SEMDM
MCID: SPN030
MIFTS: 43

Spondyloepimetaphyseal Dysplasia, Missouri Type (SEMDM)

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

Aliases & Classifications for Spondyloepimetaphyseal Dysplasia, Missouri Type

MalaCards integrated aliases for Spondyloepimetaphyseal Dysplasia, Missouri Type:

Name: Spondyloepimetaphyseal Dysplasia, Missouri Type 57 12 20 58 73 29 6 15
Metaphyseal Anadysplasia 1 57 73 13 6 71
Spondyloepimetaphyseal Dysplasia Type 2 20 58 73
Semd, Missouri Type 57 20 58
Missouri Type of Spondyloepimetaphyseal Dysplasia 20
Spondyloepimetaphyseal Dysplasia Missouri Type 20
Spondyloepimetaphyseal Dysplasia Type Missouri 73
Spondylometaepiphyseal Dysplasia Type Missouri 73
Anadysplasia, Metaphyseal, Type 1 39
Semd Missouri Type 20
Semd Type 2 58
Semd-Mo 73
Mandp1 73
Semdm 57

Characteristics:

Orphanet epidemiological data:

58
spondyloepimetaphyseal dysplasia, missouri type
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide);

OMIM®:

57 (Updated 05-Mar-2021)
Miscellaneous:
waddling gait
improvement of epimetaphyseal changes with age

Inheritance:
autosomal dominant


HPO:

31
spondyloepimetaphyseal dysplasia, missouri type:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0080030
OMIM® 57 602111
MeSH 44 D001848
ICD10 via Orphanet 33 Q77.7
UMLS via Orphanet 72 C1865832
Orphanet 58 ORPHA93356
UMLS 71 C2748495

Summaries for Spondyloepimetaphyseal Dysplasia, Missouri Type

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 93356DefinitionSpondyloepimetaphyseal dysplasia, Missouri type is characterized by moderate-to-severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood.EpidemiologyThe syndrome has been described in a large Missouri (US) kindred with 14 affected members in 4 generations.Clinical descriptionThough some spontaneous improvement of the skeletal defects may occur in adolescence, the affected individuals remained shorter than their age-matched unaffected sibs. Predisposition deformities to osteoarthritis (especially of the knees) have been noted.EtiologyThis condition is caused by mutation in the MMP13 gene (locus 11q22.3) and transmitted in an autosomal dominant manner.Visit the Orphanet disease page for more resources.

MalaCards based summary : Spondyloepimetaphyseal Dysplasia, Missouri Type, also known as metaphyseal anadysplasia 1, is related to spondyloepimetaphyseal dysplasia and odontochondrodysplasia. An important gene associated with Spondyloepimetaphyseal Dysplasia, Missouri Type is MMP13 (Matrix Metallopeptidase 13), and among its related pathways/superpathways are Metabolism of proteins and HIV Life Cycle. Affiliated tissues include bone, and related phenotypes are abnormality of the metaphysis and abnormality of epiphysis morphology

Disease Ontology : 12 A spondyloepimetaphyseal dysplasia that has material basis in mutations in the MMP13 gene which results in a pear-shaped vertebrae, abnormal metaphyseal changes, and genu varum deformities.

UniProtKB/Swiss-Prot : 73 Metaphyseal anadysplasia 1: A bone development disorder characterized by skeletal anomalies that resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.
Spondyloepimetaphyseal dysplasia, Missouri type: A bone disease characterized by moderate to severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. Epimetaphyseal changes improve with age.

More information from OMIM: 602111

Related Diseases for Spondyloepimetaphyseal Dysplasia, Missouri Type

Graphical network of the top 20 diseases related to Spondyloepimetaphyseal Dysplasia, Missouri Type:



Diseases related to Spondyloepimetaphyseal Dysplasia, Missouri Type

Symptoms & Phenotypes for Spondyloepimetaphyseal Dysplasia, Missouri Type

Human phenotypes related to Spondyloepimetaphyseal Dysplasia, Missouri Type:

58 31 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of the metaphysis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000944
2 abnormality of epiphysis morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0005930
3 femoral bowing 58 31 hallmark (90%) Very frequent (99-80%) HP:0002980
4 tibial bowing 58 31 hallmark (90%) Very frequent (99-80%) HP:0002982
5 spondyloepimetaphyseal dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002651
6 pear-shaped vertebrae 58 31 hallmark (90%) Very frequent (99-80%) HP:0004566
7 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
8 osteoarthritis 58 31 frequent (33%) Frequent (79-30%) HP:0002758
9 genu varum 58 31 frequent (33%) Frequent (79-30%) HP:0002970
10 coxa vara 58 31 frequent (33%) Frequent (79-30%) HP:0002812
11 short lower limbs 58 31 frequent (33%) Frequent (79-30%) HP:0006385
12 limitation of joint mobility 58 31 occasional (7.5%) Occasional (29-5%) HP:0001376
13 skeletal dysplasia 58 Very frequent (99-80%)
14 delayed skeletal maturation 31 HP:0002750
15 waddling gait 31 HP:0002515
16 platyspondyly 31 HP:0000926
17 rhizomelia 31 HP:0008905
18 radial bowing 31 HP:0002986
19 ulnar bowing 31 HP:0003031
20 flared iliac wings 31 HP:0002869
21 flattened epiphysis 31 HP:0003071
22 limited elbow extension 31 HP:0001377
23 flared metaphysis 31 HP:0003015
24 metaphyseal cupping 31 HP:0003021
25 flared, irregular rib ends 31 HP:0006603
26 small epiphyses 31 HP:0010585
27 irregular sclerotic endplates 31 HP:0008476

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Skeletal Limbs:
osteoarthritis
genu varum
femoral bowing
tibial bowing
radial bowing
more
Skeletal:
spondyloepimetaphyseal dysplasia
delayed bone age

Skeletal Spine:
normal odontoid process
pear-shaped vertebrae (childhood)
irregular sclerotic endplates (adults)
mild platyspondyly (adult)
schmorl nodule appearance (thoracolumbar vertebrae, adults)

Skeletal Pelvis:
coxa vara
flared iliac wings
small flattened epiphyses (proximal femur)

Chest Ribs Sternum Clavicles And Scapulae:
flared, irregular rib ends

Growth Height:
adult male height 167-173cm
adult female height 152-167cm

Clinical features from OMIM®:

602111 (Updated 05-Mar-2021)

GenomeRNAi Phenotypes related to Spondyloepimetaphyseal Dysplasia, Missouri Type according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-104 9.35 ADAMTS9
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-110 9.35 ADAMTS3
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-132 9.35 ADAMTS9
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-182 9.35 ADAMTS9
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-213 9.35 ADAMTS9
6 Decreased Tat-dependent HIV-LTR-beta-galactosidase protein expression GR00224-A-2 8.62 ADAMTS5 MMP13

Drugs & Therapeutics for Spondyloepimetaphyseal Dysplasia, Missouri Type

Search Clinical Trials , NIH Clinical Center for Spondyloepimetaphyseal Dysplasia, Missouri Type

Genetic Tests for Spondyloepimetaphyseal Dysplasia, Missouri Type

Genetic tests related to Spondyloepimetaphyseal Dysplasia, Missouri Type:

# Genetic test Affiliating Genes
1 Spondyloepimetaphyseal Dysplasia, Missouri Type 29 MMP13

Anatomical Context for Spondyloepimetaphyseal Dysplasia, Missouri Type

MalaCards organs/tissues related to Spondyloepimetaphyseal Dysplasia, Missouri Type:

40
Bone

Publications for Spondyloepimetaphyseal Dysplasia, Missouri Type

Articles related to Spondyloepimetaphyseal Dysplasia, Missouri Type:

# Title Authors PMID Year
1
MMP13 mutation causes spondyloepimetaphyseal dysplasia, Missouri type (SEMD(MO). 61 57 6
16167086 2005
2
Mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum of metaphyseal anadysplasia. 57 6
19615667 2009
3
Spondyloepimetaphyseal dysplasia: clinical and radiologic investigation of a large kindred manifesting autosomal dominant inheritance, and a review of the literature. 57 6
8412645 1993
4
MMP13 mutations are the cause of recessive metaphyseal dysplasia, Spahr type. 57
24648384 2014
5
Metaphyseal anadysplasia: evidence of genetic heterogeneity. 57
9916842 1999
6
Linkage studies of a Missouri kindred with autosomal dominant spondyloepimetaphyseal dysplasia (SEMD) indicate genetic heterogeneity. 57
9258750 1997
7
Metaphyseal anadysplasia: a metaphyseal dysplasia of early onset with radiological regression and benign course. 57
1867263 1991
8
[Metaphyseal chondrodysplasia (metaphyseal dysostosis)--a new type?]. 57
4252978 1970
9
A de novo variant in MMP13 identified in a patient with dominant metaphyseal anadysplasia. 61
30439533 2019

Variations for Spondyloepimetaphyseal Dysplasia, Missouri Type

ClinVar genetic disease variations for Spondyloepimetaphyseal Dysplasia, Missouri Type:

6 (show top 50) (show all 55)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MMP13 NM_002427.4(MMP13):c.221T>C (p.Phe74Ser) SNV Pathogenic 9444 rs121909498 11:102826122-102826122 11:102955393-102955393
2 MMP13 NM_002427.4(MMP13):c.272T>C (p.Met91Thr) SNV Pathogenic 9445 rs121909499 11:102826071-102826071 11:102955342-102955342
3 MMP13 NM_002427.4(MMP13):c.224T>C (p.Phe75Ser) SNV Pathogenic 9443 rs121909497 11:102826119-102826119 11:102955390-102955390
4 MMP13 NM_002427.4(MMP13):c.212T>C (p.Met71Thr) SNV Pathogenic 560880 rs1565256477 11:102826131-102826131 11:102955402-102955402
5 MMP13 NM_002427.4(MMP13):c.*723A>T SNV Uncertain significance 877656 11:102814272-102814272 11:102943543-102943543
6 MMP13 NM_002427.4(MMP13):c.1101C>G (p.Pro367=) SNV Uncertain significance 717251 rs781949882 11:102818730-102818730 11:102948001-102948001
7 MMP13 NM_002427.4(MMP13):c.710G>A (p.Gly237Glu) SNV Uncertain significance 877736 11:102822830-102822830 11:102952101-102952101
8 MMP13 NM_002427.4(MMP13):c.1315+15T>C SNV Uncertain significance 301975 rs373735518 11:102816360-102816360 11:102945631-102945631
9 MMP13 NM_002427.4(MMP13):c.968C>T (p.Thr323Met) SNV Uncertain significance 301981 rs185832993 11:102819837-102819837 11:102949108-102949108
10 MMP13 NM_002427.4(MMP13):c.*1219A>C SNV Uncertain significance 301958 rs188511209 11:102813776-102813776 11:102943047-102943047
11 MMP13 NM_002427.4(MMP13):c.686G>T (p.Gly229Val) SNV Uncertain significance 301988 rs782723542 11:102822854-102822854 11:102952125-102952125
12 MMP13 NM_002427.4(MMP13):c.1082A>G (p.Asp361Gly) SNV Uncertain significance 301978 rs145425594 11:102818749-102818749 11:102948020-102948020
13 MMP13 NM_002427.4(MMP13):c.138C>T (p.Tyr46=) SNV Uncertain significance 301991 rs200537937 11:102826205-102826205 11:102955476-102955476
14 MMP13 NM_002427.4(MMP13):c.509A>C (p.Lys170Thr) SNV Uncertain significance 301989 rs145243532 11:102825189-102825189 11:102954460-102954460
15 MMP13 NM_002427.4(MMP13):c.*264C>T SNV Uncertain significance 301972 rs555759372 11:102814731-102814731 11:102944002-102944002
16 MMP13 NM_002427.4(MMP13):c.*771T>G SNV Uncertain significance 301964 rs886047553 11:102814224-102814224 11:102943495-102943495
17 MMP13 NM_002427.4(MMP13):c.*275T>C SNV Uncertain significance 301971 rs781825443 11:102814720-102814720 11:102943991-102943991
18 MMP13 NM_002427.4(MMP13):c.1372C>T (p.Arg458Cys) SNV Uncertain significance 301974 rs142064825 11:102815039-102815039 11:102944310-102944310
19 MMP13 NM_002427.4(MMP13):c.1123C>T (p.Leu375Phe) SNV Uncertain significance 301977 rs886047557 11:102818708-102818708 11:102947979-102947979
20 MMP13 NM_002427.4(MMP13):c.52C>T (p.Arg18Trp) SNV Uncertain significance 301992 rs61733406 11:102826383-102826383 11:102955654-102955654
21 MMP13 NM_002427.4(MMP13):c.*1007T>C SNV Uncertain significance 301960 rs886047551 11:102813988-102813988 11:102943259-102943259
22 MMP13 NM_002427.4(MMP13):c.935A>G (p.His312Arg) SNV Uncertain significance 301983 rs142601143 11:102819870-102819870 11:102949141-102949141
23 MMP13 NM_002427.4(MMP13):c.301G>T (p.Val101Leu) SNV Uncertain significance 301990 rs151254531 11:102826042-102826042 11:102955313-102955313
24 MMP13 NM_002427.4(MMP13):c.*1102T>C SNV Uncertain significance 301959 rs886047550 11:102813893-102813893 11:102943164-102943164
25 MMP13 NM_002427.4(MMP13):c.951T>G (p.Asp317Glu) SNV Uncertain significance 301982 rs367612153 11:102819854-102819854 11:102949125-102949125
26 MMP13 NM_002427.4(MMP13):c.*160G>A SNV Uncertain significance 301973 rs17860583 11:102814835-102814835 11:102944106-102944106
27 MMP13 NM_002427.4(MMP13):c.*756A>G SNV Uncertain significance 301965 rs886047554 11:102814239-102814239 11:102943510-102943510
28 MMP13 NM_002427.4(MMP13):c.438C>T (p.Ser146=) SNV Uncertain significance 196346 rs17860530 11:102825260-102825260 11:102954531-102954531
29 MMP13 NM_002427.4(MMP13):c.*1171C>A SNV Uncertain significance 879218 11:102813824-102813824 11:102943095-102943095
30 MMP13 NM_002427.4(MMP13):c.*1052T>C SNV Uncertain significance 879219 11:102813943-102813943 11:102943214-102943214
31 MMP13 NM_002427.4(MMP13):c.*156A>G SNV Uncertain significance 879276 11:102814839-102814839 11:102944110-102944110
32 MMP13 NM_002427.4(MMP13):c.*54T>C SNV Uncertain significance 879277 11:102814941-102814941 11:102944212-102944212
33 MMP13 NM_002427.4(MMP13):c.*13A>T SNV Uncertain significance 879278 11:102814982-102814982 11:102944253-102944253
34 MMP13 NM_002427.4(MMP13):c.818C>G (p.Pro273Arg) SNV Uncertain significance 879318 11:102820938-102820938 11:102950209-102950209
35 MMP13 NM_002427.4(MMP13):c.*954G>C SNV Uncertain significance 880416 11:102814041-102814041 11:102943312-102943312
36 MMP13 NM_002427.4(MMP13):c.*852C>T SNV Uncertain significance 880417 11:102814143-102814143 11:102943414-102943414
37 MMP13 NM_002427.4(MMP13):c.1316-15T>C SNV Uncertain significance 880459 11:102815110-102815110 11:102944381-102944381
38 MMP13 NM_002427.4(MMP13):c.1315+12C>T SNV Uncertain significance 880460 11:102816363-102816363 11:102945634-102945634
39 MMP13 NM_002427.4(MMP13):c.756T>C (p.Phe252=) SNV Uncertain significance 880506 11:102822784-102822784 11:102952055-102952055
40 MMP13 NM_002427.4(MMP13):c.*436G>C SNV Uncertain significance 301967 rs886047555 11:102814559-102814559 11:102943830-102943830
41 MMP13 NM_002427.4(MMP13):c.997C>T (p.Arg333Cys) SNV Uncertain significance 301980 rs782152104 11:102819808-102819808 11:102949079-102949079
42 MMP13 NM_002427.4(MMP13):c.492G>C (p.Met164Ile) SNV Uncertain significance 976145 11:102825206-102825206 11:102954477-102954477
43 MMP13 NM_002427.4(MMP13):c.*628A>G SNV Likely benign 301966 rs114428333 11:102814367-102814367 11:102943638-102943638
44 MMP13 NM_002427.4(MMP13):c.23C>T (p.Ala8Val) SNV Likely benign 879360 11:102826412-102826412 11:102955683-102955683
45 MMP13 NM_002427.4(MMP13):c.1169A>G (p.Asp390Gly) SNV Likely benign 301976 rs17860568 11:102818662-102818662 11:102947933-102947933
46 MMP13 NM_002427.4(MMP13):c.770A>T (p.Asp257Val) SNV Likely benign 301987 rs140993310 11:102822770-102822770 11:102952041-102952041
47 MMP13 NM_002427.4(MMP13):c.1080T>C (p.Tyr360=) SNV Likely benign 301979 rs61737008 11:102818751-102818751 11:102948022-102948022
48 MMP13 NM_002427.4(MMP13):c.799+7C>T SNV Likely benign 301986 rs72987505 11:102822734-102822734 11:102952005-102952005
49 MMP13 NM_002427.4(MMP13):c.*426A>G SNV Likely benign 301968 rs182315436 11:102814569-102814569 11:102943840-102943840
50 MMP13 NM_002427.4(MMP13):c.472G>A (p.Asp158Asn) SNV Likely benign 877737 11:102825226-102825226 11:102954497-102954497

UniProtKB/Swiss-Prot genetic disease variations for Spondyloepimetaphyseal Dysplasia, Missouri Type:

73
# Symbol AA change Variation ID SNP ID
1 MMP13 p.Phe75Ser VAR_032753 rs121909497
2 MMP13 p.Phe74Ser VAR_063432 rs121909498
3 MMP13 p.Met91Thr VAR_063433 rs121909499
4 MMP13 p.His232Asn VAR_063434 rs121909500

Expression for Spondyloepimetaphyseal Dysplasia, Missouri Type

Search GEO for disease gene expression data for Spondyloepimetaphyseal Dysplasia, Missouri Type.

Pathways for Spondyloepimetaphyseal Dysplasia, Missouri Type

GO Terms for Spondyloepimetaphyseal Dysplasia, Missouri Type

Cellular components related to Spondyloepimetaphyseal Dysplasia, Missouri Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.7 MMP13 ADAMTS9 ADAMTS5 ADAMTS4 ADAMTS3 ADAMTS15
2 extracellular space GO:0005615 9.65 MMP13 ADAMTS5 ADAMTS4 ADAMTS3 ADAMTS15
3 collagen-containing extracellular matrix GO:0062023 9.43 ADAMTS9 ADAMTS5 ADAMTS4 ADAMTS3 ADAMTS15 ACAN
4 extracellular matrix GO:0031012 9.17 MMP13 ADAMTS9 ADAMTS5 ADAMTS4 ADAMTS3 ADAMTS15

Biological processes related to Spondyloepimetaphyseal Dysplasia, Missouri Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 proteolysis GO:0006508 9.5 MMP13 ADAMTS9 ADAMTS5 ADAMTS4 ADAMTS3 ADAMTS15
2 extracellular matrix disassembly GO:0022617 9.33 MMP13 ADAMTS5 ADAMTS4
3 collagen fibril organization GO:0030199 9.32 ADAMTS3 ACAN
4 collagen catabolic process GO:0030574 9.26 MMP13 ADAMTS3
5 extracellular matrix organization GO:0030198 9.17 MMP13 ADAMTS9 ADAMTS5 ADAMTS4 ADAMTS3 ADAMTS15

Molecular functions related to Spondyloepimetaphyseal Dysplasia, Missouri Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metal ion binding GO:0046872 9.91 MMP13 ADAMTS9 ADAMTS5 ADAMTS4 ADAMTS3 ADAMTS15
2 hydrolase activity GO:0016787 9.73 MMP13 ADAMTS9 ADAMTS5 ADAMTS4 ADAMTS3 ADAMTS15
3 zinc ion binding GO:0008270 9.72 MMP13 ADAMTS9 ADAMTS5 ADAMTS3 ADAMTS15
4 peptidase activity GO:0008233 9.63 MMP13 ADAMTS9 ADAMTS5 ADAMTS4 ADAMTS3 ADAMTS15
5 heparin binding GO:0008201 9.61 ADAMTS5 ADAMTS3 ADAMTS15
6 endopeptidase activity GO:0004175 9.58 MMP13 ADAMTS3 ADAMTS15
7 extracellular matrix binding GO:0050840 9.46 ADAMTS5 ADAMTS15
8 metallopeptidase activity GO:0008237 9.43 MMP13 ADAMTS9 ADAMTS5 ADAMTS4 ADAMTS3 ADAMTS15
9 metalloendopeptidase activity GO:0004222 9.1 MMP13 ADAMTS9 ADAMTS5 ADAMTS4 ADAMTS3 ADAMTS15

Sources for Spondyloepimetaphyseal Dysplasia, Missouri Type

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 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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