SMA
MCID: PRX014
MIFTS: 45

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 52 58 6 71
Sma 52 58

Characteristics:

Orphanet epidemiological data:

58
proximal spinal muscular atrophy
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Europe); Age of onset: All ages; Age of death: any age;

Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

ICD10 via Orphanet 33 G12.0 G12.1
Orphanet 58 ORPHA70
UMLS 71 C4024957

Summaries for Proximal Spinal Muscular Atrophy

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 70 Definition Proximal 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. Epidemiology Prevalence is estimated at around 1/30,000. Clinical description Four 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. Etiology Around 95% of cases of SMA are caused by homozygous deletions (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 methods Diagnosis is based on clinical history and examination and can be confirmed by genetic testing . Electromyography and muscle biopsy may also be performed. Differential diagnosis Differential diagnoses include amyotrophic lateral sclerosis, congenital muscular dystrophies, congenital myopathies, primary lateral sclerosis, myasthenia gravis, and carbohydrate metabolism disorders (see these terms). Antenatal diagnosis Antenatal diagnosis is feasible through molecular analysis of amniocytes or chorionic villus samples. Genetic counseling Transmission 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 treatment Clinical 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. Prognosis The 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 autosomal dominant proximal spinal muscular atrophy and spinal muscular atrophy with progressive myoclonic epilepsy. An important gene associated with Proximal Spinal Muscular Atrophy is SPG7 (SPG7 Matrix AAA Peptidase Subunit, Paraplegin), and among its related pathways/superpathways are Golgi-to-ER retrograde transport and Cytoskeletal Signaling. The drugs Cholinergic Agents and Pyridostigmine Bromide have been mentioned in the context of this disorder. Affiliated tissues include testes, brain and spinal cord, and related phenotypes are muscular hypotonia and emg abnormality

Related Diseases for Proximal Spinal Muscular Atrophy

Diseases in the Proximal Spinal Muscular Atrophy family:

Autosomal Dominant Adult-Onset Proximal Spinal Muscular Atrophy Autosomal Dominant 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 327)
# Related Disease Score Top Affiliating Genes
1 autosomal dominant proximal spinal muscular atrophy 34.5 SETX LMNA
2 spinal muscular atrophy with progressive myoclonic epilepsy 33.5 SMN2 SMN1
3 spinal muscular atrophy, type iv 33.2 SMN2 SMN1 NAIP
4 spinal muscular atrophy, type iii 33.1 SMN2 SMN1 NAIP
5 spinal muscular atrophy with lower extremity predominance 32.9 VAPB SETX BICD2
6 spinal muscular atrophy, type i 32.8 SMN2 SMN1 NAIP
7 spinal muscular atrophy, type ii 32.1 SMN2 SMN1 NAIP BICD2
8 charcot-marie-tooth hereditary neuropathy 30.5 SPG7 SETX
9 anterior horn cell disease 29.9 SMN2 SMN1
10 progressive muscular atrophy 29.8 VAPB SMN2 SMN1
11 spinal muscular atrophy, distal, autosomal recessive, 1 29.7 SMN2 SMN1 SETX
12 muscular atrophy 29.4 VAPB SMNDC1 SMN2 SMN1 SETX NAIP
13 childhood spinal muscular atrophy 29.3 SMN2 SMN1 NAIP BICD2
14 amyotrophic lateral sclerosis 1 29.2 VAPB SMN2 SMN1 SETX NAIP APOE
15 neuromuscular disease 28.9 SMN2 SMN1 NAIP LMNA KIF1B DES
16 motor neuron disease 28.7 VAPB SMN2 SMN1 SETX NAIP BICD2
17 charcot-marie-tooth disease 28.4 VAPB SMN2 SMN1 SETX LMNA KIF1B
18 spinal muscular atrophy 27.9 VAPB SPG7 SMNDC1 SMN2 SMN1 SETX
19 autosomal dominant childhood-onset proximal spinal muscular atrophy 12.7
20 autosomal dominant adult-onset proximal spinal muscular atrophy 12.6
21 spinal muscular atrophy, late-onset, finkel type 12.4
22 spinal muscular atrophy, lower extremity-predominant, 1, autosomal dominant 12.3
23 spinal muscular atrophy, x-linked 2 12.1
24 spinal muscular atrophy, lower extremity-predominant, 2a, childhood onset, autosomal dominant 12.0
25 superior mesenteric artery syndrome 11.8
26 autosomal dominant spinal muscular atrophy, lower extremity-predominant 2 11.7
27 werdnig-hoffman disease 11.6
28 pontocerebellar hypoplasia, type 1a 11.4
29 renal nutcracker syndrome 11.3
30 adult progressive spinal muscular atrophy aran duchenne type 11.1
31 spinal muscular atrophy, distal, autosomal recessive, 3 11.1
32 spinal muscular atrophy, distal, autosomal recessive, 5 11.1
33 mitochondrial dna depletion syndrome 18 11.1
34 amyotrophic lateral sclerosis type 15 10.5 VAPB SETX
35 amyotrophic lateral sclerosis type 14 10.5 VAPB SETX
36 cervix erosion 10.5 SPG7 SETX
37 amyotrophic lateral sclerosis 7 10.5 VAPB SETX
38 amyotrophic lateral sclerosis 18 10.4 VAPB SETX
39 amyotrophic lateral sclerosis 17 10.4 VAPB SETX
40 amyotrophic lateral sclerosis 21 10.4 VAPB SETX
41 amyotrophic lateral sclerosis 16, juvenile 10.4 VAPB SETX
42 distal hereditary motor neuropathies 10.4 SPG7 SETX
43 amyotrophic lateral sclerosis type 5 10.4 VAPB SETX
44 amyotrophic lateral sclerosis 12 10.4 VAPB SETX
45 amyotrophic lateral sclerosis 11 10.4 VAPB SETX
46 amyotrophic lateral sclerosis 10 with or without frontotemporal dementia 10.4 VAPB SETX
47 amyotrophic lateral sclerosis 9 10.4 VAPB SETX
48 amyotrophic lateral sclerosis type 6 10.3 VAPB SETX
49 scoliosis 10.3
50 muscular dystrophy 10.3

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:

58 31 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001252
2 emg abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0003457
3 hemiplegia/hemiparesis 58 31 hallmark (90%) Very frequent (99-80%) HP:0004374
4 reduced tendon reflexes 58 31 hallmark (90%) Very frequent (99-80%) HP:0001315
5 proximal lower limb amyotrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0008956
6 joint stiffness 58 31 frequent (33%) Frequent (79-30%) HP:0001387
7 lymphedema 58 31 frequent (33%) Frequent (79-30%) HP:0001004
8 intrauterine growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0001511
9 polyhydramnios 58 31 frequent (33%) Frequent (79-30%) HP:0001561
10 preauricular skin tag 58 31 frequent (33%) Frequent (79-30%) HP:0000384
11 abnormality of the ribs 58 31 frequent (33%) Frequent (79-30%) HP:0000772
12 abnormality of the voice 58 31 frequent (33%) Frequent (79-30%) HP:0001608
13 recurrent fractures 58 31 frequent (33%) Frequent (79-30%) HP:0002757
14 abnormality of movement 58 Very frequent (99-80%)
15 proximal amyotrophy 58 Very frequent (99-80%)

MGI Mouse Phenotypes related to Proximal Spinal Muscular Atrophy:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.43 BICD2 DNAI1 FBLN5 KIF1B LMNA SMN2
2 muscle MP:0005369 9.17 APOE DES FBLN5 KIF1B LMNA SMN2

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 Cholinergic Agents Phase 2
2 Pyridostigmine Bromide Phase 2 101-26-8
3 Cholinesterase Inhibitors Phase 2
4 Neurotransmitter Agents Phase 2
5 Bromides Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase II, Mono-center, Placebo-controlled, Double-blind, Crossover Trial to Investigate Effect and Efficacy of Pyridostigmine in Dutch Patients With Spinal Muscular Atrophy Types 2, 3 and 4 Completed NCT02941328 Phase 2 Pyridostigmine;Placebo
2 Quantitative Analysis of SMN1 and SMN2 Gene Based on DHPLC System: Establishing a Novel Highly Efficient and Reliable SMA Carrier Screening Test Unknown status NCT00155168
3 Establishing Novel Detection Techniques for Various Genetic-Related Diseases by Applying DHPLC Platform. Unknown status NCT00154960

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:

40
Testes, Brain, Spinal Cord, Skin, Heart

Publications for Proximal Spinal Muscular Atrophy

Articles related to Proximal Spinal Muscular Atrophy:

(show top 50) (show all 187)
# Title Authors PMID Year
1
Clinical utility gene card for: proximal spinal muscular atrophy. 61 6
22510849 2012
2
Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number. 6 61
9837824 1998
3
Genotype-phenotype relationship in 2 SMA III patients with novel mutations in the Tudor domain. 6
22323744 2012
4
Consensus statement for standard of care in spinal muscular atrophy. 6
17761659 2007
5
Molecular and functional analysis of intragenic SMN1 mutations in patients with spinal muscular atrophy. 6
15580564 2005
6
A genetic and phenotypic analysis in Spanish spinal muscular atrophy patients with c.399_402del AGAG, the most frequently found subtle mutation in the SMN1 gene. 6
12872254 2003
7
Premature termination mutations in exon 3 of the SMN1 gene are associated with exon skipping and a relatively mild SMA phenotype. 6
11313744 2001
8
Spinal Muscular Atrophy 6
20301526 2000
9
A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. 6
10339583 1999
10
Spinal muscular atrophy due to an isolated deletion of exon 8 of the telomeric survival motor neuron gene. 6
9818944 1998
11
Missense mutations in exon 6 of the survival motor neuron gene in patients with spinal muscular atrophy (SMA). 6
9158159 1997
12
A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients. 6
7581461 1995
13
Feeding and Swallowing Problems in Infants with Spinal Muscular Atrophy Type 1: an Observational Study. 61
32333596 2020
14
Participation and mental well-being of mothers of home-living patients with spinal muscular atrophy. 61
30954388 2019
15
A continuous repetitive task to detect fatigability in spinal muscular atrophy. 61
30208915 2018
16
Protocol for a phase II, monocentre, double-blind, placebo-controlled, cross-over trial to assess efficacy of pyridostigmine in patients with spinal muscular atrophy types 2-4 (SPACE trial). 61
30061431 2018
17
Recent therapeutic developments in spinal muscular atrophy 61
29714429 2018
18
Spinal muscular atrophy. 61
29478602 2018
19
Cardiac pathology in spinal muscular atrophy: a systematic review. 61
28399889 2017
20
Mutation Spectrum of the Survival of Motor Neuron 1 and Functional Analysis of Variants in Chinese Spinal Muscular Atrophy. 61
27425821 2016
21
A rare variant (c.863G>T) in exon 7 of SMN1 disrupts mRNA splicing and is responsible for spinal muscular atrophy. 61
26419278 2016
22
Protective effects of butyrate-based compounds on a mouse model for spinal muscular atrophy. 61
26892876 2016
23
Copy Number Variations in the Survival Motor Neuron Genes: Implications for Spinal Muscular Atrophy and Other Neurodegenerative Diseases. 61
27014701 2016
24
Clinical utility gene card for: Proximal spinal muscular atrophy (SMA) - update 2015. 61
25990799 2015
25
SMN expression is required in motor neurons to rescue electrophysiological deficits in the SMNΔ7 mouse model of SMA. 61
26206889 2015
26
[SMN1 Gene Point Mutations in Type I-IV Proximal Spinal Muscular Atrophy Patients with a Single Copy of SMN1]. 61
26606804 2015
27
SMN1 and SMN2 copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR. 61
26247043 2015
28
Detection of intragenic SMN1 mutations in spinal muscular atrophy patients with a single copy of SMN1. 61
24563475 2015
29
Investigational therapies for the treatment of spinal muscular atrophy. 61
25911060 2015
30
Bulbar muscle MRI changes in patients with SMA with reduced mouth opening and dysphagia. 61
25122201 2014
31
Genotype-phenotype correlation of survival motor neuron and neuronal apoptosis inhibitory protein genes in spinal muscular atrophy patients from Iran. 61
24627882 2014
32
Transcriptome profiling of spinal muscular atrophy motor neurons derived from mouse embryonic stem cells. 61
25191843 2014
33
[Two cases of a proximal spinal muscular atrophy (Werdnig-Hoffmann's disease) in one family]. 61
25591528 2014
34
Blake's pouch cyst and Werdnig-Hoffmann disease: Report of a new association and review of the literature. 61
25225621 2014
35
Proximal spinal muscular atrophy: current orthopedic perspective. 61
24399883 2013
36
Natural course of scoliosis in proximal spinal muscular atrophy type II and IIIa: descriptive clinical study with retrospective data collection of 126 patients. 61
24093531 2013
37
SMN1 gene duplications are more frequent in patients with progressive muscular atrophy. 61
23477310 2013
38
Spinal muscular atrophy: development and implementation of potential treatments. 61
23939659 2013
39
Molecular defects in the motor adaptor BICD2 cause proximal spinal muscular atrophy with autosomal-dominant inheritance. 61
23664119 2013
40
Clinical and molecular cross-sectional study of a cohort of adult type III spinal muscular atrophy patients: clues from a biomarker study. 61
23073312 2013
41
Sodium vanadate combined with L-ascorbic acid delays disease progression, enhances motor performance, and ameliorates muscle atrophy and weakness in mice with spinal muscular atrophy. 61
23409868 2013
42
Small molecule suppressors of Drosophila kinesin deficiency rescue motor axon development in a zebrafish model of spinal muscular atrophy. 61
24023935 2013
43
Colorimetric Assay for Exon 7 SMN1/SMN2 Single Nucleotide Polymorphism Using Gold Nanoprobes. 61
24455482 2013
44
VPA response in SMA is suppressed by the fatty acid translocase CD36. 61
23077215 2013
45
Operative treatment of scoliosis in proximal spinal muscular atrophy: results of 41 patients. 61
23053190 2012
46
Isolated exon 8 deletion in type 1 spinal muscular atrophy with bilateral optic atrophy: unusual genetic mutation leading to unusual manifestation? 61
23298926 2012
47
Subtle mutations in the SMN1 gene in Chinese patients with SMA: p.Arg288Met mutation causing SMN1 transcript exclusion of exon7. 61
22994313 2012
48
[Heterozygous carrier rate for type I-IV proximal spinal muscular atrophy in Chuvashes, Udmurts, and residents of the Moscow region]. 61
23035550 2012
49
Prediction of death in the SMNΔ7 mouse model of spinal muscular atrophy: insight into disease stage and progression. 61
22750651 2012
50
SETX gene mutation in a family diagnosed autosomal dominant proximal spinal muscular atrophy. 61
22088787 2012

Variations for Proximal Spinal Muscular Atrophy

ClinVar genetic disease variations for Proximal Spinal Muscular Atrophy:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SPG7 NM_003119.4(SPG7):c.233T>A (p.Leu78Ter)SNV Pathogenic 6816 rs121918358 16:89576947-89576947 16:89510539-89510539
2 SETX NM_015046.7(SETX):c.7711C>T (p.Pro2571Ser)SNV Uncertain significance 549704 rs1554801479 9:135139949-135139949 9:132264562-132264562
3 FBLN5 NM_006329.3(FBLN5):c.605G>T (p.Gly202Val)SNV Uncertain significance 549697 rs137901671 14:92357579-92357579 14:91891235-91891235

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
Show member pathways
12.08 RAB6A KIF1B DYNC1I1 BICD2
2 11.84 RAB6A MUC1 LMNA KIF1B DES
3 10.25 RAB6A DYNC1I1 BICD2

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 cytoplasm GO:0005737 9.97 VAPB SMNDC1 SMN2 SMN1 SETX NAIP
2 axon GO:0030424 9.76 SMN2 SMN1 SETX KIF1B
3 nuclear body GO:0016604 9.67 SMN2 SMN1 SETX LMNA
4 Z disc GO:0030018 9.61 SMN2 SMN1 DES
5 SMN-Sm protein complex GO:0034719 9.4 SMN2 SMN1
6 Gemini of coiled bodies GO:0097504 9.32 SMN2 SMN1
7 SMN complex GO:0032797 9.26 SMN2 SMN1
8 cytoplasmic ribonucleoprotein granule GO:0036464 9.13 SMN2 SMN1 DYNC1I1
9 Cajal body GO:0015030 8.8 SMNDC1 SMN2 SMN1

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 9.72 SPG7 SMN2 SMN1 SETX NAIP
2 spliceosomal complex assembly GO:0000245 9.43 SMN2 SMN1
3 import into nucleus GO:0051170 9.4 SMN2 SMN1
4 protein localization to Golgi apparatus GO:0034067 9.37 RAB6A BICD2
5 transport along microtubule GO:0010970 9.26 KIF1B DYNC1I1
6 microtubule-based movement GO:0007018 9.26 KIF1B DYNC1I1 DNAI1 BICD2
7 minus-end-directed organelle transport along microtubule GO:0072385 9.16 RAB6A BICD2
8 DNA-templated transcription, termination GO:0006353 8.8 SMN2 SMN1 SETX

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 9.55 VAPB SPG7 SMNDC1 SMN2 SMN1 SETX
2 motor activity GO:0003774 9.43 KIF1B DYNC1I1 DNAI1
3 dynein heavy chain binding GO:0045504 9.16 DYNC1I1 DNAI1
4 dynein light chain binding GO:0045503 8.96 DYNC1I1 DNAI1

Sources for Proximal Spinal Muscular Atrophy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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