BTHLM2
MCID: BTH006
MIFTS: 34

Bethlem Myopathy 2 (BTHLM2)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Bethlem Myopathy 2

MalaCards integrated aliases for Bethlem Myopathy 2:

Name: Bethlem Myopathy 2 57 72 29 6
Bthlm2 57 72
Edsmyp 57 72
Ehlers-Danlos Syndrome, Myopathic Type; Edsmyp 57
Ehlers-Danlos Syndrome, Myopathic Type 57
Ehlers-Danlos Syndrome Myopathic Type 36
Ehlers-Danlos Syndrome, Myopathic 72
Myopathic Ehlers-Danlos Syndrome 58
Eds/myopathy Overlap Syndrome 58
Myopathy, Bethlem, Type 2 39
Eds, Myopathic Type 57
Eds, Myopathic 72
Myopathic Eds 58

Characteristics:

OMIM®:

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

Miscellaneous:
onset in first decade
large joint contractures may resolve over time
muscle strength tends to improve during the teenage years


HPO:

31
bethlem myopathy 2:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare systemic and rhumatological diseases
Rare skin diseases
Developmental anomalies during embryogenesis


Summaries for Bethlem Myopathy 2

KEGG : 36 Ehlers-Danlos syndrome myopathic type (EDSMYP), also known as Bethlem myopathy 2 (BTHLM2), shows clinical features of both a myopathy as well as of a disorder of connective tissue. Although symptoms are similar to that of the collagen VI-related myopathy, patients don't have mutations in collagen VI. It has been reported that mutations in in collagen XII (COL12A1) cause this disease.

MalaCards based summary : Bethlem Myopathy 2, also known as bthlm2, is related to ehlers-danlos syndrome and bethlem myopathy 1. An important gene associated with Bethlem Myopathy 2 is COL12A1 (Collagen Type XII Alpha 1 Chain). Affiliated tissues include bone, and related phenotypes are joint hypermobility and generalized muscle weakness

UniProtKB/Swiss-Prot : 72 Bethlem myopathy 2: A form of Bethlem myopathy, a benign proximal myopathy characterized by early childhood onset and joint contractures most frequently affecting the elbows and ankles. BTHLM2 inheritance is autosomal dominant.

More information from OMIM: 616471 PS130000 PS158810

Related Diseases for Bethlem Myopathy 2

Diseases in the Bethlem Myopathy 1 family:

Bethlem Myopathy 2

Diseases related to Bethlem Myopathy 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 ehlers-danlos syndrome 10.9
2 bethlem myopathy 1 10.1
3 ullrich congenital muscular dystrophy 1 10.1
4 ullrich congenital muscular dystrophy 2 10.1
5 myopathy 10.1

Graphical network of the top 20 diseases related to Bethlem Myopathy 2:



Diseases related to Bethlem Myopathy 2

Symptoms & Phenotypes for Bethlem Myopathy 2

Human phenotypes related to Bethlem Myopathy 2:

58 31 (show top 50) (show all 59)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint hypermobility 58 31 hallmark (90%) Very frequent (99-80%) HP:0001382
2 generalized muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003324
3 increased variability in muscle fiber diameter 58 31 frequent (33%) Frequent (79-30%) HP:0003557
4 delayed ability to walk 58 31 frequent (33%) Frequent (79-30%) HP:0031936
5 delayed ability to stand 58 31 frequent (33%) Frequent (79-30%) HP:0025335
6 failure to thrive 58 31 occasional (7.5%) Occasional (29-5%) HP:0001508
7 hyperlordosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0003307
8 pes planus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001763
9 neonatal hypotonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001319
10 decreased muscle mass 58 31 occasional (7.5%) Occasional (29-5%) HP:0003199
11 micrognathia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000347
12 high, narrow palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0002705
13 myopia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000545
14 pectus excavatum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000767
15 pallor 58 31 occasional (7.5%) Occasional (29-5%) HP:0000980
16 elbow flexion contracture 58 31 occasional (7.5%) Occasional (29-5%) HP:0002987
17 toe walking 58 31 occasional (7.5%) Occasional (29-5%) HP:0040083
18 talipes equinovarus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001762
19 kyphoscoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002751
20 multiple joint contractures 58 31 occasional (7.5%) Occasional (29-5%) HP:0002828
21 laryngomalacia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001601
22 areflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001284
23 adducted thumb 58 31 occasional (7.5%) Occasional (29-5%) HP:0001181
24 shoulder flexion contracture 58 31 occasional (7.5%) Occasional (29-5%) HP:0003044
25 blue sclerae 58 31 occasional (7.5%) Occasional (29-5%) HP:0000592
26 hyperextensible skin 58 31 occasional (7.5%) Occasional (29-5%) HP:0000974
27 tapered finger 58 31 occasional (7.5%) Occasional (29-5%) HP:0001182
28 congenital muscular torticollis 58 31 occasional (7.5%) Occasional (29-5%) HP:0005988
29 ankle flexion contracture 58 31 occasional (7.5%) Occasional (29-5%) HP:0006466
30 congenital finger flexion contractures 58 31 occasional (7.5%) Occasional (29-5%) HP:0005879
31 mildly elevated creatine kinase 58 31 occasional (7.5%) Occasional (29-5%) HP:0008180
32 knee flexion contracture 58 31 occasional (7.5%) Occasional (29-5%) HP:0006380
33 proximal muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0003701
34 poor wound healing 58 31 occasional (7.5%) Occasional (29-5%) HP:0001058
35 congenital bilateral hip dislocation 58 31 occasional (7.5%) Occasional (29-5%) HP:0008780
36 soft skin 58 31 occasional (7.5%) Occasional (29-5%) HP:0000977
37 contractures involving the joints of the feet 58 31 occasional (7.5%) Occasional (29-5%) HP:0008366
38 exercise intolerance 58 31 occasional (7.5%) Occasional (29-5%) HP:0003546
39 delayed fine motor development 58 31 occasional (7.5%) Occasional (29-5%) HP:0010862
40 weakness of facial musculature 58 31 occasional (7.5%) Occasional (29-5%) HP:0030319
41 patellar subluxation 58 31 occasional (7.5%) Occasional (29-5%) HP:0010499
42 keratosis pilaris 31 occasional (7.5%) HP:0032152
43 hip dislocation 31 very rare (1%) HP:0002827
44 kyphosis 58 31 Occasional (29-5%) HP:0002808
45 flexion contracture 58 31 Very frequent (99-80%) HP:0001371
46 scoliosis 58 Occasional (29-5%)
47 muscular hypotonia 58 Occasional (29-5%)
48 muscle weakness 31 HP:0001324
49 myopathy 31 HP:0003198
50 elevated serum creatine kinase 31 HP:0003236

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skeletal Spine:
kyphosis
stooped posture

Skeletal:
joint laxity
proximal joint contractures

Neurologic Central Nervous System:
delayed motor development
delayed walking
inability or difficulty running

Laboratory Abnormalities:
increased serum creatine kinase
fibroblasts show a reduction of and disorganization in collagen xii in the extracellular matrix

Skeletal Pelvis:
hip dislocation (in some patients)

Skeletal Feet:
distal joint hyperlaxity

Chest Ribs Sternum Clavicles And Scapulae:
scapular winging

Muscle Soft Tissue:
hypotonia
fibrosis
muscle weakness, mainly proximal
myopathic changes, mild, seen on muscle biopsy
variability in fiber diameter, mild
more
Skin Nails Hair Skin:
atrophic scarring
hypertrophic scarring

Head And Neck Neck:
neck weakness

Skeletal Hands:
distal joint hyperlaxity
flexion finger contractures

Clinical features from OMIM®:

616471 (Updated 20-May-2021)

Drugs & Therapeutics for Bethlem Myopathy 2

Search Clinical Trials , NIH Clinical Center for Bethlem Myopathy 2

Genetic Tests for Bethlem Myopathy 2

Genetic tests related to Bethlem Myopathy 2:

# Genetic test Affiliating Genes
1 Bethlem Myopathy 2 29 COL12A1

Anatomical Context for Bethlem Myopathy 2

MalaCards organs/tissues related to Bethlem Myopathy 2:

40
Bone

Publications for Bethlem Myopathy 2

Articles related to Bethlem Myopathy 2:

# Title Authors PMID Year
1
Mutations in the collagen XII gene define a new form of extracellular matrix-related myopathy. 57 6
24334769 2014
2
Recessive and dominant mutations in COL12A1 cause a novel EDS/myopathy overlap syndrome in humans and mice. 6 57
24334604 2014
3
Collagen XII myopathy with rectus femoris atrophy and collagen XII retention in fibroblasts. 6
29342313 2018
4
Use of Exome Sequencing for Infants in Intensive Care Units: Ascertainment of Severe Single-Gene Disorders and Effect on Medical Management. 6
28973083 2017
5
Novel Col12A1 variant expands the clinical picture of congenital myopathies with extracellular matrix defects. 6
27348394 2017
6
Diagnosis and etiology of congenital muscular dystrophy: We are halfway there. 6
27159402 2016
7
Type XII collagen regulates osteoblast polarity and communication during bone formation. 57
21670218 2011
8
Collagen XII mediated cellular and extracellular mechanisms regulate establishment of tendon structure and function. 61
33096204 2021

Variations for Bethlem Myopathy 2

ClinVar genetic disease variations for Bethlem Myopathy 2:

6 (show top 50) (show all 827)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 COL12A1 NM_004370.6(COL12A1):c.7001T>C (p.Ile2334Thr) SNV Pathogenic 204295 rs796052093 GRCh37: 6:75831103-75831103
GRCh38: 6:75121387-75121387
2 COL12A1 NM_004370.6(COL12A1):c.8357G>A (p.Gly2786Asp) SNV Pathogenic 204296 rs796052094 GRCh37: 6:75812371-75812371
GRCh38: 6:75102655-75102655
3 COL12A1 NM_004370.6(COL12A1):c.5893C>T (p.Arg1965Cys) SNV Pathogenic 204297 rs200487396 GRCh37: 6:75841700-75841700
GRCh38: 6:75131984-75131984
4 COL12A1 NM_004370.6(COL12A1):c.3310C>T (p.Arg1104Ter) SNV Pathogenic 475858 rs1329022055 GRCh37: 6:75865511-75865511
GRCh38: 6:75155795-75155795
5 COL12A1 NM_004370.6(COL12A1):c.3994del (p.Ala1332fs) Deletion Pathogenic 475862 rs1554182935 GRCh37: 6:75861589-75861589
GRCh38: 6:75151873-75151873
6 COL12A1 NM_004370.6(COL12A1):c.8713C>T (p.Arg2905Ter) SNV Pathogenic 642795 rs371399251 GRCh37: 6:75801078-75801078
GRCh38: 6:75091362-75091362
7 COL12A1 NM_004370.6(COL12A1):c.3758T>G (p.Leu1253Ter) SNV Pathogenic 647130 rs1582139761 GRCh37: 6:75861924-75861924
GRCh38: 6:75152208-75152208
8 COL12A1 NM_004370.6(COL12A1):c.4738del (p.Ser1580fs) Deletion Pathogenic 657345 rs1471550984 GRCh37: 6:75853057-75853057
GRCh38: 6:75143341-75143341
9 COL12A1 NM_004370.6(COL12A1):c.4172dup (p.Leu1391fs) Duplication Pathogenic 642260 rs1582133194 GRCh37: 6:75858188-75858189
GRCh38: 6:75148472-75148473
10 COL12A1 NM_004370.6(COL12A1):c.4300C>T (p.Arg1434Ter) SNV Pathogenic 659962 rs1562223444 GRCh37: 6:75857508-75857508
GRCh38: 6:75147792-75147792
11 COL12A1 NM_004370.6(COL12A1):c.7925_7926del (p.Thr2642fs) Deletion Pathogenic 661356 rs1582068925 GRCh37: 6:75822944-75822945
GRCh38: 6:75113228-75113229
12 COL12A1 NM_004370.6(COL12A1):c.8383G>T (p.Gly2795Ter) SNV Pathogenic 835532 GRCh37: 6:75812345-75812345
GRCh38: 6:75102629-75102629
13 COL12A1 NM_004370.6(COL12A1):c.8100+2T>C SNV Pathogenic 843473 GRCh37: 6:75818732-75818732
GRCh38: 6:75109016-75109016
14 COL12A1 NM_004370.6(COL12A1):c.4240C>T (p.Arg1414Ter) SNV Pathogenic 853507 GRCh37: 6:75858121-75858121
GRCh38: 6:75148405-75148405
15 COL12A1 NM_004370.6(COL12A1):c.4177del (p.Ile1393fs) Deletion Pathogenic 861370 GRCh37: 6:75858184-75858184
GRCh38: 6:75148468-75148468
16 COL12A1 NM_004370.6(COL12A1):c.4414dup (p.Thr1472fs) Duplication Pathogenic 961675 GRCh37: 6:75857393-75857394
GRCh38: 6:75147677-75147678
17 COL12A1 NM_004370.6(COL12A1):c.6125C>A (p.Ser2042Ter) SNV Pathogenic 940321 GRCh37: 6:75839892-75839892
GRCh38: 6:75130176-75130176
18 COL12A1 NM_004370.6(COL12A1):c.6612T>A (p.Tyr2204Ter) SNV Pathogenic 945967 GRCh37: 6:75834083-75834083
GRCh38: 6:75124367-75124367
19 COL12A1 NC_000006.12:g.75117547del Deletion Pathogenic 960454 GRCh37: 6:75827261-75827261
GRCh38: 6:75117545-75117545
20 COL12A1 NM_004370.6(COL12A1):c.8319+1G>C SNV Likely pathogenic 949905 GRCh37: 6:75813472-75813472
GRCh38: 6:75103756-75103756
21 COL12A1 NM_004370.6(COL12A1):c.8415+1G>C SNV Likely pathogenic 950749 GRCh37: 6:75812312-75812312
GRCh38: 6:75102596-75102596
22 COL12A1 NM_004370.6(COL12A1):c.8179-2A>G SNV Likely pathogenic 851983 GRCh37: 6:75815010-75815010
GRCh38: 6:75105294-75105294
23 COL12A1 NM_004370.6(COL12A1):c.7001T>C (p.Ile2334Thr) SNV Likely pathogenic 204295 rs796052093 GRCh37: 6:75831103-75831103
GRCh38: 6:75121387-75121387
24 COL12A1 NM_004370.6(COL12A1):c.5230+1G>A SNV Likely pathogenic 578147 rs1274606112 GRCh37: 6:75848163-75848163
GRCh38: 6:75138447-75138447
25 COL12A1 NM_004370.6(COL12A1):c.395-2A>C SNV Likely pathogenic 579878 rs1562310723 GRCh37: 6:75899533-75899533
GRCh38: 6:75189817-75189817
26 COL12A1 NM_004370.6(COL12A1):c.3905A>G (p.Lys1302Arg) SNV Uncertain significance 580124 rs1179021269 GRCh37: 6:75861678-75861678
GRCh38: 6:75151962-75151962
27 COL12A1 NM_004370.6(COL12A1):c.2714G>A (p.Arg905His) SNV Uncertain significance 580432 rs369193482 GRCh37: 6:75875492-75875492
GRCh38: 6:75165776-75165776
28 COL12A1 NM_004370.6(COL12A1):c.6919C>T (p.Pro2307Ser) SNV Uncertain significance 580486 rs758186176 GRCh37: 6:75833073-75833073
GRCh38: 6:75123357-75123357
29 COL12A1 NM_004370.6(COL12A1):c.5547C>A (p.Asn1849Lys) SNV Uncertain significance 580588 rs1235141094 GRCh37: 6:75843691-75843691
GRCh38: 6:75133975-75133975
30 COL12A1 NM_004370.6(COL12A1):c.5873C>G (p.Pro1958Arg) SNV Uncertain significance 580676 rs755452261 GRCh37: 6:75841720-75841720
GRCh38: 6:75132004-75132004
31 COL12A1 NM_004370.6(COL12A1):c.9076C>G (p.Pro3026Ala) SNV Uncertain significance 580957 rs376189614 GRCh37: 6:75797398-75797398
GRCh38: 6:75087682-75087682
32 COL12A1 NM_004370.6(COL12A1):c.2324G>A (p.Arg775Lys) SNV Uncertain significance 580959 rs1341266694 GRCh37: 6:75887492-75887492
GRCh38: 6:75177776-75177776
33 COL12A1 NM_004370.6(COL12A1):c.5954A>G (p.Asn1985Ser) SNV Uncertain significance 580966 rs373170333 GRCh37: 6:75840681-75840681
GRCh38: 6:75130965-75130965
34 COL12A1 NM_004370.6(COL12A1):c.2038C>G (p.Pro680Ala) SNV Uncertain significance 581001 rs1562290248 GRCh37: 6:75890781-75890781
GRCh38: 6:75181065-75181065
35 COL12A1 NM_004370.6(COL12A1):c.2569C>G (p.Gln857Glu) SNV Uncertain significance 581163 rs201662983 GRCh37: 6:75884895-75884895
GRCh38: 6:75175179-75175179
36 COL12A1 NM_004370.6(COL12A1):c.4445T>C (p.Ile1482Thr) SNV Uncertain significance 581533 rs760640025 GRCh37: 6:75855933-75855933
GRCh38: 6:75146217-75146217
37 COL12A1 NM_004370.6(COL12A1):c.5615G>A (p.Arg1872His) SNV Uncertain significance 581581 rs770194625 GRCh37: 6:75843623-75843623
GRCh38: 6:75133907-75133907
38 COL12A1 NM_004370.6(COL12A1):c.4312A>G (p.Ser1438Gly) SNV Uncertain significance 581876 rs201651899 GRCh37: 6:75857496-75857496
GRCh38: 6:75147780-75147780
39 COL12A1 NM_004370.6(COL12A1):c.2968G>T (p.Asp990Tyr) SNV Uncertain significance 582140 rs201996851 GRCh37: 6:75875238-75875238
GRCh38: 6:75165522-75165522
40 COL12A1 NM_004370.6(COL12A1):c.469A>G (p.Lys157Glu) SNV Uncertain significance 582896 rs373002461 GRCh37: 6:75899457-75899457
GRCh38: 6:75189741-75189741
41 COL12A1 NM_004370.6(COL12A1):c.7048G>T (p.Val2350Leu) SNV Uncertain significance 583015 rs755159927 GRCh37: 6:75831056-75831056
GRCh38: 6:75121340-75121340
42 COL12A1 NM_004370.6(COL12A1):c.8501C>G (p.Pro2834Arg) SNV Uncertain significance 583345 rs199693016 GRCh37: 6:75811338-75811338
GRCh38: 6:75101622-75101622
43 COL12A1 NM_004370.6(COL12A1):c.266A>C (p.Glu89Ala) SNV Uncertain significance 450624 rs1278211393 GRCh37: 6:75901996-75901996
GRCh38: 6:75192280-75192280
44 COL12A1 NM_004370.6(COL12A1):c.8886G>T (p.Gly2962=) SNV Uncertain significance 639126 rs373455368 GRCh37: 6:75799881-75799881
GRCh38: 6:75090165-75090165
45 COL12A1 NM_004370.6(COL12A1):c.3350A>G (p.Tyr1117Cys) SNV Uncertain significance 639666 rs1582145759 GRCh37: 6:75865471-75865471
GRCh38: 6:75155755-75155755
46 COL12A1 NM_004370.6(COL12A1):c.6066G>A (p.Thr2022=) SNV Uncertain significance 639750 rs754929219 GRCh37: 6:75840569-75840569
GRCh38: 6:75130853-75130853
47 COL12A1 NM_004370.6(COL12A1):c.3086T>C (p.Val1029Ala) SNV Uncertain significance 639832 rs1582147110 GRCh37: 6:75866137-75866137
GRCh38: 6:75156421-75156421
48 COL12A1 NM_004370.6(COL12A1):c.185C>G (p.Thr62Arg) SNV Uncertain significance 640641 rs779409298 GRCh37: 6:75904552-75904552
GRCh38: 6:75194836-75194836
49 COL12A1 NM_004370.6(COL12A1):c.274G>T (p.Val92Leu) SNV Uncertain significance 640831 rs377482121 GRCh37: 6:75901988-75901988
GRCh38: 6:75192272-75192272
50 COL12A1 NM_004370.6(COL12A1):c.2174C>A (p.Ala725Glu) SNV Uncertain significance 640898 rs1341300538 GRCh37: 6:75887642-75887642
GRCh38: 6:75177926-75177926

UniProtKB/Swiss-Prot genetic disease variations for Bethlem Myopathy 2:

72
# Symbol AA change Variation ID SNP ID
1 COL12A1 p.Ile2334Thr VAR_074547 rs796052093
2 COL12A1 p.Gly2786Asp VAR_074548 rs796052094

Expression for Bethlem Myopathy 2

Search GEO for disease gene expression data for Bethlem Myopathy 2.

Pathways for Bethlem Myopathy 2

GO Terms for Bethlem Myopathy 2

Sources for Bethlem Myopathy 2

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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