SCA21
MCID: SPN096
MIFTS: 33

Spinocerebellar Ataxia 21 (SCA21)

Categories: Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Liver diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Spinocerebellar Ataxia 21

MalaCards integrated aliases for Spinocerebellar Ataxia 21:

Name: Spinocerebellar Ataxia 21 58 54 76 30 13 6 74
Spinocerebellar Ataxia Type 21 12 54 60 15
Sca21 58 54 60 76
Spinocerebellar Ataxia 21 with Mental Retardation and Severe Cognitive Impairment 76
Ataxia, Spinocerebellar, Type 21 41

Characteristics:

Orphanet epidemiological data:

60
spinocerebellar ataxia type 21
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
variable age of onset (range 1 to 30 years)


HPO:

33
spinocerebellar ataxia 21:
Onset and clinical course slow progression
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Spinocerebellar Ataxia 21

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 98773Disease definitionSpinocerebellar ataxia type 21 (SCA21) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by slowly progressive cerebellar ataxia, mild cognitive impairment, postural and/or resting tremor, bradykinesia, and rigidity.EpidemiologyPrevalence is unknown. Fewer than 20 cases in a 4-generation French family have been reported to date.Clinical descriptionMean age of onset is 17.4 years and is relatively early compared to most type I ADCAs. Individuals in successive generations tend to have earlier ages of onset. Parkinsonism was not responsive to L-dopa and magnetic resonance imaging (MRI) revealed cerebellar and brainstem atrophy.EtiologySCA21 maps to chromosome 7p21.3-p15.1 but the gene and gene mutation have not been identified.PrognosisThere is insufficient clinical data to draw conclusions concerning prognosis.Visit the Orphanet disease page for more resources.

MalaCards based summary : Spinocerebellar Ataxia 21, also known as spinocerebellar ataxia type 21, is related to spinocerebellar ataxia, autosomal recessive 21 and ataxia and polyneuropathy, adult-onset, and has symptoms including tremor, gait ataxia and abnormality of extrapyramidal motor function. An important gene associated with Spinocerebellar Ataxia 21 is TMEM240 (Transmembrane Protein 240). Affiliated tissues include eye, spinal cord and cerebellum, and related phenotypes are gait ataxia and abnormality of extrapyramidal motor function

Disease Ontology : 12 An autosomal dominant cerebellar ataxia that is characterized by progressive cerebellar ataxia, cognitive impairment, tremor, bradykinesia and rigidity.

OMIM : 58 Spinocerebellar ataxia-21 (SCA21) is an autosomal dominant neurologic disorder characterized by onset in the first decades of life of slowly progressive cerebellar ataxia, which is associated with cognitive impairment in most patients (summary by Delplanque et al., 2014). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400). (607454)

UniProtKB/Swiss-Prot : 76 Spinocerebellar ataxia 21: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA21 is characterized by onset in the first decades of life of slowly progressive relatively mild cerebellar ataxia associated with slight extrapyramidal features predominant in older patients and cognitive impairment predominant in younger patients.

Related Diseases for Spinocerebellar Ataxia 21

Diseases in the Spinocerebellar Ataxia 2 family:

Spinocerebellar Ataxia 31 Spinocerebellar Ataxia 29
Spinocerebellar Ataxia 34 Spinocerebellar Ataxia 1
Spinocerebellar Ataxia 7 Spinocerebellar Ataxia 6
Spinocerebellar Ataxia, Autosomal Recessive 2 Spinocerebellar Ataxia, Autosomal Recessive 3
Spinocerebellar Ataxia 4 Spinocerebellar Ataxia 5
Spinocerebellar Ataxia 10 Spinocerebellar Ataxia 12
Spinocerebellar Ataxia 11 Spinocerebellar Ataxia 13
Spinocerebellar Ataxia 14 Spinocerebellar Ataxia 15
Spinocerebellar Ataxia 17 Spinocerebellar Ataxia, Autosomal Recessive 4
Spinocerebellar Ataxia 19 Spinocerebellar Ataxia 21
Spinocerebellar Ataxia 18 Spinocerebellar Ataxia, Autosomal Recessive 6
Spinocerebellar Ataxia 20 Spinocerebellar Ataxia 25
Spinocerebellar Ataxia 8 Spinocerebellar Ataxia, Autosomal Recessive 7
Spinocerebellar Ataxia 26 Spinocerebellar Ataxia 27
Spinocerebellar Ataxia 23 Spinocerebellar Ataxia 28
Spinocerebellar Ataxia, Autosomal Recessive 8 Spinocerebellar Ataxia 9
Spinocerebellar Ataxia 30 Spinocerebellar Ataxia, Autosomal Recessive 10
Spinocerebellar Ataxia 35 Spinocerebellar Ataxia 32
Spinocerebellar Ataxia 36 Spinocerebellar Ataxia, Autosomal Recessive 11
Spinocerebellar Ataxia, Autosomal Recessive 12 Spinocerebellar Ataxia, Autosomal Recessive 13
Spinocerebellar Ataxia, Autosomal Recessive 14 Spinocerebellar Ataxia, Autosomal Recessive 15
Spinocerebellar Ataxia, Autosomal Recessive 16 Spinocerebellar Ataxia 37
Spinocerebellar Ataxia 38 Spinocerebellar Ataxia 40
Spinocerebellar Ataxia, Autosomal Recessive 17 Spinocerebellar Ataxia, Autosomal Recessive 18
Spinocerebellar Ataxia, Autosomal Recessive 20 Spinocerebellar Ataxia 41
Spinocerebellar Ataxia, Autosomal Recessive 21 Spinocerebellar Ataxia 42
Spinocerebellar Ataxia, Autosomal Recessive 22 Spinocerebellar Ataxia, Autosomal Recessive 23
Spinocerebellar Ataxia 43 Spinocerebellar Ataxia, Autosomal Recessive 24
Spinocerebellar Ataxia, Autosomal Recessive 25 Spinocerebellar Ataxia, Autosomal Recessive 26
Spinocerebellar Ataxia 44 Spinocerebellar Ataxia 45
Spinocerebellar Ataxia 46 Spinocerebellar Ataxia 47
Spinocerebellar Ataxia 48 Spinocerebellar Ataxia, Autosomal Recessive 27
Spinocerebellar Ataxia Type 19/22 Grid2-Related Spinocerebellar Ataxia
Spinocerebellar Ataxia Autosomal Recessive 5

Diseases related to Spinocerebellar Ataxia 21 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 spinocerebellar ataxia, autosomal recessive 21 11.6
2 ataxia and polyneuropathy, adult-onset 10.0
3 autosomal dominant cerebellar ataxia 10.0

Symptoms & Phenotypes for Spinocerebellar Ataxia 21

Human phenotypes related to Spinocerebellar Ataxia 21:

60 33 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 gait ataxia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002066
2 abnormality of extrapyramidal motor function 60 33 hallmark (90%) Very frequent (99-80%) HP:0002071
3 progressive cerebellar ataxia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002073
4 intermittent microsaccadic pursuits 60 33 hallmark (90%) Very frequent (99-80%) HP:0007944
5 nystagmus 60 33 occasional (7.5%) Frequent (79-30%) HP:0000639
6 intellectual disability 60 33 frequent (33%) Frequent (79-30%) HP:0001249
7 dysarthria 60 33 frequent (33%) Frequent (79-30%) HP:0001260
8 tremor 60 33 frequent (33%) Frequent (79-30%) HP:0001337
9 behavioral abnormality 60 33 frequent (33%) Frequent (79-30%) HP:0000708
10 cognitive impairment 60 33 frequent (33%) Frequent (79-30%) HP:0100543
11 rigidity 60 33 frequent (33%) Frequent (79-30%) HP:0002063
12 dysgraphia 60 33 frequent (33%) Frequent (79-30%) HP:0010526
13 cerebellar vermis atrophy 60 33 frequent (33%) Frequent (79-30%) HP:0006855
14 akinesia 60 33 frequent (33%) Frequent (79-30%) HP:0002304
15 diplopia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000651
16 global developmental delay 33 HP:0001263
17 limb ataxia 33 HP:0002070
18 aggressive behavior 33 HP:0000718
19 hyporeflexia 33 HP:0001265
20 postural tremor 33 HP:0002174
21 cerebellar atrophy 33 HP:0001272
22 impulsivity 33 HP:0100710
23 scanning speech 33 HP:0002168
24 parkinsonism 33 HP:0001300
25 apathy 33 HP:0000741
26 slow saccadic eye movements 33 HP:0000514
27 cogwheel rigidity 33 HP:0002396
28 microsaccadic pursuit 33 HP:0007792

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
nystagmus
slow saccades
microsaccadic pursuit
square wave jerks

Neurologic Behavioral Psychiatric Manifestations:
impulsivity
apathy
executive dysfunction
aggression

Neurologic Central Nervous System:
dysarthria
tremor
cognitive impairment
gait ataxia
limb ataxia
more

Clinical features from OMIM:

607454

UMLS symptoms related to Spinocerebellar Ataxia 21:


tremor, gait ataxia, abnormality of extrapyramidal motor function, scanning speech, cogwheel rigidity, cerebellar ataxia, static tremor

Drugs & Therapeutics for Spinocerebellar Ataxia 21

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Spinocerebellar Ataxia 21

Genetic Tests for Spinocerebellar Ataxia 21

Genetic tests related to Spinocerebellar Ataxia 21:

# Genetic test Affiliating Genes
1 Spinocerebellar Ataxia 21 30 TMEM240

Anatomical Context for Spinocerebellar Ataxia 21

MalaCards organs/tissues related to Spinocerebellar Ataxia 21:

42
Eye, Spinal Cord, Cerebellum, Liver, Skin

Publications for Spinocerebellar Ataxia 21

Articles related to Spinocerebellar Ataxia 21:

(show all 11)
# Title Authors Year
1
Spinocerebellar Ataxia-21 in a Turkish Child. ( 29720801 )
2018
2
The movement disorder spectrum of SCA21 (ATX-TMEM240): 3 novel families and systematic review of the literature. ( 30522958 )
2018
3
Cognition in SCA21 reflects developmental and adult onset cerebellar cognitive affective syndrome. ( 25576310 )
2015
4
Reply: Cognition in SCA21 reflects developmental and adult onset cerebellar cognitive affective syndrome. ( 25576311 )
2015
5
Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia. ( 26581903 )
2015
6
TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment. ( 25070513 )
2014
7
Identification of the SCA21 disease gene: remaining challenges and promising opportunities. ( 25217789 )
2014
8
EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias. ( 20050888 )
2010
9
Slowly progressive spinocerebellar ataxia with extrapyramidal signs and mild cognitive impairment (SCA21). ( 18418688 )
2008
10
A new locus for spinocerebellar ataxia (SCA21) maps to chromosome 7p21.3-p15.1. ( 12402269 )
2002
11
Clinical features and genetic analysis of a new form of spinocerebellar ataxia. ( 11160961 )
2001

Variations for Spinocerebellar Ataxia 21

UniProtKB/Swiss-Prot genetic disease variations for Spinocerebellar Ataxia 21:

76
# Symbol AA change Variation ID SNP ID
1 TMEM240 p.Thr80Met VAR_071906 rs606231454
2 TMEM240 p.Arg116Cys VAR_071907 rs606231453
3 TMEM240 p.Glu149Lys VAR_071908 rs546291208
4 TMEM240 p.Pro170Leu VAR_071909 rs606231451
5 TMEM240 p.Arg171Trp VAR_071910 rs606231455

ClinVar genetic disease variations for Spinocerebellar Ataxia 21:

6 (show all 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 TMEM240 NM_001114748.1(TMEM240): c.509C> T (p.Pro170Leu) single nucleotide variant Pathogenic/Likely pathogenic rs606231451 GRCh38 Chromosome 1, 1535372: 1535372
2 TMEM240 NM_001114748.1(TMEM240): c.509C> T (p.Pro170Leu) single nucleotide variant Pathogenic/Likely pathogenic rs606231451 GRCh37 Chromosome 1, 1470752: 1470752
3 TMEM240 NM_001114748.1(TMEM240): c.489C> G (p.Tyr163Ter) single nucleotide variant Pathogenic rs606231452 GRCh38 Chromosome 1, 1535392: 1535392
4 TMEM240 NM_001114748.1(TMEM240): c.489C> G (p.Tyr163Ter) single nucleotide variant Pathogenic rs606231452 GRCh37 Chromosome 1, 1470772: 1470772
5 TMEM240 NM_001114748.1(TMEM240): c.346C> T (p.Arg116Cys) single nucleotide variant Pathogenic rs606231453 GRCh38 Chromosome 1, 1535616: 1535616
6 TMEM240 NM_001114748.1(TMEM240): c.346C> T (p.Arg116Cys) single nucleotide variant Pathogenic rs606231453 GRCh37 Chromosome 1, 1470996: 1470996
7 TMEM240 NM_001114748.1(TMEM240): c.239C> T (p.Thr80Met) single nucleotide variant Pathogenic rs606231454 GRCh38 Chromosome 1, 1535723: 1535723
8 TMEM240 NM_001114748.1(TMEM240): c.239C> T (p.Thr80Met) single nucleotide variant Pathogenic rs606231454 GRCh37 Chromosome 1, 1471103: 1471103
9 TMEM240 NM_001114748.1(TMEM240): c.511C> T (p.Arg171Trp) single nucleotide variant Pathogenic rs606231455 GRCh38 Chromosome 1, 1535370: 1535370
10 TMEM240 NM_001114748.1(TMEM240): c.511C> T (p.Arg171Trp) single nucleotide variant Pathogenic rs606231455 GRCh37 Chromosome 1, 1470750: 1470750
11 SCYL1 NM_020680.3(SCYL1): c.937delG (p.Val313Cysfs) deletion Pathogenic rs864309664 GRCh38 Chromosome 11, 65530716: 65530716
12 SCYL1 NM_020680.3(SCYL1): c.937delG (p.Val313Cysfs) deletion Pathogenic rs864309664 GRCh37 Chromosome 11, 65298187: 65298187
13 SCYL1 NM_020680.3(SCYL1): c.1509_1510delTG (p.Ala504Profs) deletion Pathogenic rs864309665 GRCh38 Chromosome 11, 65536075: 65536076
14 SCYL1 NM_020680.3(SCYL1): c.1509_1510delTG (p.Ala504Profs) deletion Pathogenic rs864309665 GRCh37 Chromosome 11, 65303546: 65303547
15 SCYL1 NM_020680.3(SCYL1): c.1230+1G> A single nucleotide variant Pathogenic rs864309666 GRCh38 Chromosome 11, 65532806: 65532806
16 SCYL1 NM_020680.3(SCYL1): c.1230+1G> A single nucleotide variant Pathogenic rs864309666 GRCh37 Chromosome 11, 65300277: 65300277
17 SCYL1 NM_020680.3(SCYL1): c.1636C> T (p.Gln546Ter) single nucleotide variant Pathogenic rs864309667 GRCh38 Chromosome 11, 65536319: 65536319
18 SCYL1 NM_020680.3(SCYL1): c.1636C> T (p.Gln546Ter) single nucleotide variant Pathogenic rs864309667 GRCh37 Chromosome 11, 65303790: 65303790
19 TMEM240 NM_001114748.1(TMEM240): c.343G> A (p.Val115Met) single nucleotide variant Pathogenic rs1045410944 GRCh37 Chromosome 1, 1470999: 1470999
20 TMEM240 NM_001114748.1(TMEM240): c.343G> A (p.Val115Met) single nucleotide variant Pathogenic rs1045410944 GRCh38 Chromosome 1, 1535619: 1535619

Expression for Spinocerebellar Ataxia 21

Search GEO for disease gene expression data for Spinocerebellar Ataxia 21.

Pathways for Spinocerebellar Ataxia 21

GO Terms for Spinocerebellar Ataxia 21

Sources for Spinocerebellar Ataxia 21

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
Content
Loading form....