SMALED1
MCID: SPN385
MIFTS: 31

Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant (SMALED1)

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

Aliases & Classifications for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

MalaCards integrated aliases for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:

Name: Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant 57 20
Smaled1 57 20 58 72
Dync1h1-Related Lower Extremity-Predominant Autosomal Dominant Proximal Spinal Muscular Atrophy 20 58
Dync1h1-Related Autosomal Dominant Childhood-Onset Proximal Spinal Muscular Atrophy 20 58
Spinal Muscular Atrophy, Lower Extremity Predominant 1, Autosomal Dominant 29 6
Spinal Muscular Atrophy, Childhood, Proximal, Autosomal Dominant 57 70
Spinal Muscular Atrophy, Lower Extremity-Predominant 1, Ad 57 20
Lower Extremity-Predominant Autosomal Dominant Proximal Spinal Muscular Atrophy Without Contractures 20
Autosomal Dominant Childhood-Onset Proximal Spinal Muscular Atrophy Without Contractures 20
Autosomal Dominant Spinal Muscular Atrophy with Lower Extremity Predominance 20
Spinal Muscular Atrophy, Lower Extremity-Predominant 1, Autosomal Dominant 72
Autosomal Dominant Spinal Muscular Atrophy, Lower Extremity-Predominant 1 20
Autosomal Dominant Lower Extremity-Predominant Spinal Muscular Atrophy-1 20
Spinal Muscular Atrophy, Lower Extremity-Predominant 1, Dominant 20
Spinal Muscular Atrophy, Juvenile, Proximal, Autosomal Dominant 57
Autosomal Dominant Childhood Proximal Spinal Muscular Atrophy 72
Autosomal Dominant Juvenile Proximal Spinal Muscular Atrophy 72
Kugelberg-Welander Syndrome, Autosomal Dominant 57
Autosomal Dominant Kugelberg-Welander Syndrome 72
Sma-Led1 20
Sma-Led 72
Smaled 57

Characteristics:

Orphanet epidemiological data:

58
dync1h1-related autosomal dominant childhood-onset proximal spinal muscular atrophy
Inheritance: Autosomal dominant; Age of onset: Childhood; Age of death: adult;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
onset in early childhood
non-progressive or very slowly progressive


HPO:

31
spinal muscular atrophy, lower extremity-predominant, 1, autosomal dominant:
Inheritance autosomal dominant inheritance
Onset and clinical course slow progression childhood onset


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

OMIM® 57 158600
OMIM Phenotypic Series 57 PS158600
MeSH 44 D009134
ICD10 via Orphanet 33 G12.1
UMLS via Orphanet 71 C1834690
Orphanet 58 ORPHA209341
MedGen 41 C1834690
UMLS 70 C1834690

Summaries for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

OMIM® : 57 Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder characterized by degeneration of spinal cord motor neurons resulting in muscle weakness. SMALED shows autosomal dominant inheritance with muscle weakness predominantly affecting the proximal lower extremities (Harms et al., 2010). The most common form of SMA (see, e.g., SMA1, 253300) shows autosomal recessive inheritance and is due to mutation in the SMN1 gene (600354) on chromosome 5q. (158600) (Updated 20-May-2021)

MalaCards based summary : Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant, also known as smaled1, is related to spinal muscular atrophy with lower extremity predominance and autosomal dominant childhood-onset proximal spinal muscular atrophy, and has symptoms including waddling gait An important gene associated with Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant is DYNC1H1 (Dynein Cytoplasmic 1 Heavy Chain 1). Affiliated tissues include spinal cord, and related phenotypes are global developmental delay and waddling gait

UniProtKB/Swiss-Prot : 72 Spinal muscular atrophy, lower extremity-predominant 1, autosomal dominant: A 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. SMALED1 is characterized by muscle weakness predominantly affecting the proximal lower extremities.

Related Diseases for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

Graphical network of the top 20 diseases related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:



Diseases related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant

Symptoms & Phenotypes for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

Human phenotypes related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 occasional (7.5%) HP:0001263
2 waddling gait 31 HP:0002515
3 proximal lower limb amyotrophy 31 HP:0008956
4 proximal muscle weakness in lower limbs 31 HP:0008994
5 sensory impairment 31 HP:0003474
6 emg: neuropathic changes 31 HP:0003445
7 difficulty running 31 HP:0009046
8 decreased patellar reflex 31 HP:0011808
9 spinal muscular atrophy 31 HP:0007269
10 delayed ability to walk 31 HP:0031936
11 abnormal foot morphology 31 HP:0001760
12 type 2 muscle fiber predominance 31 HP:0010602

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
waddling gait
delayed walking
difficulty running and climbing stairs
muscle weakness, symmetric, proximal due to motor neuronopathy
cognitive delay, mild (1 patient)

Skeletal Feet:
foot deformities (variable)

Muscle Soft Tissue:
type 2 muscle fiber predominance
muscle weakness, symmetric, proximal, lower limbs
muscle atrophy, lower limbs
hip abductor weakness and atrophy
emg shows chronic denervation

Neurologic Peripheral Nervous System:
decreased patellar reflexes
no sensory impairment

Clinical features from OMIM®:

158600 (Updated 20-May-2021)

UMLS symptoms related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:


waddling gait

Drugs & Therapeutics for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

Search Clinical Trials , NIH Clinical Center for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant

Genetic Tests for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

Genetic tests related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:

# Genetic test Affiliating Genes
1 Spinal Muscular Atrophy, Lower Extremity Predominant 1, Autosomal Dominant 29 DYNC1H1

Anatomical Context for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

MalaCards organs/tissues related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:

40
Spinal Cord

Publications for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

Articles related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:

(show all 15)
# Title Authors PMID Year
1
A DYNC1H1 mutation causes a dominant spinal muscular atrophy with lower extremity predominance. 57 6
22847149 2012
2
Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy. 6 57
22459677 2012
3
Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot-Marie-Tooth disease. 6 57
21820100 2011
4
A cytoplasmic dynein tail mutation impairs motor processivity. 57 6
21102439 2010
5
Dominant spinal muscular atrophy with lower extremity predominance: linkage to 14q32. 57 6
20697106 2010
6
Mutations in dynein link motor neuron degeneration to defects in retrograde transport. 6 57
12730604 2003
7
Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly. 6
23603762 2013
8
Evidence of autosomal dominant mutations in childhood-onset proximal spinal muscular atrophy. 57
8023839 1994
9
Chronic proximal spinal muscular atrophy of childhood and adolescence: problems of classification and genetic counselling. 57
4078864 1985
10
Autosomal dominant spinal muscular atrophy: a clinical and genetic study. 57
712386 1978
11
Spinal muscular atrophy with autosomal dominant inheritance. Report of a new kindred. 57
4673381 1972
12
Kugelberg-Welander syndrome (hereditary proximal spinal muscular atrophy). 57
5933049 1966
13
Kugelberg-welander syndrome with dominant inheritance. 57
5906462 1966
14
Neurogenic muscular atrophy simulating muscular dystrophy. 57
14419782 1960
15
SMALED2 with BICD2 gene mutations: Report of two cases and portrayal of a classical phenotype. 61
32709491 2020

Variations for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

ClinVar genetic disease variations for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:

6 (show all 31)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 DYNC1H1 NM_001376.5(DYNC1H1):c.2011A>G (p.Lys671Glu) SNV Pathogenic 30033 rs387906742 GRCh37: 14:102452573-102452573
GRCh38: 14:101986236-101986236
2 DYNC1H1 NM_001376.5(DYNC1H1):c.2909A>G (p.Tyr970Cys) SNV Pathogenic 30034 rs387906743 GRCh37: 14:102457904-102457904
GRCh38: 14:101991567-101991567
3 DYNC1H1 NM_001376.5(DYNC1H1):c.3603G>T (p.Arg1201Ser) SNV Pathogenic 180211 rs727505393 GRCh37: 14:102463410-102463410
GRCh38: 14:101997073-101997073
4 DYNC1H1 NM_001376.5(DYNC1H1):c.2327C>T (p.Pro776Leu) SNV Pathogenic 372934 rs1057518083 GRCh37: 14:102452889-102452889
GRCh38: 14:101986552-101986552
5 DYNC1H1 NM_001376.5(DYNC1H1):c.1750A>C (p.Ile584Leu) SNV Pathogenic 30032 rs387906741 GRCh37: 14:102452312-102452312
GRCh38: 14:101985975-101985975
6 DYNC1H1 NM_001376.5(DYNC1H1):c.1792C>T (p.Arg598Cys) SNV Pathogenic 139652 rs587780564 GRCh37: 14:102452354-102452354
GRCh38: 14:101986017-101986017
7 DYNC1H1 NM_001376.5(DYNC1H1):c.1792C>T (p.Arg598Cys) SNV Pathogenic 139652 rs587780564 GRCh37: 14:102452354-102452354
GRCh38: 14:101986017-101986017
8 DYNC1H1 NM_001376.5(DYNC1H1):c.917A>G (p.His306Arg) SNV Pathogenic 30029 rs387906738 GRCh37: 14:102446843-102446843
GRCh38: 14:101980506-101980506
9 DYNC1H1 NM_001376.5(DYNC1H1):c.1195A>G (p.Arg399Gly) SNV Likely pathogenic 637515 rs1595599240 GRCh37: 14:102449589-102449589
GRCh38: 14:101983252-101983252
10 DYNC1H1 NM_001376.5(DYNC1H1):c.5885G>A (p.Arg1962His) SNV Likely pathogenic 373213 rs1057518287 GRCh37: 14:102474582-102474582
GRCh38: 14:102008245-102008245
11 DYNC1H1 NM_001376.5(DYNC1H1):c.3170A>G (p.Tyr1057Cys) SNV Likely pathogenic 873447 GRCh37: 14:102461023-102461023
GRCh38: 14:101994686-101994686
12 DYNC1H1 NM_001376.5(DYNC1H1):c.9607G>A (p.Val3203Met) SNV Uncertain significance 565727 rs1567017825 GRCh37: 14:102496014-102496014
GRCh38: 14:102029677-102029677
13 DYNC1H1 NM_001376.5(DYNC1H1):c.915A>G (p.Lys305=) SNV Uncertain significance 626098 rs1566996726 GRCh37: 14:102446841-102446841
GRCh38: 14:101980504-101980504
14 DYNC1H1 NM_001376.5(DYNC1H1):c.12722C>G (p.Ser4241Cys) SNV Uncertain significance 988598 GRCh37: 14:102510648-102510648
GRCh38: 14:102044311-102044311
15 DYNC1H1 NM_001376.5(DYNC1H1):c.7918G>A (p.Glu2640Lys) SNV Uncertain significance 210882 rs797045535 GRCh37: 14:102483494-102483494
GRCh38: 14:102017157-102017157
16 DYNC1H1 NM_001376.5(DYNC1H1):c.13414G>A (p.Gly4472Ser) SNV Uncertain significance 539761 rs199692678 GRCh37: 14:102515818-102515818
GRCh38: 14:102049481-102049481
17 DYNC1H1 NM_001376.5(DYNC1H1):c.12192G>A (p.Thr4064=) SNV Uncertain significance 625933 rs114906811 GRCh37: 14:102508439-102508439
GRCh38: 14:102042102-102042102
18 DYNC1H1 NM_001376.5(DYNC1H1):c.12332A>G (p.Lys4111Arg) SNV Uncertain significance 417875 rs1060499574 GRCh37: 14:102508777-102508777
GRCh38: 14:102042440-102042440
19 DYNC1H1 NM_001376.5(DYNC1H1):c.1817C>T (p.Thr606Ile) SNV Uncertain significance 560994 rs1566999079 GRCh37: 14:102452379-102452379
GRCh38: 14:101986042-101986042
20 DYNC1H1 NM_001376.5(DYNC1H1):c.9193G>A (p.Val3065Met) SNV Uncertain significance 472564 rs377668381 GRCh37: 14:102494100-102494100
GRCh38: 14:102027763-102027763
21 DYNC1H1 NM_001376.5(DYNC1H1):c.11806G>A (p.Val3936Met) SNV Uncertain significance 625931 rs780676515 GRCh37: 14:102506688-102506688
GRCh38: 14:102040351-102040351
22 DYNC1H1 NM_001376.5(DYNC1H1):c.12084C>G (p.Thr4028=) SNV Uncertain significance 625932 rs1446298826 GRCh37: 14:102508053-102508053
GRCh38: 14:102041716-102041716
23 DYNC1H1 NM_001376.5(DYNC1H1):c.13483G>A (p.Ala4495Thr) SNV Uncertain significance 625934 rs1567026040 GRCh37: 14:102515887-102515887
GRCh38: 14:102049550-102049550
24 DYNC1H1 NM_001376.5(DYNC1H1):c.13497T>C (p.Gly4499=) SNV Uncertain significance 625935 rs1555412704 GRCh37: 14:102515901-102515901
GRCh38: 14:102049564-102049564
25 DYNC1H1 NM_001376.5(DYNC1H1):c.10354G>A (p.Ala3452Thr) SNV Uncertain significance 546509 rs1555411400 GRCh37: 14:102499762-102499762
GRCh38: 14:102033425-102033425
26 DYNC1H1 NM_001376.5(DYNC1H1):c.3073C>T (p.Arg1025Trp) SNV Uncertain significance 512377 rs777387819 GRCh37: 14:102460578-102460578
GRCh38: 14:101994241-101994241
27 DYNC1H1 NM_001376.5(DYNC1H1):c.13873G>A (p.Glu4625Lys) SNV Uncertain significance 539767 rs200149883 GRCh37: 14:102516832-102516832
GRCh38: 14:102050495-102050495
28 DYNC1H1 NM_001376.5(DYNC1H1):c.7747A>G (p.Thr2583Ala) SNV Uncertain significance 1029330 GRCh37: 14:102483235-102483235
GRCh38: 14:102016898-102016898
29 DYNC1H1 NM_001376.5(DYNC1H1):c.2376C>T (p.Cys792=) SNV Uncertain significance 516911 rs35092963 GRCh37: 14:102452938-102452938
GRCh38: 14:101986601-101986601
30 DYNC1H1 NM_001376.5(DYNC1H1):c.5985C>T (p.Ala1995=) SNV Uncertain significance 210873 rs140841480 GRCh37: 14:102476187-102476187
GRCh38: 14:102009850-102009850
31 DYNC1H1 NM_001376.5(DYNC1H1):c.5114T>C (p.Val1705Ala) SNV not provided 918035 GRCh37: 14:102471163-102471163
GRCh38: 14:102004826-102004826

UniProtKB/Swiss-Prot genetic disease variations for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant:

72
# Symbol AA change Variation ID SNP ID
1 DYNC1H1 p.His306Arg VAR_066651 rs387906738
2 DYNC1H1 p.Ile584Leu VAR_067820 rs387906741
3 DYNC1H1 p.Lys671Glu VAR_067821 rs387906742
4 DYNC1H1 p.Tyr970Cys VAR_067822 rs387906743
5 DYNC1H1 p.Arg264Leu VAR_073156 rs713993043
6 DYNC1H1 p.Arg598Cys VAR_073157 rs587780564
7 DYNC1H1 p.Pro776Leu VAR_078241 rs105751808
8 DYNC1H1 p.Gly1132Glu VAR_078242

Expression for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

Search GEO for disease gene expression data for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant.

Pathways for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

GO Terms for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

Sources for Spinal Muscular Atrophy, Lower Extremity-Predominant, 1,...

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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