MCID: SPS225
MIFTS: 29

Spastic Paralysis, Infantile-Onset Ascending

Categories: Genetic 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 59 75 55
Spastic Paralysis, Infantile Onset Ascending 57 13
Hereditary Spastic Paralysis, Infantile Onset Ascending 73
Infantile-Onset Ascending Hereditary Spastic Paralysis 59
Infantile-Onset Ascending Spastic Paralysis 75

Characteristics:

Orphanet epidemiological data:

59
infantile-onset ascending hereditary spastic paralysis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: adult;

OMIM:

57
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:

32
spastic paralysis, infantile-onset ascending:
Onset and clinical course infantile onset slow progression progressive
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
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)

MalaCards based summary : Spastic Paralysis, Infantile-Onset Ascending, also known as iahsp, is related to infantile-onset ascending hereditary spastic paralysis, and has symptoms including muscle weakness and facial paresis. An important gene associated with Spastic Paralysis, Infantile-Onset Ascending is ALS2 (ALS2, Alsin Rho Guanine Nucleotide Exchange Factor). The drugs Acetylcholine and Botulinum Toxins have been mentioned in the context of this disorder. Affiliated tissues include eye and cortex, and related phenotypes are dysarthria and hyperreflexia

UniProtKB/Swiss-Prot : 75 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:

# Related Disease Score Top Affiliating Genes
1 infantile-onset ascending hereditary spastic paralysis 12.1

Symptoms & Phenotypes for Spastic Paralysis, Infantile-Onset Ascending

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
dysarthria
hyperreflexia
anarthria
delayed motor development
extensor plantar responses
more
Skeletal Feet:
pes cavus
shortening of the achilles tendon

Genitourinary Bladder:
incontinence

Head And Neck Face:
weakness of the facial muscles

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

Abdomen Gastrointestinal:
chewing difficulties
incontinence
dysphagia (onset in second decade)

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

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

59 32 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysarthria 59 32 Very frequent (99-80%) HP:0001260
2 hyperreflexia 59 32 Very frequent (99-80%) HP:0001347
3 tetraplegia 59 32 Very frequent (99-80%) HP:0002445
4 spastic tetraplegia 59 32 Very frequent (99-80%) HP:0002510
5 spastic paraplegia 59 32 Very frequent (99-80%) HP:0001258
6 anarthria 59 32 Very frequent (99-80%) HP:0002425
7 abnormality of eye movement 59 Frequent (79-30%)
8 spasticity 59 Very frequent (99-80%)
9 muscle weakness 32 HP:0001324
10 scoliosis 32 HP:0002650
11 abnormal pyramidal signs 59 Very frequent (99-80%)
12 abnormality of the eye 32 HP:0000478
13 babinski sign 32 HP:0003487
14 pes cavus 32 HP:0001761
15 motor delay 32 HP:0001270
16 chewing difficulties 59 Very frequent (99-80%)
17 urinary incontinence 32 HP:0000020
18 slow saccadic eye movements 32 HP:0000514
19 pseudobulbar behavioral symptoms 59 Frequent (79-30%)
20 achilles tendon contracture 32 HP:0001771
21 abnormality of the corticospinal tract 32 HP:0002492
22 abnormal lower motor neuron morphology 32 HP:0002366
23 impaired mastication 32 HP:0005216

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


muscle weakness, facial paresis

Drugs & Therapeutics for Spastic Paralysis, Infantile-Onset Ascending

Drugs for Spastic Paralysis, Infantile-Onset Ascending (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 8)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcholine Approved Phase 2, Phase 3 51-84-3 187
2 Botulinum Toxins Phase 2, Phase 3
3 Cholinergic Agents Phase 2, Phase 3
4 Neurotransmitter Agents Phase 2, Phase 3
5
Choline Approved, Nutraceutical 62-49-7 305
6
Creatine Approved, Investigational, Nutraceutical 57-00-1 586
7 N-Methylaspartate
8 Aspartic Acid Nutraceutical

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia Completed NCT02604186 Phase 2, Phase 3
2 Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis Completed NCT00023075
3 Studying Cognition in SPG4 Completed NCT03104088
4 Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31 Recruiting NCT02859428
5 Studying Non-motor Symptoms in SPG4 Recruiting NCT03204773
6 The Pre-SPG4 Study Recruiting NCT03206190 Not Applicable
7 Phenotype, Genotype & Biomarkers in ALS and Related Disorders Recruiting NCT02327845
8 Genetic and Physical Study of Childhood Nerve and Muscle Disorders Recruiting NCT01568658
9 A Patient Centric Motor Neuron Disease Activities of Daily Living Scale Enrolling by invitation NCT02852278

Search 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:

41
Eye, Cortex

Publications for Spastic Paralysis, Infantile-Onset Ascending

Articles related to Spastic Paralysis, Infantile-Onset Ascending:

# Title Authors Year
1
A novel homozygous mutation in ALS2 gene in four siblings with infantile-onset ascending hereditary spastic paralysis. ( 24704789 )
2014
2
Infantile-onset ascending hereditary spastic paralysis: a case report and brief literature review. ( 24144828 )
2014
3
Infantile-onset ascending hereditary spastic paralysis is associated with mutations in the alsin gene. ( 12145748 )
2002

Variations for Spastic Paralysis, Infantile-Onset Ascending

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

6
(show top 50) (show all 120)
# Gene Variation Type Significance SNP ID Assembly Location
1 ALS2 NM_020919.3(ALS2): c.3619delA (p.Met1207Terfs) deletion Pathogenic rs386134187 GRCh37 Chromosome 2, 202588058: 202588058
2 ALS2 NM_020919.3(ALS2): c.3619delA (p.Met1207Terfs) deletion Pathogenic rs386134187 GRCh38 Chromosome 2, 201723335: 201723335
3 ALS2 NM_020919.3(ALS2): c.1472_1481delTTTCCCCCAG single nucleotide variant Pathogenic rs387906316 GRCh37 Chromosome 2, 202619395: 202619395
4 ALS2 NM_020919.3(ALS2): c.1472_1481delTTTCCCCCAG single nucleotide variant Pathogenic rs387906316 GRCh38 Chromosome 2, 201754672: 201754672
5 ALS2 NM_020919.3(ALS2): c.2537_2538delAT (p.Asn846Ilefs) deletion Pathogenic rs386134183 GRCh37 Chromosome 2, 202598041: 202598042
6 ALS2 NM_020919.3(ALS2): c.2537_2538delAT (p.Asn846Ilefs) deletion Pathogenic rs386134183 GRCh38 Chromosome 2, 201733318: 201733319
7 ALS2 NM_020919.3(ALS2): c.1007_1008delTA (p.Ile336Thrfs) deletion Pathogenic rs386134175 GRCh37 Chromosome 2, 202625709: 202625710
8 ALS2 NM_020919.3(ALS2): c.1007_1008delTA (p.Ile336Thrfs) deletion Pathogenic rs386134175 GRCh38 Chromosome 2, 201760986: 201760987
9 ALS2 NM_020919.3(ALS2): c.4721delT (p.Val1574Alafs) deletion Pathogenic rs386134188 GRCh37 Chromosome 2, 202569294: 202569294
10 ALS2 NM_020919.3(ALS2): c.4721delT (p.Val1574Alafs) deletion Pathogenic rs386134188 GRCh38 Chromosome 2, 201704571: 201704571
11 ALS2 NM_020919.3(ALS2): c.2992C> T (p.Arg998Ter) single nucleotide variant Pathogenic rs121908137 GRCh37 Chromosome 2, 202591577: 202591577
12 ALS2 NM_020919.3(ALS2): c.2992C> T (p.Arg998Ter) single nucleotide variant Pathogenic rs121908137 GRCh38 Chromosome 2, 201726854: 201726854
13 ALS2 NM_020919.3(ALS2): c.470G> A (p.Cys157Tyr) single nucleotide variant Pathogenic rs121908138 GRCh37 Chromosome 2, 202626247: 202626247
14 ALS2 NM_020919.3(ALS2): c.470G> A (p.Cys157Tyr) single nucleotide variant Pathogenic rs121908138 GRCh38 Chromosome 2, 201761524: 201761524
15 ALS2 NM_020919.3(ALS2): c.2143C> T (p.Gln715Ter) single nucleotide variant Pathogenic rs121908139 GRCh37 Chromosome 2, 202609008: 202609008
16 ALS2 NM_020919.3(ALS2): c.2143C> T (p.Gln715Ter) single nucleotide variant Pathogenic rs121908139 GRCh38 Chromosome 2, 201744285: 201744285
17 ALS2 NM_020919.3(ALS2): c.1999-2A> T single nucleotide variant Pathogenic rs386134182 GRCh37 Chromosome 2, 202609154: 202609154
18 ALS2 NM_020919.3(ALS2): c.1999-2A> T single nucleotide variant Pathogenic rs386134182 GRCh38 Chromosome 2, 201744431: 201744431
19 ALS2 NM_020919.3(ALS2): c.2761C> T (p.Arg921Ter) single nucleotide variant Pathogenic/Likely pathogenic rs587777132 GRCh37 Chromosome 2, 202593315: 202593315
20 ALS2 NM_020919.3(ALS2): c.2761C> T (p.Arg921Ter) single nucleotide variant Pathogenic/Likely pathogenic rs587777132 GRCh38 Chromosome 2, 201728592: 201728592
21 ALS2 NM_020919.3(ALS2): c.3529G> T (p.Gly1177Ter) single nucleotide variant no interpretation for the single variant rs386134180 GRCh37 Chromosome 2, 202588148: 202588148
22 ALS2 NM_020919.3(ALS2): c.3529G> T (p.Gly1177Ter) single nucleotide variant no interpretation for the single variant rs386134180 GRCh38 Chromosome 2, 201723425: 201723425
23 ALS2 NM_020919.3(ALS2): c.3624+5G> C single nucleotide variant no interpretation for the single variant rs386134186 GRCh38 Chromosome 2, 201723325: 201723325
24 ALS2 NM_020919.3(ALS2): c.3624+5G> C single nucleotide variant no interpretation for the single variant rs386134186 GRCh37 Chromosome 2, 202588048: 202588048
25 ALS2 NM_020919.3(ALS2): c.4261C> T (p.Arg1421Ter) single nucleotide variant no interpretation for the single variant rs863225293 GRCh37 Chromosome 2, 202574623: 202574623
26 ALS2 NM_020919.3(ALS2): c.4261C> T (p.Arg1421Ter) single nucleotide variant no interpretation for the single variant rs863225293 GRCh38 Chromosome 2, 201709900: 201709900
27 ALS2 NM_020919.3(ALS2): c.1911C> A (p.Tyr637Ter) single nucleotide variant no interpretation for the single variant rs863225294 GRCh37 Chromosome 2, 202611376: 202611376
28 ALS2 NM_020919.3(ALS2): c.1911C> A (p.Tyr637Ter) single nucleotide variant no interpretation for the single variant rs863225294 GRCh38 Chromosome 2, 201746653: 201746653
29 ALS2 NM_020919.3(ALS2): c.3517G> A (p.Glu1173Lys) single nucleotide variant Benign rs41309046 GRCh37 Chromosome 2, 202588160: 202588160
30 ALS2 NM_020919.3(ALS2): c.3517G> A (p.Glu1173Lys) single nucleotide variant Benign rs41309046 GRCh38 Chromosome 2, 201723437: 201723437
31 ALS2 NM_020919.3(ALS2): c.4764G> A (p.Ala1588=) single nucleotide variant Benign rs35110478 GRCh38 Chromosome 2, 201704528: 201704528
32 ALS2 NM_020919.3(ALS2): c.4764G> A (p.Ala1588=) single nucleotide variant Benign rs35110478 GRCh37 Chromosome 2, 202569251: 202569251
33 ALS2 NM_020919.3(ALS2): c.4498G> A (p.Glu1500Lys) single nucleotide variant Uncertain significance rs780151065 GRCh37 Chromosome 2, 202571651: 202571651
34 ALS2 NM_020919.3(ALS2): c.4498G> A (p.Glu1500Lys) single nucleotide variant Uncertain significance rs780151065 GRCh38 Chromosome 2, 201706928: 201706928
35 ALS2 NM_020919.3(ALS2): c.2241C> T (p.Tyr747=) single nucleotide variant Conflicting interpretations of pathogenicity rs3219160 GRCh37 Chromosome 2, 202606507: 202606507
36 ALS2 NM_020919.3(ALS2): c.2241C> T (p.Tyr747=) single nucleotide variant Conflicting interpretations of pathogenicity rs3219160 GRCh38 Chromosome 2, 201741784: 201741784
37 ALS2 NM_020919.3(ALS2): c.1623C> T (p.His541=) single nucleotide variant Likely benign rs377247745 GRCh37 Chromosome 2, 202619243: 202619243
38 ALS2 NM_020919.3(ALS2): c.1623C> T (p.His541=) single nucleotide variant Likely benign rs377247745 GRCh38 Chromosome 2, 201754520: 201754520
39 ALS2 NM_020919.3(ALS2): c.1425_1428delAGAG (p.Gly477Alafs) deletion Pathogenic rs878855058 GRCh37 Chromosome 2, 202622168: 202622171
40 ALS2 NM_020919.3(ALS2): c.1425_1428delAGAG (p.Gly477Alafs) deletion Pathogenic rs878855058 GRCh38 Chromosome 2, 201757445: 201757448
41 ALS2 NM_020919.3(ALS2): c.1115C> G (p.Pro372Arg) single nucleotide variant Uncertain significance rs190369242 GRCh37 Chromosome 2, 202622481: 202622481
42 ALS2 NM_020919.3(ALS2): c.1115C> G (p.Pro372Arg) single nucleotide variant Uncertain significance rs190369242 GRCh38 Chromosome 2, 201757758: 201757758
43 ALS2 NM_020919.3(ALS2): c.475G> A (p.Glu159Lys) single nucleotide variant Benign/Likely benign rs3219155 GRCh38 Chromosome 2, 201761519: 201761519
44 ALS2 NM_020919.3(ALS2): c.475G> A (p.Glu159Lys) single nucleotide variant Benign/Likely benign rs3219155 GRCh37 Chromosome 2, 202626242: 202626242
45 ALS2 NM_020919.3(ALS2): c.3885G> A (p.Ala1295=) single nucleotide variant Benign/Likely benign rs34946105 GRCh37 Chromosome 2, 202580514: 202580514
46 ALS2 NM_020919.3(ALS2): c.3885G> A (p.Ala1295=) single nucleotide variant Benign/Likely benign rs34946105 GRCh38 Chromosome 2, 201715791: 201715791
47 ALS2 NM_020919.3(ALS2): c.1816-8C> T single nucleotide variant Conflicting interpretations of pathogenicity rs185911369 GRCh37 Chromosome 2, 202611479: 202611479
48 ALS2 NM_020919.3(ALS2): c.1816-8C> T single nucleotide variant Conflicting interpretations of pathogenicity rs185911369 GRCh38 Chromosome 2, 201746756: 201746756
49 ALS2 NM_020919.3(ALS2): c.280A> G (p.Ile94Val) single nucleotide variant Benign/Likely benign rs3219154 GRCh37 Chromosome 2, 202626437: 202626437
50 ALS2 NM_020919.3(ALS2): c.280A> G (p.Ile94Val) single nucleotide variant Benign/Likely benign rs3219154 GRCh38 Chromosome 2, 201761714: 201761714

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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