EDM1
MCID: EPP017
MIFTS: 48

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 58 45 74
Multiple Epiphyseal Dysplasia 1 12 54 76 30 6 15
Edm1 58 12 54 60 76
Multiple Epiphyseal Dysplasia Comp-Related 12 54
Polyepiphyseal Dysplasia Type 1 12 60
Med1 12 60
Multiple Epiphyseal Dysplasia, Comp-Related 58
Dysplasia, Epiphyseal, Multiple, Type 1 41
Multiple Epiphyseal Dysplasia Type 1 60
Epiphyseal Dysplasia, Multiple 1 13
Epiphyseal Dysplasia Multiple 1 54

Characteristics:

Orphanet epidemiological data:

60
multiple epiphyseal dysplasia type 1
Inheritance: Autosomal dominant; Age of onset: Childhood;

OMIM:

58
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:

33
epiphyseal dysplasia, multiple, 1:
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0070303
OMIM 58 132400
MESH via Orphanet 46 C535501
ICD10 via Orphanet 35 Q77.3
UMLS via Orphanet 75 C1838280
Orphanet 60 ORPHA93308
UMLS 74 C1838280

Summaries for Epiphyseal Dysplasia, Multiple, 1

UniProtKB/Swiss-Prot : 76 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 epiphyseal dysplasia, multiple, 3 and epiphyseal dysplasia, multiple, 2. 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, prostate and liver, and related phenotypes are osteoarthritis and epiphyseal dysplasia

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

OMIM : 58 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 36)
# Related Disease Score Top Affiliating Genes
1 epiphyseal dysplasia, multiple, 3 31.9 COL9A2 COL9A3 COMP MATN3
2 epiphyseal dysplasia, multiple, 2 31.9 COL9A1 COL9A2 COL9A3 COMP
3 multiple epiphyseal dysplasia 31.7 ACAN COL9A1 COL9A2 COL9A3 COMP MATN3
4 pseudoachondroplasia 31.4 ACAN COL9A1 COL9A2 COL9A3 COMP MATN3
5 breast cancer 10.4
6 achondrogenesis 10.3 COL9A2 SLC26A2
7 skeletal dysplasias 10.3 COMP MATN3
8 bone chondrosarcoma 10.3 ACAN COMP
9 atelosteogenesis 10.3 COL9A2 SLC26A2
10 cartilage disease 10.3 ACAN COMP
11 achondrogenesis, type ia 10.3 ACAN SLC26A2
12 prostate cancer 10.3
13 prostate cancer, hereditary, 8 10.3
14 prostate cancer, hereditary, 6 10.3
15 achondrogenesis, type ii 10.2 ACAN COMP
16 multiple epiphyseal dysplasia due to collagen 9 anomaly 10.2 COL9A1 COL9A2 COL9A3
17 autosomal recessive stickler syndrome 10.2 COL9A1 COL9A2 COL9A3
18 stickler syndrome 10.2 COL9A1 COL9A2 COL9A3
19 transient arthritis 10.2 ACAN COMP
20 hypochondrogenesis 10.2 ACAN COMP
21 dilated cardiomyopathy 10.2
22 bone deterioration disease 10.2 ACAN COL9A2 COL9A3
23 bone structure disease 10.2 ACAN COL9A2 COL9A3
24 metaphyseal chondrodysplasia, schmid type 10.1 COMP MATN3
25 spondyloepiphyseal dysplasia with congenital joint dislocations 10.1 ACAN SLC26A2
26 spinal stenosis 10.0 ACAN COL9A1 COL9A2 COL9A3
27 bladder cancer 10.0
28 nondisjunction 10.0
29 fatty liver disease, nonalcoholic 1 10.0
30 osteoarthritis 10.0 ACAN COL9A1 COMP MATN3
31 diastrophic dysplasia 10.0 COMP SLC26A2
32 epiphyseal dysplasia, multiple, 5 10.0 COL9A2 COL9A3 COMP MATN3 SLC26A2
33 halothane hepatitis 10.0 CALR HSPA5
34 epiphyseal dysplasia, multiple, 4 10.0 COL9A1 COL9A2 COL9A3 MATN3 SLC26A2
35 bone development disease 9.9 COL9A2 COMP GLI3 MATN3 SLC26A2
36 osteochondritis dissecans 9.8 ACAN COL9A1 COL9A2 COL9A3 COMP MATN3

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

Human phenotypes related to Epiphyseal Dysplasia, Multiple, 1:

60 33 (show all 29)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 osteoarthritis 60 33 hallmark (90%) Very frequent (99-80%) HP:0002758
2 epiphyseal dysplasia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002656
3 joint dislocation 60 33 frequent (33%) Frequent (79-30%) HP:0001373
4 gait disturbance 60 33 frequent (33%) Frequent (79-30%) HP:0001288
5 hip dysplasia 60 33 frequent (33%) Frequent (79-30%) HP:0001385
6 arthralgia 60 33 frequent (33%) Frequent (79-30%) HP:0002829
7 micromelia 60 33 frequent (33%) Frequent (79-30%) HP:0002983
8 short palm 60 33 frequent (33%) Frequent (79-30%) HP:0004279
9 limitation of joint mobility 60 33 frequent (33%) Frequent (79-30%) HP:0001376
10 mild short stature 60 33 frequent (33%) Frequent (79-30%) HP:0003502
11 genu valgum 60 33 occasional (7.5%) Occasional (29-5%) HP:0002857
12 genu varum 60 33 occasional (7.5%) Occasional (29-5%) HP:0002970
13 joint stiffness 33 HP:0001387
14 ovoid vertebral bodies 33 HP:0003300
15 waddling gait 33 HP:0002515
16 severe short stature 33 HP:0003510
17 disproportionate short-limb short stature 33 HP:0008873
18 short metacarpal 33 HP:0010049
19 avascular necrosis of the capital femoral epiphysis 33 HP:0005743
20 short phalanx of finger 33 HP:0009803
21 irregular vertebral endplates 33 HP:0003301
22 generalized joint laxity 33 HP:0002761
23 small epiphyses 33 HP:0010585
24 irregular epiphyses 33 HP:0010582
25 broad femoral neck 33 HP:0006429
26 short femoral neck 33 HP:0100864
27 delayed epiphyseal ossification 33 HP:0002663
28 limited hip movement 33 HP:0008800
29 hip osteoarthritis 33 HP:0008843

Symptoms via clinical synopsis from OMIM:

58
Skeletal Spine:
ovoid vertebral bodies
mild irregularity of vertebral endplates

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

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

Skeletal:
generalized joint laxity

Skeletal Hands:
short metacarpals
short phalanges

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

Clinical features from OMIM:

132400

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

47
# Description MGI Source Accession Score Top Affiliating Genes
1 limbs/digits/tail MP:0005371 9.1 COL9A1 COL9A2 COMP GLI3 MATN3 SLC26A2

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 30 COMP

Anatomical Context for Epiphyseal Dysplasia, Multiple, 1

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

42
Bone, Prostate, Liver, Breast

Publications for Epiphyseal Dysplasia, Multiple, 1

Articles related to Epiphyseal Dysplasia, Multiple, 1:

# Title Authors Year
1
Novel types of COMP mutations and genotype-phenotype association in pseudoachondroplasia and multiple epiphyseal dysplasia. ( 12483304 )
2003
2
A recurrent R718W mutation in COMP results in multiple epiphyseal dysplasia with mild myopathy: clinical and pathogenetic overlap with collagen IX mutations. ( 14684695 )
2003
3
Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene. ( 9887340 )
1999
4
Multiple epiphyseal dysplasia, ribbing type: a novel point mutation in the COMP gene in a South African family. ( 9021009 )
1997

Variations for Epiphyseal Dysplasia, Multiple, 1

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

76 (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 rs131184574
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 30)
# 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 GRCh37 Chromosome 19, 18896845: 18896847
4 COMP NM_000095.2(COMP): c.1417_1419dupGAC (p.Asp473_Asn474insAsp) duplication Pathogenic 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_1158del (p.Asn386del) deletion Pathogenic rs397515510 GRCh37 Chromosome 19, 18897438: 18897440
16 COMP NM_000095.2(COMP): c.1156_1158del (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 rs1555791556 GRCh38 Chromosome 19, 18787500: 18787500
28 COMP NM_000095.2(COMP): c.1126G> T (p.Asp376Tyr) single nucleotide variant Likely pathogenic rs1555791556 GRCh37 Chromosome 19, 18898309: 18898309
29 COMP NM_000095.3(COMP): c.1265A> C (p.Asp422Ala) single nucleotide variant Likely pathogenic GRCh38 Chromosome 19, 18786281: 18786281
30 COMP NM_000095.3(COMP): c.1265A> C (p.Asp422Ala) single nucleotide variant Likely pathogenic GRCh37 Chromosome 19, 18897091: 18897091

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 space GO:0005615 9.86 CA2 CALR COL9A1 COL9A2 COL9A3 COMP
2 melanosome GO:0042470 9.61 HSP90B1 HSPA5 PDIA4
3 collagen trimer GO:0005581 9.54 COL9A1 COL9A2 COL9A3
4 smooth endoplasmic reticulum GO:0005790 9.49 CALR HSPA5
5 endocytic vesicle lumen GO:0071682 9.46 CALR HSP90B1
6 extracellular matrix GO:0031012 9.43 ACAN COL9A1 COL9A2 COL9A3 COMP MATN3
7 collagen type IX trimer GO:0005594 9.33 COL9A1 COL9A2 COL9A3
8 endoplasmic reticulum chaperone complex GO:0034663 9.32 HSP90B1 HSPA5
9 endoplasmic reticulum lumen GO:0005788 9.23 CALR COL9A1 COL9A2 COL9A3 HSP90B1 HSPA5
10 extracellular region GO:0005576 10.08 ACAN CALR COL9A1 COL9A2 COL9A3 COMP
11 extracellular exosome GO:0070062 10.01 ATP6AP1 CA2 CALR COMP EIF2S1 HSP90B1

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 9.67 CALR HSP90B1 PDIA4
3 skeletal system development GO:0001501 9.62 ACAN COL9A2 COMP MATN3
4 positive regulation of bone resorption GO:0045780 9.46 ATP6AP1 CA2
5 response to endoplasmic reticulum stress GO:0034976 9.46 EIF2S1 HSP90B1 HSPA5 PDIA4
6 PERK-mediated unfolded protein response GO:0036499 9.43 EIF2S1 HSPA5
7 protein folding in endoplasmic reticulum GO:0034975 9.43 CALR HSP90B1 HSPA5
8 sequestering of calcium ion GO:0051208 9.37 CALR HSP90B1
9 chaperone-mediated protein folding GO:0061077 9.18 PDIA4
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 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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