MCID: KNS001
MIFTS: 53

Kniest Dysplasia

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

Aliases & Classifications for Kniest Dysplasia

MalaCards integrated aliases for Kniest Dysplasia:

Name: Kniest Dysplasia 57 12 76 53 25 59 75 37 29 13 55 6 15 73
Metatropic Dwarfism, Type Ii 25 73
Kniest Syndrome 25 75
Swiss Cheese Cartilage Dysplasia 25
Metatropic Dysplasia Type Ii 25
Metatropic Dwarfism Type Ii 75
Kniest Chondrodystrophy 25
Dysplasia, Kniest 40
Kd 75
Ks 75

Characteristics:

Orphanet epidemiological data:

59
kniest dysplasia
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
delayed motor milestones
abnormal gait
parental somatic mosaicism in 2 cases produced mild phenotype in the patients


HPO:

32
kniest dysplasia:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Kniest Dysplasia

NIH Rare Diseases : 53 Kniest dysplasia is a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities and problems with vision and hearing. It is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene. This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

MalaCards based summary : Kniest Dysplasia, also known as metatropic dwarfism, type ii, is related to spondyloepiphyseal dysplasia with congenital joint dislocations and kawasaki disease, and has symptoms including large joints, wide set eyes and round flat face. An important gene associated with Kniest Dysplasia is COL2A1 (Collagen Type II Alpha 1 Chain), and among its related pathways/superpathways are PI3K-Akt signaling pathway and Focal adhesion. Affiliated tissues include bone and eye, and related phenotypes are osteoarthritis and ptosis

UniProtKB/Swiss-Prot : 75 Kniest dysplasia: Moderately severe chondrodysplasia phenotype that results from mutations in the COL2A1 gene. Characteristics of the disorder include a short trunk and extremities, mid-face hypoplasia, cleft palate, myopia, retinal detachment, and hearing loss.

Genetics Home Reference : 25 Kniest dysplasia is a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities and problems with vision and hearing.

Disease Ontology : 12 An osteochondrodysplasia that has material basis in a mutation in the COL2A1 gene which results in dwarfism with a short trunk and limbs as well as vision and hearing problems. The disease has symptom large joints, has symptom wide set eyes, has symptom round flat face.

Wikipedia : 76 Kniest Dysplasia is a rare form of dwarfism caused by a mutation in the COL2A1 gene on chromosome 12.... more...

Description from OMIM: 156550

Related Diseases for Kniest Dysplasia

Diseases related to Kniest Dysplasia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 109)
# Related Disease Score Top Affiliating Genes
1 spondyloepiphyseal dysplasia with congenital joint dislocations 30.6 COL2A1 GALNS
2 kawasaki disease 11.8
3 kaposi sarcoma 11.6
4 hypogonadotropic hypogonadism 11.5
5 kleefstra syndrome 11.5
6 kallmann syndrome 11.4
7 krabbe disease 11.4
8 spinal and bulbar muscular atrophy, x-linked 1 11.2
9 47, xxy 11.1
10 kniest-like dysplasia, lethal 11.0
11 dyssegmental dysplasia with glaucoma 11.0
12 keutel syndrome 11.0
13 kindler syndrome 11.0
14 yt blood group antigen 10.9
15 malignant hyperthermia 1 10.9
16 zap-70 deficiency 10.9
17 hypogonadotropic hypogonadism 7 with or without anosmia 10.9
18 hypogonadotropic hypogonadism 2 with or without anosmia 10.9
19 hypogonadotropic hypogonadism 3 with or without anosmia 10.9
20 hypogonadotropic hypogonadism 1 with or without anosmia 10.9
21 hypogonadotropic hypogonadism 4 with or without anosmia 10.9
22 hypogonadotropic hypogonadism 5 with or without anosmia 10.9
23 hypogonadotropic hypogonadism 6 with or without anosmia 10.9
24 hypogonadotropic hypogonadism 8 with or without anosmia 10.9
25 hypogonadotropic hypogonadism 9 with or without anosmia 10.9
26 hypogonadotropic hypogonadism 10 with or without anosmia 10.9
27 hypogonadotropic hypogonadism 11 with or without anosmia 10.9
28 hypogonadotropic hypogonadism 12 with or without anosmia 10.9
29 hypogonadotropic hypogonadism 13 with or without anosmia 10.9
30 hypogonadotropic hypogonadism 14 with or without anosmia 10.9
31 hypogonadotropic hypogonadism 15 with or without anosmia 10.9
32 hypogonadotropic hypogonadism 16 with or without anosmia 10.9
33 hypogonadotropic hypogonadism 17 with or without anosmia 10.9
34 hypogonadotropic hypogonadism 18 with or without anosmia 10.9
35 hypogonadotropic hypogonadism 19 with or without anosmia 10.9
36 hypogonadotropic hypogonadism 20 with or without anosmia 10.9
37 hypogonadotropic hypogonadism 21 with or without anosmia 10.9
38 hypogonadotropic hypogonadism 22 with or without anosmia 10.9
39 kallmann syndrome with spastic paraplegia 10.7
40 spondyloepimetaphyseal dysplasia, strudwick type 10.6 COL2A1 SEMA3A
41 spondyloepimetaphyseal dysplasia, matrilin-3 related 10.5 COL2A1 SEMA3A
42 marshall syndrome 10.5 COL11A1 COL2A1
43 retinal perforation 10.5 COL11A1 COL2A1
44 otospondylomegaepiphyseal dysplasia 10.5 COL11A1 COL2A1
45 vitreous syneresis 10.5 COL11A1 COL2A1
46 macroglossia 10.4 COL11A1 COL2A1
47 vitreoretinal degeneration 10.4 COL11A1 COL2A1
48 sarcoma 10.3
49 familial avascular necrosis of the femoral head 10.3 COL2A1 TRPV4
50 stickler syndrome 10.3 COL11A1 COL2A1

Graphical network of the top 20 diseases related to Kniest Dysplasia:



Diseases related to Kniest Dysplasia

Symptoms & Phenotypes for Kniest Dysplasia

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Neck:
short neck

Skeletal Spine:
platyspondyly
lumbar kyphoscoliosis
coronal vertebral clefts
occipitoatlantal instability

Head And Neck Eyes:
myopia
retinal detachment
cataracts
prominent eyes

Head And Neck Face:
round face
flat midface

Skeletal Hands:
flattened, squared-off epiphyses of tubular bones

Head And Neck Nose:
low nasal bridge

Abdomen External Features:
inguinal hernias
umbilical hernias

Head And Neck Mouth:
cleft palate

Respiratory Airways:
respiratory distress
tracheomalacia

Skeletal Pelvis:
hip dislocation
coxa vara
flexion contractures of hips
hypoplastic pelvic bones

Skeletal Limbs:
enlarged joints
short, dumbbell appearance of long bones
splayed epiphyses and metaphyses
delayed epiphyseal ossification (early)
megaepiphyses (late)
more
Head And Neck Ears:
conductive hearing loss
frequent otitis media

Growth Height:
short stature, disproportionate (short trunk)
final adult height 106-145cm

Laboratory Abnormalities:
abnormal cartilage collagen on em
keratan sulfaturia in some patients


Clinical features from OMIM:

156550

Symptoms:

12
  • large joints
  • wide set eyes
  • round flat face

Human phenotypes related to Kniest Dysplasia:

59 32 (show top 50) (show all 55)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 osteoarthritis 59 32 hallmark (90%) Very frequent (99-80%) HP:0002758
2 ptosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000508
3 scoliosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0002650
4 kyphosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0002808
5 hyperlordosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0003307
6 hearing impairment 59 32 frequent (33%) Frequent (79-30%) HP:0000365
7 cataract 59 32 occasional (7.5%) Occasional (29-5%) HP:0000518
8 skeletal dysplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002652
9 depressed nasal bridge 59 32 hallmark (90%) Very frequent (99-80%) HP:0005280
10 joint stiffness 59 32 hallmark (90%) Very frequent (99-80%) HP:0001387
11 retinopathy 59 32 hallmark (90%) Very frequent (99-80%) HP:0000488
12 glossoptosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000162
13 cleft palate 59 32 frequent (33%) Frequent (79-30%) HP:0000175
14 micrognathia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000347
15 disproportionate short-trunk short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0003521
16 platyspondyly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000926
17 respiratory distress 59 32 occasional (7.5%) Occasional (29-5%) HP:0002098
18 micromelia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002983
19 short thorax 59 32 hallmark (90%) Very frequent (99-80%) HP:0010306
20 enlarged thorax 59 32 hallmark (90%) Very frequent (99-80%) HP:0100625
21 myopia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000545
22 hip dislocation 59 32 frequent (33%) Frequent (79-30%) HP:0002827
23 rhizomelia 59 32 hallmark (90%) Very frequent (99-80%) HP:0008905
24 glaucoma 59 32 occasional (7.5%) Occasional (29-5%) HP:0000501
25 retinal detachment 59 32 frequent (33%) Frequent (79-30%) HP:0000541
26 ectopia lentis 59 32 occasional (7.5%) Occasional (29-5%) HP:0001083
27 round face 59 32 frequent (33%) Frequent (79-30%) HP:0000311
28 tracheal stenosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002777
29 midface retrusion 59 32 hallmark (90%) Very frequent (99-80%) HP:0011800
30 hypoplastic pelvis 59 32 hallmark (90%) Very frequent (99-80%) HP:0008839
31 proptosis 59 32 frequent (33%) Frequent (79-30%) HP:0000520
32 tracheomalacia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002779
33 coxa vara 59 32 frequent (33%) Frequent (79-30%) HP:0002812
34 vitreoretinal degeneration 59 32 hallmark (90%) Very frequent (99-80%) HP:0000655
35 dumbbell-shaped long bone 59 32 hallmark (90%) Very frequent (99-80%) HP:0000947
36 flared metaphysis 59 32 hallmark (90%) Very frequent (99-80%) HP:0003015
37 flattened, squared-off epiphyses of tubular bones 59 32 hallmark (90%) Very frequent (99-80%) HP:0006172
38 malar flattening 32 HP:0000272
39 short neck 32 HP:0000470
40 joint dislocation 59 Very frequent (99-80%)
41 abnormality of epiphysis morphology 59 Very frequent (99-80%)
42 gait disturbance 32 HP:0001288
43 inguinal hernia 32 HP:0000023
44 umbilical hernia 32 HP:0001537
45 abnormality of the metaphysis 59 Very frequent (99-80%)
46 recurrent otitis media 32 HP:0000403
47 conductive hearing impairment 32 HP:0000405
48 hip contracture 32 HP:0003273
49 motor delay 32 HP:0001270
50 lumbar kyphoscoliosis 32 HP:0004619

UMLS symptoms related to Kniest Dysplasia:


arthralgia, respiratory distress

MGI Mouse Phenotypes related to Kniest Dysplasia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.03 ADAMTS18 CKM COL11A1 COL2A1 COMP FMOD
2 cardiovascular system MP:0005385 10.02 CKM COL2A1 COMP FMOD HSPG2 SEMA3A
3 cellular MP:0005384 10 GALNS HSPG2 SEMA3A CKM COL2A1 COMP
4 immune system MP:0005387 9.91 ADAMTS18 COL11A1 COL2A1 COMP FMOD HSPG2
5 limbs/digits/tail MP:0005371 9.8 ASPN COL11A1 COL2A1 COMP FMOD HSPG2
6 hearing/vestibular/ear MP:0005377 9.71 COL11A1 COL2A1 HSPG2 TRPV4
7 muscle MP:0005369 9.65 CKM COMP FMOD HSPG2 TRPV4
8 respiratory system MP:0005388 9.63 ADAMTS18 COL11A1 COL2A1 HSPG2 SEMA3A TRPV4
9 skeleton MP:0005390 9.5 COL11A1 COL2A1 COMP FMOD GALNS HSPG2
10 vision/eye MP:0005391 9.1 HSPG2 TRPV4 ADAMTS18 COL2A1 FMOD GALNS

Drugs & Therapeutics for Kniest Dysplasia

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of Skeletal Disorders and Short Stature Completed NCT00001754

Search NIH Clinical Center for Kniest Dysplasia

Genetic Tests for Kniest Dysplasia

Genetic tests related to Kniest Dysplasia:

# Genetic test Affiliating Genes
1 Kniest Dysplasia 29 COL2A1

Anatomical Context for Kniest Dysplasia

MalaCards organs/tissues related to Kniest Dysplasia:

41
Bone, Eye

Publications for Kniest Dysplasia

Articles related to Kniest Dysplasia:

(show all 36)
# Title Authors Year
1
Surgery of the head and neck in patient with Kniest dysplasia: Is wound healing an issue? ( 28109507 )
2017
2
Association between kniest dysplasia and chondrosarcoma in a child. ( 26345137 )
2015
3
[Kniest dysplasia due to mutation of COL2A1 gene]. ( 26037341 )
2015
4
Ophthalmic and molecular genetic findings in Kniest dysplasia. ( 25592122 )
2015
5
Novel splice (IVS18+1G>C) mutation in COL2A1 causing Kniest dysplasia. ( 23188137 )
2013
6
Prenatal diagnosis of Kniest dysplasia with three-dimensional helical computed tomography. ( 21250907 )
2011
7
Fetal MR imaging of Kniest dysplasia. ( 20020120 )
2010
8
Kniest Dysplasia: New Radiographic Features in the Skeleton. ( 27303468 )
2007
9
Kniest dysplasia: MR correlation of histologic and radiographic peculiarities. ( 15338083 )
2005
10
Cataract in Kniest dysplasia: clinicopathologic correlation. ( 15197068 )
2004
11
Undelayed femoral head ossification in Kniest dysplasia. Evolution of hip abnormalities, 30-year follow-up. ( 14649117 )
2003
12
A case of Kniest dysplasia with retinal detachment and the mutation analysis. ( 14644246 )
2003
13
Tracheomalacia in a neonate with kniest dysplasia: histopathologic and ultrastructural features. ( 11297324 )
2001
14
Growth causes difficult tracheal intubation in a patient with Kniest dysplasia. ( 14566532 )
2001
15
Small deletions in the type II collagen triple helix produce kniest dysplasia. ( 10406661 )
1999
16
Structurally abnormal type II collagen in a severe form of Kniest dysplasia caused by an exon 24 skipping mutation. ( 9468540 )
1998
17
Kniest dysplasia: Dr. W. Kniest, his patient, the molecular defect. ( 9066888 )
1997
18
Kniest dysplasia: patient's growth progress and development--evolution of abnormalities, 30 year follow up. ( 9359927 )
1997
19
Abnormal skeletal growth in Kniest dysplasia caused by type II collagen mutations. ( 9269170 )
1997
20
Recurrent transition at a CG dinucleotide in exon 12 of COL2A1 produces kniest dysplasia with abnormal RNA splicing by chondrocytes and lymphoblasts and interruption of the triple helix of type II collagen. ( 8702139 )
1996
21
The deletion of six amino acids at the C-terminus of the alpha 1 (II) chain causes overmodification of type II and type XI collagen: further evidence for the association between small deletions in COL2A1 and Kniest dysplasia. ( 8863156 )
1996
22
Kniest dysplasia: radiologic, histopathological, and scanning electronmicroscopic findings. ( 8723084 )
1996
23
A single amino acid substitution (G103D) in the type II collagen triple helix produces Kniest dysplasia. ( 7874117 )
1994
24
Expression, in cartilage, of a 7-amino-acid deletion in type II collagen from two unrelated individuals with Kniest dysplasia. ( 7977371 )
1994
25
Kniest dysplasia is caused by dominant collagen II (COL2A1) mutations: parental somatic mosaicism manifesting as Stickler phenotype and mild spondyloepiphyseal dysplasia. ( 7700721 )
1994
26
Alternative splicing as the result of a type II procollagen gene (COL2A1) mutation in a patient with Kniest dysplasia. ( 7849719 )
1994
27
MR demonstrates cartilaginous megaepiphyses of the hips in Kniest dysplasia of the young child. ( 1523061 )
1992
28
Kniest dysplasia is characterized by an apparent abnormal processing of the C-propeptide of type II cartilage collagen resulting in imperfect fibril assembly. ( 3276736 )
1988
29
Kniest dysplasia: a probable type II collagen defect. ( 3222213 )
1988
30
Craniofacial and mucopolysaccharide abnormalities in Kniest dysplasia. ( 2931448 )
1985
31
The ocular findings in Kniest dysplasia. ( 4014370 )
1985
32
The ocular findings in Kniest dysplasia. ( 4073190 )
1985
33
A distinct chondrodysplasia resembling Kniest dysplasia: clinical, roentgenographic, histologic, and ultrastructural findings. ( 6358440 )
1983
34
Kniest dysplasia: neonatal death with necropsy. ( 7446563 )
1980
35
Keratan sulphate excretion in a patient with Kniest dysplasia. ( 6458738 )
1980
36
Kniest dysplasia. A histochemical study of the growth plate. ( 514691 )
1979

Variations for Kniest Dysplasia

UniProtKB/Swiss-Prot genetic disease variations for Kniest Dysplasia:

75
# Symbol AA change Variation ID SNP ID
1 COL2A1 p.Gly303Asp VAR_001741 rs121912877

ClinVar genetic disease variations for Kniest Dysplasia:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 COL2A1 COL2A1, 28-BP DEL deletion Pathogenic
2 COL2A1 COL2A1, IVS20, A-G, -2 single nucleotide variant Pathogenic
3 COL2A1 NM_001844.4(COL2A1): c.908G> A (p.Gly303Asp) single nucleotide variant Pathogenic rs121912877 GRCh37 Chromosome 12, 48387608: 48387608
4 COL2A1 NM_001844.4(COL2A1): c.908G> A (p.Gly303Asp) single nucleotide variant Pathogenic rs121912877 GRCh38 Chromosome 12, 47993825: 47993825
5 COL2A1 NM_001844.4(COL2A1): c.1266+1delG deletion Pathogenic rs587776847 GRCh37 Chromosome 12, 48381051: 48381051
6 COL2A1 NM_001844.4(COL2A1): c.1266+1delG deletion Pathogenic rs587776847 GRCh38 Chromosome 12, 47987268: 47987268
7 COL2A1 COL2A1, IVS24, G-A, +5 single nucleotide variant Pathogenic
8 COL2A1 NM_001844.4(COL2A1): c.1023+1G> A single nucleotide variant Pathogenic rs886043794 GRCh37 Chromosome 12, 48386660: 48386660
9 COL2A1 NM_001844.4(COL2A1): c.1023+1G> A single nucleotide variant Pathogenic rs886043794 GRCh38 Chromosome 12, 47992877: 47992877

Expression for Kniest Dysplasia

Search GEO for disease gene expression data for Kniest Dysplasia.

Pathways for Kniest Dysplasia

Pathways related to Kniest Dysplasia according to KEGG:

37
# Name Kegg Source Accession
1 PI3K-Akt signaling pathway hsa04151
2 Focal adhesion hsa04510
3 ECM-receptor interaction hsa04512

Pathways related to Kniest Dysplasia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.56 COL11A1 COL2A1 HSPG2 SEMA3A
2
Show member pathways
11.82 ADAMTS18 ASPN COL11A1 COL2A1 COMP FMOD
3
Show member pathways
11.67 COL2A1 COMP HSPG2
4
Show member pathways
11.6 ADAMTS18 FMOD HSPG2
5 11.09 ASPN COMP FMOD
6 10.69 COL2A1 COMP FMOD

GO Terms for Kniest Dysplasia

Cellular components related to Kniest Dysplasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 9.73 COL11A1 COL2A1 COMP FMOD HSPG2 SEMA3A
2 extracellular region GO:0005576 9.61 ADAMTS18 ASPN COL11A1 COL2A1 COMP FMOD
3 lysosomal lumen GO:0043202 9.33 FMOD GALNS HSPG2
4 extracellular matrix GO:0031012 9.1 ASPN COL11A1 COL2A1 COMP FMOD HSPG2

Biological processes related to Kniest Dysplasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 collagen catabolic process GO:0030574 9.48 COL11A1 COL2A1
2 negative regulation of neuron projection development GO:0010977 9.46 SEMA3A TRPV4
3 heart morphogenesis GO:0003007 9.43 COL11A1 COL2A1
4 skeletal system morphogenesis GO:0048705 9.4 COL11A1 COL2A1
5 cartilage condensation GO:0001502 9.37 COL11A1 COL2A1
6 keratan sulfate catabolic process GO:0042340 9.32 FMOD GALNS
7 proteoglycan metabolic process GO:0006029 9.26 COL11A1 COL2A1
8 extracellular matrix organization GO:0030198 9.26 COL11A1 COL2A1 COMP HSPG2
9 cartilage development involved in endochondral bone morphogenesis GO:0060351 9.16 COL2A1 TRPV4
10 collagen fibril organization GO:0030199 8.8 COL11A1 COL2A1 FMOD

Molecular functions related to Kniest Dysplasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 collagen binding GO:0005518 8.96 ASPN COMP
2 extracellular matrix structural constituent GO:0005201 8.8 COL11A1 COL2A1 COMP

Sources for Kniest Dysplasia

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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