MCID: SPN416
MIFTS: 25

Spinal Muscular Atrophy, Lower Extremity-Predominant, 2, Autosomal Dominant

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

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

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

Name: Spinal Muscular Atrophy, Lower Extremity-Predominant, 2, Autosomal Dominant 57 73
Smaled2 57 53 59 75
Lower Extremity-Predominant Autosomal Dominant Proximal Spinal Muscular Atrophy with Contractures 53 59
Autosomal Dominant Childhood-Onset Proximal Spinal Muscular Atrophy with Contractures 53 59
Spinal Muscular Atrophy, Lower Extremity-Predominant 2, Autosomal Dominant 53 75
Spinal Muscular Atrophy, Lower Extremity Predominant 2, Autosomal Dominant 29 6
Spinal Muscular Atrophy, Lower Extremity-Predominant, 2, Ad 57 6
Atrophy, Muscular, Spinal, Lower Extremity Predominant, Type 2, Autosomal Dominant 40
Autosomal Dominant Spinal Muscular Atrophy, Lower Extremity-Predominant 2 53

Characteristics:

Orphanet epidemiological data:

59
autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
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:

32
spinal muscular atrophy, lower extremity-predominant, 2, autosomal dominant:
Onset and clinical course variable expressivity
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


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

NIH Rare Diseases : 53 Autosomal dominant spinal muscular atrophy, lower extremity-predominant 2 (SMALED2) is a rare neurological disease characterized by early-childhood onset of muscle weakness and loss of muscle tissue (muscle atrophy), mostly affecting the muscles of the thighs. It is a subtype of the group of diseases known as spinal muscular atrophy. Symptoms include delayed walking, waddling gait, difficulty walking, foot deformities, and loss of some reflexes. Joint contractures are reported frequently, and a few patients present with congenital hip dysplasia. Other symptoms that have being described are an exaggerated curvature of the lower back (hyperlordosis), increased or decreased muscle tone, small chin (micrognathia), respiratory insufficiency, small head (microcephaly), and extra ridges or folds in the brain surface (polymicrogyria).  Sensation and cognitive function are normal in most cases. Many patients show evident atrophy of the lower limbs and a very broad upper body, which resembles a bodybuilder-like shape. The disease has very slow progression throughout life. It is caused by mutations in the BICD2 gene. Inheritance is autosomal dominant. There is no cure and treatment is directed to the symptoms present in each individual patient.

MalaCards based summary : Spinal Muscular Atrophy, Lower Extremity-Predominant, 2, Autosomal Dominant, also known as smaled2, is related to spinal muscular atrophy with lower extremity predominance, and has symptoms including waddling gait An important gene associated with Spinal Muscular Atrophy, Lower Extremity-Predominant, 2, Autosomal Dominant is BICD2 (BICD Cargo Adaptor 2). Affiliated tissues include brain and spinal cord, and related phenotypes are spasticity and hyporeflexia

OMIM : 57 SMALED2 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)

UniProtKB/Swiss-Prot : 75 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, 2,...

Diseases in the Spinal Muscular Atrophy, Lower Extremity-Predominant, 1, Autosomal Dominant family:

Spinal Muscular Atrophy, Lower Extremity-Predominant, 2, Autosomal Dominant

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

# Related Disease Score Top Affiliating Genes
1 spinal muscular atrophy with lower extremity predominance 11.6

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

Symptoms via clinical synopsis from OMIM:

57
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

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

32 (show all 19)
# Description HPO Frequency HPO Source Accession
1 spasticity 32 occasional (7.5%) HP:0001257
2 hyporeflexia 32 HP:0001265
3 motor delay 32 HP:0001270
4 areflexia 32 HP:0001284
5 hyperreflexia 32 occasional (7.5%) HP:0001347
6 hip dysplasia 32 occasional (7.5%) HP:0001385
7 talipes equinovarus 32 HP:0001762
8 achilles tendon contracture 32 HP:0001771
9 fasciculations 32 occasional (7.5%) HP:0002380
10 waddling gait 32 HP:0002515
11 hip contracture 32 occasional (7.5%) HP:0003273
12 hyperlordosis 32 occasional (7.5%) HP:0003307
13 axial muscle weakness 32 HP:0003327
14 gowers sign 32 HP:0003391
15 scapular winging 32 occasional (7.5%) HP:0003691
16 knee flexion contracture 32 occasional (7.5%) HP:0006380
17 spinal muscular atrophy 32 HP:0007269
18 difficulty running 32 HP:0009046
19 toe walking 32 HP:0040083

UMLS symptoms related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 2, Autosomal Dominant:


waddling gait

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

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

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

Genetic tests related to Spinal Muscular Atrophy, Lower Extremity-Predominant, 2, Autosomal Dominant:

# Genetic test Affiliating Genes
1 Spinal Muscular Atrophy, Lower Extremity Predominant 2, Autosomal Dominant 29 BICD2

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

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

41
Brain, Spinal Cord

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

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

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

75
# 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, 2, Autosomal Dominant:

6
(show top 50) (show all 134)
# 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_015250.3(BICD2): c.563A> C (p.Asn188Thr) single nucleotide variant Pathogenic rs398123029 GRCh37 Chromosome 9, 95484981: 95484981
4 BICD2 NM_015250.3(BICD2): c.563A> C (p.Asn188Thr) single nucleotide variant Pathogenic rs398123029 GRCh38 Chromosome 9, 92722699: 92722699
5 BICD2 NM_001003800.1(BICD2): c.2321A> G (p.Glu774Gly) single nucleotide variant Pathogenic rs398123030 GRCh37 Chromosome 9, 95477683: 95477683
6 BICD2 NM_001003800.1(BICD2): c.2321A> G (p.Glu774Gly) single nucleotide variant Pathogenic rs398123030 GRCh38 Chromosome 9, 92715401: 92715401
7 BICD2 NM_015250.3(BICD2): c.1523A> C (p.Lys508Thr) single nucleotide variant Pathogenic rs398123031 GRCh37 Chromosome 9, 95481404: 95481404
8 BICD2 NM_015250.3(BICD2): c.1523A> C (p.Lys508Thr) single nucleotide variant Pathogenic rs398123031 GRCh38 Chromosome 9, 92719122: 92719122
9 BICD2 NM_015250.3(BICD2): c.1502G> C (p.Arg501Pro) single nucleotide variant Pathogenic rs398123032 GRCh37 Chromosome 9, 95481425: 95481425
10 BICD2 NM_015250.3(BICD2): c.1502G> C (p.Arg501Pro) single nucleotide variant Pathogenic rs398123032 GRCh38 Chromosome 9, 92719143: 92719143
11 BICD2 NM_001003800.1(BICD2): c.2080C> T (p.Arg694Cys) single nucleotide variant Likely pathogenic rs797045412 GRCh37 Chromosome 9, 95480847: 95480847
12 BICD2 NM_001003800.1(BICD2): c.2080C> T (p.Arg694Cys) single nucleotide variant Likely pathogenic rs797045412 GRCh38 Chromosome 9, 92718565: 92718565
13 BICD2 NM_001003800.1(BICD2): c.269A> G (p.Lys90Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs61754130 GRCh37 Chromosome 9, 95491490: 95491490
14 BICD2 NM_001003800.1(BICD2): c.269A> G (p.Lys90Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs61754130 GRCh38 Chromosome 9, 92729208: 92729208
15 BICD2 NM_001003800.1(BICD2): c.1044G> A (p.Leu348=) single nucleotide variant Benign/Likely benign rs77530912 GRCh38 Chromosome 9, 92720318: 92720318
16 BICD2 NM_001003800.1(BICD2): c.1044G> A (p.Leu348=) single nucleotide variant Benign/Likely benign rs77530912 GRCh37 Chromosome 9, 95482600: 95482600
17 BICD2 NM_001003800.1(BICD2): c.2445G> A (p.Pro815=) single nucleotide variant Benign/Likely benign rs34451610 GRCh37 Chromosome 9, 95477559: 95477559
18 BICD2 NM_001003800.1(BICD2): c.2445G> A (p.Pro815=) single nucleotide variant Benign/Likely benign rs34451610 GRCh38 Chromosome 9, 92715277: 92715277
19 BICD2 NM_001003800.1(BICD2): c.1620C> T (p.His540=) single nucleotide variant Likely benign rs375331979 GRCh37 Chromosome 9, 95481307: 95481307
20 BICD2 NM_001003800.1(BICD2): c.1620C> T (p.His540=) single nucleotide variant Likely benign rs375331979 GRCh38 Chromosome 9, 92719025: 92719025
21 BICD2 NM_001003800.1(BICD2): c.1250A> G (p.Asp417Gly) single nucleotide variant Uncertain significance rs55658812 GRCh37 Chromosome 9, 95481677: 95481677
22 BICD2 NM_001003800.1(BICD2): c.1250A> G (p.Asp417Gly) single nucleotide variant Uncertain significance rs55658812 GRCh38 Chromosome 9, 92719395: 92719395
23 BICD2 NM_001003800.1(BICD2): c.1806G> A (p.Thr602=) single nucleotide variant Benign/Likely benign rs138300993 GRCh37 Chromosome 9, 95481121: 95481121
24 BICD2 NM_001003800.1(BICD2): c.1806G> A (p.Thr602=) single nucleotide variant Benign/Likely benign rs138300993 GRCh38 Chromosome 9, 92718839: 92718839
25 BICD2 NM_001003800.1(BICD2): c.72C> G (p.Ala24=) single nucleotide variant Benign/Likely benign rs545512590 GRCh37 Chromosome 9, 95526955: 95526955
26 BICD2 NM_001003800.1(BICD2): c.72C> G (p.Ala24=) single nucleotide variant Benign/Likely benign rs545512590 GRCh38 Chromosome 9, 92764673: 92764673
27 BICD2 NM_001003800.1(BICD2): c.1069C> T (p.Arg357Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs202119238 GRCh38 Chromosome 9, 92719576: 92719576
28 BICD2 NM_001003800.1(BICD2): c.1069C> T (p.Arg357Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs202119238 GRCh37 Chromosome 9, 95481858: 95481858
29 BICD2 NM_001003800.1(BICD2): c.355C> A (p.Leu119Ile) single nucleotide variant Uncertain significance rs377156663 GRCh37 Chromosome 9, 95491404: 95491404
30 BICD2 NM_001003800.1(BICD2): c.355C> A (p.Leu119Ile) single nucleotide variant Uncertain significance rs377156663 GRCh38 Chromosome 9, 92729122: 92729122
31 BICD2 NM_001003800.1(BICD2): c.1659G> A (p.Met553Ile) single nucleotide variant Uncertain significance rs374912668 GRCh37 Chromosome 9, 95481268: 95481268
32 BICD2 NM_001003800.1(BICD2): c.1659G> A (p.Met553Ile) single nucleotide variant Uncertain significance rs374912668 GRCh38 Chromosome 9, 92718986: 92718986
33 BICD2 NM_001003800.1(BICD2): c.1376C> T (p.Thr459Met) single nucleotide variant Uncertain significance rs777065935 GRCh37 Chromosome 9, 95481551: 95481551
34 BICD2 NM_001003800.1(BICD2): c.1376C> T (p.Thr459Met) single nucleotide variant Uncertain significance rs777065935 GRCh38 Chromosome 9, 92719269: 92719269
35 BICD2 NM_001003800.1(BICD2): c.1725C> G (p.Pro575=) single nucleotide variant Likely benign rs201343832 GRCh37 Chromosome 9, 95481202: 95481202
36 BICD2 NM_001003800.1(BICD2): c.1725C> G (p.Pro575=) single nucleotide variant Likely benign rs201343832 GRCh38 Chromosome 9, 92718920: 92718920
37 BICD2 NM_001003800.1(BICD2): c.1438G> A (p.Ala480Thr) single nucleotide variant Uncertain significance rs140188204 GRCh37 Chromosome 9, 95481489: 95481489
38 BICD2 NM_001003800.1(BICD2): c.1438G> A (p.Ala480Thr) single nucleotide variant Uncertain significance rs140188204 GRCh38 Chromosome 9, 92719207: 92719207
39 BICD2 NM_001003800.1(BICD2): c.1556G> T (p.Ser519Ile) single nucleotide variant Uncertain significance rs940304129 GRCh37 Chromosome 9, 95481371: 95481371
40 BICD2 NM_001003800.1(BICD2): c.1556G> T (p.Ser519Ile) single nucleotide variant Uncertain significance rs940304129 GRCh38 Chromosome 9, 92719089: 92719089
41 BICD2 NM_001003800.1(BICD2): c.2536T> C (p.Cys846Arg) single nucleotide variant Uncertain significance rs760624844 GRCh38 Chromosome 9, 92715186: 92715186
42 BICD2 NM_001003800.1(BICD2): c.2536T> C (p.Cys846Arg) single nucleotide variant Uncertain significance rs760624844 GRCh37 Chromosome 9, 95477468: 95477468
43 BICD2 NM_001003800.1(BICD2): c.1749C> T (p.Pro583=) single nucleotide variant Likely benign rs777813587 GRCh38 Chromosome 9, 92718896: 92718896
44 BICD2 NM_001003800.1(BICD2): c.1749C> T (p.Pro583=) single nucleotide variant Likely benign rs777813587 GRCh37 Chromosome 9, 95481178: 95481178
45 BICD2 NM_001003800.1(BICD2): c.1725C> T (p.Pro575=) single nucleotide variant Likely benign rs201343832 GRCh38 Chromosome 9, 92718920: 92718920
46 BICD2 NM_001003800.1(BICD2): c.1725C> T (p.Pro575=) single nucleotide variant Likely benign rs201343832 GRCh37 Chromosome 9, 95481202: 95481202
47 BICD2 NM_001003800.1(BICD2): c.1674C> T (p.Arg558=) single nucleotide variant Uncertain significance rs35535468 GRCh38 Chromosome 9, 92718971: 92718971
48 BICD2 NM_001003800.1(BICD2): c.1674C> T (p.Arg558=) single nucleotide variant Uncertain significance rs35535468 GRCh37 Chromosome 9, 95481253: 95481253
49 BICD2 NM_001003800.1(BICD2): c.1371C> T (p.Arg457=) single nucleotide variant Likely benign rs770158042 GRCh38 Chromosome 9, 92719274: 92719274
50 BICD2 NM_001003800.1(BICD2): c.1371C> T (p.Arg457=) single nucleotide variant Likely benign rs770158042 GRCh37 Chromosome 9, 95481556: 95481556

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

Search GEO for disease gene expression data for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2, Autosomal Dominant.

Pathways for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2,...

GO Terms for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2,...

Sources for Spinal Muscular Atrophy, Lower Extremity-Predominant, 2,...

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
Content
Loading form....