MCID: PRX014
MIFTS: 42

Proximal Spinal Muscular Atrophy

Categories: Rare diseases, Muscle diseases, Neuronal diseases

Aliases & Classifications for Proximal Spinal Muscular Atrophy

MalaCards integrated aliases for Proximal Spinal Muscular Atrophy:

Name: Proximal Spinal Muscular Atrophy 49 55 69
Sma 49 55

Characteristics:

Orphanet epidemiological data:

55
proximal spinal muscular atrophy
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Europe); Age of onset: All ages; Age of death: any age;

Classifications:

Orphanet: 55  
Rare neurological diseases


Summaries for Proximal Spinal Muscular Atrophy

NIH Rare Diseases : 49 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. Last updated: 7/7/2009

MalaCards based summary : Proximal Spinal Muscular Atrophy, also known as sma, is related to spinal muscular atrophy, type i and spinal muscular atrophy, type ii, and has symptoms including preauricular skin tag, lymphedema and muscular hypotonia. An important gene associated with Proximal Spinal Muscular Atrophy is SMN1 (Survival Of Motor Neuron 1, Telomeric), and among its related pathways/superpathways are Cytoskeletal Signaling and COPI-independent Golgi-to-ER retrograde traffic. The drugs Pyridostigmine Bromide and Cholinergic Agents have been mentioned in the context of this disorder. Affiliated tissues include testes, spinal cord and brain, and related phenotype is Negative genetic interaction between BLM-/- and BLM+/+.

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 all 50)
# Related Disease Score Top Affiliating Genes
1 spinal muscular atrophy, type i 33.0 NAIP SMN1 SMN2
2 spinal muscular atrophy, type ii 32.6 NAIP SMN1 SMN2
3 spinal muscular atrophy, type iv 32.5 SMN1 SMN2
4 spinal muscular atrophy, type iii 32.1 NAIP SMN1 SMN2
5 muscular atrophy 30.6 BICD2 NAIP SMN1 SMN2 SMNDC1
6 spinal muscular atrophy 30.6 BICD2 NAIP SMN1 SMN2 SMNDC1
7 survival motor neuron spinal muscular atrophy 30.4 NAIP SMN1 SMN2
8 amyotrophic lateral sclerosis 1 29.6 NAIP SETX SMN1 SMN2
9 autosomal dominant childhood-onset proximal spinal muscular atrophy 12.3
10 spinal muscular atrophy, late-onset, finkel type 11.9
11 spinal muscular atrophy, lower extremity-predominant, 1, autosomal dominant 11.5
12 spinal muscular atrophy, lower extremity-predominant, 2, autosomal dominant 11.5
13 progressive muscular atrophy 10.4 SMN1 SMN2
14 anterior horn cell disease 10.3 SMN1 SMN2
15 nervous system disease 10.2 APOE SMN1 SMN2
16 juvenile spinal muscular atrophy 10.2 NAIP SMN1 SMN2
17 spinal disease 10.2 NAIP SMN1 SMN2
18 scoliosis 10.0
19 spindle cell thymoma 10.0 DES MUC1
20 parachordoma 10.0 DES MUC1
21 ossifying fibromyxoid tumor 10.0 DES MUC1
22 spindle cell rhabdomyosarcoma 10.0 DES MUC1
23 biphasic synovial sarcoma 10.0 DES MUC1
24 myxofibrosarcoma 10.0 DES MUC1
25 syringocystadenoma papilliferum 10.0 DES MUC1
26 syringoma 10.0 DES MUC1
27 pleomorphic liposarcoma 9.9 DES MUC1
28 ischemic fasciitis 9.9 DES MUC1
29 plasmablastic lymphoma 9.9 DES MUC1
30 perivascular epithelioid cell tumor 9.9 DES MUC1
31 reticulum cell sarcoma 9.9 DES MUC1
32 spindle cell sarcoma 9.9 DES MUC1
33 mesenchymal chondrosarcoma 9.9 DES MUC1
34 muscular dystrophy 9.9
35 dysautonomia 9.9
36 blood group, i system 9.9
37 lateral sclerosis 9.9
38 extraskeletal ewing sarcoma 9.9 DES MUC1
39 motor neuron disease 9.9 NAIP SETX SMN1 SMN2
40 hemangiopericytoma, malignant 9.9 DES MUC1
41 benign mesothelioma 9.8 DES MUC1
42 malignant fibroxanthoma 9.8 DES MUC1
43 fasciitis 9.8 DES MUC1
44 spindle cell carcinoma 9.7 DES MUC1
45 muscle tissue disease 9.7 LMNA NAIP SMN1 SMN2
46 chordoma 9.7 DES MUC1
47 rhabdoid cancer 9.6 DES MUC1
48 cardiomyopathy, dilated, 1e 9.6 DES LMNA
49 neuromuscular disease 9.6 DES NAIP SMN1 SMN2
50 desmoplastic small round cell tumor 9.5 DES MUC1

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:

55 31 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 preauricular skin tag 55 31 frequent (33%) Frequent (79-30%) HP:0000384
2 lymphedema 55 31 frequent (33%) Frequent (79-30%) HP:0001004
3 muscular hypotonia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001252
4 reduced tendon reflexes 55 31 hallmark (90%) Very frequent (99-80%) HP:0001315
5 joint stiffness 55 31 frequent (33%) Frequent (79-30%) HP:0001387
6 intrauterine growth retardation 55 31 frequent (33%) Frequent (79-30%) HP:0001511
7 polyhydramnios 55 31 frequent (33%) Frequent (79-30%) HP:0001561
8 abnormality of the voice 55 31 frequent (33%) Frequent (79-30%) HP:0001608
9 recurrent fractures 55 31 frequent (33%) Frequent (79-30%) HP:0002757
10 emg abnormality 55 31 hallmark (90%) Very frequent (99-80%) HP:0003457
11 hemiplegia/hemiparesis 55 31 hallmark (90%) Very frequent (99-80%) HP:0004374
12 proximal lower limb amyotrophy 55 31 hallmark (90%) Very frequent (99-80%) HP:0008956
13 abnormality of movement 55 31 hallmark (90%) Very frequent (99-80%) HP:0100022
14 abnormality of the ribs 55 31 frequent (33%) Frequent (79-30%) HP:0000772
15 proximal amyotrophy 55 Very frequent (99-80%)

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

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Negative genetic interaction between BLM-/- and BLM+/+ GR00255-A-1 8.92 APOE BICD2 LMNA SMNDC1

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

38
Testes, Spinal Cord, Brain, Skin

Publications for Proximal Spinal Muscular Atrophy

Articles related to Proximal Spinal Muscular Atrophy:

(show top 50) (show all 54)
# Title Authors Year
1
[SMN1 Gene Point Mutations in Type I-IV Proximal Spinal Muscular Atrophy Patients with a Single Copy of SMN1]. ( 26606804 )
2015
2
Clinical utility gene card for: Proximal spinal muscular atrophy (SMA) - update 2015. ( 25990799 )
2015
3
Molecular defects in the motor adaptor BICD2 cause proximal spinal muscular atrophy with autosomal-dominant inheritance. ( 23664119 )
2013
4
Natural course of scoliosis in proximal spinal muscular atrophy type II and IIIa: descriptive clinical study with retrospective data collection of 126 patients. ( 24093531 )
2013
5
Proximal spinal muscular atrophy: current orthopedic perspective. ( 24399883 )
2013
6
Clinical utility gene card for: proximal spinal muscular atrophy. ( 22510849 )
2012
7
Operative treatment of scoliosis in proximal spinal muscular atrophy: results of 41 patients. ( 23053190 )
2012
8
SETX gene mutation in a family diagnosed autosomal dominant proximal spinal muscular atrophy. ( 22088787 )
2012
9
Gene dosage analysis of proximal spinal muscular atrophy carriers using real-time PCR. ( 21529108 )
2011
10
Use of orthoses and orthopaedic technical devices in proximal spinal muscular atrophy. Results of survey in 194 SMA patients. ( 20939690 )
2011
11
Fractures in proximal spinal muscular atrophy. ( 20364429 )
2010
12
Neurophysiological findings of the late-onset, dominant, proximal spinal muscular atrophies with dysautonomia because of the VAPB PRO56SER mutation. ( 18677189 )
2008
13
Brachial amyotrophic diplegia (segmental proximal spinal muscular atrophy) associated with HIV infection. ( 19010950 )
2008
14
Mutations of the LMNA gene can mimic autosomal dominant proximal spinal muscular atrophy. ( 17136397 )
2007
15
SMA carrier testing--validation of hemizygous SMN exon 7 deletion test for the identification of proximal spinal muscular atrophy carriers and patients with a single allele deletion. ( 10757638 )
2000
16
No evidence of association between apolipoprotein E genotype and phenotypic severity in childhood onset proximal spinal muscular atrophy. ( 10545039 )
1999
17
Analysis of creatine kinase activity in 504 patients with proximal spinal muscular atrophy types I-III from the point of view of progression and severity. ( 9605392 )
1998
18
The role of the SMN gene in proximal spinal muscular atrophy. ( 9735373 )
1998
19
Different entities of proximal spinal muscular atrophy within one family. ( 9341891 )
1997
20
Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number. ( 9199562 )
1997
21
A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients. ( 9077498 )
1997
22
Biphasic intra-abdominal desmoplastic small cell tumor in a patient with proximal spinal muscular atrophy. ( 10846550 )
1996
23
Apparent autosomal recessive inheritance in families with proximal spinal muscular atrophy affecting individuals in two generations. ( 8900246 )
1996
24
Allelic association and deletions in autosomal recessive proximal spinal muscular atrophy: association of marker genotype with disease severity and candidate cDNAs. ( 7581364 )
1995
25
Prenatal prediction in families with autosomal recessive proximal spinal muscular atrophy (5q11.2-q13.3): molecular genetics and clinical experience in 109 cases. ( 7644431 )
1995
26
Evidence of autosomal dominant mutations in childhood-onset proximal spinal muscular atrophy. ( 8023839 )
1994
27
Biochemical and immunocytochemical analysis in chronic proximal spinal muscular atrophy. ( 8170486 )
1994
28
Autosomal recessive proximal spinal muscular atrophy in 101 sibs out of 48 families: clinical picture, influence of gender, and genetic implications. ( 8030672 )
1994
29
Association between Ag1-CA alleles and severity of autosomal recessive proximal spinal muscular atrophy. ( 7977383 )
1994
30
Prenatal diagnosis of the acute form of proximal spinal muscular atrophy: experience on the acceptance of linkage analyses by the families. ( 8105458 )
1993
31
The use of chromosome 5q markers for confirming the diagnosis of proximal spinal muscular atrophy. ( 7907903 )
1993
32
Proximal spinal muscular atrophy (SMA) types II and III in the same sibship are not caused by different alleles at the SMA locus on 5q. ( 1570842 )
1992
33
Becker's model and prenatal diagnosis in proximal spinal muscular atrophy (SMA): a note of caution. ( 2063872 )
1991
34
Heterogeneity in proximal spinal muscular atrophy. ( 1975919 )
1990
35
Clinical and morphometric analysis of biopsied biceps brachii muscles in adult-onset chronic proximal spinal muscular atrophy. With special reference to intramuscular nerves. ( 3401687 )
1988
36
Electromyographic findings in different forms of infantile and juvenile proximal spinal muscular atrophy. ( 3951479 )
1986
37
Chronic proximal spinal muscular atrophy of childhood and adolescence: problems of classification and genetic counselling. ( 4078864 )
1985
38
Chronic proximal spinal muscular atrophy of childhood and adolescence: sex influence. ( 6512833 )
1984
39
Clinical study of proximal spinal muscular atrophy. Report on 89 cases. ( 6530365 )
1984
40
Juvenile proximal spinal muscular atrophy with early hypertrophy of calves. ( 6878107 )
1983
41
Gastrointestinal radiologic manifestations of proximal spinal muscular atrophy (Kugelberg-Welander syndrome). ( 7120481 )
1982
42
Diaphragm paralysis and ventilatory failure in chronic proximal spinal muscular atrophy. ( 7224359 )
1981
43
A family of juvenile proximal spinal muscular atrophy with dominant inheritance. ( 933110 )
1976
44
A clinical and genetic study of chronic proximal spinal muscular atrophy. ( 1182487 )
1975
45
The Kugelberg-Welander syndrome (hereditary proximal spinal muscular atrophy). ( 5173132 )
1971
46
Chronic proximal spinal muscular atrophy. ( 5503267 )
1970
47
Familial adult-onset proximal spinal muscular atrophy. Report of a family with type II hyperlipoproteinemia. ( 5439897 )
1970
48
Familial proximal spinal muscular atrophy. ( 4952447 )
1966
49
Kugelberg-Welander syndrome (hereditary proximal spinal muscular atrophy). ( 5933049 )
1966
50
Proximal spinal muscular atrophy. ( 5910575 )
1966

Variations for Proximal Spinal Muscular Atrophy

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 9.5 DES SMN1 SMN2
2 perikaryon GO:0043204 9.43 NAIP SMN1 SMN2
3 SMN-Sm protein complex GO:0034719 9.37 SMN1 SMN2
4 SMN complex GO:0032797 9.16 SMN1 SMN2
5 Gemini of coiled bodies GO:0097504 8.96 SMN1 SMN2
6 Cajal body GO:0015030 8.8 SMN1 SMN2 SMNDC1
7 nucleus GO:0005634 10.13 APOE BICD2 DES LMNA MUC1 NAIP
8 cytoplasm GO:0005737 10.1 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 9.71 NAIP SETX SMN1 SMN2
2 spliceosomal snRNP assembly GO:0000387 9.37 SMN1 SMN2
3 spliceosomal complex assembly GO:0000245 9.32 SMN1 SMN2
4 nuclear import GO:0051170 9.26 SMN1 SMN2
5 protein targeting to Golgi GO:0000042 9.16 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 9.4 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
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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