AMDG
MCID: CHN057
MIFTS: 43

Chondrodysplasia, Grebe Type (AMDG)

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

Aliases & Classifications for Chondrodysplasia, Grebe Type

MalaCards integrated aliases for Chondrodysplasia, Grebe Type:

Name: Chondrodysplasia, Grebe Type 56 52 58 13 71
Acromesomelic Dysplasia, Grebe Type 56 12 52 58 15
Grebe Chondrodysplasia 56 12 52 54
Grebe Dysplasia 56 52 36
Grebe Syndrome 52 29 6
Amdg 56 52 73
Chondrodysplasia, Acromesomelic, Type Grebe 39
Acromesomelic Chondrodysplasia, Grebe Type 73
Acromesomelic Dysplasia, Grebe Type; Amdg 56
Achondrogenesis, Type Ii, Formerly 56
Achondrogenesis, Brazilian 56
Brazilian Achondrogenesis 52

Characteristics:

Orphanet epidemiological data:

58
acromesomelic dysplasia, grebe type
Inheritance: Autosomal recessive; Age of onset: Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
stillborn or death in infancy
heterozygote individuals are average stature and can have mild skeletal abnormalities including brachydactyly, delayed bone age, metatarsus adductus, and finger flexion contractures
increased frequency in the state of bahia, brazil
allelic to acromesomelic dysplasia, hunter-thompson type , brachydactyly, type c , and fibular hypoplasia nd complex brachydactyly


HPO:

31
chondrodysplasia, grebe type:
Clinical modifier death in infancy stillbirth
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Chondrodysplasia, Grebe Type

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 2098 Definition A rare autosomal recessive acromesomelic dysplasia characterized by severe dwarfism at birth, abnormalities confined to limbs, severe shortening and deformity of long bones, fusion or absence of carpal and tarsal bones, ball shaped fingers and, occasionally, polydactyly and absent joints. As seen in acromesomelic dysplasia, Hunter-Thomson type and acromesomelic dysplasia, Maroteaux Type, facial features and intelligence are normal. Visit the Orphanet disease page for more resources.

MalaCards based summary : Chondrodysplasia, Grebe Type, also known as acromesomelic dysplasia, grebe type, is related to acromesomelic dysplasia, hunter-thompson type and acromesomelic dysplasia, maroteaux type. An important gene associated with Chondrodysplasia, Grebe Type is GDF5 (Growth Differentiation Factor 5), and among its related pathways/superpathways are TGF-beta signaling pathway and ERK Signaling. Affiliated tissues include bone, skin and heart, and related phenotypes are skeletal dysplasia and bowing of the long bones

Disease Ontology : 12 An acromesomelic dysplasia that has material basis in mutation in CDMP-1 which results in micromelia, absence of middle and proximal phalanges and some metacarpal and metatarsal bones.

OMIM : 56 Grebe chondrodysplasia is an autosomal recessive disorder characterized by severe abnormality of the limbs and limb joints. The severity of limb shortening progresses in a proximal-distal gradient, with the hands and feet being most affected. The fingers and toes lack articulation and appear as skin appendages. In contrast, axial skeletal structures and the craniofacial skeleton are not affected. Heterozygous individuals are of average stature and have mild skeletal abnormalities (summary by Thomas et al., 1997). (200700)

KEGG : 36 Acromesomelic dysplasia is a rare form of severe acromesomelic limb shortening inherited in autosomal recessive fashion. Lower limbs are more affected than the upper limbs, showing nonfunctional fingers. Homozygous mutations in GDF5 are the cause of the disease.

UniProtKB/Swiss-Prot : 73 Acromesomelic chondrodysplasia, Grebe type: An autosomal recessive acromesomelic chondrodysplasia. Acromesomelic chondrodysplasias are rare hereditary skeletal disorders characterized by short stature, very short limbs and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMDG is characterized by normal axial skeletons and missing or fused skeletal elements within the hands and feet.

Related Diseases for Chondrodysplasia, Grebe Type

Diseases related to Chondrodysplasia, Grebe Type via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 37)
# Related Disease Score Top Affiliating Genes
1 acromesomelic dysplasia, hunter-thompson type 32.2 NPR2 GDF5 BMPR1B
2 acromesomelic dysplasia, maroteaux type 32.2 NPR2 GDF5 BMPR1B
3 fibular hypoplasia and complex brachydactyly 30.8 GDF5 BMPR1B
4 brachydactyly, type c 30.3 GDF5 BMPR1B
5 acromesomelic dysplasia 29.5 NPR2 GDF5 COL2A1 BMPR1B
6 brachydactyly 29.5 NPR2 GDF5 COL2A1 BMPR1B
7 dwarfism 10.5
8 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.2
9 tooth agenesis 10.2
10 autosomal recessive disease 10.2
11 skeletal dysplasias 10.2
12 sugarman brachydactyly 10.2 GDF5 BMPR1B
13 synostoses, tarsal, carpal, and digital 10.2 GDF5 BMPR1B
14 brachydactyly, type a1 10.2 GDF5 BMPR1B
15 brachydactyly, type a1, b 10.2 GDF5 BMPR1B
16 proximal symphalangism 10.2 GDF5 BMPR1B
17 multiple synostoses syndrome 10.1 GDF5 BMPR1B
18 brachydactyly, type a2 10.1 GDF5 BMPR1B
19 polydactyly, postaxial, type a1 10.0
20 polydactyly 10.0
21 heart disease 10.0
22 fibular hemimelia 10.0
23 metatarsus adductus 10.0
24 bunion 10.0
25 hemimelia 10.0
26 fibrochondrogenesis 10.0 GDF5 COL2A1
27 bone deterioration disease 9.9 GDF5 COL2A1
28 thanatophoric dysplasia, type i 9.9 NPR2 COL2A1
29 hypochondroplasia 9.9 NPR2 COL2A1
30 bone structure disease 9.8 GDF5 COL2A1
31 clubfoot 9.8 GDF5 COL2A1
32 chromosome 2q35 duplication syndrome 9.7 GDF5 BMPR1B
33 bone development disease 9.7 NPR2 GDF5 COL2A1
34 cartilage disease 9.6 SOX5 COL2A1
35 campomelic dysplasia 9.5 SOX5 COL2A1
36 odontochondrodysplasia 9.1 SOX5 NPR2 GDF5 COL2A1
37 scoliosis 9.0 SOX5 NPR2 COL2A1

Graphical network of the top 20 diseases related to Chondrodysplasia, Grebe Type:



Diseases related to Chondrodysplasia, Grebe Type

Symptoms & Phenotypes for Chondrodysplasia, Grebe Type

Human phenotypes related to Chondrodysplasia, Grebe Type:

58 31 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 skeletal dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002652
2 bowing of the long bones 58 31 hallmark (90%) Very frequent (99-80%) HP:0006487
3 joint stiffness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001387
4 brachydactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001156
5 micromelia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002983
6 short foot 58 31 hallmark (90%) Very frequent (99-80%) HP:0001773
7 short toe 58 31 hallmark (90%) Very frequent (99-80%) HP:0001831
8 sarcoma 58 31 hallmark (90%) Very frequent (99-80%) HP:0100242
9 disproportionate short-limb short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0008873
10 synostosis of carpal bones 58 31 hallmark (90%) Very frequent (99-80%) HP:0005048
11 tarsal synostosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0008368
12 aplasia/hypoplasia involving the metacarpal bones 58 31 hallmark (90%) Very frequent (99-80%) HP:0005914
13 aplasia of the middle phalanges of the toes 58 31 hallmark (90%) Very frequent (99-80%) HP:0100387
14 postaxial hand polydactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001162
15 aplasia/hypoplasia of the thumb 58 31 frequent (33%) Frequent (79-30%) HP:0009601
16 fibular hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0003038
17 short tibia 58 31 frequent (33%) Frequent (79-30%) HP:0005736
18 flexion contracture 31 HP:0001371
19 death in infancy 58 Occasional (29-5%)
20 hypoplasia of the ulna 31 HP:0003022
21 aplasia/hypoplasia of the patella 31 HP:0006498
22 hypoplasia of the radius 31 HP:0002984
23 short phalanx of finger 31 HP:0009803
24 pes valgus 31 HP:0008081
25 short humerus 31 HP:0005792
26 acromesomelia 31 HP:0003086
27 short femur 31 HP:0003097
28 aplasia/hypoplasia of metatarsal bones 31 HP:0001964
29 short digit 31 HP:0011927
30 valgus hand deformity 31 HP:0006228

Symptoms via clinical synopsis from OMIM:

56
Skeletal Limbs:
short tibia
short radii
short fibulae
short ulna
limb reduction, especially distally (acromesomelia)
more
Skeletal Feet:
short feet
rudimentary phalanges (distal phalanges present)
valgus foot deformity
fused tarsal bone
absent or hypoplastic metatarsal

Growth Height:
short limb dwarfism
average adult male height, 100.5cm
average adult female height, 99.5cm

Skeletal Hands:
postaxial polydactyly
valgus hand deformity
very short digits
rudimentary carpal bones
rudimentary phalanges (distal phalanges present)
more
Neurologic Central Nervous System:
normal intelligence

Clinical features from OMIM:

200700

MGI Mouse Phenotypes related to Chondrodysplasia, Grebe Type:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.65 BMPR1B COL2A1 NPR2 SOX12 SOX5
2 limbs/digits/tail MP:0005371 9.63 BMPR1B COL2A1 GDF5 NPR2 SOX12 SOX5
3 normal MP:0002873 9.35 BMPR1B COL2A1 SOX12 SOX15 SOX5
4 skeleton MP:0005390 9.1 BMPR1B COL2A1 GDF5 NPR2 SOX12 SOX5

Drugs & Therapeutics for Chondrodysplasia, Grebe Type

Search Clinical Trials , NIH Clinical Center for Chondrodysplasia, Grebe Type

Genetic Tests for Chondrodysplasia, Grebe Type

Genetic tests related to Chondrodysplasia, Grebe Type:

# Genetic test Affiliating Genes
1 Grebe Syndrome 29 GDF5

Anatomical Context for Chondrodysplasia, Grebe Type

MalaCards organs/tissues related to Chondrodysplasia, Grebe Type:

40
Bone, Skin, Heart

Publications for Chondrodysplasia, Grebe Type

Articles related to Chondrodysplasia, Grebe Type:

(show all 14)
# Title Authors PMID Year
1
Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1. 61 56 6
9288098 1997
2
Clinical and molecular analysis of Grebe acromesomelic dysplasia in an Omani family. 6
12900894 2003
3
Frameshift mutation in the cartilage-derived morphogenetic protein 1 (CDMP1) gene and severe acromesomelic chondrodysplasia resembling Grebe-type chondrodysplasia. 6
12124730 2002
4
Grebe syndrome in Vietnamese sisters: not Agent Orange. 56
11168021 2001
5
Grebe syndrome: clinical and radiographic findings in affected individuals and heterozygous carriers. 56
9489798 1998
6
Assignment of a new TGF-beta superfamily member, human cartilage-derived morphogenetic protein-1, to chromosome 20q11.2. 56
8661040 1996
7
Severe short-limb dwarfism resembling Grebe chondrodysplasia. 56
3793102 1986
8
Heterozygote expression in Grebe chondrodysplasia. 56
3742853 1986
9
Grebe chondrodysplasia and brachydactyly in a family. 56
6705242 1984
10
A rare genetic syndrome. 56
4173015 1968
11
A NEW TYPE OF DWARFISM WITH VARIOUS BONE APLASIAS AND HYPOPLASIAS OF THE EXTREMITIES. 56
14159881 1964
12
Novel homozygous sequence variants in the GDF5 gene underlie acromesomelic dysplasia type-grebe in consanguineous families. 61
27577507 2017
13
Characterization of an acromesomelic dysplasia, Grebe type case: novel mutation affecting the recognition motif at the processing site of GDF5. 61
26275437 2016
14
Grebe dysplasia and the spectrum of CDMP1 mutations. 54
12687891 2003

Variations for Chondrodysplasia, Grebe Type

ClinVar genetic disease variations for Chondrodysplasia, Grebe Type:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GDF5 NM_000557.5(GDF5):c.1199G>A (p.Cys400Tyr)SNV Pathogenic 8379 rs74315387 20:34022014-34022014 20:35434216-35434216
2 GDF5 NM_000557.5(GDF5):c.297dup (p.Arg100fs)duplication Pathogenic 8380 20:34025411-34025412 20:35437631-35437632
3 GDF5 NM_000557.5(GDF5):c.1144del (p.Ala382fs)deletion Pathogenic/Likely pathogenic 623302 rs1568731526 20:34022069-34022069 20:35434271-35434271

UniProtKB/Swiss-Prot genetic disease variations for Chondrodysplasia, Grebe Type:

73
# Symbol AA change Variation ID SNP ID
1 GDF5 p.Cys400Tyr VAR_017407 rs74315387

Expression for Chondrodysplasia, Grebe Type

Search GEO for disease gene expression data for Chondrodysplasia, Grebe Type.

Pathways for Chondrodysplasia, Grebe Type

Pathways related to Chondrodysplasia, Grebe Type according to KEGG:

36
# Name Kegg Source Accession
1 TGF-beta signaling pathway hsa04350

Pathways related to Chondrodysplasia, Grebe Type according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.57 SOX5 SOX15 SOX12 GDF5 COL2A1 BMPR1B
2 11.13 GDF5 BMPR1B
3 10.77 SOX5 COL2A1

GO Terms for Chondrodysplasia, Grebe Type

Cellular components related to Chondrodysplasia, Grebe Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear transcription factor complex GO:0044798 8.62 SOX15 SOX12

Biological processes related to Chondrodysplasia, Grebe Type according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription by RNA polymerase II GO:0045944 9.8 SOX5 SOX15 SOX12 BMPR1B
2 ossification GO:0001503 9.52 NPR2 COL2A1
3 BMP signaling pathway GO:0030509 9.51 GDF5 BMPR1B
4 cell fate commitment GO:0045165 9.48 SOX5 SOX12
5 bone development GO:0060348 9.46 NPR2 COL2A1
6 chondrocyte differentiation GO:0002062 9.43 COL2A1 BMPR1B
7 cellular response to BMP stimulus GO:0071773 9.4 COL2A1 BMPR1B
8 limb morphogenesis GO:0035108 9.37 COL2A1 BMPR1B
9 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007178 9.32 GDF5 BMPR1B
10 cartilage condensation GO:0001502 9.26 COL2A1 BMPR1B
11 positive regulation of cartilage development GO:0061036 9.16 SOX5 BMPR1B
12 cartilage development GO:0051216 9.13 GDF5 COL2A1 BMPR1B
13 positive regulation of chondrocyte differentiation GO:0032332 8.8 SOX5 GDF5 BMPR1B

Sources for Chondrodysplasia, Grebe Type

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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