PLSJ
MCID: PRM195
MIFTS: 35

Primary Lateral Sclerosis, Juvenile (PLSJ)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Primary Lateral Sclerosis, Juvenile

MalaCards integrated aliases for Primary Lateral Sclerosis, Juvenile:

Name: Primary Lateral Sclerosis, Juvenile 57 53 25 13
Juvenile Primary Lateral Sclerosis 75 53 25 59 74 37 29 6
Jpls 53 25 59 74
Juvenile Pls 25 59
Plsj 57 25
Sclerosis, Lateral, Juvenile Primary 40
Primary Lateral Sclerosis Juvenile 72
Pls, Juvenile 57
Pls Juvenile 53

Characteristics:

Orphanet epidemiological data:

59
juvenile primary lateral sclerosis
Inheritance: Autosomal recessive; Age of onset: Childhood; Age of death: any age;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
slowly progressive
onset in early childhood
allelic disorder to infantile-onset ascending spastic paralysis (iahsp, )
allelic disorder to juvenile amyotrophic lateral sclerosis 2 (als2, )


HPO:

32
primary lateral sclerosis, juvenile:
Inheritance autosomal recessive inheritance
Onset and clinical course juvenile onset slow progression childhood onset


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 606353
KEGG 37 H00970
MeSH 44 D016472
MESH via Orphanet 45 C536416
ICD10 via Orphanet 34 G12.2
UMLS via Orphanet 73 C1853396
Orphanet 59 ORPHA247604
MedGen 42 C1853396
UMLS 72 C1853396

Summaries for Primary Lateral Sclerosis, Juvenile

Genetics Home Reference : 25 Juvenile primary lateral sclerosis is a rare disorder characterized by progressive weakness and tightness (spasticity) of muscles in the arms, legs, and face. The features of this disorder are caused by damage to motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement. Symptoms of juvenile primary lateral sclerosis begin in early childhood and progress slowly over many years. Early symptoms include clumsiness, muscle weakness and spasticity in the legs, and difficulty with balance. As symptoms progress, the spasticity spreads to the arms and hands and individuals develop slurred speech, drooling, difficulty swallowing, and an inability to walk.

MalaCards based summary : Primary Lateral Sclerosis, Juvenile, also known as juvenile primary lateral sclerosis, is related to hereditary spastic paraplegia and infantile-onset ascending hereditary spastic paralysis, and has symptoms including upper motor neuron signs An important gene associated with Primary Lateral Sclerosis, Juvenile is ALS2 (Alsin Rho Guanine Nucleotide Exchange Factor ALS2). Affiliated tissues include brain, spinal cord and tongue, and related phenotypes are muscle weakness and hyperreflexia

NIH Rare Diseases : 53 Juvenile primary lateral sclerosis is a rare disorder characterized by progressive weakness and stiffness of muscles in the arms, legs, and face. This disorder damages motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement. Symptoms begin in early childhood and progress over a period of 15 to 20 years. Juvenile primary lateral sclerosis is caused by mutations in the ALS2 gene. It is inherited in an autosomal recessive pattern.

OMIM : 57 Although primary lateral sclerosis is similar to amyotrophic lateral sclerosis (ALS; 105400), they are considered to be clinically distinct progressive paralytic neurodegenerative disorders. Following a period of diagnostic confusion, the clinical distinction between ALS and PLS became clear and diagnostic criteria established (Pringle et al., 1992). PLS is characterized by degeneration of the upper motor neurons and the corticospinal and corticobulbar tracts, whereas ALS is a more severe disorder characterized by degeneration of both the upper and lower motor neurons. A diagnosis of PLS is essentially one of exclusion (Sotaniemi and Myllyla, 1985; Younger et al., 1988; Yang et al., 2001). (606353)

KEGG : 37
Juvenile primary lateral sclerosis is a very rare progressive paralytic disorder characterized by increasing weakness and stiffness of muscles in the arms, legs and face. Although primary lateral sclerosis (PLS) is a sporadic disorder of adult middle age, this disease is also observed in children as JSPS. JSPS arises from dysfunction of the upper motoneurons and the causative gene is ALS2.

UniProtKB/Swiss-Prot : 74 Juvenile primary lateral sclerosis: A neurodegenerative disorder which is closely related to but clinically distinct from amyotrophic lateral sclerosis. It is a progressive paralytic disorder which results from dysfunction of the upper motor neurons while the lower neurons are unaffected.

Wikipedia : 75 Juvenile primary lateral sclerosis , also known as primary lateral sclerosis (PLSJ), is a rare genetic... more...

Related Diseases for Primary Lateral Sclerosis, Juvenile

Diseases in the Lateral Sclerosis family:

Primary Lateral Sclerosis, Juvenile Primary Lateral Sclerosis, Adult, 1

Diseases related to Primary Lateral Sclerosis, Juvenile via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 16)
# Related Disease Score Top Affiliating Genes
1 hereditary spastic paraplegia 28.7 ERLIN2 ALS2
2 infantile-onset ascending hereditary spastic paralysis 11.4
3 triiodothyronine receptor auxiliary protein 10.1
4 spastic paralysis, infantile-onset ascending 10.1
5 brain cancer 10.1
6 glioblastoma multiforme 10.1
7 paraplegia 10.1
8 glioblastoma 10.1
9 dysphagia 10.1
10 spasticity 10.1
11 amyotrophic lateral sclerosis 1 9.9
12 spastic paraplegia 18, autosomal recessive 9.9
13 primary lateral sclerosis, adult, 1 9.9
14 lateral sclerosis 9.9
15 als2-related disorders 9.9
16 juvenile amyotrophic lateral sclerosis 9.9

Graphical network of the top 20 diseases related to Primary Lateral Sclerosis, Juvenile:



Diseases related to Primary Lateral Sclerosis, Juvenile

Symptoms & Phenotypes for Primary Lateral Sclerosis, Juvenile

Human phenotypes related to Primary Lateral Sclerosis, Juvenile:

59 32 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 muscle weakness 59 32 hallmark (90%) Very frequent (99-80%) HP:0001324
2 hyperreflexia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001347
3 abnormal pyramidal sign 59 32 hallmark (90%) Very frequent (99-80%) HP:0007256
4 gait imbalance 59 32 hallmark (90%) Very frequent (99-80%) HP:0002141
5 spastic gait 59 32 hallmark (90%) Very frequent (99-80%) HP:0002064
6 spastic tetraparesis 59 32 hallmark (90%) Very frequent (99-80%) HP:0001285
7 abnormal upper motor neuron morphology 59 32 hallmark (90%) Very frequent (99-80%) HP:0002127
8 pseudobulbar behavioral symptoms 59 32 hallmark (90%) Very frequent (99-80%) HP:0002193
9 dysphagia 59 32 frequent (33%) Frequent (79-30%) HP:0002015
10 loss of speech 59 32 frequent (33%) Frequent (79-30%) HP:0002371
11 spastic dysarthria 59 32 frequent (33%) Frequent (79-30%) HP:0002464
12 skeletal muscle atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0003202
13 sensory neuropathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0000763
14 abnormality of the bladder 59 32 occasional (7.5%) Occasional (29-5%) HP:0000014
15 spasticity 59 Very frequent (99-80%)
16 pallor 32 HP:0000980
17 babinski sign 32 HP:0003487
18 cerebral cortical atrophy 32 HP:0002120
19 saccadic smooth pursuit 32 HP:0001152
20 difficulty in tongue movements 32 HP:0000183
21 spasticity of facial muscles 32 HP:0002491
22 spasticity of pharyngeal muscles 32 HP:0002501

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
hyperreflexia
spastic gait
spastic tetraparesis
spastic dysarthria
upper motor neuron signs
more
Head And Neck Eyes:
saccadic smooth pursuit

Head And Neck Face:
spasticity of the facial muscles

Abdomen Gastrointestinal:
dysphagia

Head And Neck Mouth:
difficulty in tongue movements

Neurologic Peripheral Nervous System:
no sensory abnormalities

Clinical features from OMIM:

606353

UMLS symptoms related to Primary Lateral Sclerosis, Juvenile:


upper motor neuron signs

Drugs & Therapeutics for Primary Lateral Sclerosis, Juvenile

Search Clinical Trials , NIH Clinical Center for Primary Lateral Sclerosis, Juvenile

Genetic Tests for Primary Lateral Sclerosis, Juvenile

Genetic tests related to Primary Lateral Sclerosis, Juvenile:

# Genetic test Affiliating Genes
1 Juvenile Primary Lateral Sclerosis 29 ALS2

Anatomical Context for Primary Lateral Sclerosis, Juvenile

MalaCards organs/tissues related to Primary Lateral Sclerosis, Juvenile:

41
Brain, Spinal Cord, Tongue, Skeletal Muscle, Cortex

Publications for Primary Lateral Sclerosis, Juvenile

Articles related to Primary Lateral Sclerosis, Juvenile:

(show all 24)
# Title Authors PMID Year
1
A novel ALS2 splice-site mutation in a Cypriot juvenile-onset primary lateral sclerosis family. 8 71
19122027 2009
2
Genetic inroads in familial ALS. 8 71
11586285 2001
3
The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. 8 71
11586297 2001
4
A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. 8 71
11586298 2001
5
Infantile onset of hereditary ascending spastic paralysis with bulbar involvement. 8 71
8745388 1996
6
ALS2-Related Disorders 38 71
20301421 2005
7
Familial childhood primary lateral sclerosis with associated gaze paresis. 8
8719747 1995
8
Primary lateral sclerosis. Clinical features, neuropathology and diagnostic criteria. 8
1606479 1992
9
Primary lateral sclerosis in a child. 8
2812336 1989
10
Primary lateral sclerosis. A clinical diagnosis reemerges. 8
3196189 1988
11
Primary lateral sclerosis; a debated entity. 8
4003039 1985
12
Clinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an ALS2 founder variant. 38
30128655 2018
13
Absence of alsin function leads to corticospinal motor neuron vulnerability via novel disease mechanisms. 38
26755825 2016
14
Identification of two novel ALS2 mutations in infantile-onset ascending hereditary spastic paraplegia. 38
26751646 2016
15
Infantile-onset ascending hereditary spastic paraplegia with bulbar involvement due to the novel ALS2 mutation c.2761C>T. 38
24315819 2014
16
Alsin related disorders: literature review and case study with novel mutations. 38
25302125 2014
17
Are alsin and spartin novel interaction partners? 38
22982304 2012
18
Loss of ERLIN2 function leads to juvenile primary lateral sclerosis. 38
23109145 2012
19
Novel FUS deletion in a patient with juvenile amyotrophic lateral sclerosis. 38
22248478 2012
20
Alfa-class prefoldin protein UXT is a novel interacting partner of Amyotrophic Lateral Sclerosis 2 (Als2) protein. 38
21907703 2011
21
Distal axonopathy in an alsin-deficient mouse model. 38
17855450 2007
22
Molecular and cellular function of ALS2/alsin: implication of membrane dynamics in neuronal development and degeneration. 38
17566607 2007
23
Alsin is partially associated with centrosome in human cells. 38
16085057 2005
24
[Recessive motor neuron diseases: mutations in the ALS2 gene and molecular pathogenesis for the upper motor neurodegeneration]. 38
15651293 2004

Variations for Primary Lateral Sclerosis, Juvenile

ClinVar genetic disease variations for Primary Lateral Sclerosis, Juvenile:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 ALS2 NM_020919.4(ALS2): c.1233T> G (p.Tyr411Ter) single nucleotide variant Pathogenic rs369577952 2:202622363-202622363 2:201757640-201757640
2 ALS2 NM_020919.4(ALS2): c.1867_1868del (p.Leu623fs) deletion Pathogenic rs386134181 2:202611419-202611420 2:201746696-201746697
3 ALS2 NM_020919.4(ALS2): c.1425_1426AG[1] (p.Glu476fs) short repeat Pathogenic rs386134176 2:202622170-202622171 2:201757447-201757448
4 ALS2 NM_020919.4(ALS2): c.2980-2A> G single nucleotide variant Pathogenic rs386134184 2:202591591-202591591 2:201726868-201726868
5 ALS2 NM_020919.4(ALS2): c.1619G> A (p.Gly540Glu) single nucleotide variant Pathogenic rs386134178 2:202619247-202619247 2:201754524-201754524
6 ALS2 NM_020919.4(ALS2): c.1115C> G (p.Pro372Arg) single nucleotide variant Uncertain significance rs190369242 2:202622481-202622481 2:201757758-201757758
7 ALS2 NM_020919.4(ALS2): c.3134A> T (p.Lys1045Met) single nucleotide variant Uncertain significance 2:202591435-202591435 2:201726712-201726712

Expression for Primary Lateral Sclerosis, Juvenile

Search GEO for disease gene expression data for Primary Lateral Sclerosis, Juvenile.

Pathways for Primary Lateral Sclerosis, Juvenile

GO Terms for Primary Lateral Sclerosis, Juvenile

Cellular components related to Primary Lateral Sclerosis, Juvenile according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein-containing complex GO:0032991 8.62 ERLIN2 ALS2

Sources for Primary Lateral Sclerosis, Juvenile

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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