IAHSP
MCID: SPS225
MIFTS: 33

Spastic Paralysis, Infantile-Onset Ascending (IAHSP)

Categories: Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Spastic Paralysis, Infantile-Onset Ascending

MalaCards integrated aliases for Spastic Paralysis, Infantile-Onset Ascending:

Name: Spastic Paralysis, Infantile-Onset Ascending 57
Iahsp 57 58 72 54
Spastic Paralysis, Infantile Onset Ascending 57 13 6
Hereditary Spastic Paralysis, Infantile Onset Ascending 70
Infantile-Onset Ascending Hereditary Spastic Paralysis 58
Infantile-Onset Ascending Spastic Paralysis 72

Characteristics:

Orphanet epidemiological data:

58
infantile-onset ascending hereditary spastic paralysis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: adult;

OMIM®:

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

Miscellaneous:
progressive disorder
allelic disorder to juvenile primary lateral sclerosis (plsj, )
most patients become wheelchair-bound
onset within first 2 years of life
some patients never achieve walking or running
allelic disorder to juvenile-onset amyotrophic lateral sclerosis (als2, )


HPO:

31
spastic paralysis, infantile-onset ascending:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset progressive slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Spastic Paralysis, Infantile-Onset Ascending

OMIM® : 57 Infantile-onset ascending spastic paralysis is an autosomal recessive neurodegenerative disorder characterized by onset in the first years of life of progressive upper and lower motor neuron degeneration resulting in loss of ability to walk in childhood. It initially affects the lower limbs and then ascends to the upper limbs and bulbar muscles, causing dysarthria and dysphagia. Cognition is unaffected (summary by Wakil et al., 2014). (607225) (Updated 05-Apr-2021)

MalaCards based summary : Spastic Paralysis, Infantile-Onset Ascending, also known as iahsp, is related to infantile-onset ascending hereditary spastic paralysis and amyotrophic lateral sclerosis 1, and has symptoms including muscle weakness and facial paresis. An important gene associated with Spastic Paralysis, Infantile-Onset Ascending is ALS2 (Alsin Rho Guanine Nucleotide Exchange Factor ALS2). Affiliated tissues include eye and cortex, and related phenotypes are hyperreflexia and dysarthria

UniProtKB/Swiss-Prot : 72 Infantile-onset ascending spastic paralysis: Characterized by progressive spasticity and weakness of limbs.

Related Diseases for Spastic Paralysis, Infantile-Onset Ascending

Diseases in the Spastic Paralysis, Infantile-Onset Ascending family:

Infantile-Onset Ascending Hereditary Spastic Paralysis

Diseases related to Spastic Paralysis, Infantile-Onset Ascending via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 16)
# Related Disease Score Top Affiliating Genes
1 infantile-onset ascending hereditary spastic paralysis 11.6
2 amyotrophic lateral sclerosis 1 10.2
3 scoliosis 10.2
4 hereditary spastic paraplegia 10.2
5 juvenile amyotrophic lateral sclerosis 10.2
6 spastic paraparesis 10.2
7 primary lateral sclerosis, juvenile 10.2
8 dystonia 10.2
9 quadriplegia 9.9
10 lateral sclerosis 9.9
11 motor neuron disease 9.9
12 paraplegia 9.9
13 als2-related disorders 9.9
14 chromosomal triplication 9.9
15 dysphagia 9.9
16 maternal uniparental disomy 9.9

Graphical network of the top 20 diseases related to Spastic Paralysis, Infantile-Onset Ascending:



Diseases related to Spastic Paralysis, Infantile-Onset Ascending

Symptoms & Phenotypes for Spastic Paralysis, Infantile-Onset Ascending

Human phenotypes related to Spastic Paralysis, Infantile-Onset Ascending:

58 31 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperreflexia 58 31 Very frequent (99-80%) HP:0001347
2 dysarthria 58 31 Very frequent (99-80%) HP:0001260
3 tetraplegia 58 31 Very frequent (99-80%) HP:0002445
4 spastic tetraplegia 58 31 Very frequent (99-80%) HP:0002510
5 spastic paraplegia 58 31 Very frequent (99-80%) HP:0001258
6 anarthria 58 31 Very frequent (99-80%) HP:0002425
7 impaired mastication 58 31 Very frequent (99-80%) HP:0005216
8 spasticity 58 Very frequent (99-80%)
9 scoliosis 31 HP:0002650
10 abnormal pyramidal sign 58 Very frequent (99-80%)
11 abnormality of eye movement 58 Frequent (79-30%)
12 dysphagia 31 HP:0002015
13 muscle weakness 31 HP:0001324
14 achilles tendon contracture 31 HP:0001771
15 motor delay 31 HP:0001270
16 abnormality of the eye 31 HP:0000478
17 pes cavus 31 HP:0001761
18 babinski sign 31 HP:0003487
19 urinary incontinence 31 HP:0000020
20 pseudobulbar behavioral symptoms 58 Frequent (79-30%)
21 slow saccadic eye movements 31 HP:0000514
22 abnormal lower motor neuron morphology 31 HP:0002366
23 morphological abnormality of the corticospinal tract 31 HP:0002492

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
hyperreflexia
dysarthria
anarthria
delayed motor development
extensor plantar responses
more
Abdomen Gastrointestinal:
bowel incontinence
dysphagia (onset in second decade)
chewing difficulties

Genitourinary Bladder:
urinary incontinence

Head And Neck Face:
weakness of the facial muscles

Muscle Soft Tissue:
muscle weakness
normal muscle biopsy
reduction of voluntary recruitment seen on emg

Skeletal Feet:
pes cavus
shortening of the achilles tendon

Skeletal Spine:
scoliosis (less common)

Head And Neck Eyes:
slow eye movements (onset in second decade)
ocular gaze palsies (onset in second decade)

Clinical features from OMIM®:

607225 (Updated 05-Apr-2021)

UMLS symptoms related to Spastic Paralysis, Infantile-Onset Ascending:


muscle weakness; facial paresis

Drugs & Therapeutics for Spastic Paralysis, Infantile-Onset Ascending

Search Clinical Trials , NIH Clinical Center for Spastic Paralysis, Infantile-Onset Ascending

Genetic Tests for Spastic Paralysis, Infantile-Onset Ascending

Anatomical Context for Spastic Paralysis, Infantile-Onset Ascending

MalaCards organs/tissues related to Spastic Paralysis, Infantile-Onset Ascending:

40
Eye, Cortex

Publications for Spastic Paralysis, Infantile-Onset Ascending

Articles related to Spastic Paralysis, Infantile-Onset Ascending:

(show all 20)
# Title Authors PMID Year
1
Novel missense mutation in ALS2 gene results in infantile ascending hereditary spastic paralysis. 6 57 54 61
16718699 2006
2
Infantile-onset ascending hereditary spastic paralysis is associated with mutations in the alsin gene. 6 54 61 57
12145748 2002
3
Infantile-onset ascending hereditary spastic paraplegia with bulbar involvement due to the novel ALS2 mutation c.2761C>T. 61 6 57
24315819 2014
4
Novel homozygous ALS2 nonsense mutation (p.Gln715X) in sibs with infantile-onset ascending spastic paralysis: the first cases from northwestern Europe. 57 54 6
18523452 2008
5
First case of compound heterozygosity in ALS2 gene in infantile-onset ascending spastic paralysis with bulbar involvement. 6 54 57
18394004 2008
6
An ALS2 gene mutation causes hereditary spastic paraplegia in a Pakistani kindred. 6 57
12509863 2003
7
Maternal uniparental heterodisomy with partial isodisomy of a chromosome 2 carrying a splice acceptor site mutation (IVS9-2A>T) in ALS2 causes infantile-onset ascending spastic paralysis (IAHSP). 54 61 57
18810511 2009
8
Infantile ascending hereditary spastic paralysis (IAHSP): clinical features in 11 families. 61 57 54
12601111 2003
9
ALS2-Related Disorders 61 6
20301421 2005
10
The first nonsense mutation in alsin results in a homogeneous phenotype of infantile-onset ascending spastic paralysis with bulbar involvement in two siblings. 6 54
12919135 2003
11
A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. 6
11586298 2001
12
The first ALS2 missense mutation associated with JPLS reveals new aspects of alsin biological function. 54 61
16670179 2006
13
Genotype-phenotype correlation in seven motor neuron disease families with novel ALS2 mutations. 61
33155358 2021
14
A p.Arg499His Mutation in SPAST Is Associated with Infantile Onset Ascending Spastic Paralysis Complicated with Dysarthria and Anarthria. 61
31486053 2019
15
Clinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an ALS2 founder variant. 61
30128655 2018
16
A novel mutation in ALS2 associated with severe and progressive infantile onset of spastic paralysis. 61
28502191 2017
17
Identification of two novel ALS2 mutations in infantile-onset ascending hereditary spastic paraplegia. 61
26751646 2016
18
Infantile-onset ascending hereditary spastic paralysis: a case report and brief literature review. 61
24144828 2014
19
Are alsin and spartin novel interaction partners? 61
22982304 2012
20
Alfa-class prefoldin protein UXT is a novel interacting partner of Amyotrophic Lateral Sclerosis 2 (Als2) protein. 61
21907703 2011

Variations for Spastic Paralysis, Infantile-Onset Ascending

ClinVar genetic disease variations for Spastic Paralysis, Infantile-Onset Ascending:

6 (show top 50) (show all 173)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ALS2 NM_020919.4(ALS2):c.3619del (p.Lys1206_Met1207insTer) Deletion Pathogenic 4408 rs386134187 GRCh37: 2:202588058-202588058
GRCh38: 2:201723335-201723335
2 ALS2 NM_020919.4(ALS2):c.2537_2538del (p.Asn846fs) Deletion Pathogenic 4410 rs386134183 GRCh37: 2:202598041-202598042
GRCh38: 2:201733318-201733319
3 ALS2 NM_020919.4(ALS2):c.1007_1008del (p.Ile336fs) Deletion Pathogenic 4411 rs386134175 GRCh37: 2:202625709-202625710
GRCh38: 2:201760986-201760987
4 ALS2 NM_020919.4(ALS2):c.2992C>T (p.Arg998Ter) SNV Pathogenic 4413 rs121908137 GRCh37: 2:202591577-202591577
GRCh38: 2:201726854-201726854
5 ALS2 NM_020919.4(ALS2):c.2143C>T (p.Gln715Ter) SNV Pathogenic 4417 rs121908139 GRCh37: 2:202609008-202609008
GRCh38: 2:201744285-201744285
6 ALS2 NM_020919.4(ALS2):c.1999-2A>T SNV Pathogenic 42060 rs386134182 GRCh37: 2:202609154-202609154
GRCh38: 2:201744431-201744431
7 ALS2 NM_020919.4(ALS2):c.2761C>T (p.Arg921Ter) SNV Pathogenic 100653 rs587777132 GRCh37: 2:202593315-202593315
GRCh38: 2:201728592-201728592
8 ALS2 NM_020919.4(ALS2):c.4261C>T (p.Arg1421Ter) SNV Pathogenic 217879 rs863225293 GRCh37: 2:202574623-202574623
GRCh38: 2:201709900-201709900
9 ALS2 NM_020919.4(ALS2):c.1425_1428del (p.Gly477fs) Deletion Pathogenic 241308 rs878855058 GRCh37: 2:202622168-202622171
GRCh38: 2:201757445-201757448
10 ALS2 NM_020919.4(ALS2):c.1233T>G (p.Tyr411Ter) SNV Pathogenic 533743 rs369577952 GRCh37: 2:202622363-202622363
GRCh38: 2:201757640-201757640
11 ALS2 NM_020919.4(ALS2):c.1921C>T (p.Gln641Ter) SNV Pathogenic 533744 rs1553511680 GRCh37: 2:202611366-202611366
GRCh38: 2:201746643-201746643
12 ALS2 NM_020919.4(ALS2):c.1233T>G (p.Tyr411Ter) SNV Pathogenic 533743 rs369577952 GRCh37: 2:202622363-202622363
GRCh38: 2:201757640-201757640
13 ALS2 NM_020919.4(ALS2):c.3520A>T (p.Lys1174Ter) SNV Pathogenic 645923 rs757972700 GRCh37: 2:202588157-202588157
GRCh38: 2:201723434-201723434
14 ALS2 NM_020919.4(ALS2):c.1044C>G (p.Tyr348Ter) SNV Pathogenic 694320 GRCh37: 2:202625673-202625673
GRCh38: 2:201760950-201760950
15 ALS2 NM_020919.4(ALS2):c.2016_2026del (p.Val673fs) Deletion Pathogenic 946562 GRCh37: 2:202609125-202609135
GRCh38: 2:201744402-201744412
16 ALS2 NM_020919.4(ALS2):c.4544_4547dup (p.Ile1517fs) Duplication Pathogenic 958880 GRCh37: 2:202571601-202571602
GRCh38: 2:201706878-201706879
17 ALS2 NM_020919.4(ALS2):c.2221C>T (p.Arg741Ter) SNV Pathogenic 961004 GRCh37: 2:202606527-202606527
GRCh38: 2:201741804-201741804
18 ALS2 NM_020919.4(ALS2):c.1867_1868del (p.Leu623fs) Deletion Pathogenic 4406 rs386134181 GRCh37: 2:202611419-202611420
GRCh38: 2:201746696-201746697
19 ALS2 NM_020919.4(ALS2):c.913del (p.Glu304_Leu305insTer) Deletion Pathogenic 807369 rs1574786641 GRCh37: 2:202625804-202625804
GRCh38: 2:201761081-201761081
20 ALS2 NM_020919.4(ALS2):c.601C>T (p.Arg201Ter) SNV Pathogenic 804392 rs1574787779 GRCh37: 2:202626116-202626116
GRCh38: 2:201761393-201761393
21 ALS2 NM_020919.3(ALS2):c.1472_1481delTTTCCCCCAG SNV Pathogenic 4409 rs387906316 GRCh37: 2:202619395-202619395
GRCh38: 2:201754672-201754672
22 ALS2 NM_020919.4(ALS2):c.4721del (p.Val1574fs) Deletion Pathogenic 4412 rs386134188 GRCh37: 2:202569294-202569294
GRCh38: 2:201704571-201704571
23 ALS2 NM_020919.4(ALS2):c.1054_1061del (p.Leu352fs) Deletion Likely pathogenic 800527 rs1574786170 GRCh37: 2:202625656-202625663
GRCh38: 2:201760933-201760940
24 ALS2 NM_020919.4(ALS2):c.601C>T (p.Arg201Ter) SNV Likely pathogenic 804392 rs1574787779 GRCh37: 2:202626116-202626116
GRCh38: 2:201761393-201761393
25 ALS2 NM_020919.4(ALS2):c.4838+1del Deletion Likely pathogenic 947373 GRCh37: 2:202569176-202569176
GRCh38: 2:201704453-201704453
26 ALS2 NM_020919.4(ALS2):c.1718C>A (p.Ala573Glu) SNV Likely pathogenic 694319 GRCh37: 2:202617888-202617888
GRCh38: 2:201753165-201753165
27 ALS2 NM_020919.4(ALS2):c.3161T>C (p.Leu1054Pro) SNV Likely pathogenic 694321 GRCh37: 2:202591408-202591408
GRCh38: 2:201726685-201726685
28 ALS2 NM_020919.4(ALS2):c.4573dup (p.Val1525fs) Duplication Likely pathogenic 183240 rs730882256 GRCh37: 2:202571575-202571576
GRCh38: 2:201706852-201706853
29 ALS2 NM_020919.4(ALS2):c.1471+1G>A SNV Likely pathogenic 694323 GRCh37: 2:202622124-202622124
GRCh38: 2:201757401-201757401
30 ALS2 NM_020919.4(ALS2):c.4261C>T (p.Arg1421Ter) SNV Likely pathogenic 242457 rs863225293 GRCh37: 2:202574623-202574623
GRCh38: 2:201709900-201709900
31 ALS2 NM_020919.4(ALS2):c.1911C>A (p.Tyr637Ter) SNV Likely pathogenic 242456 rs863225294 GRCh37: 2:202611376-202611376
GRCh38: 2:201746653-201746653
32 ALS2 NM_020919.4(ALS2):c.2104G>T (p.Glu702Ter) SNV Likely pathogenic 804391 rs1574748038 GRCh37: 2:202609047-202609047
GRCh38: 2:201744324-201744324
33 ALS2 NM_020919.4(ALS2):c.470G>A (p.Cys157Tyr) SNV Likely pathogenic 4415 rs121908138 GRCh37: 2:202626247-202626247
GRCh38: 2:201761524-201761524
34 ALS2 NM_020919.4(ALS2):c.1816-1G>A SNV Likely pathogenic 412209 rs1060503672 GRCh37: 2:202611472-202611472
GRCh38: 2:201746749-201746749
35 ALS2 NM_020919.4(ALS2):c.2222G>A (p.Arg741Gln) SNV Uncertain significance 412227 rs753349655 GRCh37: 2:202606526-202606526
GRCh38: 2:201741803-201741803
36 ALS2 NM_020919.4(ALS2):c.4498G>A (p.Glu1500Lys) SNV Uncertain significance 241311 rs780151065 GRCh37: 2:202571651-202571651
GRCh38: 2:201706928-201706928
37 ALS2 NM_020919.4(ALS2):c.4021C>T (p.Arg1341Cys) SNV Uncertain significance 412224 rs771371026 GRCh37: 2:202575815-202575815
GRCh38: 2:201711092-201711092
38 ALS2 NM_020919.4(ALS2):c.1037A>G (p.Asn346Ser) SNV Uncertain significance 533745 rs199757764 GRCh37: 2:202625680-202625680
GRCh38: 2:201760957-201760957
39 ALS2 NM_020919.4(ALS2):c.3785C>T (p.Thr1262Ile) SNV Uncertain significance 533746 rs1553503506 GRCh37: 2:202582851-202582851
GRCh38: 2:201718128-201718128
40 ALS2 NM_020919.4(ALS2):c.358G>T (p.Ala120Ser) SNV Uncertain significance 533747 rs202084736 GRCh37: 2:202626359-202626359
GRCh38: 2:201761636-201761636
41 ALS2 NM_020919.4(ALS2):c.1600G>C (p.Gly534Arg) SNV Uncertain significance 533748 rs1553513641 GRCh37: 2:202619266-202619266
GRCh38: 2:201754543-201754543
42 ALS2 NM_020919.4(ALS2):c.4004+6T>A SNV Uncertain significance 465190 rs1553502811 GRCh37: 2:202580389-202580389
GRCh38: 2:201715666-201715666
43 ALS2 NM_020919.4(ALS2):c.2581-5T>A SNV Uncertain significance 465187 rs1171928153 GRCh37: 2:202593911-202593911
GRCh38: 2:201729188-201729188
44 ALS2 NM_020919.4(ALS2):c.1171G>A (p.Ala391Thr) SNV Uncertain significance 465179 rs41308816 GRCh37: 2:202622425-202622425
GRCh38: 2:201757702-201757702
45 ALS2 NM_020919.4(ALS2):c.2875C>A (p.Leu959Met) SNV Uncertain significance 465188 rs1553506293 GRCh37: 2:202592465-202592465
GRCh38: 2:201727742-201727742
46 ALS2 NM_020919.4(ALS2):c.1433G>C (p.Gly478Ala) SNV Uncertain significance 465180 rs373603368 GRCh37: 2:202622163-202622163
GRCh38: 2:201757440-201757440
47 ALS2 NM_020919.4(ALS2):c.2566A>G (p.Thr856Ala) SNV Uncertain significance 652809 rs758153067 GRCh37: 2:202598013-202598013
GRCh38: 2:201733290-201733290
48 ALS2 NM_020919.4(ALS2):c.1325G>C (p.Gly442Ala) SNV Uncertain significance 655414 rs780750146 GRCh37: 2:202622271-202622271
GRCh38: 2:201757548-201757548
49 ALS2 NM_020919.4(ALS2):c.2833C>T (p.His945Tyr) SNV Uncertain significance 657160 rs768066388 GRCh37: 2:202593243-202593243
GRCh38: 2:201728520-201728520
50 ALS2 NM_020919.4(ALS2):c.1439G>A (p.Arg480Gln) SNV Uncertain significance 657700 rs762706628 GRCh37: 2:202622157-202622157
GRCh38: 2:201757434-201757434

Expression for Spastic Paralysis, Infantile-Onset Ascending

Search GEO for disease gene expression data for Spastic Paralysis, Infantile-Onset Ascending.

Pathways for Spastic Paralysis, Infantile-Onset Ascending

GO Terms for Spastic Paralysis, Infantile-Onset Ascending

Sources for Spastic Paralysis, Infantile-Onset Ascending

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