SPAX8
MCID: SPS209
MIFTS: 24

Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy (SPAX8)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating...

MalaCards integrated aliases for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy:

Name: Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy 57 72 29 6
Spax8 57 58 72
Autosomal Recessive Hypomyelinating Leukodystrophy-Progressive Spastic Ataxia 58
Nkx6-2-Related Autosomal Recessive Hypomyelinating Leukodystrophy 58

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in first year of life
most patients become wheelchair-bound
three consanguineous families have been reported (last curated july 2017)


HPO:

31
spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset progressive


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating...

OMIM® : 57 Spastic ataxia-8 with hypomyelinating leukodystrophy is an autosomal recessive progressive neurodegenerative disorder characterized by onset of primarily motor dysfunction within the first year of life. Affected individuals initially have hypotonia and later develop ataxia, spasticity, and a pyramidal syndrome with weakness and loss of ambulation. Other features may include dystonia, dysarthria, and abnormal eye movements. Brain imaging shows cerebellar atrophy and hypomyelinating leukodystrophy. One family with cognitive impairment has also been reported (summary by Chelban et al., 2017). For a discussion of genetic heterogeneity of spastic ataxia, see SPAX1 (108600). (617560) (Updated 05-Apr-2021)

MalaCards based summary : Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy, also known as spax8, is related to nkx6-2-related disorder. An important gene associated with Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy is NKX6-2 (NK6 Homeobox 2). Affiliated tissues include eye, and related phenotypes are abnormal pyramidal sign and nystagmus

UniProtKB/Swiss-Prot : 72 Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy: An autosomal recessive neurodegenerative disorder characterized by early-onset hypotonia which progresses to a pyramidal syndrome with ataxia, spasticity, hyperreflexia, weakness and loss of ambulation. Brain imaging shows cerebellar atrophy and hypomyelinating leukodystrophy.

Related Diseases for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating...

Diseases related to Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 nkx6-2-related disorder 11.0

Symptoms & Phenotypes for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating...

Human phenotypes related to Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy:

58 31 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormal pyramidal sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0007256
2 nystagmus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000639
3 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
4 hypometric saccades 58 31 hallmark (90%) Very frequent (99-80%) HP:0000571
5 hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001347
6 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
7 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
8 dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0001332
9 progressive spasticity 58 31 frequent (33%) Frequent (79-30%) HP:0002191
10 leukodystrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002415
11 paroxysmal involuntary eye movements 58 31 frequent (33%) Frequent (79-30%) HP:0007704
12 generalized hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001290
13 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
14 cns hypomyelination 58 31 frequent (33%) Frequent (79-30%) HP:0003429
15 head titubation 58 31 frequent (33%) Frequent (79-30%) HP:0002599
16 hyperintensity of cerebral white matter on mri 58 31 frequent (33%) Frequent (79-30%) HP:0030890
17 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
18 strabismus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000486
19 cerebellar atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001272
20 cerebral atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002059
21 hirsutism 58 31 occasional (7.5%) Occasional (29-5%) HP:0001007
22 seizure 31 occasional (7.5%) HP:0001250
23 intellectual disability 58 31 very rare (1%) Very rare (<4-1%) HP:0001249
24 hypoplasia of the corpus callosum 58 31 very rare (1%) Very rare (<4-1%) HP:0002079
25 seizures 58 Occasional (29-5%)
26 spasticity 31 HP:0001257
27 neonatal hypotonia 31 HP:0001319
28 cognitive impairment 31 HP:0100543
29 motor delay 31 HP:0001270
30 dysesthesia 58 Excluded (0%)
31 limb ataxia 31 HP:0002070
32 truncal ataxia 31 HP:0002078

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
spasticity
dysarthria
dystonia
cerebellar atrophy
limb ataxia
more
Head And Neck Eyes:
nystagmus
hypometric saccades
abnormal eye movements
limited eye movements

Muscle Soft Tissue:
hypotonia, neonatal

Neurologic Peripheral Nervous System:
hyperreflexia

Head And Neck Head:
head titubation

Clinical features from OMIM®:

617560 (Updated 05-Apr-2021)

Drugs & Therapeutics for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating...

Search Clinical Trials , NIH Clinical Center for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy

Genetic Tests for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating...

Genetic tests related to Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy:

# Genetic test Affiliating Genes
1 Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy 29 NKX6-2

Anatomical Context for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating...

MalaCards organs/tissues related to Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy:

40
Eye

Publications for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating...

Articles related to Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy:

# Title Authors PMID Year
1
Mutations in NKX6-2 Cause Progressive Spastic Ataxia and Hypomyelination. 57 6
28575651 2017
2
CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure. 57
15601927 2004

Variations for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating...

ClinVar genetic disease variations for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy:

6 (show all 12)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NKX6-2 NM_177400.3(NKX6-2):c.565G>T (p.Glu189Ter) SNV Pathogenic 627615 rs776560015 GRCh37: 10:134598798-134598798
GRCh38: 10:132785294-132785294
2 NKX6-2 NM_177400.3(NKX6-2):c.589C>T (p.Gln197Ter) SNV Pathogenic 627616 rs1565019976 GRCh37: 10:134598665-134598665
GRCh38: 10:132785161-132785161
3 NKX6-2 NM_177400.3(NKX6-2):c.599G>A (p.Arg200Gln) SNV Pathogenic 627617 rs1008088032 GRCh37: 10:134598655-134598655
GRCh38: 10:132785151-132785151
4 NKX6-2 NM_177400.3(NKX6-2):c.606delinsTA (p.Lys202fs) Indel Pathogenic 627618 rs1565019932 GRCh37: 10:134598648-134598648
GRCh38: 10:132785144-132785144
5 NKX6-2 NM_177400.3(NKX6-2):c.121A>T (p.Lys41Ter) SNV Pathogenic 430622 rs1131692047 GRCh37: 10:134599332-134599332
GRCh38: 10:132785828-132785828
6 NKX6-2 NM_177400.3(NKX6-2):c.406+1G>T SNV Pathogenic 1031743 GRCh37: 10:134599046-134599046
GRCh38: 10:132785542-132785542
7 NKX6-2 NM_177400.3(NKX6-2):c.487C>G (p.Leu163Val) SNV Pathogenic 430623 rs1131692048 GRCh37: 10:134598876-134598876
GRCh38: 10:132785372-132785372
8 NKX6-2 NM_177400.3(NKX6-2):c.196del (p.Arg66fs) Deletion Likely pathogenic 503871 rs1554961118 GRCh37: 10:134599257-134599257
GRCh38: 10:132785753-132785753
9 NKX6-2 NM_177400.3(NKX6-2):c.608G>A (p.Trp203Ter) SNV Likely pathogenic 627619 rs1565019928 GRCh37: 10:134598646-134598646
GRCh38: 10:132785142-132785142
10 NKX6-2 NM_177400.3(NKX6-2):c.450C>G (p.His150Gln) SNV Uncertain significance 1031744 GRCh37: 10:134598913-134598913
GRCh38: 10:132785409-132785409
11 NKX6-2 NM_177400.3(NKX6-2):c.59A>G (p.His20Arg) SNV Uncertain significance 1031745 GRCh37: 10:134599394-134599394
GRCh38: 10:132785890-132785890
12 NKX6-2 NM_177400.3(NKX6-2):c.501C>G (p.Phe167Leu) SNV Uncertain significance 638677 rs1375888398 GRCh37: 10:134598862-134598862
GRCh38: 10:132785358-132785358

Expression for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating...

Search GEO for disease gene expression data for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy.

Pathways for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating...

GO Terms for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating...

Sources for Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating...

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
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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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