Lee-Chen GJ, Hsieh-Li HM, Wu CH, Lin JY
Drug Des Devel Ther 2016;10:723-31. Epub 2016 Feb 18 doi: 10.2147/DDDT.S98156. PMID: 26937174Free PMC Article
Cardoso F
Neurodegener Dis Manag 2014;4(1):67-72. doi: 10.2217/nmt.13.78. PMID: 24640980

Recent clinical studies

Etiology

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
Lee SU, Kim JS, Yoo D, Kim A, Kim HJ, Choi JY, Park JY, Jeong SH, Kim JM, Park KW
Cerebellum 2023 Feb;22(1):1-13. Epub 2022 Jan 7 doi: 10.1007/s12311-021-01356-2. PMID: 34993890
Huang S, Zhu S, Li XJ, Li S
Neuroscientist 2019 Oct;25(5):512-520. Epub 2019 Jan 7 doi: 10.1177/1073858418822993. PMID: 30614396Free PMC Article
Mariotti C, Alpini D, Fancellu R, Soliveri P, Grisoli M, Ravaglia S, Lovati C, Fetoni V, Giaccone G, Castucci A, Taroni F, Gellera C, Di Donato S
J Neurol 2007 Nov;254(11):1538-46. Epub 2007 Oct 15 doi: 10.1007/s00415-007-0579-7. PMID: 17934876
Alendar A, Euljković B, Savić D, Djarmati A, Keckarević M, Ristić A, Dragasević N, Kosić V, Romac S
Acta Neurol Scand 2004 Mar;109(3):185-7. doi: 10.1034/j.1600-0404.2003.00196.x. PMID: 14763955

Diagnosis

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
Saito R, Tada Y, Oikawa D, Sato Y, Seto M, Satoh A, Kume K, Ueki N, Nakashima M, Hayashi S, Toyoshima Y, Tokunaga F, Kawakami H, Kakita A
Acta Neuropathol Commun 2022 Dec 7;10(1):177. doi: 10.1186/s40478-022-01486-6. PMID: 36476347Free PMC Article
Magri S, Nanetti L, Gellera C, Sarto E, Rizzo E, Mongelli A, Ricci B, Fancellu R, Sambati L, Cortelli P, Brusco A, Bruzzone MG, Mariotti C, Di Bella D, Taroni F
Genet Med 2022 Jan;24(1):29-40. Epub 2021 Nov 30 doi: 10.1016/j.gim.2021.08.003. PMID: 34906452
Toyoshima Y, Takahashi H
Adv Exp Med Biol 2018;1049:219-231. doi: 10.1007/978-3-319-71779-1_10. PMID: 29427105
Kim JY, Kim SY, Kim JM, Kim YK, Yoon KY, Kim JY, Lee BC, Kim JS, Paek SH, Park SS, Kim SE, Jeon BS
Neurology 2009 Apr 21;72(16):1385-9. doi: 10.1212/WNL.0b013e3181a18876. PMID: 19380697

Therapy

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
Chen CM, Chen WL, Hung CT, Lin TH, Lee MC, Chen IC, Lin CH, Chao CY, Wu YR, Chang KH, Hsieh-Li HM, Lee-Chen GJ
Aging (Albany NY) 2019 Feb 13;11(3):986-1007. doi: 10.18632/aging.101804. PMID: 30760647Free PMC Article
Huang DS, Lin HY, Lee-Chen GJ, Hsieh-Li HM, Wu CH, Lin JY
Drug Des Devel Ther 2016;10:723-31. Epub 2016 Feb 18 doi: 10.2147/DDDT.S98156. PMID: 26937174Free PMC Article
Lee YC, Liao YC, Wang PS, Lee IH, Lin KP, Soong BW
Mov Disord 2011 Sep;26(11):2081-7. Epub 2011 May 28 doi: 10.1002/mds.23809. PMID: 21626567
Chang YC, Lin CY, Hsu CM, Lin HC, Chen YH, Lee-Chen GJ, Su MT, Ro LS, Chen CM, Hsieh-Li HM
J Neurochem 2011 Jul;118(2):288-303. Epub 2011 Jun 2 doi: 10.1111/j.1471-4159.2011.07304.x. PMID: 21554323

Prognosis

Kim JY, Kim SY, Kim JM, Kim YK, Yoon KY, Kim JY, Lee BC, Kim JS, Paek SH, Park SS, Kim SE, Jeon BS
Neurology 2009 Apr 21;72(16):1385-9. doi: 10.1212/WNL.0b013e3181a18876. PMID: 19380697

Clinical prediction guides

Lee SU, Kim JS, Yoo D, Kim A, Kim HJ, Choi JY, Park JY, Jeong SH, Kim JM, Park KW
Cerebellum 2023 Feb;22(1):1-13. Epub 2022 Jan 7 doi: 10.1007/s12311-021-01356-2. PMID: 34993890
Huang DS, Lin HY, Lee-Chen GJ, Hsieh-Li HM, Wu CH, Lin JY
Drug Des Devel Ther 2016;10:723-31. Epub 2016 Feb 18 doi: 10.2147/DDDT.S98156. PMID: 26937174Free PMC Article
Kim JY, Kim SY, Kim JM, Kim YK, Yoon KY, Kim JY, Lee BC, Kim JS, Paek SH, Park SS, Kim SE, Jeon BS
Neurology 2009 Apr 21;72(16):1385-9. doi: 10.1212/WNL.0b013e3181a18876. PMID: 19380697
Mariotti C, Alpini D, Fancellu R, Soliveri P, Grisoli M, Ravaglia S, Lovati C, Fetoni V, Giaccone G, Castucci A, Taroni F, Gellera C, Di Donato S
J Neurol 2007 Nov;254(11):1538-46. Epub 2007 Oct 15 doi: 10.1007/s00415-007-0579-7. PMID: 17934876
Alendar A, Euljković B, Savić D, Djarmati A, Keckarević M, Ristić A, Dragasević N, Kosić V, Romac S
Acta Neurol Scand 2004 Mar;109(3):185-7. doi: 10.1034/j.1600-0404.2003.00196.x. PMID: 14763955

Recent systematic reviews

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

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