MCID: SPN423
MIFTS: 25

Spinal Muscular Atrophy with Lower Extremity Predominance

Categories: Genetic diseases, Muscle diseases, Neuronal diseases

Aliases & Classifications for Spinal Muscular Atrophy with Lower Extremity Predominance

MalaCards integrated aliases for Spinal Muscular Atrophy with Lower Extremity Predominance:

Name: Spinal Muscular Atrophy with Lower Extremity Predominance 12 43 15
Lower Extremity-Predominant Autosomal Dominant Proximal Spinal Muscular Atrophy with Contractures 43
Autosomal Dominant Childhood-Onset Proximal Spinal Muscular Atrophy with Contractures 43
Spinal Muscular Atrophy, Childhood, Proximal, Autosomal Dominant 43
Spinal Muscular Atrophy, Juvenile, Proximal, Autosomal Dominant 43
Atrophy, Muscular, Spinal, Lower Extremity, Autosomal Dominant 39
Spinal Muscular Atrophy, Lower Extremity, Autosomal Dominant 43
Spinal Muscular Atrophy, Lower Extremity, Dominant 43
Kugelberg-Welander Syndrome, Autosomal Dominant 43
Sma-Led 43

Classifications:



External Ids:

Disease Ontology 12 DOID:0070348

Summaries for Spinal Muscular Atrophy with Lower Extremity Predominance

MedlinePlus Genetics : 43 Spinal muscular atrophy with lower extremity predominance (SMA-LED) is characterized by muscle weakness and wasting (atrophy) in the lower limbs, most severely affecting the thigh muscles (quadriceps). (In SMA-LED, the "D" stands for dominant, which refers to the inheritance pattern of this condition.) The loss of nerve cells that control muscle movement (motor neurons) leads to atrophy of the muscles in the lower limbs. Affected individuals often have a waddling or unsteady walk and walk on the balls of their feet. They may have difficulty rising from a seated position and climbing stairs. Some people with SMA-LED also have weakness in upper limb muscles.Joint deformities (contractures) in the hips, knees, feet, and ankles can occur in SMA-LED, and in severe cases are present from birth and can impair walking. Some individuals with this disorder have rigidity of joints (arthrogryposis) in their shoulders, elbows, and hands.In most people with SMA-LED, the muscle problems are apparent in infancy or early childhood; however, about one-quarter of affected individuals do not develop muscle weakness until adulthood. The muscle weakness and related health problems typically do not worsen over time.

MalaCards based summary : Spinal Muscular Atrophy with Lower Extremity Predominance, also known as lower extremity-predominant autosomal dominant proximal spinal muscular atrophy with contractures, is related to spinal muscular atrophy and autosomal dominant childhood-onset proximal spinal muscular atrophy. An important gene associated with Spinal Muscular Atrophy with Lower Extremity Predominance is DYNC1H1 (Dynein Cytoplasmic 1 Heavy Chain 1), and among its related pathways/superpathways are Lissencephaly gene (LIS1) in neuronal migration and development and COPI-independent Golgi-to-ER retrograde traffic. Affiliated tissues include skeletal muscle, and related phenotype is behavior/neurological.

Disease Ontology : 12 A spinal muscular atrophy that has material basis in autosomal dominant inheritance and is characterized by muscle weakness and wasting in the lower limbs, most affecting the thigh muscles.

Related Diseases for Spinal Muscular Atrophy with Lower Extremity Predominance

Diseases in the Spinal Muscular Atrophy with Lower Extremity Predominance family:

Spinal Muscular Atrophy with Lower Extremity Predominance 2a Spinal Muscular Atrophy with Lower Extremity Predominance 1

Diseases related to Spinal Muscular Atrophy with Lower Extremity Predominance via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 81)
# Related Disease Score Top Affiliating Genes
1 spinal muscular atrophy 31.5 VAPB SETX IGHMBP2 GARS1 DYNC1H1 BICD2
2 autosomal dominant childhood-onset proximal spinal muscular atrophy 31.2 DYNC1H1 BICD2
3 distal hereditary motor neuropathies 30.7 SETX GARS1
4 muscular atrophy 30.2 VAPB SETX IGHMBP2 GARS1 DYNC1H1 BICD2
5 tooth disease 30.1 IGHMBP2 GDAP1 GARS1 DYNC1H1
6 charcot-marie-tooth disease 29.5 SETX IGHMBP2 GDAP1 GARS1 DYNC1H1 BICD2
7 spinal muscular atrophy with lower extremity predominance 1 12.0
8 spinal muscular atrophy with lower extremity predominance 2a 11.9
9 spinal muscular atrophy, lower extremity-predominant, 2a, childhood onset, autosomal dominant 11.8
10 spinal muscular atrophy, lower extremity-predominant, 1, autosomal dominant 11.6
11 spinal muscular atrophy with lower extremity predominante 2b 11.5
12 charcot-marie-tooth disease, axonal, type 2o 10.5
13 mental retardation, autosomal dominant 13 10.3 DYNC1H1 BICD2
14 scoliosis 10.3
15 polyhydramnios 10.3
16 autosomal dominant spinal muscular atrophy, lower extremity-predominant 2 10.3
17 congenital amyoplasia 10.3
18 respiratory failure 10.2
19 clubfoot 10.2
20 charcot-marie-tooth disease type 5 10.2 GARS1 DYNC1H1
21 autosomal dominant adult-onset proximal spinal muscular atrophy 10.2 VAPB SGSM1
22 charcot-marie-tooth hereditary neuropathy 10.2 IGHMBP2 GARS1
23 neuronopathy, distal hereditary motor, type iib 10.2 IGHMBP2 GARS1
24 amyotrophic lateral sclerosis type 15 10.2 VAPB SETX
25 amyotrophic lateral sclerosis type 14 10.2 VAPB SETX
26 amyotrophic lateral sclerosis 7 10.2 VAPB SETX
27 amyotrophic lateral sclerosis 18 10.2 VAPB SETX
28 progressive bulbar palsy 10.2 VAPB SETX
29 charcot-marie-tooth disease, dominant intermediate e 10.2 GDAP1 DYNC1H1
30 amyotrophic lateral sclerosis 21 10.2 VAPB SETX
31 spinal muscular atrophy, distal, autosomal recessive, 2 10.2 GARS1 BICD2
32 amyotrophic lateral sclerosis 11 10.2 VAPB SETX
33 amyotrophic lateral sclerosis 16, juvenile 10.1 VAPB SETX
34 charcot-marie-tooth disease, axonal, type 2k 10.1 GDAP1 DYNC1H1
35 amyotrophic lateral sclerosis type 5 10.1 VAPB SETX
36 amyotrophic lateral sclerosis 10 with or without frontotemporal dementia 10.1 VAPB SETX
37 charcot-marie-tooth disease, demyelinating, type 1f 10.1 GDAP1 DYNC1H1
38 distal hereditary motor neuronopathy type 7 10.1 PAFAH1B1 DYNC1H1
39 amyotrophic lateral sclerosis type 12 10.1 VAPB SETX
40 neuronopathy, distal hereditary motor, type viib 10.1 PAFAH1B1 DYNC1H1
41 charcot-marie-tooth disease, axonal, type 2t 10.1 IGHMBP2 GDAP1
42 amyotrophic lateral sclerosis 8 10.1 VAPB SETX
43 neuronal migration disorders 10.1 PAFAH1B1 DYNC1H1
44 charcot-marie-tooth disease, axonal, type 2i 10.1 GDAP1 GARS1
45 brown-vialetto-van laere syndrome 10.1 IGHMBP2 BICD2
46 amyotrophic lateral sclerosis type 6 10.1 VAPB SETX
47 charcot-marie-tooth disease, axonal, type 2n 10.1 GDAP1 GARS1
48 charcot-marie-tooth disease, demyelinating, type 1d 10.1 GDAP1 GARS1
49 charcot-marie-tooth disease intermediate type 10.1 GDAP1 GARS1
50 charcot-marie-tooth disease type x 10.1 GDAP1 GARS1

Graphical network of the top 20 diseases related to Spinal Muscular Atrophy with Lower Extremity Predominance:



Diseases related to Spinal Muscular Atrophy with Lower Extremity Predominance

Symptoms & Phenotypes for Spinal Muscular Atrophy with Lower Extremity Predominance

MGI Mouse Phenotypes related to Spinal Muscular Atrophy with Lower Extremity Predominance:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.28 BICD2 DYNC1H1 GARS1 GDAP1 HOOK3 IGHMBP2

Drugs & Therapeutics for Spinal Muscular Atrophy with Lower Extremity Predominance

Search Clinical Trials , NIH Clinical Center for Spinal Muscular Atrophy with Lower Extremity Predominance

Genetic Tests for Spinal Muscular Atrophy with Lower Extremity Predominance

Anatomical Context for Spinal Muscular Atrophy with Lower Extremity Predominance

MalaCards organs/tissues related to Spinal Muscular Atrophy with Lower Extremity Predominance:

40
Skeletal Muscle

Publications for Spinal Muscular Atrophy with Lower Extremity Predominance

Articles related to Spinal Muscular Atrophy with Lower Extremity Predominance:

(show all 18)
# Title Authors PMID Year
1
A case of severe autosomal dominant spinal muscular atrophy with lower extremity predominance caused by a de novo BICD2 mutation. 61
32888736 2021
2
The Genotypic and Phenotypic Spectrum of BICD2 Variants in Spinal Muscular Atrophy. 61
32057122 2020
3
Adult-onset SMALED2 due to a novel BICD2 mutation presenting with asymmetrical lower limb involvement. 61
30738493 2019
4
A recurrent de novo DYNC1H1 tail domain mutation causes spinal muscular atrophy with lower extremity predominance, learning difficulties and mild brain abnormality. 61
30122514 2018
5
A missense mutation in DYNC1H1 gene causing spinal muscular atrophy - Lower extremity, dominant. 61
29306600 2018
6
Exome Sequencing Identifies De Novo DYNC1H1 Mutations Associated With Distal Spinal Muscular Atrophy and Malformations of Cortical Development. 61
28193117 2017
7
DYNC1H1 mutations associated with neurological diseases compromise processivity of dynein-dynactin-cargo adaptor complexes. 61
28196890 2017
8
Expanding the phenotype of BICD2 mutations toward skeletal muscle involvement. 61
27784775 2016
9
Autosomal dominant spinal muscular atrophy with lower extremity predominance: A recognizable phenotype of BICD2 mutations. 61
26998597 2016
10
A novel DYNC1H1 mutation causing spinal muscular atrophy with lower extremity predominance. 61
27066557 2015
11
Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy. 61
25609763 2015
12
Exome Sequencing Identifies DYNC1H1 Variant Associated With Vertebral Abnormality and Spinal Muscular Atrophy With Lower Extremity Predominance. 61
25484024 2015
13
DYNC1H1 mutation alters transport kinetics and ERK1/2-cFos signalling in a mouse model of distal spinal muscular atrophy. 61
24755273 2014
14
Morphological changes and altered expression of antioxidant proteins in a heterozygous dynein mutant; a mouse model of spinal muscular atrophy. 61
25866698 2014
15
Dynein mutations associated with hereditary motor neuropathies impair mitochondrial morphology and function with age. 61
23742762 2013
16
A DYNC1H1 mutation causes a dominant spinal muscular atrophy with lower extremity predominance. 61
22847149 2012
17
Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy. 61
22459677 2012
18
Dominant spinal muscular atrophy with lower extremity predominance: linkage to 14q32. 61
20697106 2010

Variations for Spinal Muscular Atrophy with Lower Extremity Predominance

Expression for Spinal Muscular Atrophy with Lower Extremity Predominance

Search GEO for disease gene expression data for Spinal Muscular Atrophy with Lower Extremity Predominance.

Pathways for Spinal Muscular Atrophy with Lower Extremity Predominance

Pathways related to Spinal Muscular Atrophy with Lower Extremity Predominance according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.45 PAFAH1B1 DYNC1H1
2 10.25 PAFAH1B1 DYNC1H1 BICD2

GO Terms for Spinal Muscular Atrophy with Lower Extremity Predominance

Cellular components related to Spinal Muscular Atrophy with Lower Extremity Predominance according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.92 SGSM1 PAFAH1B1 HOOK3 GDAP1 GARS1 DYNC1H1
2 centrosome GO:0005813 9.56 PAFAH1B1 HOOK3 DYNC1H1 BICD2
3 cytoplasm GO:0005737 9.36 VAPB SGSM1 SETX PAFAH1B1 IGHMBP2 HOOK3
4 growth cone GO:0030426 9.33 SETX PAFAH1B1 IGHMBP2
5 axon GO:0030424 9.26 SETX PAFAH1B1 IGHMBP2 GARS1

Biological processes related to Spinal Muscular Atrophy with Lower Extremity Predominance according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasmic microtubule organization GO:0031122 9.26 HOOK3 DYNC1H1
2 regulation of microtubule cytoskeleton organization GO:0070507 9.16 PAFAH1B1 BICD2
3 nuclear migration GO:0007097 8.96 PAFAH1B1 DYNC1H1
4 retrograde axonal transport GO:0008090 8.62 PAFAH1B1 DYNC1H1

Molecular functions related to Spinal Muscular Atrophy with Lower Extremity Predominance according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 microtubule binding GO:0008017 9.5 VAPB PAFAH1B1 HOOK3
2 dynein intermediate chain binding GO:0045505 9.33 PAFAH1B1 HOOK3 DYNC1H1
3 dynein complex binding GO:0070840 9.26 PAFAH1B1 BICD2
4 dynein light intermediate chain binding GO:0051959 9.13 HOOK3 DYNC1H1 BICD2
5 dynactin binding GO:0034452 8.8 PAFAH1B1 HOOK3 BICD2

Sources for Spinal Muscular Atrophy with Lower Extremity Predominance

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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