SMA
MCID: PRX014
MIFTS: 46

Proximal Spinal Muscular Atrophy (SMA)

Categories: Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Proximal Spinal Muscular Atrophy

MalaCards integrated aliases for Proximal Spinal Muscular Atrophy:

Name: Proximal Spinal Muscular Atrophy 53 59 6 73
Sma 53 59

Characteristics:

Orphanet epidemiological data:

59
proximal spinal muscular atrophy
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Europe); Age of onset: All ages; Age of death: any age;

Classifications:

Orphanet: 59  
Rare neurological diseases


Summaries for Proximal Spinal Muscular Atrophy

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 70Disease definitionProximal spinal muscular atrophies are a group of neuromuscular disorders characterized by progressive muscle weakness resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei.EpidemiologyPrevalence is estimated at around 1/30,000.Clinical descriptionFour subtypes have been defined according to the age of onset and severity of the disease: type 1 (SMA1), the most severe form, with onset before six months of age; type 2 (SMA2), with onset between 6 and 18 months of age, type 3 (SMA3), with onset between childhood and adolescence, and type 4 (SMA4), the least severe form, with adult onset (see these terms). All types are characterized by muscle weakness and atrophy of varying severity, particularly affecting the lower limbs and respiratory muscles. The weakness is almost always symmetric and progressive. Scoliosis, muscle retractions, and joint contractures may occur. Constipation and gastroesophageal reflux are frequent.EtiologyAround 95% of cases of SMA are caused by homozygousdeletions (either of exon 7, or of exons 7 and 8) in the SMN1 gene (5q12.2-q13.3) encoding the SMN (survival motor neuron) protein. A second SMN gene (SMN2; 5q13.2) has also been identified and contributes to the production of only 10% of the full-length SMN protein. However, although there is some variation, disease severity in SMA is inversely correlated with the number of copies of the SMN2 gene, with patients with three or four copies more frequently manifesting SMA3/4, rather than SMA1. Deletions of the NAIP (5q13.1) gene have also been identified and may play a role in modifying disease severity.Diagnostic methodsDiagnosis is based on clinical history and examination and can be confirmed by genetic testing. Electromyography and muscle biopsy may also be performed.Differential diagnosisDifferential diagnoses include amyotrophic lateral sclerosis, congenital muscular dystrophies, congenital myopathies, primary lateral sclerosis, myasthenia gravis, and carbohydrate metabolism disorders (see these terms).Antenatal diagnosisAntenatal diagnosis is feasible through molecular analysis of amniocytes or chorionic villus samples.Genetic counselingTransmission of SMN1 and NAIP deletions is autosomal recessive. Around 2% of cases are caused by de novo mutations. Genetic counseling should be offered to patients and their families.Management and treatmentClinical trials are ongoing to identify potential drug treatments for SMA, mainly targeted towards increasing the levels of the full length SMN protein. However, at present, management remains symptomatic, involving a multidisciplinary approach that aims to improve quality of life. Physiotherapy and occupational and respiratory therapies are necessary. Noninvasive ventilation and gastrostomy may be required. Antibiotic therapy is used in case of pulmonary infection. The scoliosis and joint manifestations may require surgical correction. Patients may require a wheelchair, or use a corset/back brace for support.PrognosisThe prognosis depends on the severity of the disease, which generally correlates with the age of onset: earlier-onset forms are generally associated with a poor prognosis, whereas life expectancy may be close to normal in later-onset forms. Death may occur due to respiratory insufficiency and infections.Visit the Orphanet disease page for more resources.

MalaCards based summary : Proximal Spinal Muscular Atrophy, also known as sma, is related to spinal muscular atrophy, type ii and spinal muscular atrophy, type i. An important gene associated with Proximal Spinal Muscular Atrophy is SPG7 (SPG7, Paraplegin Matrix AAA Peptidase Subunit), and among its related pathways/superpathways are Cytoskeletal Signaling and COPI-independent Golgi-to-ER retrograde traffic. The drugs Neurotransmitter Agents and Cholinergic Agents have been mentioned in the context of this disorder. Affiliated tissues include testes, brain and spinal cord, and related phenotypes are muscular hypotonia and joint stiffness

Related Diseases for Proximal Spinal Muscular Atrophy

Diseases related to Proximal Spinal Muscular Atrophy via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 147)
# Related Disease Score Top Affiliating Genes
1 spinal muscular atrophy, type ii 32.6 NAIP SMN1 SMN2
2 spinal muscular atrophy, type i 32.5 NAIP SMN1 SMN2
3 spinal muscular atrophy, type iv 32.4 SMN1 SMN2
4 spinal muscular atrophy, type iii 32.1 NAIP SMN1 SMN2
5 juvenile spinal muscular atrophy 31.8 NAIP SMN1 SMN2
6 spinal muscular atrophy 31.0 BICD2 NAIP SMN1 SMN2 SMNDC1
7 muscular atrophy 31.0 BICD2 NAIP SMN1 SMN2 SMNDC1
8 motor neuron disease 29.9 NAIP SETX SMN1 SMN2
9 anterior horn cell disease 29.8 SMN1 SMN2
10 amyotrophic lateral sclerosis 1 29.7 NAIP SETX SMN1 SMN2
11 neuromuscular disease 29.4 DES LMNA NAIP SMN1 SMN2
12 autosomal dominant childhood-onset proximal spinal muscular atrophy 12.4
13 spinal muscular atrophy, late-onset, finkel type 12.1
14 spinal muscular atrophy, x-linked 2 11.9
15 spinal muscular atrophy, lower extremity-predominant, 1, autosomal dominant 11.8
16 spinal muscular atrophy with progressive myoclonic epilepsy 11.7
17 spinal muscular atrophy, lower extremity-predominant, 2, autosomal dominant 11.7
18 spinal muscular atrophy with lower extremity predominance 11.5
19 superior mesenteric artery syndrome 11.4
20 renal nutcracker syndrome 11.2
21 adult progressive spinal muscular atrophy aran duchenne type 11.0
22 spinal muscular atrophy, distal, autosomal recessive, 3 11.0
23 pontocerebellar hypoplasia, type 1a 11.0
24 spinal muscular atrophy, distal, autosomal recessive, 5 11.0
25 arthrogryposis multiplex congenita, neurogenic type 10.2 SMN1 SMN2
26 culler-jones syndrome 10.2 SMN1 SMN2
27 spinal muscular atrophy, distal, autosomal recessive, 1 10.2 SMN1 SMN2
28 spinal disease 10.2 SMN1 SMN2
29 spindle cell thymoma 10.2 DES MUC1
30 progressive muscular atrophy 10.2 SMN1 SMN2
31 parachordoma 10.2 DES MUC1
32 syringocystadenoma papilliferum 10.2 DES MUC1
33 ossifying fibromyxoid tumor 10.2 DES MUC1
34 spindle cell rhabdomyosarcoma 10.2 DES MUC1
35 biphasic synovial sarcoma 10.2 DES MUC1
36 syringoma 10.2 DES MUC1
37 scoliosis 10.2
38 pleomorphic liposarcoma 10.1 DES MUC1
39 desmoplastic small round cell tumor 10.1 DES MUC1
40 perivascular epithelioid cell tumor 10.1 DES MUC1
41 ischemic fasciitis 10.1 DES MUC1
42 fasciitis 10.1 DES MUC1
43 reticulum cell sarcoma 10.1 DES MUC1
44 mesenchymal chondrosarcoma 10.1 DES MUC1
45 extraskeletal ewing sarcoma 10.1 DES MUC1
46 plasmablastic lymphoma 10.1 DES MUC1
47 spindle cell sarcoma 10.1 DES MUC1
48 hemangiopericytoma, malignant 10.1 DES MUC1
49 epilepsy 10.1
50 nervous system disease 10.1 APOE SMN1 SMN2

Graphical network of the top 20 diseases related to Proximal Spinal Muscular Atrophy:



Diseases related to Proximal Spinal Muscular Atrophy

Symptoms & Phenotypes for Proximal Spinal Muscular Atrophy

Human phenotypes related to Proximal Spinal Muscular Atrophy:

59 32 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001252
2 joint stiffness 59 32 frequent (33%) Frequent (79-30%) HP:0001387
3 emg abnormality 59 32 hallmark (90%) Very frequent (99-80%) HP:0003457
4 hemiplegia/hemiparesis 59 32 hallmark (90%) Very frequent (99-80%) HP:0004374
5 lymphedema 59 32 frequent (33%) Frequent (79-30%) HP:0001004
6 intrauterine growth retardation 59 32 frequent (33%) Frequent (79-30%) HP:0001511
7 reduced tendon reflexes 59 32 hallmark (90%) Very frequent (99-80%) HP:0001315
8 proximal lower limb amyotrophy 59 32 hallmark (90%) Very frequent (99-80%) HP:0008956
9 abnormality of the voice 59 32 frequent (33%) Frequent (79-30%) HP:0001608
10 polyhydramnios 59 32 frequent (33%) Frequent (79-30%) HP:0001561
11 abnormality of the ribs 59 32 frequent (33%) Frequent (79-30%) HP:0000772
12 recurrent fractures 59 32 frequent (33%) Frequent (79-30%) HP:0002757
13 preauricular skin tag 59 32 frequent (33%) Frequent (79-30%) HP:0000384
14 abnormality of movement 59 Very frequent (99-80%)
15 proximal amyotrophy 59 Very frequent (99-80%)

Drugs & Therapeutics for Proximal Spinal Muscular Atrophy

Drugs for Proximal Spinal Muscular Atrophy (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Neurotransmitter Agents Phase 2
2 Cholinergic Agents Phase 2
3 Pyridostigmine Bromide Phase 2 101-26-8
4 Cholinesterase Inhibitors Phase 2
5 Bromides Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 SPACE Trial: Pyridostigmine vs Placebo in SMA Types 2, 3 and 4 Completed NCT02941328 Phase 2 Pyridostigmine;Placebo

Search NIH Clinical Center for Proximal Spinal Muscular Atrophy

Genetic Tests for Proximal Spinal Muscular Atrophy

Anatomical Context for Proximal Spinal Muscular Atrophy

MalaCards organs/tissues related to Proximal Spinal Muscular Atrophy:

41
Testes, Brain, Spinal Cord, Liver, Smooth Muscle, Skin, Cortex

Publications for Proximal Spinal Muscular Atrophy

Articles related to Proximal Spinal Muscular Atrophy:

(show top 50) (show all 695)
# Title Authors Year
1
Impact of styrene maleic anhydride (SMA) based hydrogel on rat fallopian tube as contraceptive implant with selective antimicrobial property. ( 30423783 )
2019
2
The use of styrene-maleic acid copolymer (SMA) for studies on T cell membrane rafts. ( 30463696 )
2019
3
A new case of SMA phenotype without epilepsy due to biallelic variants in ASAH1. ( 30291339 )
2018
4
Multi-Study Proteomic and Bioinformatic Identification of Molecular Overlap between Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA). ( 30518112 )
2018
5
Discovery of small molecule splicing modulators of survival motor neuron-2 (SMN2) for the treatment of Spinal Muscular Atrophy (SMA). ( 30407821 )
2018
6
Changing respiratory expectations with the new disease trajectory of nusinersen treated spinal muscular atrophy [SMA] type 1. ( 30414815 )
2018
7
Impact of missense mutations in survival motor neuron protein (SMN1) leading to Spinal Muscular Atrophy (SMA): A computational approach. ( 30006696 )
2018
8
Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 ( SMN2) Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy (SMA). ( 30044619 )
2018
9
Prospective and longitudinal natural history study of patients with Type 2 and 3 spinal muscular atrophy: Baseline data NatHis-SMA study. ( 30048507 )
2018
10
Patient Reported Impact of Symptoms in Spinal Muscular Atrophy (PRISM-SMA). ( 30143566 )
2018
11
Ki67, CD105, and α-SMA expression supports the transformation relevant dysplastic features in the atrophic epithelium of oral submucous fibrosis. ( 30001387 )
2018
12
Mechanism research of Bu-Shen-Huo-Xue formula against renal fibrosis in rats with 5/6 nephrectomy via E-cadherin, α-SMA, and TGF-β1
. ( 29750635 )
2018
13
Acid ceramidase deficiency: Farber disease and SMA-PME. ( 30029679 )
2018
14
Posterior Superior Mesenteric Artery (SMA) First Approach vs. Standard Pancreaticoduodenectomy in Patients with Resectable Periampullary Cancers: a Prospective Comparison Focusing on Circumferential Resection Margins. ( 28315190 )
2018
15
The Actin Cytoskeleton in SMA and ALS: How Does It Contribute to Motoneuron Degeneration? ( 28459188 )
2018
16
SMA-like syndrome with variant mesenteric venous anatomy. ( 29055874 )
2018
17
The modulatory role of pre-SMA in speed-accuracy tradeoff: A bi-directional TMS study. ( 29274342 )
2018
18
Influence of Embedding SMA Fibres and SMA Fibre Surface Modification on the Mechanical Performance of BFRP Composite Laminates. ( 29300321 )
2018
19
Investigation on the Mechanical Properties of SMA/GF/Epoxy Hybrid Composite Laminates: Flexural, Impact, and Interfacial Shear Performance. ( 29415451 )
2018
20
Correlation between SMA type and SMN2 copy number revisited: An analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases. ( 29433793 )
2018
21
Electrical/Mechanical Monitoring of Shape Memory Alloy Reinforcing Fibers Obtained by Pullout Tests in SMA/Cement Composite Materials. ( 29470413 )
2018
22
Achieving a tunable metasurface based on a structurally reconfigurable array using SMA. ( 29475281 )
2018
23
Update on Standard Operating Procedures in Preclinical Research for DMD and SMA Report of TREAT-NMD Alliance Workshop, Schiphol Airport, 26 April 2015, The Netherlands. ( 29480217 )
2018
24
Phenotypic and genotypic studies of ALS cases in ALS-SMA families. ( 29493298 )
2018
25
Role of Coulombic Repulsion in Collisional Lipid Transfer Among SMA(2:1)-Bounded Nanodiscs. ( 29508005 )
2018
26
Neural basis for categorical boundaries in the primate pre-SMA during relative categorization of time intervals. ( 29545587 )
2018
27
Nusinersen for SMA: expanded access programme. ( 29549190 )
2018
28
The heterogenic tumor microenvironment of hepatocellular carcinoma and prognostic analysis based on tumor neo-vessels, macrophages and α-SMA. ( 29552120 )
2018
29
Purification of membrane proteins free from conventional detergents: SMA, new polymers, new opportunities and new insights. ( 29608964 )
2018
30
Critical period of neuromuscular development: Importance for a new treatment of SMA. ( 29610000 )
2018
31
An overview of the Cure SMA membership database: Highlights of key demographic and clinical characteristics of SMA members. ( 29614694 )
2018
32
Curcumin accelerates cutaneous wound healing via multiple biological actions: The involvement of TNF-α, MMP-9, α-SMA, and collagen. ( 29659146 )
2018
33
Evaluation of Children with SMA Type 1 Under Treatment with Nusinersen within the Expanded Access Program in Germany. ( 29689734 )
2018
34
Publisher Correction: Functional interaction between FUS and SMN underlies SMA-like splicing changes in wild-type hFUS mice. ( 29712963 )
2018
35
Shape Memory Alloy (SMA)-Based Microscale Actuators with 60% Deformation Rate and 1.6 kHz Actuation Speed. ( 29717811 )
2018
36
N-SmA-SmC phase transitions probed by a pair of elastically bound colloids. ( 29776110 )
2018
37
Evaluation of Exon Inclusion Induced by Splice Switching Antisense Oligonucleotides in SMA Patient Fibroblasts. ( 29806836 )
2018
38
Activation of TGF-β1/α-SMA/Col I Profibrotic Pathway in Fibroblasts by Galectin-3 Contributes to Atrial Fibrosis in Experimental Models and Patients. ( 29807358 )
2018
39
Evaluator Training and Reliability for SMA Global Nusinersen Trials1. ( 29865090 )
2018
40
Interactome analyses revealed that the U1 snRNP machinery overlaps extensively with the RNAP II machinery and contains multiple ALS/SMA-causative proteins. ( 29884807 )
2018
41
Accumulation of poly(A) RNA in nuclear granules enriched in Sam68 in motor neurons from the SMNΔ7 mouse model of SMA. ( 29941967 )
2018
42
Nusinersen in type 1 SMA infants, children and young adults: Preliminary results on motor function. ( 29960818 )
2018
43
Compositional, ultrastructural and nanotechnological characterization of the SMA strain of Saccharomyces pastorianus: Towards a more complete fermentation yeast cell analysis. ( 29995965 )
2018
44
Intrathecal administration of Nusinersen in type 1 SMA: successful psychological program in a single Italian center. ( 30043247 )
2018
45
Precious SMA natural history data: A benchmark to measure future treatment successes. ( 30045956 )
2018
46
An observational study of functional abilities in infants, children, and adults with type 1 SMA. ( 30045959 )
2018
47
A High-Level Control Algorithm Based on sEMG Signalling for an Elbow Joint SMA Exoskeleton. ( 30072609 )
2018
48
Recruitment & retention program for the NeuroNEXT SMA Biomarker Study: Super Babies for SMA! ( 30094386 )
2018
49
Life cycle analysis of electrically actuated SMA spring using Talbot interferometry. ( 30118047 )
2018
50
Non-Sporadic PEComa Simulating Myolipoma of Tongue, in a Pediatric Patient with Immunohistochemical Analysis Using HMB-45 and SMA. ( 30158045 )
2018

Variations for Proximal Spinal Muscular Atrophy

ClinVar genetic disease variations for Proximal Spinal Muscular Atrophy:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 SPG7 NM_003119.3(SPG7): c.233T> A (p.Leu78Ter) single nucleotide variant Pathogenic rs121918358 GRCh37 Chromosome 16, 89576947: 89576947
2 SPG7 NM_003119.3(SPG7): c.233T> A (p.Leu78Ter) single nucleotide variant Pathogenic rs121918358 GRCh38 Chromosome 16, 89510539: 89510539
3 SETX NM_015046.6(SETX): c.7711C> T (p.Pro2571Ser) single nucleotide variant Uncertain significance GRCh38 Chromosome 9, 132264562: 132264562
4 SETX NM_015046.6(SETX): c.7711C> T (p.Pro2571Ser) single nucleotide variant Uncertain significance GRCh37 Chromosome 9, 135139949: 135139949
5 FBLN5 NM_006329.3(FBLN5): c.605G> T (p.Gly202Val) single nucleotide variant Uncertain significance rs137901671 GRCh38 Chromosome 14, 91891235: 91891235
6 FBLN5 NM_006329.3(FBLN5): c.605G> T (p.Gly202Val) single nucleotide variant Uncertain significance rs137901671 GRCh37 Chromosome 14, 92357579: 92357579

Expression for Proximal Spinal Muscular Atrophy

Search GEO for disease gene expression data for Proximal Spinal Muscular Atrophy.

Pathways for Proximal Spinal Muscular Atrophy

Pathways related to Proximal Spinal Muscular Atrophy according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.41 DES LMNA MUC1 RAB6A
2 10.4 BICD2 RAB6A

GO Terms for Proximal Spinal Muscular Atrophy

Cellular components related to Proximal Spinal Muscular Atrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Z disc GO:0030018 9.43 DES SMN1 SMN2
2 SMN-Sm protein complex GO:0034719 9.32 SMN1 SMN2
3 Gemini of coiled bodies GO:0097504 9.16 SMN1 SMN2
4 SMN complex GO:0032797 8.96 SMN1 SMN2
5 Cajal body GO:0015030 8.8 SMN1 SMN2 SMNDC1
6 cytoplasm GO:0005737 10.07 APOE BICD2 DES DNAI1 MUC1 NAIP

Biological processes related to Proximal Spinal Muscular Atrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nervous system development GO:0007399 9.55 NAIP SETX SMN1 SMN2 SPG7
2 spliceosomal snRNP assembly GO:0000387 9.4 SMN1 SMN2
3 spliceosomal complex assembly GO:0000245 9.37 SMN1 SMN2
4 import into nucleus GO:0051170 9.32 SMN1 SMN2
5 protein localization to Golgi apparatus GO:0034067 9.26 BICD2 RAB6A
6 minus-end-directed organelle transport along microtubule GO:0072385 8.96 BICD2 RAB6A
7 DNA-templated transcription, termination GO:0006353 8.8 SETX SMN1 SMN2

Molecular functions related to Proximal Spinal Muscular Atrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.44 APOE BICD2 DES DNAI1 LMNA MUC1
2 identical protein binding GO:0042802 9.35 APOE DES SETX SMN1 SMN2

Sources for Proximal Spinal Muscular Atrophy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....