SCAR4
MCID: SPN288
MIFTS: 37

Spinocerebellar Ataxia, Autosomal Recessive 4 (SCAR4)

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, Autosomal Recessive 4

MalaCards integrated aliases for Spinocerebellar Ataxia, Autosomal Recessive 4:

Name: Spinocerebellar Ataxia, Autosomal Recessive 4 58 76 13 74
Scar4 58 54 60 76
Scasi 58 54 60 76
Spinocerebellar Ataxia with Saccadic Intrusions 58 54 76
Spinocerebellar Ataxia Autosomal Recessive 4 54 30 6
Autosomal Recessive Cerebellar Ataxia-Saccadic Intrusion Syndrome 60
Spinocerebellar Ataxia with Saccadic Intrusions; Scasi 58
Spinocerebellar Ataxia 24, Formerly; Sca24, Formerly 58
Spinocerebellar Ataxia 24, Formerly 58
Spinocerebellar Ataxia 24 76
Sca24, Formerly 58
Sca24 76

Characteristics:

Orphanet epidemiological data:

60
autosomal recessive cerebellar ataxia-saccadic intrusion syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
variable age at onset (range infancy to adulthood)
some patients become wheelchair-bound in adulthood


HPO:

33
spinocerebellar ataxia, autosomal recessive 4:
Onset and clinical course variable expressivity adult onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Spinocerebellar Ataxia, Autosomal Recessive 4

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 95434Disease definitionAutosomal recessive cerebellar ataxia-saccadic intrusion syndrome is a rare hereditary ataxia characterized by a progressive cerebellar ataxia associated with disruption of visual fixation by saccadic intrusions (overshooting horizontal saccades with macrosaccadic oscillations and increased velocity of larger saccades). It presents with progressive gait, trunk and limb ataxia with pyramidal tract signs (increased tendon reflexes and Babinski sign), myoclonic jerks, fasciculations, cerebellar dysarthria, sensorimotor axonal neuropathy with impaired joint position, vibration, temperature, pain sensations, pes cavus, and saccadic intrusions with characteristic overshooting horizontal saccades, macrosaccadic oscillations, and increased velocity of larger saccades, without other eye movement disturbances.Visit the Orphanet disease page for more resources.

MalaCards based summary : Spinocerebellar Ataxia, Autosomal Recessive 4, also known as scar4, is related to cone-rod dystrophy and hearing loss 2, and has symptoms including myoclonus, gait ataxia and muscular fasciculation. An important gene associated with Spinocerebellar Ataxia, Autosomal Recessive 4 is VPS13D (Vacuolar Protein Sorting 13 Homolog D). The drugs Pirfenidone and Triamcinolone have been mentioned in the context of this disorder. Affiliated tissues include eye, brain and spinal cord, and related phenotypes are abnormal pyramidal sign and gait ataxia

OMIM : 58 SCAR4 is an autosomal recessive neurologic disorder characterized by abnormal movements. Most patients have ataxic gait with spasticity and hyperreflexia of the lower limbs resulting in difficulty walking. The age at onset is highly variable: some have onset in early childhood with delayed walking, whereas others have onset of gait difficulties in adulthood. Additional features may include dysarthria, oculomotor abnormalities, distal sensory impairment, dystonia, chorea, hypotonia, pyramidal signs, and cerebellar atrophy on brain imaging. The disorder is slowly progressive. Some patients with onset in childhood may have global developmental delay with mild intellectual disability (summary by Seong et al., 2018). (607317)

UniProtKB/Swiss-Prot : 76 Spinocerebellar ataxia, autosomal recessive 4: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR4 patients manifest ataxic gait with spasticity and hyperreflexia of the lower limbs resulting in difficulty walking. The age at onset is highly variable, ranging from early childhood to adulthood.

Related Diseases for Spinocerebellar Ataxia, Autosomal Recessive 4

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, Autosomal Recessive 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 cone-rod dystrophy and hearing loss 2 11.1

Symptoms & Phenotypes for Spinocerebellar Ataxia, Autosomal Recessive 4

Human phenotypes related to Spinocerebellar Ataxia, Autosomal Recessive 4:

60 33 (show all 36)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormal pyramidal sign 60 33 hallmark (90%) Very frequent (99-80%) HP:0007256
2 gait ataxia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002066
3 limb ataxia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002070
4 progressive cerebellar ataxia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002073
5 truncal ataxia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002078
6 abnormal lower motor neuron morphology 60 33 hallmark (90%) Very frequent (99-80%) HP:0002366
7 abnormal visual fixation 60 33 hallmark (90%) Very frequent (99-80%) HP:0025404
8 dysarthria 60 33 frequent (33%) Frequent (79-30%) HP:0001260
9 impaired proprioception 60 33 frequent (33%) Frequent (79-30%) HP:0010831
10 pes cavus 60 33 frequent (33%) Frequent (79-30%) HP:0001761
11 fasciculations 60 33 frequent (33%) Frequent (79-30%) HP:0002380
12 dyslexia 60 33 frequent (33%) Frequent (79-30%) HP:0010522
13 sensorimotor neuropathy 60 33 frequent (33%) Frequent (79-30%) HP:0007141
14 unsteady gait 60 33 frequent (33%) Frequent (79-30%) HP:0002317
15 hypermetric saccades 60 33 frequent (33%) Frequent (79-30%) HP:0007338
16 myoclonus 60 33 occasional (7.5%) Occasional (29-5%) HP:0001336
17 intellectual disability, mild 33 very rare (1%) HP:0001256
18 motor delay 33 very rare (1%) HP:0001270
19 abnormality of the cerebral white matter 33 very rare (1%) HP:0002500
20 abnormality of eye movement 60 Frequent (79-30%)
21 nystagmus 33 HP:0000639
22 ataxia 33 HP:0001251
23 spasticity 33 HP:0001257
24 tremor 33 HP:0001337
25 hyperreflexia 33 HP:0001347
26 babinski sign 33 HP:0003487
27 abnormality of saccadic eye movements 60 Frequent (79-30%)
28 dystonia 33 HP:0001332
29 frequent falls 33 HP:0002359
30 peripheral axonal neuropathy 33 HP:0003477
31 distal muscle weakness 33 HP:0002460
32 sensory impairment 60 Very frequent (99-80%)
33 upper motor neuron dysfunction 60 Very frequent (99-80%)
34 distal amyotrophy 33 HP:0003693
35 muscular hypotonia of the trunk 33 HP:0008936
36 macrosaccadic oscillations 33 HP:0032105

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
nystagmus
difficulty reading
overshooting horizontal saccades
macrosaccadic oscillations
increased velocity of larger saccades

Skeletal Feet:
pes cavus

Head And Neck Head:
microcephaly (in some patients)

Neurologic Central Nervous System:
spasticity
dysarthria
tremor
hyperreflexia
dystonia
more
Muscle Soft Tissue:
distal muscle weakness
distal muscle atrophy
axial hypotonia
abnormal mitochondria seen on muscle biopsy

Neurologic Peripheral Nervous System:
impaired distal sensation
sensorimotor axonal neuropathy

Clinical features from OMIM:

607317

UMLS symptoms related to Spinocerebellar Ataxia, Autosomal Recessive 4:


myoclonus, gait ataxia, muscular fasciculation, abnormal pyramidal signs

Drugs & Therapeutics for Spinocerebellar Ataxia, Autosomal Recessive 4

Drugs for Spinocerebellar Ataxia, Autosomal Recessive 4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 17)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Pirfenidone Approved, Investigational Phase 3 53179-13-8 40632
2
Triamcinolone Approved, Vet_approved Phase 3 124-94-7 31307
3 Immunologic Factors Phase 3
4 Immunosuppressive Agents Phase 3
5 glucocorticoids Phase 3
6 Triamcinolone diacetate Phase 3
7 Triamcinolone hexacetonide Phase 3
8 triamcinolone acetonide Phase 3
9 Analgesics, Non-Narcotic Phase 3
10 Hormone Antagonists Phase 3
11 Analgesics Phase 3
12 Hormones Phase 3
13 Anti-Inflammatory Agents Phase 3
14 Anti-Inflammatory Agents, Non-Steroidal Phase 3
15 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 3
16 Peripheral Nervous System Agents Phase 3
17 Antirheumatic Agents Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Efficacy of Intralesional Triamcinolone and 8% Topical Pirfenidone for Treatment of Keloid Scars Recruiting NCT02823236 Phase 3 Topical Pirfenidone;Triamcinolone + Pirfenidone;Intralesional Triamcinolone
2 SIL-TEP vs TEP for Inguinal Hernia Repair in Day Surgery Unknown status NCT02415543 Not Applicable
3 Multiplex Laser vs. PDL (Pulsed Dye Laser ) in the Treatment of Surgical Scars Completed NCT02472405 Not Applicable

Search NIH Clinical Center for Spinocerebellar Ataxia, Autosomal Recessive 4

Genetic Tests for Spinocerebellar Ataxia, Autosomal Recessive 4

Genetic tests related to Spinocerebellar Ataxia, Autosomal Recessive 4:

# Genetic test Affiliating Genes
1 Spinocerebellar Ataxia Autosomal Recessive 4 30 VPS13D

Anatomical Context for Spinocerebellar Ataxia, Autosomal Recessive 4

MalaCards organs/tissues related to Spinocerebellar Ataxia, Autosomal Recessive 4:

42
Eye, Brain, Spinal Cord, Cerebellum, Skin, Liver

Publications for Spinocerebellar Ataxia, Autosomal Recessive 4

Articles related to Spinocerebellar Ataxia, Autosomal Recessive 4:

# Title Authors Year
1
Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects. ( 29604224 )
2018
2
Recessive mutations in >VPS13D cause childhood onset movement disorders. ( 29518281 )
2018
3
A form of inherited cerebellar ataxia with saccadic intrusions, increased saccadic speed, sensory neuropathy, and myoclonus. ( 11960835 )
2002

Variations for Spinocerebellar Ataxia, Autosomal Recessive 4

UniProtKB/Swiss-Prot genetic disease variations for Spinocerebellar Ataxia, Autosomal Recessive 4:

76
# Symbol AA change Variation ID SNP ID
1 VPS13D p.Thr865Ala VAR_080911 rs138395840
2 VPS13D p.Gly1200Asp VAR_080912 rs768331333
3 VPS13D p.Leu2900Ser VAR_080913
4 VPS13D p.Arg3253Gln VAR_080914 rs119162557
5 VPS13D p.Asn3521Ser VAR_080915
6 VPS13D p.Arg4228Gln VAR_080916
7 VPS13D p.Gly1190Asp VAR_081498
8 VPS13D p.Ala4210Val VAR_081505

ClinVar genetic disease variations for Spinocerebellar Ataxia, Autosomal Recessive 4:

6 (show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 VPS13D NM_015378.4(VPS13D): c.3569G> A (p.Gly1190Asp) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 12277157: 12277157
2 VPS13D NM_015378.4(VPS13D): c.3569G> A (p.Gly1190Asp) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 12337214: 12337214
3 VPS13D NM_015378.4(VPS13D): c.3316C> T (p.Gln1106Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 12276904: 12276904
4 VPS13D NM_015378.4(VPS13D): c.3316C> T (p.Gln1106Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 12336961: 12336961
5 VPS13D NM_015378.4(VPS13D): c.12629C> T (p.Ala4210Val) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 12460363: 12460363
6 VPS13D NM_015378.4(VPS13D): c.12629C> T (p.Ala4210Val) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 12520418: 12520418
7 VPS13D NM_015378.4(VPS13D): c.5409C> A (p.Tyr1803Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 12283511: 12283511
8 VPS13D NM_015378.4(VPS13D): c.5409C> A (p.Tyr1803Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 12343568: 12343568
9 VPS13D NM_015378.4(VPS13D): c.7332_7333del (p.Val2445Glufs) deletion Pathogenic GRCh38 Chromosome 1, 12318255: 12318256
10 VPS13D NM_015378.4(VPS13D): c.7332_7333del (p.Val2445Glufs) deletion Pathogenic GRCh37 Chromosome 1, 12378312: 12378313
11 VPS13D NM_015378.4(VPS13D): c.10562A> G (p.Asn3521Ser) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 12428636: 12428636
12 VPS13D NM_015378.4(VPS13D): c.10562A> G (p.Asn3521Ser) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 12368581: 12368581
13 VPS13D NM_015378.4(VPS13D): c.12683G> A (p.Arg4228Gln) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 12557574: 12557574
14 VPS13D NM_015378.4(VPS13D): c.12683G> A (p.Arg4228Gln) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 12497520: 12497520

Expression for Spinocerebellar Ataxia, Autosomal Recessive 4

Search GEO for disease gene expression data for Spinocerebellar Ataxia, Autosomal Recessive 4.

Pathways for Spinocerebellar Ataxia, Autosomal Recessive 4

GO Terms for Spinocerebellar Ataxia, Autosomal Recessive 4

Sources for Spinocerebellar Ataxia, Autosomal Recessive 4

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