EDM1
MCID: EPP017
MIFTS: 46

Epiphyseal Dysplasia, Multiple, 1 (EDM1)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Epiphyseal Dysplasia, Multiple, 1

MalaCards integrated aliases for Epiphyseal Dysplasia, Multiple, 1:

Name: Epiphyseal Dysplasia, Multiple, 1 57 44 73
Multiple Epiphyseal Dysplasia 1 12 53 75 29 6 15
Edm1 57 12 53 59 75
Multiple Epiphyseal Dysplasia Comp-Related 12 53
Polyepiphyseal Dysplasia Type 1 12 59
Med1 12 59
Multiple Epiphyseal Dysplasia, Comp-Related 57
Dysplasia, Epiphyseal, Multiple, Type 1 40
Multiple Epiphyseal Dysplasia Type 1 59
Epiphyseal Dysplasia, Multiple 1 13
Epiphyseal Dysplasia Multiple 1 53

Characteristics:

Orphanet epidemiological data:

59
multiple epiphyseal dysplasia type 1
Inheritance: Autosomal dominant; Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity (see edm2 )
allelic to pseudoachondroplasia
hip joint replacement often necessary
symptoms usually manifest in childhood including waddling gait and painful, stiff joints


HPO:

32
epiphyseal dysplasia, multiple, 1:
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 132400
Disease Ontology 12 DOID:0070303
Orphanet 59 ORPHA93308
MESH via Orphanet 45 C535501
UMLS via Orphanet 74 C1838280
ICD10 via Orphanet 34 Q77.3
UMLS 73 C1838280

Summaries for Epiphyseal Dysplasia, Multiple, 1

UniProtKB/Swiss-Prot : 75 Multiple epiphyseal dysplasia 1: A generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers and of the centers of the carpal and tarsal bones. Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank and the milder Ribbing types. The Fairbank type is characterized by shortness of stature, short and stubby fingers, small epiphyses in several joints, including the knee, ankle, hand, and hip. The Ribbing type is confined predominantly to the hip joints and is characterized by hands that are normal and stature that is normal or near-normal.

MalaCards based summary : Epiphyseal Dysplasia, Multiple, 1, also known as multiple epiphyseal dysplasia 1, is related to multiple epiphyseal dysplasia and epiphyseal dysplasia, multiple, 3. An important gene associated with Epiphyseal Dysplasia, Multiple, 1 is COMP (Cartilage Oligomeric Matrix Protein), and among its related pathways/superpathways are PI3K-Akt signaling pathway and Degradation of the extracellular matrix. The drug Ropivacaine has been mentioned in the context of this disorder. Affiliated tissues include bone, breast and prostate, and related phenotypes are joint dislocation and osteoarthritis

Disease Ontology : 12 A multiple epiphyseal dysplasia that has material basis in heterozygous mutation in the COMP gene on chromosome 19p13.

OMIM : 57 Multiple epiphyseal dysplasia is a skeletal disorder characterized by short stature and early-onset osteoarthrosis (Briggs et al., 1995). (132400)

Related Diseases for Epiphyseal Dysplasia, Multiple, 1

Diseases in the Multiple Epiphyseal Dysplasia family:

Epiphyseal Dysplasia, Multiple, 1 Epiphyseal Dysplasia, Multiple, 4
Epiphyseal Dysplasia, Multiple, 2 Epiphyseal Dysplasia, Multiple, 3
Epiphyseal Dysplasia, Multiple, 5 Epiphyseal Dysplasia, Multiple, 6
Epiphyseal Dysplasia, Multiple, 7 Multiple Epiphyseal Dysplasia Due to Collagen 9 Anomaly
Multiple Epiphyseal Dysplasia, Autosomal Dominant Multiple Epiphyseal Dysplasia, Recessive

Diseases related to Epiphyseal Dysplasia, Multiple, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 33)
# Related Disease Score Top Affiliating Genes
1 multiple epiphyseal dysplasia 31.8 SLC26A2 MATN3 COMP COL9A3 COL9A2 COL9A1
2 epiphyseal dysplasia, multiple, 3 31.7 MATN3 COMP COL9A3 COL9A2
3 epiphyseal dysplasia, multiple, 2 31.7 COMP COL9A3 COL9A2 COL9A1
4 pseudoachondroplasia 31.5 SLC26A2 MATN3 COMP COL9A3 COL9A2 COL9A1
5 skeletal dysplasias 10.2 MATN3 COMP
6 achondrogenesis 10.2 SLC26A2 COL9A2
7 bone chondrosarcoma 10.2 COMP ACAN
8 breast cancer 10.2
9 prostate cancer 10.2
10 dilated cardiomyopathy 10.2
11 atelosteogenesis 10.2 SLC26A2 COL9A2
12 cartilage disease 10.2 COMP ACAN
13 achondrogenesis, type ia 10.2 SLC26A2 ACAN
14 multiple epiphyseal dysplasia due to collagen 9 anomaly 10.1 COL9A3 COL9A2 COL9A1
15 achondrogenesis, type ii 10.1 COMP ACAN
16 autosomal recessive stickler syndrome 10.1 COL9A3 COL9A2 COL9A1
17 stickler syndrome 10.1 COL9A3 COL9A2 COL9A1
18 transient arthritis 10.1 COMP ACAN
19 hypochondrogenesis 10.1 COMP ACAN
20 diastrophic dysplasia 10.1 SLC26A2 COMP
21 bone deterioration disease 10.1 COL9A3 COL9A2 ACAN
22 bone structure disease 10.1 COL9A3 COL9A2 ACAN
23 metaphyseal chondrodysplasia, schmid type 10.1 MATN3 COMP
24 bladder cancer 10.0
25 nondisjunction 10.0
26 spinal stenosis 10.0 COL9A3 COL9A2 COL9A1 ACAN
27 osteoarthritis 10.0 MATN3 COMP COL9A1 ACAN
28 epiphyseal dysplasia, multiple, 5 10.0 SLC26A2 MATN3 COMP COL9A3 COL9A2
29 halothane hepatitis 10.0 HSPA5 CALR
30 epiphyseal dysplasia, multiple, 4 10.0 SLC26A2 MATN3 COL9A3 COL9A2 COL9A1
31 spondyloepiphyseal dysplasia with congenital joint dislocations 9.9 SLC26A2 ACAN
32 bone development disease 9.9 SLC26A2 MATN3 GLI3 COMP COL9A2
33 osteochondritis dissecans 9.9 MATN3 COMP COL9A3 COL9A2 COL9A1 ACAN

Graphical network of the top 20 diseases related to Epiphyseal Dysplasia, Multiple, 1:



Diseases related to Epiphyseal Dysplasia, Multiple, 1

Symptoms & Phenotypes for Epiphyseal Dysplasia, Multiple, 1

Symptoms via clinical synopsis from OMIM:

57
Skeletal Spine:
ovoid vertebral bodies
mild irregularity of vertebral endplates

Skeletal:
generalized joint laxity

Growth Height:
short stature, mild to moderate
dwarfism, mild short-limb
final adult height 145-170cm

Skeletal Pelvis:
limited hip movement
avascular necrosis of femoral head
broad, short femoral neck
hip osteoarthritis (early-onset)

Skeletal Hands:
short metacarpals
short phalanges

Skeletal Limbs:
late ossifying epiphyses
small, irregular epiphyses
genua valga


Clinical features from OMIM:

132400

Human phenotypes related to Epiphyseal Dysplasia, Multiple, 1:

59 32 (show all 29)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint dislocation 59 32 frequent (33%) Frequent (79-30%) HP:0001373
2 osteoarthritis 59 32 hallmark (90%) Very frequent (99-80%) HP:0002758
3 genu valgum 59 32 occasional (7.5%) Occasional (29-5%) HP:0002857
4 gait disturbance 59 32 frequent (33%) Frequent (79-30%) HP:0001288
5 hip dysplasia 59 32 frequent (33%) Frequent (79-30%) HP:0001385
6 arthralgia 59 32 frequent (33%) Frequent (79-30%) HP:0002829
7 epiphyseal dysplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002656
8 micromelia 59 32 frequent (33%) Frequent (79-30%) HP:0002983
9 short palm 59 32 frequent (33%) Frequent (79-30%) HP:0004279
10 limitation of joint mobility 59 32 frequent (33%) Frequent (79-30%) HP:0001376
11 genu varum 59 32 occasional (7.5%) Occasional (29-5%) HP:0002970
12 mild short stature 59 32 frequent (33%) Frequent (79-30%) HP:0003502
13 joint stiffness 32 HP:0001387
14 ovoid vertebral bodies 32 HP:0003300
15 waddling gait 32 HP:0002515
16 severe short stature 32 HP:0003510
17 disproportionate short-limb short stature 32 HP:0008873
18 short metacarpal 32 HP:0010049
19 avascular necrosis of the capital femoral epiphysis 32 HP:0005743
20 short phalanx of finger 32 HP:0009803
21 limited hip movement 32 HP:0008800
22 irregular vertebral endplates 32 HP:0003301
23 generalized joint laxity 32 HP:0002761
24 small epiphyses 32 HP:0010585
25 irregular epiphyses 32 HP:0010582
26 broad femoral neck 32 HP:0006429
27 short femoral neck 32 HP:0100864
28 delayed epiphyseal ossification 32 HP:0002663
29 hip osteoarthritis 32 HP:0008843

MGI Mouse Phenotypes related to Epiphyseal Dysplasia, Multiple, 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 limbs/digits/tail MP:0005371 9.43 COL9A1 COL9A2 COMP GLI3 MATN3 SLC26A2
2 skeleton MP:0005390 9.17 CA2 COL9A1 COL9A2 COMP GLI3 MATN3

Drugs & Therapeutics for Epiphyseal Dysplasia, Multiple, 1

Drugs for Epiphyseal Dysplasia, Multiple, 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ropivacaine Approved Phase 4 84057-95-4 175805 71273

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Pre-emptive Sciatic Bloc to Prevent Lower Limb Phantom Pain Completed NCT00528463 Phase 4
2 Detecting Diabetes Sooner With a Risk Survey for the Family Doctor:Comparing Internet and Traditional Methods of Communication for Patients and Doctors Unknown status NCT01529918 Not Applicable

Search NIH Clinical Center for Epiphyseal Dysplasia, Multiple, 1

Cochrane evidence based reviews: epiphyseal dysplasia, multiple, 1

Genetic Tests for Epiphyseal Dysplasia, Multiple, 1

Genetic tests related to Epiphyseal Dysplasia, Multiple, 1:

# Genetic test Affiliating Genes
1 Multiple Epiphyseal Dysplasia 1 29 COMP

Anatomical Context for Epiphyseal Dysplasia, Multiple, 1

MalaCards organs/tissues related to Epiphyseal Dysplasia, Multiple, 1:

41
Bone, Breast, Prostate

Publications for Epiphyseal Dysplasia, Multiple, 1

Variations for Epiphyseal Dysplasia, Multiple, 1

UniProtKB/Swiss-Prot genetic disease variations for Epiphyseal Dysplasia, Multiple, 1:

75 (show all 29)
# Symbol AA change Variation ID SNP ID
1 COMP p.Asp342Tyr VAR_007617 rs137852652
2 COMP p.Asp361Val VAR_007619
3 COMP p.Asp361Tyr VAR_007620
4 COMP p.Cys371Ser VAR_007622
5 COMP p.Asp408Tyr VAR_007627
6 COMP p.Asn453Ser VAR_007630 rs28936668
7 COMP p.Asn523Lys VAR_007640 rs137852654
8 COMP p.Thr585Arg VAR_007642 rs312262900
9 COMP p.Pro276Arg VAR_026239
10 COMP p.Asp420Ala VAR_026240
11 COMP p.Gly167Glu VAR_066789 rs763887855
12 COMP p.Ser298Leu VAR_066792
13 COMP p.Ala311Asp VAR_066793
14 COMP p.Asp317Gly VAR_066794
15 COMP p.Asp326Gly VAR_066795
16 COMP p.Cys348Phe VAR_066798
17 COMP p.Cys371Tyr VAR_066800 rs105752113
18 COMP p.Asp374Asn VAR_066801
19 COMP p.Asp376Asn VAR_066802
20 COMP p.Asp385Asn VAR_066804
21 COMP p.Asp385Tyr VAR_066805
22 COMP p.Asp397His VAR_066808
23 COMP p.Gly404Arg VAR_066810
24 COMP p.Cys410Tyr VAR_066811
25 COMP p.Asn415Lys VAR_066812
26 COMP p.Gly427Glu VAR_066813
27 COMP p.Gly501Asp VAR_066821
28 COMP p.Arg718Pro VAR_066826 rs149551600
29 COMP p.Arg718Trp VAR_066827 rs28936368

ClinVar genetic disease variations for Epiphyseal Dysplasia, Multiple, 1:

6 (show all 28)
# Gene Variation Type Significance SNP ID Assembly Location
1 COMP NM_000095.2(COMP): c.1569C> G (p.Asn523Lys) single nucleotide variant Pathogenic rs137852654 GRCh37 Chromosome 19, 18896582: 18896582
2 COMP NM_000095.2(COMP): c.1569C> G (p.Asn523Lys) single nucleotide variant Pathogenic rs137852654 GRCh38 Chromosome 19, 18785772: 18785772
3 COMP NM_000095.2(COMP): c.1417_1419dupGAC (p.Asp473_Asn474insAsp) duplication Pathogenic rs312262898 GRCh37 Chromosome 19, 18896845: 18896847
4 COMP NM_000095.2(COMP): c.1417_1419dupGAC (p.Asp473_Asn474insAsp) duplication Pathogenic rs312262898 GRCh38 Chromosome 19, 18786035: 18786037
5 COMP NM_000095.2(COMP): c.2223dupC (p.Asn742Glnfs) duplication Pathogenic rs869320730 GRCh38 Chromosome 19, 18783058: 18783058
6 COMP NM_000095.2(COMP): c.2223dupC (p.Asn742Glnfs) duplication Pathogenic rs869320730 GRCh37 Chromosome 19, 18893868: 18893868
7 COMP NM_000095.2(COMP): c.2152C> T (p.Arg718Trp) single nucleotide variant Pathogenic rs28936368 GRCh37 Chromosome 19, 18893939: 18893939
8 COMP NM_000095.2(COMP): c.2152C> T (p.Arg718Trp) single nucleotide variant Pathogenic rs28936368 GRCh38 Chromosome 19, 18783129: 18783129
9 COMP NM_000095.2(COMP): c.1156A> G (p.Asn386Asp) single nucleotide variant Benign/Likely benign rs61739916 GRCh37 Chromosome 19, 18897440: 18897440
10 COMP NM_000095.2(COMP): c.1156A> G (p.Asn386Asp) single nucleotide variant Benign/Likely benign rs61739916 GRCh38 Chromosome 19, 18786630: 18786630
11 COMP NM_000095.2(COMP): c.1754C> G (p.Thr585Arg) single nucleotide variant Pathogenic rs312262900 GRCh37 Chromosome 19, 18895866: 18895866
12 COMP NM_000095.2(COMP): c.1754C> G (p.Thr585Arg) single nucleotide variant Pathogenic rs312262900 GRCh38 Chromosome 19, 18785056: 18785056
13 COMP NM_000095.2(COMP): c.1754C> T (p.Thr585Met) single nucleotide variant Pathogenic rs312262900 GRCh37 Chromosome 19, 18895866: 18895866
14 COMP NM_000095.2(COMP): c.1754C> T (p.Thr585Met) single nucleotide variant Pathogenic rs312262900 GRCh38 Chromosome 19, 18785056: 18785056
15 COMP NM_000095.2(COMP): c.1156_1158delAAC (p.Asn386del) deletion Pathogenic rs397515510 GRCh37 Chromosome 19, 18897438: 18897440
16 COMP NM_000095.2(COMP): c.1156_1158delAAC (p.Asn386del) deletion Pathogenic rs397515510 GRCh38 Chromosome 19, 18786628: 18786630
17 COMP NM_000095.2(COMP): c.1665C> A (p.Asn555Lys) single nucleotide variant Pathogenic rs397515511 GRCh37 Chromosome 19, 18896486: 18896486
18 COMP NM_000095.2(COMP): c.1665C> A (p.Asn555Lys) single nucleotide variant Pathogenic rs397515511 GRCh38 Chromosome 19, 18785676: 18785676
19 COMP NM_000095.2(COMP): c.1813G> A (p.Asp605Asn) single nucleotide variant Pathogenic rs397515512 GRCh37 Chromosome 19, 18895807: 18895807
20 COMP NM_000095.2(COMP): c.1813G> A (p.Asp605Asn) single nucleotide variant Pathogenic rs397515512 GRCh38 Chromosome 19, 18784997: 18784997
21 COMP NM_000095.2(COMP): c.2042C> G (p.Ser681Cys) single nucleotide variant Pathogenic rs397515513 GRCh37 Chromosome 19, 18895046: 18895046
22 COMP NM_000095.2(COMP): c.2042C> G (p.Ser681Cys) single nucleotide variant Pathogenic rs397515513 GRCh38 Chromosome 19, 18784236: 18784236
23 COMP NM_000095.2(COMP): c.2153G> C (p.Arg718Pro) single nucleotide variant Pathogenic rs149551600 GRCh37 Chromosome 19, 18893938: 18893938
24 COMP NM_000095.2(COMP): c.2153G> C (p.Arg718Pro) single nucleotide variant Pathogenic rs149551600 GRCh38 Chromosome 19, 18783128: 18783128
25 COMP NM_000095.2(COMP): c.1489+2T> A single nucleotide variant Uncertain significance rs1131692038 GRCh38 Chromosome 19, 18785963: 18785963
26 COMP NM_000095.2(COMP): c.1489+2T> A single nucleotide variant Uncertain significance rs1131692038 GRCh37 Chromosome 19, 18896773: 18896773
27 COMP NM_000095.2(COMP): c.1126G> T (p.Asp376Tyr) single nucleotide variant Likely pathogenic GRCh38 Chromosome 19, 18787500: 18787500
28 COMP NM_000095.2(COMP): c.1126G> T (p.Asp376Tyr) single nucleotide variant Likely pathogenic GRCh37 Chromosome 19, 18898309: 18898309

Expression for Epiphyseal Dysplasia, Multiple, 1

Search GEO for disease gene expression data for Epiphyseal Dysplasia, Multiple, 1.

Pathways for Epiphyseal Dysplasia, Multiple, 1

GO Terms for Epiphyseal Dysplasia, Multiple, 1

Cellular components related to Epiphyseal Dysplasia, Multiple, 1 according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 9.92 ATP6AP1 CA2 CALR COMP EIF2S1 HSP90B1
2 extracellular space GO:0005615 9.86 CA2 CALR COL9A1 COL9A2 COL9A3 COMP
3 melanosome GO:0042470 9.61 HSP90B1 HSPA5 PDIA4
4 collagen trimer GO:0005581 9.58 COL9A1 COL9A2 COL9A3
5 extracellular matrix GO:0031012 9.5 ACAN COL9A1 COL9A2 COL9A3 COMP HSP90B1
6 smooth endoplasmic reticulum GO:0005790 9.49 CALR HSPA5
7 endocytic vesicle lumen GO:0071682 9.48 CALR HSP90B1
8 endoplasmic reticulum chaperone complex GO:0034663 9.37 HSP90B1 HSPA5
9 collagen type IX trimer GO:0005594 9.33 COL9A1 COL9A2 COL9A3
10 endoplasmic reticulum lumen GO:0005788 9.23 CALR COL9A1 COL9A2 COL9A3 HSP90B1 HSPA5
11 extracellular region GO:0005576 10.06 ACAN CALR COL9A1 COL9A2 COL9A3 COMP

Biological processes related to Epiphyseal Dysplasia, Multiple, 1 according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of apoptotic process GO:0043066 9.8 COMP GLI3 GOLPH3 HSP90B1 HSPA5
2 protein folding GO:0006457 9.65 CALR HSP90B1 PDIA4
3 skeletal system development GO:0001501 9.62 ACAN COL9A2 COMP MATN3
4 chaperone-mediated protein folding GO:0061077 9.49 CALR PDIA4
5 positive regulation of bone resorption GO:0045780 9.46 ATP6AP1 CA2
6 response to endoplasmic reticulum stress GO:0034976 9.46 EIF2S1 HSP90B1 HSPA5 PDIA4
7 PERK-mediated unfolded protein response GO:0036499 9.43 EIF2S1 HSPA5
8 protein folding in endoplasmic reticulum GO:0034975 9.43 CALR HSP90B1 HSPA5
9 sequestering of calcium ion GO:0051208 9.37 CALR HSP90B1
10 ATF6-mediated unfolded protein response GO:0036500 9.13 CALR HSP90B1 HSPA5
11 extracellular matrix organization GO:0030198 9.1 ACAN COL9A1 COL9A2 COL9A3 COMP MATN3

Molecular functions related to Epiphyseal Dysplasia, Multiple, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 calcium ion binding GO:0005509 9.63 ACAN CALR COMP HSP90B1 HSPA5 MATN3
2 unfolded protein binding GO:0051082 9.43 CALR HSP90B1 HSPA5
3 protein binding involved in protein folding GO:0044183 9.32 CALR HSPA5
4 extracellular matrix structural constituent conferring tensile strength GO:0030020 9.13 COL9A1 COL9A2 COL9A3
5 extracellular matrix structural constituent GO:0005201 9.1 ACAN COL9A1 COL9A2 COL9A3 COMP MATN3

Sources for Epiphyseal Dysplasia, Multiple, 1

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
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