MCID: SPN394
MIFTS: 45

Spinal Muscular Atrophy, Type Iii

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

Aliases & Classifications for Spinal Muscular Atrophy, Type Iii

MalaCards integrated aliases for Spinal Muscular Atrophy, Type Iii:

Name: Spinal Muscular Atrophy, Type Iii 57
Kugelberg-Welander Disease 59 29 6
Sma Iii 57 75 55
Sma3 57 59 75
Juvenile Spinal Muscular Atrophy 59 73
Kugelberg-Welander Syndrome 57 75
Spinal Muscular Atrophy-3 57 13
Kws 57 75
Spinal Muscular Atrophy, Mild Childhood and Adolescent Form 57
Spinal Muscular Atrophy Mild Childhood and Adolescent Form 75
Spinal Muscular Atrophy, Type Iii, Modifier of 57
Proximal Spinal Muscular Atrophy Type 3 59
Wohlfart-Kugelberg-Welander Disease 75
Atrophy, Muscular, Spinal, Type Iii 40
Kugelberg-Welander Syndrome; Kws 57
Spinal Muscular Atrophy Type Iii 75
Muscular Atrophy, Juvenile 57
Spinal Muscular Atrophy 3 75
Sma Type Iii 59
Sma Type 3 59
Sma-Iii 59

Characteristics:

Orphanet epidemiological data:

59
proximal spinal muscular atrophy type 3
Inheritance: Autosomal recessive; Age of onset: Childhood; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset usually in childhood or adolescence
presentation after 18 months
individuals develop ability to stand and walk
deletions in naip gene found in 18% of sma2 patients


HPO:

32
spinal muscular atrophy, type iii:
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 253400
Orphanet 59 ORPHA83419
UMLS via Orphanet 74 C0152109
ICD10 via Orphanet 34 G12.1
MedGen 42 C0152109
MeSH 44 D014897

Summaries for Spinal Muscular Atrophy, Type Iii

NINDS : 54 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, Type Iii, also known as kugelberg-welander disease, is related to juvenile spinal muscular atrophy and spinal muscular atrophy, type i, and has symptoms including muscle cramp and tremor of hands. An important gene associated with Spinal Muscular Atrophy, Type Iii is SMN1 (Survival Of Motor Neuron 1, Telomeric), and among its related pathways/superpathways is RNA transport. The drugs Hydroxyurea and Anticonvulsants have been mentioned in the context of this disorder. Affiliated tissues include spinal cord and tongue, and related phenotypes are muscle weakness and emg abnormality

OMIM : 57 SMA is an autosomal recessive neuromuscular disorder characterized by progressive proximal muscle weakness and atrophy affecting the upper and lower limbs. By convention, SMA is classified into 4 types: I (SMA1; 253300), II (SMA2; 253550), III (SMA3), and IV (271150), by increasing age at onset and decreasing clinical severity. SMA1 is the most severe form of the disorder and often results in death in early childhood. SMA3, known as the juvenile form, tends to show onset in childhood or adolescence (summary by Fraidakis et al., 2012). (253400)

UniProtKB/Swiss-Prot : 75 Spinal muscular atrophy 3: 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 after 18 months. Patients develop ability to stand and walk and survive into adulthood.

Related Diseases for Spinal Muscular Atrophy, Type Iii

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
Juvenile Spinal Muscular Atrophy Congenital Benign Spinal Muscular Atrophy Dominant

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

(show all 23)
# Related Disease Score Top Affiliating Genes
1 juvenile spinal muscular atrophy 31.2 NAIP SMN1 SMN2
2 spinal muscular atrophy, type i 30.0 NAIP SMN1 SMN2
3 proximal spinal muscular atrophy 29.8 NAIP SMN1 SMN2
4 muscular atrophy 29.0 NAIP SMN1 SMN2
5 spinal muscular atrophy 28.9 NAIP SMN1 SMN2
6 spinal muscular atrophy, lower extremity-predominant, 1, autosomal dominant 11.4
7 polyglucosan body myopathy 1 with or without immunodeficiency 9.9
8 joint disorders 9.9
9 atrial heart septal defect 9.9
10 neuronitis 9.9
11 spinal muscular atrophy, type iv 9.8 SMN1 SMN2
12 progressive muscular atrophy 9.8 SMN1 SMN2
13 anterior horn cell disease 9.7 SMN1 SMN2
14 peripheral nervous system disease 9.6 SMN1 SMN2
15 central nervous system disease 9.5 SMN1 SMN2
16 nervous system disease 9.2 SMN1 SMN2
17 survival motor neuron spinal muscular atrophy 9.0 NAIP SMN1 SMN2
18 spinal muscular atrophy, type ii 9.0 NAIP SMN1 SMN2
19 spinal disease 9.0 NAIP SMN1 SMN2
20 muscle tissue disease 8.9 NAIP SMN1 SMN2
21 neuromuscular disease 8.9 NAIP SMN1 SMN2
22 motor neuron disease 8.9 NAIP SMN1 SMN2
23 amyotrophic lateral sclerosis 1 8.7 NAIP SMN1 SMN2

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



Diseases related to Spinal Muscular Atrophy, Type Iii

Symptoms & Phenotypes for Spinal Muscular Atrophy, Type Iii

Symptoms via clinical synopsis from OMIM:

57
Muscle Soft Tissue:
muscle cramps
proximal muscle weakness and atrophy
chronic denervation seen on emg
neuropathic process seen on muscle biopsy

Neurologic Central Nervous System:
hand tremor
degeneration of anterior horn cells
muscle weakness, symmetric, proximal (lower limbs more affected than upper limbs) due to motor neuronopathy
tongue fasciculation/fibrillation
limb fasciculation

Neurologic Peripheral Nervous System:
hyporeflexia
areflexia of the lower limbs


Clinical features from OMIM:

253400

Human phenotypes related to Spinal Muscular Atrophy, Type Iii:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 muscle weakness 32 HP:0001324
2 emg abnormality 32 HP:0003457
3 areflexia of lower limbs 32 HP:0002522
4 muscle cramps 32 HP:0003394
5 hyporeflexia 32 HP:0001265
6 limb fasciculations 32 HP:0007289
7 tongue fasciculations 32 HP:0001308
8 hand tremor 32 HP:0002378
9 degeneration of anterior horn cells 32 HP:0002398
10 spinal muscular atrophy 32 HP:0007269

UMLS symptoms related to Spinal Muscular Atrophy, Type Iii:


muscle cramp, tremor of hands

Drugs & Therapeutics for Spinal Muscular Atrophy, Type Iii

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

(show all 10)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Hydroxyurea Approved Phase 1, Phase 2 127-07-1 3657
2 Anticonvulsants Phase 2
3 Bromides Phase 2
4 Cholinergic Agents Phase 2
5 Cholinesterase Inhibitors Phase 2
6 Neurotransmitter Agents Phase 2
7 Pyridostigmine Bromide Phase 2 101-26-8
8 Nucleic Acid Synthesis Inhibitors Phase 1, Phase 2
9 4-phenylbutyric acid Phase 1, Phase 2
10
Menthol Approved Not Applicable 2216-51-5 16666

Interventional clinical trials:

(show all 12)
# Name Status NCT ID Phase Drugs
1 Safety and Efficacy Study of Pyridostigmine on Patients With Spinal Muscular Atrophy Type 3 Unknown status NCT02227823 Phase 2 Pyridostigmine Bromide
2 A Pilot Therapeutic Trial Using Hydroxyurea in Type II and Type III Spinal Muscular Atrophy Patients Unknown status NCT00568802 Phase 1, Phase 2 Hydroxyurea
3 Safety and Efficacy of Olesoxime (TRO19622) in 3-25 Years SMA Patients. Completed NCT01302600 Phase 2 Olesoxime;Placebo
4 SPACE Trial: Pyridostigmine vs Placebo in SMA Types 2, 3 and 4 Completed NCT02941328 Phase 2 Pyridostigmine;Placebo
5 Clinical Trial of Sodium Phenylbutyrate in Children With Spinal Muscular Atrophy Types II or III Terminated NCT00439569 Phase 1, Phase 2 sodium phenylbutyrate
6 Motor Development and Orthoses in Spinal Muscular Atrophy (SMA) Unknown status NCT00961103
7 Aerobic Training in Patients With Spinal Muscular Atrophy Type III Completed NCT02003937 Not Applicable
8 A Pilot Study of Biomarkers for Spinal Muscular Atrophy Completed NCT00756821
9 Whole Body Vibration Therapy in Children With Spinal Muscular Atrophy Recruiting NCT03056144 Not Applicable
10 Oxidative Capacity and Exercise Tolerance in Ambulatory SMA Recruiting NCT02895789
11 Prospective Evaluation of Infants With Spinal Muscular Atrophy: Recruiting NCT02831296
12 International SMA Patient Registry Active, not recruiting NCT00466349

Search NIH Clinical Center for Spinal Muscular Atrophy, Type Iii

Genetic Tests for Spinal Muscular Atrophy, Type Iii

Genetic tests related to Spinal Muscular Atrophy, Type Iii:

# Genetic test Affiliating Genes
1 Kugelberg-Welander Disease 29 SMN1 SMN2

Anatomical Context for Spinal Muscular Atrophy, Type Iii

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

41
Spinal Cord, Tongue

Publications for Spinal Muscular Atrophy, Type Iii

Articles related to Spinal Muscular Atrophy, Type Iii:

(show all 15)
# Title Authors Year
1
Atrial Septal Defect, Neuromuscular Junction and Skeletal Abnormalities in Spinal Muscular Atrophy Type III. ( 28937047 )
2017
2
Compensatory axon sprouting for very slow axonal die-back in a transgenic model of spinal muscular atrophy type III. ( 27891608 )
2016
3
Spinal Muscular Atrophy Type III: Molecular Genetic Characterization of Turkish Patients. ( 26548498 )
2015
4
Training improves oxidative capacity, but not function, in spinal muscular atrophy type III. ( 25418505 )
2015
5
Reversal of neuromuscular blockade with sugammadex in a patient with spinal muscular atrophy type III (Kugelberg-Welander syndrome). ( 22198219 )
2012
6
Spinal muscular atrophy type III: trying to understand subtle functional change over time--a case report. ( 22156787 )
2012
7
Dexmedetomidine for awake fiberoptic intubation in a parturient with spinal muscular atrophy type III for cesarean delivery. ( 19733055 )
2009
8
Conservative care of temporomandibular joint disorder in a 35-year-old patient with spinal muscular atrophy type III: a case study. ( 19948309 )
2009
9
Malignant ventricular arrhythmia in a case of adult onset of spinal muscular atrophy (Kugelberg-Welander disease). ( 19175839 )
2009
10
Compensatory mechanisms during walking in response to muscle weakness in spinal muscular atrophy, type III. ( 17980600 )
2008
11
Reduced survival motor neuron (Smn) gene dose in mice leads to motor neuron degeneration: an animal model for spinal muscular atrophy type III. ( 10655542 )
2000
12
Differentiation of Becker muscular dystrophy from limb-girdle muscular dystrophy and Kugelberg-Welander disease using a cDNA probe. ( 2255288 )
1990
13
Juvenile spinal muscular atrophy (Wohlfart Kugelberg Welander Disease): a case report. ( 977103 )
1976
14
Spinal muscular atrophy type II. A separate genetic and clinical entity from type I (Werdnig-Hoffmann disease) and type 3 (Kugelberg-Welander disease). ( 5146579 )
1971
15
Neurogenic muscular atrophy simulating facioscapulohumeral muscular dystrophy with particular reference to the heterogeneity of Kugelberg-Welander disease. ( 5345117 )
1969

Variations for Spinal Muscular Atrophy, Type Iii

UniProtKB/Swiss-Prot genetic disease variations for Spinal Muscular Atrophy, Type Iii:

75
# Symbol AA change Variation ID SNP ID
1 SMN1 p.Ala2Gly VAR_005615 rs75030631
2 SMN1 p.Ser262Ile VAR_005616 rs75660264
3 SMN1 p.Thr274Ile VAR_005618 rs76871093
4 SMN1 p.Gly275Ser VAR_005619 rs77301881
5 SMN1 p.Gly279Cys VAR_007990 rs77969175
6 SMN1 p.Pro245Leu VAR_010051 rs75586164
7 SMN1 p.Asp44Val VAR_034804 rs104893931
8 SMN1 p.Gly95Arg VAR_034805 rs104893927
9 SMN1 p.Ser262Gly VAR_034809 rs104893932

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

6
(show all 25)
# Gene Variation Type Significance SNP ID Assembly Location
1 SMN2 NM_017411.3(SMN2): c.859G> C (p.Gly287Arg) single nucleotide variant Pathogenic,risk factor rs121909192 GRCh37 Chromosome 5, 69372372: 69372372
2 SMN2 NM_017411.3(SMN2): c.859G> C (p.Gly287Arg) single nucleotide variant Pathogenic,risk factor rs121909192 GRCh38 Chromosome 5, 70076545: 70076545
3 SMN1 NM_000344.3(SMN1): c.821C> T (p.Thr274Ile) single nucleotide variant Pathogenic rs76871093 GRCh37 Chromosome 5, 70241990: 70241990
4 SMN1 NM_000344.3(SMN1): c.821C> T (p.Thr274Ile) single nucleotide variant Pathogenic rs76871093 GRCh38 Chromosome 5, 70946163: 70946163
5 SMN1 NM_000344.3(SMN1): c.785G> T (p.Ser262Ile) single nucleotide variant Pathogenic rs75660264 GRCh37 Chromosome 5, 70241954: 70241954
6 SMN1 NM_000344.3(SMN1): c.785G> T (p.Ser262Ile) single nucleotide variant Pathogenic rs75660264 GRCh38 Chromosome 5, 70946127: 70946127
7 SMN1 NM_000344.3(SMN1): c.5C> G (p.Ala2Gly) single nucleotide variant Pathogenic rs75030631 GRCh37 Chromosome 5, 70220935: 70220935
8 SMN1 NM_000344.3(SMN1): c.5C> G (p.Ala2Gly) single nucleotide variant Pathogenic rs75030631 GRCh38 Chromosome 5, 70925108: 70925108
9 SMN1 SMN1, EX8DEL deletion Pathogenic
10 SMN1 SMN1, IVS7DS, T-G, +6 single nucleotide variant Pathogenic
11 SMN1 NM_000344.3(SMN1): c.131A> T (p.Asp44Val) single nucleotide variant Pathogenic rs104893931 GRCh37 Chromosome 5, 70234715: 70234715
12 SMN1 NM_000344.3(SMN1): c.131A> T (p.Asp44Val) single nucleotide variant Pathogenic rs104893931 GRCh38 Chromosome 5, 70938888: 70938888
13 SMN1 NM_000344.3(SMN1): c.305G> A (p.Trp102Ter) single nucleotide variant Pathogenic rs77804083 GRCh37 Chromosome 5, 70238216: 70238216
14 SMN1 NM_000344.3(SMN1): c.305G> A (p.Trp102Ter) single nucleotide variant Pathogenic rs77804083 GRCh38 Chromosome 5, 70942389: 70942389
15 SMN1 SMN1, 4-BP DEL, 399AGAG deletion Pathogenic
16 SMN1 NM_000344.3(SMN1): c.283G> C (p.Gly95Arg) single nucleotide variant Pathogenic rs104893927 GRCh37 Chromosome 5, 70238194: 70238194
17 SMN1 NM_000344.3(SMN1): c.283G> C (p.Gly95Arg) single nucleotide variant Pathogenic rs104893927 GRCh38 Chromosome 5, 70942367: 70942367
18 SMN1 NM_000344.3(SMN1): c.784A> G (p.Ser262Gly) single nucleotide variant Pathogenic rs104893932 GRCh37 Chromosome 5, 70241953: 70241953
19 SMN1 NM_000344.3(SMN1): c.784A> G (p.Ser262Gly) single nucleotide variant Pathogenic rs104893932 GRCh38 Chromosome 5, 70946126: 70946126
20 SMN1 SMN1, DEL deletion Pathogenic
21 SMN1 NM_000344.3(SMN1): c.389A> G (p.Tyr130Cys) single nucleotide variant Pathogenic rs397514517 GRCh37 Chromosome 5, 70238300: 70238300
22 SMN1 NM_000344.3(SMN1): c.389A> G (p.Tyr130Cys) single nucleotide variant Pathogenic rs397514517 GRCh38 Chromosome 5, 70942473: 70942473
23 SMN1 NM_000344.3(SMN1): c.388T> C (p.Tyr130His) single nucleotide variant Pathogenic rs397514518 GRCh37 Chromosome 5, 70238299: 70238299
24 SMN1 NM_000344.3(SMN1): c.388T> C (p.Tyr130His) single nucleotide variant Pathogenic rs397514518 GRCh38 Chromosome 5, 70942472: 70942472
25 SMN1 NC_000005.9: g.70241893_70242003del deletion Pathogenic GRCh37 Chromosome 5, 70241893: 70242003

Expression for Spinal Muscular Atrophy, Type Iii

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

Pathways for Spinal Muscular Atrophy, Type Iii

Pathways related to Spinal Muscular Atrophy, Type Iii according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.86 SMN1 SMN2

GO Terms for Spinal Muscular Atrophy, Type Iii

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

# Name GO ID Score Top Affiliating Genes
1 neuron projection GO:0043005 9.5 NAIP SMN1 SMN2
2 Z disc GO:0030018 9.43 SMN1 SMN2
3 cytoplasmic ribonucleoprotein granule GO:0036464 9.4 SMN1 SMN2
4 Cajal body GO:0015030 9.37 SMN1 SMN2
5 SMN-Sm protein complex GO:0034719 9.26 SMN1 SMN2
6 SMN complex GO:0032797 9.16 SMN1 SMN2
7 Gemini of coiled bodies GO:0097504 8.96 SMN1 SMN2
8 perikaryon GO:0043204 8.8 NAIP SMN1 SMN2

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

# Name GO ID Score Top Affiliating Genes
1 nervous system development GO:0007399 9.5 NAIP SMN1 SMN2
2 RNA splicing GO:0008380 9.37 SMN1 SMN2
3 spliceosomal complex assembly GO:0000245 9.26 SMN1 SMN2
4 spliceosomal snRNP assembly GO:0000387 9.16 SMN1 SMN2
5 import into nucleus GO:0051170 8.96 SMN1 SMN2
6 DNA-templated transcription, termination GO:0006353 8.62 SMN1 SMN2

Sources for Spinal Muscular Atrophy, Type Iii

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
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