SCA34
MCID: SPN104
MIFTS: 40

Spinocerebellar Ataxia 34 (SCA34)

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

Aliases & Classifications for Spinocerebellar Ataxia 34

MalaCards integrated aliases for Spinocerebellar Ataxia 34:

Name: Spinocerebellar Ataxia 34 57 20 72 13
Erythrokeratodermia with Ataxia 57 73 20 58 72 39 70
Spinocerebellar Ataxia Type 34 12 58 29 6 15
Sca34 57 20 58 72
Spinocerebellar Ataxia and Erythrokeratodermia 58
Erythrokeratodermia - Ataxia 20
Erythrokeratodermia Ataxia 73
Giroux Barbeau Syndrome 20

Characteristics:

Orphanet epidemiological data:

58
spinocerebellar ataxia type 34
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
incomplete penetrance
one family of french-canadian origin had skin lesions
skin lesion appear shortly after birth and tend to disappear in young adulthood
skin lesions tend to occur on distal extremities or at elbows and knees
skin lesions improve in the summer
cerebellar ataxia shows onset in young adulthood
ataxia is slowly progressive
many patients become wheelchair-bound later in life

Inheritance:
autosomal dominant


HPO:

31
spinocerebellar ataxia 34:
Inheritance autosomal dominant inheritance
Onset and clinical course incomplete penetrance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare skin diseases


External Ids:

Disease Ontology 12 DOID:0050981
OMIM® 57 133190
OMIM Phenotypic Series 57 PS164400
MESH via Orphanet 45 C535514 C535738
ICD10 via Orphanet 33 G11.1
UMLS via Orphanet 71 C1851481 C2930921
Orphanet 58 ORPHA1955
MedGen 41 C1851481
UMLS 70 C1851481

Summaries for Spinocerebellar Ataxia 34

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1955 Definition An autosomal dominant cerebellar ataxia type I that is characterized by papulosquamous, ichthyosiform plaques on the limbs appearing shortly after birth and later manifestations including progressive ataxia, dysarthria, nystagmus and decreased reflexes. Epidemiology To date the disorder has been reported in 45 patients including 4 asymptomatic carriers, from one French-Canadian family and three Japanese families. Clinical description Disease onset occurs from shortly after birth to adolescence with the appearance of papulosquamous, ichthyosiform plaques on the limbs, which are often only present in the winter. After the age of 25 years they tend to disappear completely. Progressive ataxia, dysarthria, decreased reflexes, and nystagmus are further clinical signs of the disease that occur after the onset of skin manifestations, generally from the third to fifth decade of life. Patients occasionally present with autonomic dysfunction and pyramidal signs. Cerebellar and pontine atrophy is visible with magnetic resonance imaging (MRI) in individuals who develop cerebellar ataxia. Etiology The disorder is due to a mutation in the ELOVL4 gene (6q14). Diagnostic methods Diagnosis is based on characteristic clinical findings (skin lesions occurring shortly after birth and adult-onset slowly progressive cerebellar ataxia), and on the molecular genetic testing. Mutations in the ELOVL4 gene confirms diagnosis of SCA34. Magnetic resonance imaging usually shows marked atrophy of the cerebellum and pontine which is sometimes accompanied by Hot Cross Bun sign that is common in cerebellar type of multiple system atrophy. Differential diagnosis Differential diagnoses include other forms of autosomal dominant cerebellar ataxia. From the view point of radiological findings, multiple system atrophy is important in differential diagnosis, especially in patients who also develop autonomic dysfunction. Antenatal diagnosis Antenatal diagnosis is possible in families with a known ELOVL4 mutation. Genetic counseling The disorder is inherited in an autosomal dominant manner and genetic counseling is possible. Genetic counseling should be proposed to individuals having the disease-causing mutation informing them that there is 50% risk of passing the mutation to offspring. Management and treatment Treatment is only supportive. Physical activity should be maintained as much as possible with the help of prosthetic devices. Motorized chairs/scooters are eventually necessary. Speech therapy and communication devices should be offered to those with severe dysarthria. Prognosis Disease progression is slow; the patients require cane or walker in their late 60s, and wheelchair in their 70s.

MalaCards based summary : Spinocerebellar Ataxia 34, also known as erythrokeratodermia with ataxia, is related to epilepsy, progressive myoclonic, 4, with or without renal failure and macular degeneration, age-related, 1, and has symptoms including ataxia, dysdiadochokinesis and gait ataxia. An important gene associated with Spinocerebellar Ataxia 34 is ELOVL4 (ELOVL Fatty Acid Elongase 4), and among its related pathways/superpathways are Metabolism and Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha). Affiliated tissues include skin, cerebellum and eye, and related phenotypes are nystagmus and dysarthria

Disease Ontology : 12 An autosomal dominant cerebellar ataxia that is characterized by papulosquamous, ichthyosiform plaques at birth and progressive ataxia, dysarthria, nystagmus and hyporeflexia, has material basis in mutation in the ELOVL4 gene.

OMIM® : 57 Spinocerebellar ataxia-34 is an autosomal dominant disorder characterized by slowly progressive cerebellar ataxia. The age at onset is usually during the young adult years, and most patients remain ambulatory until late in life. One family with SCA34 also had onset of erythema and hyperkeratosis in early childhood (Cadieux-Dion et al., 2014), whereas other families have additional neurologic signs, including ocular movement disturbances and pyramidal tract signs (Ozaki et al., 2015). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400). (133190) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Spinocerebellar ataxia 34: 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. SCA34 is an autosomal dominant form characterized by the association of progressive cerebellar ataxia with erythrokeratodermia variabilis.

Wikipedia : 73 Erythrokeratodermia with ataxia is a condition characterized by erythematous, hyperkeratotic plaques... more...

Related Diseases for Spinocerebellar Ataxia 34

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, Autosomal Recessive 28 Spinocerebellar Ataxia Type 19/22
Grid2-Related Spinocerebellar Ataxia Spinocerebellar Ataxia Autosomal Recessive 5

Diseases related to Spinocerebellar Ataxia 34 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 15)
# Related Disease Score Top Affiliating Genes
1 epilepsy, progressive myoclonic, 4, with or without renal failure 10.2
2 macular degeneration, age-related, 1 10.2
3 hereditary ataxia 10.2
4 keratosis 10.2
5 ichthyosis 10.2
6 paraplegia 10.2
7 erythrokeratodermia variabilis et progressiva 1 10.1
8 erythrokeratodermia variabilis et progressiva 5 10.1
9 ataxia and polyneuropathy, adult-onset 10.0
10 stargardt disease 3 10.0
11 autosomal dominant cerebellar ataxia 10.0
12 spasticity 10.0
13 multiple system atrophy 1 9.9
14 zellweger syndrome 9.5 HACD3 ELOVL4
15 sarcocystosis 9.2 HACD4 HACD3 HACD2

Graphical network of the top 20 diseases related to Spinocerebellar Ataxia 34:



Diseases related to Spinocerebellar Ataxia 34

Symptoms & Phenotypes for Spinocerebellar Ataxia 34

Human phenotypes related to Spinocerebellar Ataxia 34:

58 31 (show all 29)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000639
2 dysarthria 58 31 hallmark (90%) Very frequent (99-80%) HP:0001260
3 gait disturbance 58 31 hallmark (90%) Very frequent (99-80%) HP:0001288
4 dry skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0000958
5 hypohidrosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000966
6 dysdiadochokinesis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002075
7 macule 58 31 hallmark (90%) Very frequent (99-80%) HP:0012733
8 urticaria 58 31 hallmark (90%) Very frequent (99-80%) HP:0001025
9 hyporeflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001265
10 papule 58 31 hallmark (90%) Very frequent (99-80%) HP:0200034
11 progressive cerebellar ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002073
12 strabismus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000486
13 facial asymmetry 58 31 occasional (7.5%) Occasional (29-5%) HP:0000324
14 abnormality of the musculature 58 31 occasional (7.5%) Occasional (29-5%) HP:0003011
15 spasticity 31 occasional (7.5%) HP:0001257
16 fasciculations 31 occasional (7.5%) HP:0002380
17 intention tremor 31 occasional (7.5%) HP:0002080
18 peripheral axonal neuropathy 31 very rare (1%) HP:0003477
19 hyperreflexia 31 HP:0001347
20 neurological speech impairment 58 Very frequent (99-80%)
21 abnormal pyramidal sign 31 HP:0007256
22 hyperkeratosis 31 HP:0000962
23 abnormality of movement 58 Frequent (79-30%)
24 gait ataxia 31 HP:0002066
25 cerebellar atrophy 31 HP:0001272
26 abnormality of the skin 31 HP:0000951
27 limb ataxia 31 HP:0002070
28 supranuclear gaze palsy 31 HP:0000605
29 impaired smooth pursuit 31 HP:0007772

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Peripheral Nervous System:
hyperreflexia
hyporeflexia
axonal peripheral neuropathy, mild (in some patients)

Neurologic Central Nervous System:
dysarthria
cerebellar atrophy
limb ataxia
pyramidal signs
ataxic gait
more
Skin Nails Hair Skin:
erythrokeratodermia (1 family)
papulosquamous erythematous plaques (1 family)

Muscle Soft Tissue:
fasciculations (less common)

Head And Neck Eyes:
nystagmus
supranuclear gaze palsy
impaired smooth pursuit

Genitourinary Bladder:
bladder dysfunction

Skin Nails Hair Skin Histology:
hyperkeratosis (1 family)
increased granular cell layer with vacuolization and clumping of keratohyaline granules (1 family)
papillomatosis (1 family)

Clinical features from OMIM®:

133190 (Updated 05-Apr-2021)

UMLS symptoms related to Spinocerebellar Ataxia 34:


ataxia; dysdiadochokinesis; gait ataxia

Drugs & Therapeutics for Spinocerebellar Ataxia 34

Search Clinical Trials , NIH Clinical Center for Spinocerebellar Ataxia 34

Genetic Tests for Spinocerebellar Ataxia 34

Genetic tests related to Spinocerebellar Ataxia 34:

# Genetic test Affiliating Genes
1 Spinocerebellar Ataxia Type 34 29 ELOVL4

Anatomical Context for Spinocerebellar Ataxia 34

MalaCards organs/tissues related to Spinocerebellar Ataxia 34:

40
Skin, Cerebellum, Eye, Spinal Cord

Publications for Spinocerebellar Ataxia 34

Articles related to Spinocerebellar Ataxia 34:

# Title Authors PMID Year
1
Erythrokeratodermia with ataxia. 57 6 61
5048218 1972
2
A Novel Mutation in ELOVL4 Leading to Spinocerebellar Ataxia (SCA) With the Hot Cross Bun Sign but Lacking Erythrokeratodermia: A Broadened Spectrum of SCA34. 57 6
26010696 2015
3
Expanding the clinical phenotype associated with ELOVL4 mutation: study of a large French-Canadian family with autosomal dominant spinocerebellar ataxia and erythrokeratodermia. 6 57
24566826 2014
4
The Elovl4 Spinocerebellar Ataxia-34 Mutation 736T>G (p.W246G) Impairs Retinal Function in the Absence of Photoreceptor Degeneration. 61
32780351 2020
5
Characterization of the phenotype with cognitive impairment and protein mislocalization in SCA34. 61
32211516 2020
6
A family with spinocerebellar ataxia and retinitis pigmentosa attributed to an ELOVL4 mutation. 61
31750392 2019
7
ELOVL4: Very long-chain fatty acids serve an eclectic role in mammalian health and function. 61
30982505 2019
8
Novel Cellular Functions of Very Long Chain-Fatty Acids: Insight From ELOVL4 Mutations. 61
31616255 2019
9
Linkage studies in erythrokeratodermias: fine mapping, genetic heterogeneity and analysis of candidate genes. 61
9347797 1997

Variations for Spinocerebellar Ataxia 34

ClinVar genetic disease variations for Spinocerebellar Ataxia 34:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ELOVL4 NM_022726.4(ELOVL4):c.504G>C (p.Leu168Phe) SNV Pathogenic 143056 rs587777598 GRCh37: 6:80631379-80631379
GRCh38: 6:79921662-79921662
2 ELOVL4 NM_022726.4(ELOVL4):c.736T>G (p.Trp246Gly) SNV Pathogenic 430572 rs1131692036 GRCh37: 6:80626534-80626534
GRCh38: 6:79916817-79916817
3 ELOVL4 NM_022726.4(ELOVL4):c.512T>C (p.Ile171Thr) SNV Likely pathogenic 435057 rs1554162301 GRCh37: 6:80631371-80631371
GRCh38: 6:79921654-79921654
4 ELOVL4 NM_022726.4(ELOVL4):c.351T>A (p.Asn117Lys) SNV Uncertain significance 358148 rs148018494 GRCh37: 6:80634687-80634687
GRCh38: 6:79924970-79924970
5 ELOVL4 NM_022726.4(ELOVL4):c.163C>G (p.Leu55Val) SNV Uncertain significance 1028774 GRCh37: 6:80636036-80636036
GRCh38: 6:79926319-79926319

UniProtKB/Swiss-Prot genetic disease variations for Spinocerebellar Ataxia 34:

72
# Symbol AA change Variation ID SNP ID
1 ELOVL4 p.Leu168Phe VAR_072565 rs587777598

Expression for Spinocerebellar Ataxia 34

Search GEO for disease gene expression data for Spinocerebellar Ataxia 34.

Pathways for Spinocerebellar Ataxia 34

GO Terms for Spinocerebellar Ataxia 34

Cellular components related to Spinocerebellar Ataxia 34 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of membrane GO:0016021 9.65 HACD4 HACD3 HACD2 HACD1 ELOVL4
2 endoplasmic reticulum GO:0005783 9.55 HACD4 HACD3 HACD2 HACD1 ELOVL4
3 endoplasmic reticulum membrane GO:0005789 9.35 HACD4 HACD3 HACD2 HACD1 ELOVL4
4 integral component of endoplasmic reticulum membrane GO:0030176 9.02 HACD4 HACD3 HACD2 HACD1 ELOVL4

Biological processes related to Spinocerebellar Ataxia 34 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.8 HACD4 HACD3 HACD2 HACD1 ELOVL4
2 fatty acid metabolic process GO:0006631 9.72 HACD4 HACD3 HACD2 HACD1 ELOVL4
3 fatty acid biosynthetic process GO:0006633 9.65 HACD4 HACD3 HACD2 HACD1 ELOVL4
4 sphingolipid biosynthetic process GO:0030148 9.55 HACD4 HACD3 HACD2 HACD1 ELOVL4
5 long-chain fatty-acyl-CoA biosynthetic process GO:0035338 9.54 HACD2 HACD1 ELOVL4
6 fatty acid elongation GO:0030497 9.26 HACD4 HACD3 HACD2 HACD1
7 very long-chain fatty acid biosynthetic process GO:0042761 9.02 HACD4 HACD3 HACD2 HACD1 ELOVL4

Molecular functions related to Spinocerebellar Ataxia 34 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 enzyme binding GO:0019899 9.71 HACD4 HACD3 HACD2 HACD1
2 lyase activity GO:0016829 9.67 HACD4 HACD3 HACD2 HACD1
3 3-hydroxyacyl-CoA dehydratase activity GO:0018812 9.62 HACD4 HACD3 HACD2 HACD1
4 3-hydroxy-lignoceroyl-CoA dehydratase activity GO:0102345 9.56 HACD4 HACD3 HACD2 HACD1
5 3-hydroxy-behenoyl-CoA dehydratase activity GO:0102344 9.46 HACD4 HACD3 HACD2 HACD1
6 3-hydroxy-arachidoyl-CoA dehydratase activity GO:0102343 9.26 HACD4 HACD3 HACD2 HACD1
7 very-long-chain 3-hydroxyacyl-CoA dehydratase activity GO:0102158 8.92 HACD4 HACD3 HACD2 HACD1

Sources for Spinocerebellar Ataxia 34

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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