Spinal Muscular Atrophy, Type Iv (SMA4)

Categories: Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Spinal Muscular Atrophy, Type Iv

MalaCards integrated aliases for Spinal Muscular Atrophy, Type Iv:

Name: Spinal Muscular Atrophy, Type Iv 56 12 71
Sma4 56 12 52 58 73
Spinal Muscular Atrophy, Adult Form 56 12 52 58
Adult Spinal Muscular Atrophy 12 29 6 15
Spinal Muscular Atrophy 4 12 52 73 71
Spinal Muscular Atrophy, Proximal, Adult, Autosomal Recessive 56 52
Proximal Spinal Muscular Atrophy Type 4 52 58
Spinal Muscular Atrophy-4 56 13
Sma Type Iv 52 58
Sma Type 4 52 58
Sma-Iv 52 58
Spinal Muscular Atrophy Proximal Adult Autosomal Recessive 73
Adult-Onset Spinal Muscular Atrophy 52
Spinal Muscular Atrophy Adult Form 73
Atrophy, Muscular, Spinal, Type Iv 39
Spinal Muscular Atrophy Type Iv 73
Spinal Muscular Atrophy Type 4 52
Myelopathic Muscular Atrophy 71
Sma Iv 73
Sma 4 52


Orphanet epidemiological data:

proximal spinal muscular atrophy type 4
Inheritance: Autosomal recessive; Age of onset: Adult; Age of death: normal life expectancy;


autosomal recessive

mean age at onset 35 years (range 20-60)
slow disease progression
allelic disorder to spinal muscular atrophy type i


spinal muscular atrophy, type iv:
Inheritance autosomal recessive inheritance
Onset and clinical course adult onset slow progression


Orphanet: 58  
Rare neurological diseases

External Ids:

Disease Ontology 12 DOID:0050529
OMIM 56 271150
MeSH 43 D009134
ICD10 via Orphanet 33 G12.1
UMLS via Orphanet 72 C1838230
Orphanet 58 ORPHA83420
MedGen 41 C1838230
UMLS 71 C0270765 C1838230 C2931844

Summaries for Spinal Muscular Atrophy, Type Iv

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 83420 Definition Proximal spinal muscular atrophy type 4 (SMA4) is the adult-onset form of proximal spinal muscular atrophy (see this term) characterized by muscle weakness and hypotonia 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 1/300,000. Clinical description SMA4 usually manifests in the second or third decade of life. The muscle weakness predominantly affects the legs and hip muscles and then progresses to the shoulders and arms. Waddling gait is common. Finger trembling, fasciculation and calf hypertrophy may occur. The clinical picture is similar to that seen in SMA3 (see this term) but the motor weakness is less severe in SMA4. Etiology As for the other forms of SMA, SMA4 has been associated with deletions in the SMN1 gene (5q12.2-q13.3) encoding the SMN (survival motor neuron) protein . Although there is some variation, disease severity in SMA is inversely correlated with the number of copies of the second SMN gene (SMN2 ; 5q13.2) and some studies have shown that patients with the mild SMA4 form have multiple (four to six) SMN2 copies. However, no SMN1 gene mutations are found in some patients diagnosed with SMA4 and in these cases the genetic anomalies remain to be identified. Diagnostic methods The diagnosis is based on clinical history and examination. In patients with SMN1 anomalies, the diagnosis may be confirmed by genetic testing . Electromyography and muscle biopsy may be necessary. Differential diagnosis Differential diagnoses include the amyotrophic lateral sclerosis, primary lateral sclerosis, myasthenia gravis, and carbohydrate metabolism disorders (see these terms). Antenatal diagnosis Prenatal diagnosis is possible for families in which the mutations in the SMN1 gene have been identified. Genetic counseling The SMN1 gene deletions are transmitted in an autosomal recessive manner. Genetic counseling should be provided. Management and treatment Management is symptomatic, involves a multidisciplinary approach, and aims to improve quality of life. Physiotherapy and occupational therapies are recommended. Clinical trials to identify specific drug treatments for SMA are ongoing, and preliminary studies have indicated that valproic acid (as a histone deacetylase inhibitor) may improve quantitative muscle strength and subjective motor function in SMA4 patients. Prognosis SMA4 is the mildest form of SMA and in general the disease course is benign with patients having a normal life expectancy. Visit the Orphanet disease page for more resources.

MalaCards based summary : Spinal Muscular Atrophy, Type Iv, also known as sma4, is related to proximal spinal muscular atrophy and spinal muscular atrophy, type iii, and has symptoms including tremor of hands An important gene associated with Spinal Muscular Atrophy, Type Iv is SMN1 (Survival Of Motor Neuron 1, Telomeric), and among its related pathways/superpathways are VEGF Signaling and Integrated Breast Cancer Pathway. The drugs 4-Aminopyridine and Potassium Channel Blockers have been mentioned in the context of this disorder. Affiliated tissues include spinal cord, testes and brain, and related phenotypes are proximal amyotrophy and proximal muscle weakness

Disease Ontology : 12 A spinal muscular atrophy that is characterized by progressive muscular weakness and motor disability that typically presents in the third decade of life and has material basis in mutations in the SMN1 or SMN2 genes that are required for the survival of motor neurons.

UniProtKB/Swiss-Prot : 73 Spinal muscular atrophy 4: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Onset is in adulthood, disease progression is slow, and patients can stand and walk.

More information from OMIM: 271150

Related Diseases for Spinal Muscular Atrophy, Type Iv

Diseases in the Spinal Muscular Atrophy family:

Spinal Muscular Atrophy, Type I Spinal Muscular Atrophy, Type Iii
Spinal Muscular Atrophy, Type Ii Spinal Muscular Atrophy, Type Iv
Spinal Muscular Atrophy Type 0 Congenital Benign Spinal Muscular Atrophy Dominant

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

(show all 35)
# Related Disease Score Top Affiliating Genes
1 proximal spinal muscular atrophy 32.5 SMN2 SMN1
2 spinal muscular atrophy, type iii 30.5 TUBB SNORD63 SMN2 SMN1 SMAD7 SMAD6
3 progressive muscular atrophy 30.0 SMN2 SMN1
4 spinal muscular atrophy 11.9
5 spinal muscular atrophy, distal, autosomal recessive, 4 11.8
6 neuronopathy, distal hereditary motor, type iia 11.5
7 werdnig-hoffman disease 11.4
8 spinal muscular atrophy, late-onset, finkel type 11.2
9 nephrolithiasis/osteoporosis, hypophosphatemic, 2 10.5 SMN2 SMN1
10 small intestine adenocarcinoma 10.4 SMAD4 LCOR
11 autosomal recessive distal hereditary motor neuronopathy 10.4 SMN2 SMN1
12 anterior horn cell disease 10.4 SMN2 SMN1
13 amelogenesis imperfecta, type ia 10.4 SMN2 SMN1
14 spinal muscular atrophy, distal, autosomal recessive, 1 10.3 SMN2 SMN1
15 nephrogenic systemic fibrosis 10.3 SMAD7 SMAD4
16 dubowitz syndrome 10.3 SMN2 SMN1
17 loeys-dietz syndrome 3 10.3 SMAD6 SMAD4
18 fibrodysplasia ossificans progressiva 10.2 SMAD7 SMAD5 SMAD1
19 spinal muscular atrophy with progressive myoclonic epilepsy 10.2 SMN2 SMN1
20 amyotrophic lateral sclerosis 1 10.2
21 lateral sclerosis 10.2
22 motor neuron disease 10.2
23 spinal and bulbar muscular atrophy, x-linked 1 10.1
24 allergic hypersensitivity disease 10.0
25 muscular atrophy 10.0
26 hypotonia 10.0
27 scoliosis 10.0
28 intestinal pseudo-obstruction 10.0
29 constipation 10.0
30 cerebellar degeneration 10.0
31 myotonia 10.0
32 pik3ca-related overgrowth syndrome 10.0
33 genetic motor neuron disease 10.0
34 childhood spinal muscular atrophy 9.4 SMN2 SMN1 SMAD5 SMAD4 SCGB1D4 NCALD
35 spinal muscular atrophy, type ii 8.9 TUBB SMN2 SMN1 SMAD7 SMAD6 SMAD5

Graphical network of the top 20 diseases related to Spinal Muscular Atrophy, Type Iv:

Diseases related to Spinal Muscular Atrophy, Type Iv

Symptoms & Phenotypes for Spinal Muscular Atrophy, Type Iv

Human phenotypes related to Spinal Muscular Atrophy, Type Iv:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 proximal amyotrophy 31 HP:0007126
2 proximal muscle weakness 31 HP:0003701
3 degeneration of anterior horn cells 31 HP:0002398
4 hand tremor 31 HP:0002378
5 emg: neuropathic changes 31 HP:0003445
6 areflexia of lower limbs 31 HP:0002522
7 tongue fasciculations 31 HP:0001308
8 spinal muscular atrophy 31 HP:0007269

Symptoms via clinical synopsis from OMIM:

Neurologic Central Nervous System:
hand tremor
tongue fasciculations
emg shows neurogenic abnormalities
muscle atrophy, proximal
muscle weakness, proximal, symmetric (lower limbs more affected than upper limbs) due to motor neuronopathy
Muscle Soft Tissue:
hypertrophy of calves (in 3 of 6 patients)

Clinical features from OMIM:


UMLS symptoms related to Spinal Muscular Atrophy, Type Iv:

tremor of hands

Drugs & Therapeutics for Spinal Muscular Atrophy, Type Iv

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

# Name Status Phase Clinical Trials Cas Number PubChem Id
4-Aminopyridine Approved Phase 2, Phase 3 504-24-5 1727
2 Potassium Channel Blockers Phase 2, Phase 3

Interventional clinical trials:

# Name Status NCT ID Phase Drugs
1 Columbia SMA Project: 4-AP as a Potential SMA Therapeutic Agent and Biological Mechanisms of Action Completed NCT01645787 Phase 2, Phase 3 4-aminopyridine;Placebo
2 International Spinal Muscular Atrophy Patient Registry Completed NCT00466349
3 UK Spinal Muscular Atrophy Patient Registry Recruiting NCT04292574
4 Effect of Nusinersen on Motor Function in Adult Patients With Spinal Muscular Atrophy Types 2 and 3 Active, not recruiting NCT03878030 nusinersen

Search NIH Clinical Center for Spinal Muscular Atrophy, Type Iv

Genetic Tests for Spinal Muscular Atrophy, Type Iv

Genetic tests related to Spinal Muscular Atrophy, Type Iv:

# Genetic test Affiliating Genes
1 Adult Spinal Muscular Atrophy 29 SMN1

Anatomical Context for Spinal Muscular Atrophy, Type Iv

MalaCards organs/tissues related to Spinal Muscular Atrophy, Type Iv:

Spinal Cord, Testes, Brain, Tongue

Publications for Spinal Muscular Atrophy, Type Iv

Articles related to Spinal Muscular Atrophy, Type Iv:

(show all 28)
# Title Authors PMID Year
Clinical utility gene card for: proximal spinal muscular atrophy. 6
22510849 2012
A humanized Smn gene containing the SMN2 nucleotide alteration in exon 7 mimics SMN2 splicing and the SMA disease phenotype. 56
20705738 2010
Consensus statement for standard of care in spinal muscular atrophy. 6
17761659 2007
Valproate may improve strength and function in patients with type III/IV spinal muscle atrophy. 56
16775228 2006
Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number. 56
16508748 2006
Gene conversion events in adult-onset spinal muscular atrophy. 56
14705979 2004
Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy. 56
12915451 2003
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
Spinal Muscular Atrophy 6
20301526 2000
SMN gene deletions in adult-onset spinal muscular atrophy. 56
8551862 1995
A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients. 6
7581461 1995
Molecular analysis of candidate genes on chromosome 5q13 in autosomal recessive spinal muscular atrophy: evidence of homozygous deletions of the SMN gene in unaffected individuals. 56
8595417 1995
Genetic basis of adult-onset spinal muscular atrophy. 56
7475624 1995
Genetic homogeneity between childhood-onset and adult-onset autosomal recessive spinal muscular atrophy. 56
7658877 1995
A clinical and genetic study of spinal muscular atrophy of adult onset: the autosomal recessive form as a discrete disease entity. 56
737522 1978
14295959 1965
Spinal muscular atrophy - new therapies, new challenges. 61
31922583 2020
Effect of Wuzi Yanzong on Reproductive Hormones and TGF-β1/Smads Signal Pathway in Rats with Oligoasthenozoospermia. 61
31118967 2019
Spinal Muscular Atrophy and Ependymoma. 61
30787777 2017
[Molecular Features of SMA-related Genes in Spinal Muscular Atrophy Patients of Han Nationality in Southwest China.] 61
28598128 2016
Signal transducer and activator of transcription 2 (STAT2) metabolism coupling postmitotic outgrowth to visual and sound perception network in human left cerebrum by biocomputation. 61
22219046 2012
Using General Anesthesia plus Muscle Relaxant in a Patient with Spinal Muscular Atrophy Type IV: A Case Report. 61
22606392 2011
Mutations in LACS2, a long-chain acyl-coenzyme A synthetase, enhance susceptibility to avirulent Pseudomonas syringae but confer resistance to Botrytis cinerea in Arabidopsis. 61
17434992 2007
[Frequency of hereditary neurologic diseases. A clinical study]. 61
8247316 1993
Lectin binding pattern in the testes of several tetrapode vertebrates. 61
1768726 1991
Maturation antigen of the mouse sperm flagellum. I. Analysis of its secretion, association with sperm, and function. 61
3279744 1988
Maturation antigen of the mouse sperm flagellum: II. Origin from holocrine cells of the distal caput epididymis. 61
3034104 1987
Determination of haematocrit using the SMA4. 61
5697358 1968

Variations for Spinal Muscular Atrophy, Type Iv

ClinVar genetic disease variations for Spinal Muscular Atrophy, Type Iv:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SMN1 deletion Pathogenic 431179 rs1554082110 5:70241892-70242002 5:70946065-70946175
2 SMN1 NM_022874.2(SMN1):c.397_398AG[1] (p.Glu134fs)short repeat Pathogenic 634947 5:70238308-70238311 5:70942481-70942484
3 SMN1 NM_000344.3(SMN1):c.835-3C>TSNV Conflicting interpretations of pathogenicity 495829 rs772466166 5:70247765-70247765 5:70951938-70951938

Expression for Spinal Muscular Atrophy, Type Iv

Search GEO for disease gene expression data for Spinal Muscular Atrophy, Type Iv.

Pathways for Spinal Muscular Atrophy, Type Iv

GO Terms for Spinal Muscular Atrophy, Type Iv

Cellular components related to Spinal Muscular Atrophy, Type Iv according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein-containing complex GO:0032991 9.8 TUBB SMAD7 SMAD6 SMAD5 SMAD1
2 SMN-Sm protein complex GO:0034719 9.37 SMN2 SMN1
3 transcription factor complex GO:0005667 9.35 SMAD7 SMAD6 SMAD5 SMAD4 SMAD1
4 cytoplasmic ribonucleoprotein granule GO:0036464 9.33 TUBB SMN2 SMN1
5 Gemini of coiled bodies GO:0097504 9.32 SMN2 SMN1
6 SMN complex GO:0032797 9.26 SMN2 SMN1
7 SMAD protein complex GO:0071141 8.8 SMAD5 SMAD4 SMAD1

Biological processes related to Spinal Muscular Atrophy, Type Iv according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 SMAD protein signal transduction GO:0060395 9.61 SMAD5 SMAD4 SMAD1
2 ureteric bud development GO:0001657 9.56 SMAD7 SMAD6 SMAD5 SMAD1
3 spliceosomal complex assembly GO:0000245 9.55 SMN2 SMN1
4 regulation of transforming growth factor beta receptor signaling pathway GO:0017015 9.54 SMAD7 SMAD4
5 negative regulation of ossification GO:0030279 9.52 SMAD7 SMAD6
6 import into nucleus GO:0051170 9.51 SMN2 SMN1
7 cellular response to BMP stimulus GO:0071773 9.5 SMAD5 SMAD4 SMAD1
8 negative regulation of pathway-restricted SMAD protein phosphorylation GO:0060394 9.49 SMAD7 SMAD6
9 DNA-templated transcription, termination GO:0006353 9.48 SMN2 SMN1
10 response to laminar fluid shear stress GO:0034616 9.46 SMAD7 SMAD6
11 SMAD protein complex assembly GO:0007183 9.4 SMAD4 SMAD1
12 osteoblast fate commitment GO:0002051 9.37 SMAD5 SMAD1
13 transforming growth factor beta receptor signaling pathway GO:0007179 9.35 SMAD7 SMAD6 SMAD5 SMAD4 SMAD1
14 positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus GO:1901522 9.33 SMAD5 SMAD4 SMAD1
15 BMP signaling pathway GO:0030509 9.02 SMAD7 SMAD6 SMAD5 SMAD4 SMAD1

Molecular functions related to Spinal Muscular Atrophy, Type Iv according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.85 SMAD7 SMAD6 SMAD5 SMAD4 SMAD1 LCOR
2 ubiquitin protein ligase binding GO:0031625 9.73 TUBB SMAD7 SMAD6 SMAD5
3 R-SMAD binding GO:0070412 9.46 SMAD6 SMAD4
4 co-SMAD binding GO:0070410 9.4 SMAD6 SMAD1
5 type I transforming growth factor beta receptor binding GO:0034713 9.32 SMAD7 SMAD6
6 DEAD/H-box RNA helicase binding GO:0017151 9.26 SMAD5 SMAD1
7 transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity GO:0030618 9.16 SMAD5 SMAD1
8 transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity GO:0030617 8.96 SMAD7 SMAD6
9 I-SMAD binding GO:0070411 8.92 SMAD7 SMAD6 SMAD4 SMAD1

Sources for Spinal Muscular Atrophy, Type Iv

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
54 Novoseek
57 OMIM via Orphanet
61 PubMed
70 Tocris
72 UMLS via Orphanet
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