Spinal Muscular Atrophy-1

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

Aliases & Classifications for Spinal Muscular Atrophy-1

MalaCards integrated aliases for Spinal Muscular Atrophy-1:

Name: Spinal Muscular Atrophy-1 54 13
Werdnig-Hoffmann Disease 12 50 56 29 52 14
Werdnig-Hoffman Disease 12 51 71
Sma1 50 56 71
Proximal Spinal Muscular Atrophy Type 1 50 56
Infantile Muscular Atrophy 12 71
Spinal Muscular Atrophy 1 50 71
Hmn Proximal Type I 12 69
Sma Type 1 50 56
Sma Type I 50 56
Sma-I 50 56
Hereditary Motor Neuropathy Proximal Type I 12
Proximal Hereditary Motor Neuropathy Type I 71
Proximal Spinal Muscular Atrophy, Type 1 50
Progressive Muscular Atrophy of Infancy 12
Infantile Spinal Muscular Atrophy 56
Spinal Muscular Atrophy Type I 71
Muscular Atrophy, Infantile 50
Sma, Infantile Acute Form 50
Werdnig Hoffmann Disease 50
Sma Infantile Acute Form 71
Sma I 71


Orphanet epidemiological data:

proximal spinal muscular atrophy type 1
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;


autosomal recessive

death secondary to respiratory infection or failure before age 2 years
onset birth to 6 months
incidence 1 in 6,000 to 1 in 8,000 live births
approximately 45% of sma1 patients also are missing both homologs of neuronal apoptosis inhibitory protein (naip, ), which may play a role in modifying disease severity
exon 7 of smn1 is absent in 95.6% of sma1 patients


spinal muscular atrophy-1:
Inheritance autosomal recessive inheritance


Orphanet: 56  
Rare neurological diseases

External Ids:

OMIM 54 253300
Disease Ontology 12 DOID:13137
ICD10 33 G12.0
ICD9CM 35 335.0
MeSH 42 D014897
NCIt 47 C98670
Orphanet 56 ORPHA83330
UMLS via Orphanet 70 C0043116
ICD10 via Orphanet 34 G12.0
MedGen 40 C0043116
UMLS 69 C0043116

Summaries for Spinal Muscular Atrophy-1

NINDS : 51 Spinal Muscular Atrophy (SMA) Types I, II, and III belong to a group of hereditary diseases that cause weakness and wasting of the voluntary muscles in the arms and legs of infants and children. The disorders are caused by an abnormal or missing gene known as the survival motor neuron gene 1 (SMN1), which is responsible for the production of a protein essential to motor neurons. Without this protein, lower motor neurons in the spinal cord degenerate and die. The type of SMA (I, II, or III) is determined by the age of onset and the severity of symptoms. Type I (also known as Werdnig-Hoffman disease, or infantile-onset SMA) is evident at birth or within the first few months. Symptoms include floppy limbs and trunk, feeble movements of the arms and legs, swallowing and feeding difficulties, and impaired breathing. Type II (the intermediate form) usually begins 6 and 18 months of age. Legs tend to be more impaired than arms. Children with Type II may able to sit and some may be able to stand or walk with help. Symptoms of Type III (also called Kugelberg-Welander disease) appear between 2 and 17 years of age and include difficulty running, climbing steps, or rising from a chair.  The lower extremities are most often affected.  Complications include scoliosis and chronic shortening of muscles or tendons around joints.  

MalaCards based summary : Spinal Muscular Atrophy-1, also known as werdnig-hoffmann disease, is related to spinal muscular atrophy-3 and spinal muscular atrophy-2, and has symptoms including recurrent respiratory infections, atrial septal defect and respiratory failure. An important gene associated with Spinal Muscular Atrophy-1 is SMN1 (Survival Of Motor Neuron 1, Telomeric). The drugs Hydroxyurea and Valproic Acid have been mentioned in the context of this disorder. Affiliated tissues include spinal cord, brain and tongue.

NIH Rare Diseases : 50 spinal muscular atrophy 1 (sma1), also known as werdnig hoffmann disease, is a severe type of spinal muscular atrophy. symptoms of sma1 become apparent before 6 months of age and include worsening muscle weakness and poor muscle tone (hypotonia) due to loss of the lower motor neurons in the spinal cord and brain stem. feeding and breathing problems are also present. sma1 is caused by changes (mutations) in the smn1 gene and is typically inherited in an autosomal recessive manner. around 2% of cases are not inherited and are due to new mutations in the affected person. treatment is symptomatic and aims to improve quality of life. last updated: 9/21/2016

UniProtKB/Swiss-Prot : 71 Spinal muscular atrophy 1: A form of spinal muscular atrophy, a group of neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Autosomal recessive forms are classified according to the age of onset, the maximum muscular activity achieved, and survivorship. The severity of the disease is mainly determined by the copy number of SMN2, a copy gene which predominantly produces exon 7-skipped transcripts and only low amount of full-length transcripts that encode for a protein identical to SMN1. Only about 4% of SMA patients bear one SMN1 copy with an intragenic mutation. SMA1 is a severe form, with onset before 6 months of age. SMA1 patients never achieve the ability to sit.

OMIM : 54
Spinal muscular atrophy refers to a group of autosomal recessive neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy (summary by Wirth, 2000). Four types of SMA are recognized depending on the age of onset, the maximum muscular activity achieved, and survivorship: type I, severe infantile acute SMA, or Werdnig-Hoffman disease; type II (253550), or infantile chronic SMA; type III (253400), juvenile SMA, or Wohlfart-Kugelberg-Welander disease; and type IV (271150), or adult-onset SMA. All types are caused by recessive mutations in the SMN1 gene. Lunn and Wang (2008) provided a detailed review of clinical features, molecular pathogenesis, and therapeutic strategies for SMA. (253300)

Related Diseases for Spinal Muscular Atrophy-1

Diseases in the Spinal Muscular Atrophy family:

Spinal Muscular Atrophy-1 Spinal Muscular Atrophy-2
Spinal Muscular Atrophy-3 Spinal Muscular Atrophy-4
Congenital Benign Spinal Muscular Atrophy Dominant

Diseases related to Spinal Muscular Atrophy-1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 45)
id Related Disease Score Top Affiliating Genes
1 spinal muscular atrophy-3 31.6 NAIP SMN1 SMN2
2 spinal muscular atrophy-2 26.0 COX14 IGHMBP2 MAP1B NAIP SCO2 SMN1
3 spinal muscular atrophy 11.6
4 neuronopathy, distal hereditary motor, type vi 11.2
5 spinal muscular atrophy, x-linked 2, infantile 10.9
6 proximal spinal muscular atrophy 10.8
7 muscular atrophy 10.6
8 neuronitis 10.5
9 lateral sclerosis 10.4
10 stargardt disease, autosomal recessive 10.4 SMN1 SMN2
11 retinitis pigmentosa with or without skeletal anomalies 10.3 SMN1 SMN2
12 pancreatic acinar cell adenocarcinoma 10.2 SMN1 SMN2
13 myopathy 10.1
14 motor neuron disease 10.1
15 erythema elevatum diutinum 10.1 NAIP SMN1 SMN2
16 pseudoachondroplastic dysplasia 2 10.1 NAIP SMN1 SMN2
17 spinal muscular atrophy-4 10.1 NAIP SMN1 SMN2
18 eosinophilic variant of chromophobe renal cell carcinoma 10.1 NAIP SMN1 SMN2
19 spongiotic dermatitis 10.0 NAIP SMN1 SMN2
20 syphilis 10.0 MAP1B SMN1
21 congenital hypothyroidism 10.0
22 locked-in syndrome 10.0
23 ataxia 10.0
24 biliary atresia 10.0
25 hypothyroidism 10.0
26 multiple system atrophy 10.0
27 nemaline myopathy 10.0
28 laryngitis 10.0
29 cystic fibrosis 10.0
30 ataxia-telangiectasia 10.0
31 neuropathy 10.0
32 diabetes insipidus 10.0
33 cerebellar hypoplasia 10.0
34 acardia 10.0
35 mannosidosis 10.0
36 amyotonia congenita 10.0
37 cytoplasmic body myopathy 10.0
38 juvenile amyotrophic lateral sclerosis 10.0
39 spinal cord oligodendroglioma 9.9 SMN1 SMN2
40 mucopolysaccharidosis iii 9.8 NAIP SMN1 SMN2
41 long qt syndrome 5 9.5 NAIP SMN1 SMN2 SYP
42 esophageal adenoid cystic carcinoma 9.3 IGHMBP2 SMN1 SMN2 VRK1
43 sphenoid sinus inverted papilloma 8.4 IGHMBP2 NAIP SMN1 SMN2 VRK1 ZPR1
44 pain disorder 7.7 COX14 MAP1B NAIP SMN1 SMN2 VRK1
45 splenic marginal zone lymphoma 7.5 IGHMBP2 MAP1B NAIP SCO2 SMN1 SMN2

Graphical network of the top 20 diseases related to Spinal Muscular Atrophy-1:

Diseases related to Spinal Muscular Atrophy-1

Symptoms & Phenotypes for Spinal Muscular Atrophy-1

Symptoms via clinical synopsis from OMIM:


Cardiovascular- Heart:
atrial septal defect
ventricular septal defect
congenital cardiac malformations have been rarely reported in severe cases

Neurologic- Central Nervous System:
muscle atrophy
emg shows neurogenic abnormalities
muscle weakness, symmetric, proximal (lower limbs more affected than upper limbs) due to motor neuronopathy
affected children are unable to sit without support
respiratory failure

Prenatal Manifestations- Movement:
decreased fetal movement

Clinical features from OMIM:


Human phenotypes related to Spinal Muscular Atrophy-1:

32 (show all 11)
id Description HPO Frequency HPO Source Accession
1 recurrent respiratory infections 32 HP:0002205
2 atrial septal defect 32 HP:0001631
3 respiratory failure 32 HP:0002878
4 areflexia 32 HP:0001284
5 ventricular septal defect 32 HP:0001629
6 spinal muscular atrophy 32 HP:0007269
7 decreased fetal movement 32 HP:0001558
8 tongue fasciculations 32 HP:0001308
9 proximal muscle weakness in lower limbs 32 HP:0008994
10 proximal amyotrophy 32 HP:0007126
11 emg 32 HP:0003445

Drugs & Therapeutics for Spinal Muscular Atrophy-1

Drugs for Spinal Muscular Atrophy-1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 13)
id Name Status Phase Clinical Trials Cas Number PubChem Id
Hydroxyurea Approved Phase 1, Phase 2 127-07-1 3657
Valproic Acid Approved, Investigational Phase 1, Phase 2 99-66-1 3121
3 Nucleic Acid Synthesis Inhibitors Phase 1, Phase 2
4 Anticonvulsants Phase 1, Phase 2
5 Antimanic Agents Phase 1, Phase 2
6 Central Nervous System Depressants Phase 1, Phase 2
7 GABA Agents Phase 1, Phase 2
8 Neurotransmitter Agents Phase 1, Phase 2
9 Psychotropic Drugs Phase 1, Phase 2
10 Tranquilizing Agents Phase 1, Phase 2
11 4-phenylbutyric acid Phase 1, Phase 2
12 carnitine Nutraceutical Phase 1, Phase 2
Menthol Approved 2216-51-5 16666

Interventional clinical trials:

(show all 16)

id Name Status NCT ID Phase Drugs
1 Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1 Recruiting NCT03306277 Phase 3
2 A Pilot Therapeutic Trial Using Hydroxyurea in Type I Spinal Muscular Atrophy Patients Completed NCT00568698 Phase 1, Phase 2 Hydroxyurea
3 CARNIVAL Type I: Valproic Acid and Carnitine in Infants With Spinal Muscular Atrophy (SMA) Type I Completed NCT00661453 Phase 1, Phase 2 Valproic Acid and Levocarnitine
4 Study to Evaluate Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy Completed NCT00528268 Phase 1, Phase 2 Sodium phenylbutyrate (NaPB)
5 Allogeneic Adipose Derived Stem Cells for Werdnig Hoffman Patients Recruiting NCT02855112 Phase 1, Phase 2
6 Clinical Trial of Sodium Phenylbutyrate in Children With Spinal Muscular Atrophy Type I Terminated NCT00439218 Phase 1, Phase 2 sodium phenylbutyrate
7 Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1 Active, not recruiting NCT02122952 Phase 1
8 Natural History of Spinal Muscular Atrophy Type 1 in Taiwan Completed NCT02466529
9 A Pilot Study of Biomarkers for Spinal Muscular Atrophy Completed NCT00756821
10 Smartphone Application, Mood and Stress Completed NCT02365220
11 Pilot Study of an Innovative Physiotherapy in Patients With Infantile Spinal Muscular Atrophy (SMA) Recruiting NCT02061189
12 Prospective Evaluation of Infants With Spinal Muscular Atrophy: Recruiting NCT02831296
13 Palliative Care in Spinal Muscular Atrophy (SMA) 1 Active, not recruiting NCT01862042
14 International SMA Patient Registry Active, not recruiting NCT00466349
15 Development of a Space Exploration Assessment for Children With Spinal Muscular Atrophy Not yet recruiting NCT03223051
16 Infants With Spinal Muscular Atrophy Type I Terminated NCT01547871

Search NIH Clinical Center for Spinal Muscular Atrophy-1

Genetic Tests for Spinal Muscular Atrophy-1

Genetic tests related to Spinal Muscular Atrophy-1:

id Genetic test Affiliating Genes
1 Werdnig-Hoffmann Disease 29

Anatomical Context for Spinal Muscular Atrophy-1

MalaCards organs/tissues related to Spinal Muscular Atrophy-1:

Spinal Cord, Brain, Tongue

Publications for Spinal Muscular Atrophy-1

Articles related to Spinal Muscular Atrophy-1:

id Title Authors Year
Spinal muscular atrophy-1 and gastrostomy. ( 25041302 )

Variations for Spinal Muscular Atrophy-1

UniProtKB/Swiss-Prot genetic disease variations for Spinal Muscular Atrophy-1:

id Symbol AA change Variation ID SNP ID
1 SMN1 p.Tyr272Cys VAR_005617 rs104893922
2 SMN1 p.Gly279Val VAR_005620 rs76163360
3 SMN1 p.Ile116Phe VAR_034807 rs104893933
4 SMN1 p.Gln136Glu VAR_034808 rs104893934

ClinVar genetic disease variations for Spinal Muscular Atrophy-1:

6 (show all 18)
id Gene Variation Type Significance SNP ID Assembly Location
1 IGHMBP2 NM_002180.2(IGHMBP2): c.1540G> A (p.Glu514Lys) single nucleotide variant Pathogenic rs137852665 GRCh37 Chromosome 11, 68701934: 68701934
2 IGHMBP2 NM_002180.2(IGHMBP2): c.638A> G (p.His213Arg) single nucleotide variant Pathogenic rs137852666 GRCh37 Chromosome 11, 68678998: 68678998
3 IGHMBP2 NM_002180.2(IGHMBP2): c.1738G> A (p.Val580Ile) single nucleotide variant Pathogenic rs137852667 GRCh37 Chromosome 11, 68702872: 68702872
4 IGHMBP2 NM_002180.2(IGHMBP2): c.121C> T (p.Gln41Ter) single nucleotide variant Pathogenic rs137852668 GRCh37 Chromosome 11, 68673571: 68673571
5 IGHMBP2 NM_002180.2(IGHMBP2): c.675delT (p.Glu226Argfs) deletion Pathogenic rs786205089 GRCh38 Chromosome 11, 68911567: 68911567
6 IGHMBP2 NM_002180.2(IGHMBP2): c.707T> G (p.Leu236Ter) single nucleotide variant Pathogenic rs137852669 GRCh37 Chromosome 11, 68679067: 68679067
7 IGHMBP2 NM_002180.2(IGHMBP2): c.2611+1G> T single nucleotide variant Pathogenic rs786205090 GRCh38 Chromosome 11, 68937092: 68937092
8 IGHMBP2 NM_002180.2(IGHMBP2): c.1107C> G (p.Phe369Leu) single nucleotide variant Pathogenic rs137852670 GRCh37 Chromosome 11, 68696697: 68696697
9 IGHMBP2 NG_007976.1: g.(7904_7936)_(26407_26439)del deletion Pathogenic GRCh38 Chromosome 11, 68906754: 68925289
10 SMN1 SMN1, 11-BP DUP, 801-811 duplication Pathogenic
11 SMN1 NM_000344.3(SMN1): c.815A> G (p.Tyr272Cys) single nucleotide variant Pathogenic rs104893922 GRCh37 Chromosome 5, 70241984: 70241984
12 SMN1 NM_000344.3(SMN1): c.836G> T (p.Gly279Val) single nucleotide variant Pathogenic rs76163360 GRCh37 Chromosome 5, 70247769: 70247769
13 SMN1 SMN1, 5-BP DEL, 425 deletion Pathogenic
14 SMN1 SMN1, 4-BP DEL, 399AGAG deletion Pathogenic
15 SMN1 NM_000344.3(SMN1): c.332C> G (p.Ala111Gly) single nucleotide variant Pathogenic rs104893935 GRCh37 Chromosome 5, 70238243: 70238243
16 SMN1 NM_000344.3(SMN1): c.346A> T (p.Ile116Phe) single nucleotide variant Pathogenic rs104893933 GRCh37 Chromosome 5, 70238257: 70238257
17 SMN1 NM_000344.3(SMN1): c.406C> G (p.Gln136Glu) single nucleotide variant Pathogenic rs104893934 GRCh37 Chromosome 5, 70238317: 70238317
18 SMN1 NC_000005.9: g.70241893_70242003del deletion Pathogenic GRCh37 Chromosome 5, 70241893: 70242003

Expression for Spinal Muscular Atrophy-1

Search GEO for disease gene expression data for Spinal Muscular Atrophy-1.

Pathways for Spinal Muscular Atrophy-1

GO Terms for Spinal Muscular Atrophy-1

Cellular components related to Spinal Muscular Atrophy-1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 cell projection GO:0042995 9.77 IGHMBP2 MAP1B SMN1 SMN2 ZPR1
2 neuron projection GO:0043005 9.62 NAIP SMN1 SMN2 SYP
3 perikaryon GO:0043204 9.46 NAIP SMN1 SMN2 ZPR1
4 cytoplasmic ribonucleoprotein granule GO:0036464 9.43 SMN1 SMN2
5 Cajal body GO:0015030 9.43 SMN1 SMN2 ZPR1
6 SMN-Sm protein complex GO:0034719 9.4 SMN1 SMN2
7 Gemini of coiled bodies GO:0097504 9.13 SMN1 SMN2 ZPR1
8 SMN complex GO:0032797 8.92 IGHMBP2 SMN1 SMN2 ZPR1

Biological processes related to Spinal Muscular Atrophy-1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 mRNA processing GO:0006397 9.58 SMN1 SMN2 ZPR1
2 RNA splicing GO:0008380 9.54 SMN1 SMN2 ZPR1
3 nervous system development GO:0007399 9.46 MAP1B NAIP SMN1 SMN2
4 spliceosomal snRNP assembly GO:0000387 9.32 SMN1 SMN2
5 spliceosomal complex assembly GO:0000245 9.26 SMN1 SMN2
6 nuclear import GO:0051170 8.96 SMN1 SMN2
7 DNA-templated transcription, termination GO:0006353 8.62 SMN1 SMN2

Sources for Spinal Muscular Atrophy-1

9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
32 HPO
33 ICD10
34 ICD10 via Orphanet
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
52 Novoseek
55 OMIM via Orphanet
59 PubMed
66 SNOMED-CT via Orphanet
68 Tocris
70 UMLS via Orphanet
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