PLSA1
MCID: PRM092
MIFTS: 52

Primary Lateral Sclerosis, Adult, 1 (PLSA1)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Primary Lateral Sclerosis, Adult, 1

MalaCards integrated aliases for Primary Lateral Sclerosis, Adult, 1:

Name: Primary Lateral Sclerosis, Adult, 1 56 13 71
Primary Lateral Sclerosis 58 54
Adult-Onset Primary Lateral Sclerosis 58
Lateral Sclerosis 71
Pls, Adult; Plsa 56
Adult-Onset Pls 58
Pls, Adult 56
Plsa1 56
Plsa 56
Pls 58

Characteristics:

Orphanet epidemiological data:

58
primary lateral sclerosis
Inheritance: Autosomal recessive,Not applicable; Prevalence: 1-9/100000 (Europe); Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
average age at onset between 40 and 50 years


HPO:

31
primary lateral sclerosis, adult, 1:
Inheritance autosomal dominant inheritance
Onset and clinical course adult onset slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

OMIM 56 611637
ICD10 via Orphanet 33 G12.2
UMLS via Orphanet 72 C0154682 C1968845
Orphanet 58 ORPHA35689
MedGen 41 C1968845
UMLS 71 C0154682 C1968845

Summaries for Primary Lateral Sclerosis, Adult, 1

NINDS : 53 Primary lateral sclerosis (PLS) is a rare neuromuscular disease with slowly progressive weakness in voluntary muscle movement. PLS belongs to a group of disorders known as motor neuron diseases. PLS affects the upper motor neurons (also called corticospinal neurons) in the arms, legs, and face.  It occurs when nerve cells in the motor regions of the cerebral cortex (the thin layer of cells covering the brain which is responsible for most higher level mental functions) gradually degenerate, causing movements to be slow and effortful.  The disorder often affects the legs first, followed by the body, trunk, arms and hands, and, finally the bulbar muscles (muscles that control speech, swallowing, and chewing).  Symptoms include weakness, muscle stiffness and spasticity, clumsiness, slowing of movement, and problems with balance and speech. PLS is more common in men than in women, with a varied gradual onset that generally occurs between ages 40 and 60. PLS progresses gradually over a number of years, or even decades. Scientists do not believe PLS has a simple hereditary cause.  The diagnosis of PLS requires extensive testing to exclude other diseases. When symptoms begin, PLS may be mistaken for amyotrophic lateral sclerosis (ALS) or spastic paraplegia.  Most neurologists follow an affected individual's clinical course for at least 3 to 4 years before making a diagnosis of PLS.

MalaCards based summary : Primary Lateral Sclerosis, Adult, 1, also known as primary lateral sclerosis, is related to spastic paraparesis and hereditary spastic paraplegia, and has symptoms including upper motor neuron signs An important gene associated with Primary Lateral Sclerosis, Adult, 1 is SPG7 (SPG7 Matrix AAA Peptidase Subunit, Paraplegin), and among its related pathways/superpathways are Neuroscience and Copper homeostasis. The drugs Mexiletine and Minocycline have been mentioned in the context of this disorder. Affiliated tissues include brain, bone and testes, and related phenotypes are babinski sign and abnormal upper motor neuron morphology

OMIM : 56 Although primary lateral sclerosis (PLS) 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 were 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. See 606353 for autosomal recessive juvenile-onset PLS, which is caused by mutations in the ALS2 gene (606352). (611637)

Wikipedia : 74 Primary lateral sclerosis (PLS) is a rare neuromuscular disease characterized by progressive muscle... more...

Related Diseases for Primary Lateral Sclerosis, Adult, 1

Diseases in the Lateral Sclerosis family:

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

Diseases related to Primary Lateral Sclerosis, Adult, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 313)
# Related Disease Score Top Affiliating Genes
1 spastic paraparesis 30.4 SPG7 SPAST
2 hereditary spastic paraplegia 30.0 SPG7 SPAST ALS2
3 spasticity 29.9 SPG7 SPAST
4 spastic paraplegia 4, autosomal dominant 29.5 SPG7 SPAST ALS2
5 frontotemporal dementia 29.3 SOD1 SNCA MAPT
6 supranuclear palsy, progressive, 1 29.2 SOD1 SNCA MAPT
7 aphasia 29.1 SNCA MAPT
8 tremor 29.1 SNCA MAPT
9 frontotemporal dementia and/or amyotrophic lateral sclerosis 1 28.9 SOD1 MAPT ALS2
10 amyotrophic lateral sclerosis 1 28.6 SPAST SOD1 SNCA MAPT ALS2
11 aceruloplasminemia 28.5 SOD1 SNCA MAPT
12 dementia 28.5 SPAST SOD1 SNCA MAPT
13 motor neuron disease 27.8 SPAST SOD1 SNCA MAPT ARHGEF2 ALS2
14 papillon-lefevre syndrome 12.4
15 platelet groups--pl system 12.2
16 lateral sclerosis 12.2
17 primary lateral sclerosis, juvenile 12.1
18 pityriasis lichenoides 11.5
19 pleomorphic liposarcoma 11.5
20 enthesopathy 11.5
21 pancreatic lipase deficiency 11.3
22 haim-munk syndrome 11.3
23 spinal muscular atrophy, type iii 11.2
24 spinal muscular atrophy, type iv 11.2
25 infantile-onset ascending hereditary spastic paralysis 11.2
26 proximal spinal muscular atrophy 11.2
27 potocki-lupski syndrome 11.2
28 xanthomatosis 11.2
29 skin tag 11.2
30 proteus-like syndrome 11.2
31 allergic encephalomyelitis 10.4
32 ischemia 10.3
33 attention deficit-hyperactivity disorder 10.2
34 polydactyly 10.2
35 cardiogenic shock 10.2
36 spastic paraplegia 64, autosomal recessive 10.2 SPG7 ALS2
37 coronary thrombosis 10.2
38 spastic paraplegia 5a, autosomal recessive 10.2 SPG7 SPAST
39 spastic paraplegia 31, autosomal dominant 10.2 SPG7 SPAST
40 pseudobulbar affect 10.2
41 spastic paraplegia 13, autosomal dominant 10.2 SPG7 SPAST
42 spastic paraplegia 15, autosomal recessive 10.2 SPG7 SPAST
43 spastic paraplegia 7, autosomal recessive 10.2
44 ornithosis 10.1
45 spastic paraplegia 10, autosomal dominant 10.1 SPG7 SPAST
46 spastic paraplegia 2, x-linked 10.1 SPG7 SPAST
47 spastic paraplegia 20, autosomal recessive 10.1 SPG7 SPAST
48 pseudobulbar palsy 10.1
49 progressive bulbar palsy 10.1 SOD1 ALS2
50 amyotrophic lateral sclerosis 19 10.1 SOD1 ALS2

Comorbidity relations with Primary Lateral Sclerosis, Adult, 1 via Phenotypic Disease Network (PDN):


Acute Cystitis Intermittent Claudication

Graphical network of the top 20 diseases related to Primary Lateral Sclerosis, Adult, 1:



Diseases related to Primary Lateral Sclerosis, Adult, 1

Symptoms & Phenotypes for Primary Lateral Sclerosis, Adult, 1

Human phenotypes related to Primary Lateral Sclerosis, Adult, 1:

58 31 (show all 20)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 babinski sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0003487
2 abnormal upper motor neuron morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0002127
3 generalized hyperreflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0007034
4 dysphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002015
5 spastic gait 58 31 frequent (33%) Frequent (79-30%) HP:0002064
6 progressive spastic paraparesis 58 31 frequent (33%) Frequent (79-30%) HP:0007199
7 loss of speech 58 31 frequent (33%) Frequent (79-30%) HP:0002371
8 pseudobulbar signs 58 31 frequent (33%) Frequent (79-30%) HP:0002200
9 spastic dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0002464
10 emg: chronic denervation signs 58 31 frequent (33%) Frequent (79-30%) HP:0003444
11 motor axonal neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0007002
12 cervical spinal cord atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0010873
13 spasticity 58 Very frequent (99-80%)
14 hyperreflexia 31 HP:0001347
15 spastic tetraparesis 31 HP:0001285
16 sensory impairment 58 Excluded (0%)
17 upper motor neuron dysfunction 58 Very frequent (99-80%)
18 atrophy of the spinal cord 58 Occasional (29-5%)
19 abnormal lower motor neuron morphology 58 Excluded (0%)
20 weakness due to upper motor neuron dysfunction 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
hyperreflexia
spastic gait
spastic tetraparesis
spastic dysarthria
upper motor neuron signs
more
Neurologic Peripheral Nervous System:
no sensory abnormalities

Abdomen Gastrointestinal:
dysphagia

Clinical features from OMIM:

611637

UMLS symptoms related to Primary Lateral Sclerosis, Adult, 1:


upper motor neuron signs

MGI Mouse Phenotypes related to Primary Lateral Sclerosis, Adult, 1:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 9.17 ALS2 ARHGEF2 MAPT SNCA SOD1 SPAST

Drugs & Therapeutics for Primary Lateral Sclerosis, Adult, 1

Drugs for Primary Lateral Sclerosis, Adult, 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 364)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Mexiletine Approved, Investigational Phase 4 31828-71-4 4178
2
Minocycline Approved, Investigational Phase 4 10118-90-8 5281021
3
Modafinil Approved, Investigational Phase 4 68693-11-8 4236
4 Anti-Inflammatory Agents Phase 4
5 Central Nervous System Stimulants Phase 4
6 Cytochrome P-450 CYP3A Inducers Phase 4
7 Nootropic Agents Phase 4
8 Hormone Antagonists Phase 4
9 Hormones Phase 4
10 Thyrotropin-Releasing Hormone Phase 4
11 TA 0910 Phase 4
12
Olanzapine Approved, Investigational Phase 2, Phase 3 132539