SMALED2A
MCID: SPN426
MIFTS: 22

Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a, Childhood Onset, Autosomal Dominant (SMALED2A)

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

Aliases & Classifications for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a,...

MalaCards integrated aliases for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a, Childhood Onset, Autosomal Dominant:

Name: Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a, Childhood Onset, Autosomal Dominant 58
Smaled2 60 76
Bicd2-Related Lower Extremity-Predominant Autosomal Dominant Proximal Spinal Muscular Atrophy with Contractures 60
Bicd2-Related Autosomal Dominant Childhood-Onset Proximal Spinal Muscular Atrophy 60
Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a, Autosomal Dominant 58
Spinal Muscular Atrophy, Lower Extremity-Predominant 2, Autosomal Dominant 76
Smaled2a 58

Characteristics:

Orphanet epidemiological data:

60
bicd2-related autosomal dominant childhood-onset proximal spinal muscular atrophy
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
variable severity
onset in early first decade, although some patients have onset at birth or early in infancy
slowly or non-progressive


HPO:

33
spinal muscular atrophy, lower extremity-predominant, 2a, childhood onset, autosomal dominant:
Onset and clinical course variable expressivity
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a,...

OMIM : 58 SMALED2A is an autosomal dominant form of spinal muscular atrophy characterized by early childhood onset of muscle weakness and atrophy predominantly affecting the proximal and distal muscles of the lower extremity, although some patients may show upper extremity involvement. The disorder results in delayed walking, waddling gait, difficulty walking, and loss of distal reflexes. Some patients may have foot deformities or hyperlordosis, and some show mild upper motor signs, such as spasticity. Sensation, bulbar function, and cognitive function are preserved. The disorder shows very slow progression throughout life (summary by Oates et al., 2013). For discussion of genetic heterogeneity of lower extremity-predominant spinal muscular atrophy, see SMALED1 (158600). (615290)

MalaCards based summary : Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a, Childhood Onset, Autosomal Dominant, also known as smaled2, is related to autosomal dominant spinal muscular atrophy, lower extremity-predominant 2. An important gene associated with Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a, Childhood Onset, Autosomal Dominant is BICD2 (BICD Cargo Adaptor 2). Affiliated tissues include spinal cord, and related phenotypes are waddling gait and difficulty walking

UniProtKB/Swiss-Prot : 76 Spinal muscular atrophy, lower extremity-predominant 2, autosomal dominant: An autosomal dominant form of spinal muscular atrophy characterized by early-childhood onset of muscle weakness and atrophy predominantly affecting the proximal and distal muscles of the lower extremity, although some patients may show upper extremity involvement. The disorder results in delayed walking, waddling gait, difficulty walking, and loss of distal reflexes. Some patients may have foot deformities or hyperlordosis, and some show mild upper motor signs, such as spasticity. Sensation, bulbar function, and cognitive function are preserved. The disorder shows very slow progression throughout life.

Related Diseases for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a,...

Diseases related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a, Childhood Onset, Autosomal Dominant via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 autosomal dominant spinal muscular atrophy, lower extremity-predominant 2 11.8

Symptoms & Phenotypes for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a,...

Human phenotypes related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a, Childhood Onset, Autosomal Dominant:

60 33 (show all 29)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 waddling gait 60 33 frequent (33%) Frequent (79-30%) HP:0002515
2 difficulty walking 60 33 frequent (33%) Frequent (79-30%) HP:0002355
3 gowers sign 60 33 frequent (33%) Frequent (79-30%) HP:0003391
4 distal muscle weakness 60 33 frequent (33%) Frequent (79-30%) HP:0002460
5 distal lower limb amyotrophy 60 33 frequent (33%) Frequent (79-30%) HP:0008944
6 congenital foot contraction deformities 60 33 frequent (33%) Frequent (79-30%) HP:0005853
7 hyperreflexia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001347
8 hyperlordosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0003307
9 hip dysplasia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001385
10 motor delay 60 33 occasional (7.5%) Occasional (29-5%) HP:0001270
11 hyporeflexia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001265
12 decreased fetal movement 60 33 occasional (7.5%) Occasional (29-5%) HP:0001558
13 abnormality of the achilles tendon 60 33 occasional (7.5%) Occasional (29-5%) HP:0005109
14 spasticity 33 occasional (7.5%) HP:0001257
15 scapular winging 33 occasional (7.5%) HP:0003691
16 fasciculations 33 occasional (7.5%) HP:0002380
17 hip contracture 33 occasional (7.5%) HP:0003273
18 knee flexion contracture 33 occasional (7.5%) HP:0006380
19 hand muscle weakness 60 33 very rare (1%) Very rare (<4-1%) HP:0030237
20 shoulder girdle muscle weakness 60 33 very rare (1%) Very rare (<4-1%) HP:0003547
21 flexion contracture 60 Occasional (29-5%)
22 achilles tendon contracture 33 HP:0001771
23 toe walking 33 HP:0040083
24 talipes equinovarus 33 HP:0001762
25 areflexia 33 HP:0001284
26 proximal muscle weakness 60 Frequent (79-30%)
27 axial muscle weakness 33 HP:0003327
28 difficulty running 33 HP:0009046
29 spinal muscular atrophy 33 HP:0007269

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
waddling gait
difficulty running
delayed motor development
spasticity (in some patients)
toe-walking
more
Skeletal Feet:
foot deformities
achilles tendon contractures
pes equinovarus

Chest Ribs Sternum Clavicles And Scapulae:
scapular winging (in some patients)

Skeletal Limbs:
knee contractures (in some patients)

Muscle Soft Tissue:
axial muscle weakness
gower sign
muscle weakness, proximal and distal (predominant lower limb involvement)
muscle atrophy, proximal and distal (predominant lower limb involvement)
fasciculations (in some patients)
more
Skeletal Pelvis:
hip contractures (in some patients)
hip dysplasia (in some patients)

Skeletal Spine:
hyperlordosis (in some patients)

Neurologic Peripheral Nervous System:
hyporeflexia, distal
areflexia, distal

Clinical features from OMIM:

615290

Drugs & Therapeutics for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a,...

Search Clinical Trials , NIH Clinical Center for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a, Childhood Onset, Autosomal Dominant

Genetic Tests for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a,...

Anatomical Context for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a,...

MalaCards organs/tissues related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a, Childhood Onset, Autosomal Dominant:

42
Spinal Cord

Publications for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a,...

Variations for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a,...

UniProtKB/Swiss-Prot genetic disease variations for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a, Childhood Onset, Autosomal Dominant:

76
# Symbol AA change Variation ID SNP ID
1 BICD2 p.Ser107Leu VAR_070112 rs398123028
2 BICD2 p.Asn188Thr VAR_070113 rs398123029
3 BICD2 p.Ile189Phe VAR_070114
4 BICD2 p.Arg501Pro VAR_070115 rs398123032
5 BICD2 p.Lys508Thr VAR_070116 rs398123031
6 BICD2 p.Thr703Met VAR_070117 rs371707778
7 BICD2 p.Glu774Gly VAR_070118 rs398123030

ClinVar genetic disease variations for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a, Childhood Onset, Autosomal Dominant:

6 (show top 50) (show all 184)
# Gene Variation Type Significance SNP ID Assembly Location
1 BICD2 NM_001003800.1(BICD2): c.320C> T (p.Ser107Leu) single nucleotide variant Pathogenic rs398123028 GRCh37 Chromosome 9, 95491439: 95491439
2 BICD2 NM_001003800.1(BICD2): c.320C> T (p.Ser107Leu) single nucleotide variant Pathogenic rs398123028 GRCh38 Chromosome 9, 92729157: 92729157
3 BICD2 NM_001003800.1(BICD2): c.2108C> T (p.Thr703Met) single nucleotide variant Pathogenic/Likely pathogenic rs371707778 GRCh37 Chromosome 9, 95480229: 95480229
4 BICD2 NM_001003800.1(BICD2): c.2108C> T (p.Thr703Met) single nucleotide variant Pathogenic/Likely pathogenic rs371707778 GRCh38 Chromosome 9, 92717947: 92717947
5 BICD2 NM_015250.3(BICD2): c.563A> C (p.Asn188Thr) single nucleotide variant Pathogenic rs398123029 GRCh37 Chromosome 9, 95484981: 95484981
6 BICD2 NM_015250.3(BICD2): c.563A> C (p.Asn188Thr) single nucleotide variant Pathogenic rs398123029 GRCh38 Chromosome 9, 92722699: 92722699
7 BICD2 NM_001003800.1(BICD2): c.2321A> G (p.Glu774Gly) single nucleotide variant Pathogenic rs398123030 GRCh37 Chromosome 9, 95477683: 95477683
8 BICD2 NM_001003800.1(BICD2): c.2321A> G (p.Glu774Gly) single nucleotide variant Pathogenic rs398123030 GRCh38 Chromosome 9, 92715401: 92715401
9 BICD2 NM_015250.3(BICD2): c.1523A> C (p.Lys508Thr) single nucleotide variant Pathogenic rs398123031 GRCh37 Chromosome 9, 95481404: 95481404
10 BICD2 NM_015250.3(BICD2): c.1523A> C (p.Lys508Thr) single nucleotide variant Pathogenic rs398123031 GRCh38 Chromosome 9, 92719122: 92719122
11 BICD2 NM_015250.3(BICD2): c.1502G> C (p.Arg501Pro) single nucleotide variant Pathogenic rs398123032 GRCh37 Chromosome 9, 95481425: 95481425
12 BICD2 NM_015250.3(BICD2): c.1502G> C (p.Arg501Pro) single nucleotide variant Pathogenic rs398123032 GRCh38 Chromosome 9, 92719143: 92719143
13 BICD2 NM_001003800.2(BICD2): c.2080C> T (p.Arg694Cys) single nucleotide variant Likely pathogenic rs797045412 GRCh37 Chromosome 9, 95480847: 95480847
14 BICD2 NM_001003800.2(BICD2): c.2080C> T (p.Arg694Cys) single nucleotide variant Likely pathogenic rs797045412 GRCh38 Chromosome 9, 92718565: 92718565
15 BICD2 NM_001003800.1(BICD2): c.269A> G (p.Lys90Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs61754130 GRCh37 Chromosome 9, 95491490: 95491490
16 BICD2 NM_001003800.1(BICD2): c.269A> G (p.Lys90Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs61754130 GRCh38 Chromosome 9, 92729208: 92729208
17 BICD2 NM_001003800.1(BICD2): c.2142G> C (p.Lys714Asn) single nucleotide variant Uncertain significance rs777986224 GRCh37 Chromosome 9, 95480195: 95480195
18 BICD2 NM_001003800.1(BICD2): c.2142G> C (p.Lys714Asn) single nucleotide variant Uncertain significance rs777986224 GRCh38 Chromosome 9, 92717913: 92717913
19 BICD2 NM_001003800.1(BICD2): c.1044G> A (p.Leu348=) single nucleotide variant Benign/Likely benign rs77530912 GRCh37 Chromosome 9, 95482600: 95482600
20 BICD2 NM_001003800.1(BICD2): c.1044G> A (p.Leu348=) single nucleotide variant Benign/Likely benign rs77530912 GRCh38 Chromosome 9, 92720318: 92720318
21 BICD2 NM_001003800.1(BICD2): c.2445G> A (p.Pro815=) single nucleotide variant Benign/Likely benign rs34451610 GRCh37 Chromosome 9, 95477559: 95477559
22 BICD2 NM_001003800.1(BICD2): c.2445G> A (p.Pro815=) single nucleotide variant Benign/Likely benign rs34451610 GRCh38 Chromosome 9, 92715277: 92715277
23 BICD2 NM_001003800.1(BICD2): c.1620C> T (p.His540=) single nucleotide variant Likely benign rs375331979 GRCh37 Chromosome 9, 95481307: 95481307
24 BICD2 NM_001003800.1(BICD2): c.1620C> T (p.His540=) single nucleotide variant Likely benign rs375331979 GRCh38 Chromosome 9, 92719025: 92719025
25 BICD2 NM_001003800.1(BICD2): c.1250A> G (p.Asp417Gly) single nucleotide variant Uncertain significance rs55658812 GRCh37 Chromosome 9, 95481677: 95481677
26 BICD2 NM_001003800.1(BICD2): c.1250A> G (p.Asp417Gly) single nucleotide variant Uncertain significance rs55658812 GRCh38 Chromosome 9, 92719395: 92719395
27 BICD2 NM_001003800.1(BICD2): c.1806G> A (p.Thr602=) single nucleotide variant Benign/Likely benign rs138300993 GRCh37 Chromosome 9, 95481121: 95481121
28 BICD2 NM_001003800.1(BICD2): c.1806G> A (p.Thr602=) single nucleotide variant Benign/Likely benign rs138300993 GRCh38 Chromosome 9, 92718839: 92718839
29 BICD2 NM_001003800.1(BICD2): c.72C> G (p.Ala24=) single nucleotide variant Benign/Likely benign rs545512590 GRCh37 Chromosome 9, 95526955: 95526955
30 BICD2 NM_001003800.1(BICD2): c.72C> G (p.Ala24=) single nucleotide variant Benign/Likely benign rs545512590 GRCh38 Chromosome 9, 92764673: 92764673
31 BICD2 NM_001003800.1(BICD2): c.1069C> T (p.Arg357Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs202119238 GRCh38 Chromosome 9, 92719576: 92719576
32 BICD2 NM_001003800.1(BICD2): c.1069C> T (p.Arg357Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs202119238 GRCh37 Chromosome 9, 95481858: 95481858
33 BICD2 NM_001003800.1(BICD2): c.355C> A (p.Leu119Ile) single nucleotide variant Uncertain significance rs377156663 GRCh37 Chromosome 9, 95491404: 95491404
34 BICD2 NM_001003800.1(BICD2): c.355C> A (p.Leu119Ile) single nucleotide variant Uncertain significance rs377156663 GRCh38 Chromosome 9, 92729122: 92729122
35 BICD2 NM_001003800.1(BICD2): c.1659G> A (p.Met553Ile) single nucleotide variant Uncertain significance rs374912668 GRCh37 Chromosome 9, 95481268: 95481268
36 BICD2 NM_001003800.1(BICD2): c.1659G> A (p.Met553Ile) single nucleotide variant Uncertain significance rs374912668 GRCh38 Chromosome 9, 92718986: 92718986
37 BICD2 NM_001003800.1(BICD2): c.1376C> T (p.Thr459Met) single nucleotide variant Uncertain significance rs777065935 GRCh37 Chromosome 9, 95481551: 95481551
38 BICD2 NM_001003800.1(BICD2): c.1376C> T (p.Thr459Met) single nucleotide variant Uncertain significance rs777065935 GRCh38 Chromosome 9, 92719269: 92719269
39 BICD2 NM_001003800.1(BICD2): c.1725C> G (p.Pro575=) single nucleotide variant Likely benign rs201343832 GRCh37 Chromosome 9, 95481202: 95481202
40 BICD2 NM_001003800.1(BICD2): c.1725C> G (p.Pro575=) single nucleotide variant Likely benign rs201343832 GRCh38 Chromosome 9, 92718920: 92718920
41 BICD2 NM_001003800.1(BICD2): c.1438G> A (p.Ala480Thr) single nucleotide variant Uncertain significance rs140188204 GRCh37 Chromosome 9, 95481489: 95481489
42 BICD2 NM_001003800.1(BICD2): c.1438G> A (p.Ala480Thr) single nucleotide variant Uncertain significance rs140188204 GRCh38 Chromosome 9, 92719207: 92719207
43 BICD2 NM_001003800.1(BICD2): c.1556G> T (p.Ser519Ile) single nucleotide variant Uncertain significance rs940304129 GRCh37 Chromosome 9, 95481371: 95481371
44 BICD2 NM_001003800.1(BICD2): c.1556G> T (p.Ser519Ile) single nucleotide variant Uncertain significance rs940304129 GRCh38 Chromosome 9, 92719089: 92719089
45 BICD2 NM_001003800.1(BICD2): c.2536T> C (p.Cys846Arg) single nucleotide variant Uncertain significance rs760624844 GRCh38 Chromosome 9, 92715186: 92715186
46 BICD2 NM_001003800.1(BICD2): c.2536T> C (p.Cys846Arg) single nucleotide variant Uncertain significance rs760624844 GRCh37 Chromosome 9, 95477468: 95477468
47 BICD2 NM_001003800.1(BICD2): c.1749C> T (p.Pro583=) single nucleotide variant Likely benign rs777813587 GRCh37 Chromosome 9, 95481178: 95481178
48 BICD2 NM_001003800.1(BICD2): c.1749C> T (p.Pro583=) single nucleotide variant Likely benign rs777813587 GRCh38 Chromosome 9, 92718896: 92718896
49 BICD2 NM_001003800.1(BICD2): c.1725C> T (p.Pro575=) single nucleotide variant Likely benign rs201343832 GRCh38 Chromosome 9, 92718920: 92718920
50 BICD2 NM_001003800.1(BICD2): c.1725C> T (p.Pro575=) single nucleotide variant Likely benign rs201343832 GRCh37 Chromosome 9, 95481202: 95481202

Expression for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2a,...

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