MCID: SPN302
MIFTS: 28

Spondylometaphyseal Dysplasia, Kozlowski Type

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

Aliases & Classifications for Spondylometaphyseal Dysplasia, Kozlowski Type

MalaCards integrated aliases for Spondylometaphyseal Dysplasia, Kozlowski Type:

Name: Spondylometaphyseal Dysplasia, Kozlowski Type 57 53 59 29 13 6 40
Jequier Kozlowski Skeletal Dysplasia 53 73
Smd Kozlowski Type 53 75
Smdk 57 75
Dysmorphism Arthrogryposis Skeletal Maturation Advanced 53
Spondylometaphyseal Dysplasia Kozlowski Type 75
Skeletal Dysplasia Jequier-Kozlowski Type 53
Jequier-Kozlowski Syndrome 53
Smd, Kozlowski Type 57

Characteristics:

Orphanet epidemiological data:

59
spondylometaphyseal dysplasia, kozlowski type
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Europe);

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
normal at birth
waddling gait noted at age 15-20 months


HPO:

32
spondylometaphyseal dysplasia, kozlowski type:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 184252
Orphanet 59 ORPHA93314
ICD10 via Orphanet 34 Q77.8
MESH via Orphanet 45 C535797
UMLS via Orphanet 74 C0265280
MedGen 42 C0265280
MeSH 44 D010009
UMLS 73 C2931534

Summaries for Spondylometaphyseal Dysplasia, Kozlowski Type

NIH Rare Diseases : 53 Spondylometaphyseal dysplasia, Kozlowski type is a bone disease characterized by short stature involving the trunk. "Spondylo"refers to the spine (vertebrae), "metaphysis" refers to the wide part of the bone that contains the growth plate (the part of the bone that grows during childhood), and "dysplasia" means abnormal growth. It usually starts in early childhood when poor growth with uneven stature and a waddling gait with bow legs (genu varum) is noticed. Early osteoarthritis of the joints is also common. Other signs and symptoms include small hands and fingers, spine deformities, and X-ray showing short vertebra, mild metaphyseal changes, severe delay in ossification, square, short, flared iliac wings (the broadest part of the pelvic bone) and a flat and irregular hipbone.  Spondylometaphyseal dysplasia, Kozlowski type is caused by mutations in the TRPV4 gene. Inheritance is autosomal dominant. Treatment is surgical or the use of braces to align the spine.

MalaCards based summary : Spondylometaphyseal Dysplasia, Kozlowski Type, also known as jequier kozlowski skeletal dysplasia, is related to brachyolmia type 3 and spondyloepimetaphyseal dysplasia, strudwick type. An important gene associated with Spondylometaphyseal Dysplasia, Kozlowski Type is TRPV4 (Transient Receptor Potential Cation Channel Subfamily V Member 4). Affiliated tissues include bone, and related phenotypes are platyspondyly and gait disturbance

OMIM : 57 SMD Kozlowski (SMDK) is an autosomal dominant disorder characterized by significant scoliosis and mild metaphyseal abnormalities in the pelvis. The vertebrae exhibit platyspondyly and overfaced pedicles (Krakow et al., 2009). (184252)

UniProtKB/Swiss-Prot : 75 Spondylometaphyseal dysplasia Kozlowski type: A form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. It is characterized by postnatal dwarfism, significant scoliosis and mild metaphyseal abnormalities in the pelvis. The vertebrae exhibit platyspondyly and overfaced pedicles.

Related Diseases for Spondylometaphyseal Dysplasia, Kozlowski Type

Diseases related to Spondylometaphyseal Dysplasia, Kozlowski Type via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 brachyolmia type 3 11.3
2 spondyloepimetaphyseal dysplasia, strudwick type 10.3
3 metatropic dysplasia 10.2

Symptoms & Phenotypes for Spondylometaphyseal Dysplasia, Kozlowski Type

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Neck:
short neck

Skeletal:
delayed skeletal maturation

Skeletal Pelvis:
coxa vara
square, short iliac wings
flaring of iliac wings
flat, irregular acetabula
supra-acetabular notches (in some patients)

Head And Neck Face:
normal facies

Skeletal Skull:
sphenoid hypoplasia

Skeletal Feet:
short, stubby feet

Skeletal Spine:
scoliosis
platyspondyly
kyphoscoliosis
vertebral bodies broader than interpedicular distance
odontoid hypoplasia
more
Chest External Features:
pectus carinatum

Skeletal Limbs:
metaphyseal irregularity
metaphyseal flaring
irregular, rachitic-like metaphyses
mildly curved limbs (varus)
prominent joints (in some patients)

Growth Height:
short-trunked dwarfism
adult height 130-150 cm

Skeletal Hands:
hypoplastic carpal bones
severe carpal ossification delay
short, stubby hands


Clinical features from OMIM:

184252

Human phenotypes related to Spondylometaphyseal Dysplasia, Kozlowski Type:

59 32 (show all 34)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 platyspondyly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000926
2 gait disturbance 59 32 hallmark (90%) Very frequent (99-80%) HP:0001288
3 spondylometaphyseal dysplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002657
4 coxa vara 59 32 hallmark (90%) Very frequent (99-80%) HP:0002812
5 flared metaphysis 59 32 hallmark (90%) Very frequent (99-80%) HP:0003015
6 short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0004322
7 short thorax 59 32 hallmark (90%) Very frequent (99-80%) HP:0010306
8 high forehead 59 32 frequent (33%) Frequent (79-30%) HP:0000348
9 short neck 59 32 frequent (33%) Frequent (79-30%) HP:0000470
10 pectus carinatum 59 32 frequent (33%) Frequent (79-30%) HP:0000768
11 brachydactyly 59 32 frequent (33%) Frequent (79-30%) HP:0001156
12 limitation of joint mobility 59 32 frequent (33%) Frequent (79-30%) HP:0001376
13 scoliosis 59 32 frequent (33%) Frequent (79-30%) HP:0002650
14 delayed skeletal maturation 59 32 frequent (33%) Frequent (79-30%) HP:0002750
15 kyphosis 59 32 frequent (33%) Frequent (79-30%) HP:0002808
16 genu valgum 59 32 frequent (33%) Frequent (79-30%) HP:0002857
17 enlarged joints 59 32 occasional (7.5%) Frequent (79-30%) HP:0003037
18 depressed nasal bridge 59 32 frequent (33%) Frequent (79-30%) HP:0005280
19 narrow chest 59 32 occasional (7.5%) Occasional (29-5%) HP:0000774
20 hypoplasia of the odontoid process 59 32 occasional (7.5%) Occasional (29-5%) HP:0003311
21 abnormality of epiphysis morphology 59 32 occasional (7.5%) Occasional (29-5%) HP:0005930
22 aplastic clavicles 59 Occasional (29-5%)
23 abnormality of the face 32 HP:0000271
24 carpal bone hypoplasia 32 HP:0001498
25 abnormality of the rib cage 32 HP:0001547
26 abnormality of the foot 32 HP:0001760
27 waddling gait 32 HP:0002515
28 kyphoscoliosis 32 HP:0002751
29 flat acetabular roof 32 HP:0003180
30 disproportionate short-trunk short stature 32 HP:0003521
31 irregular, rachitic-like metaphyses 32 HP:0005042
32 severe carpal ossification delay 32 HP:0006069
33 irregular acetabular roof 32 HP:0008833
34 aplastic clavicle 32 occasional (7.5%) HP:0006660

Drugs & Therapeutics for Spondylometaphyseal Dysplasia, Kozlowski Type

Search Clinical Trials , NIH Clinical Center for Spondylometaphyseal Dysplasia, Kozlowski Type

Genetic Tests for Spondylometaphyseal Dysplasia, Kozlowski Type

Genetic tests related to Spondylometaphyseal Dysplasia, Kozlowski Type:

# Genetic test Affiliating Genes
1 Spondylometaphyseal Dysplasia, Kozlowski Type 29 TRPV4

Anatomical Context for Spondylometaphyseal Dysplasia, Kozlowski Type

MalaCards organs/tissues related to Spondylometaphyseal Dysplasia, Kozlowski Type:

41
Bone

Publications for Spondylometaphyseal Dysplasia, Kozlowski Type

Articles related to Spondylometaphyseal Dysplasia, Kozlowski Type:

# Title Authors Year
1
Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia. ( 19232556 )
2009
2
Spondylometaphyseal dysplasia (Kozlowski type): case report. ( 8233993 )
1993

Variations for Spondylometaphyseal Dysplasia, Kozlowski Type

UniProtKB/Swiss-Prot genetic disease variations for Spondylometaphyseal Dysplasia, Kozlowski Type:

75
# Symbol AA change Variation ID SNP ID
1 TRPV4 p.Asp333Gly VAR_062332 rs121912634
2 TRPV4 p.Arg594His VAR_062333 rs77975504
3 TRPV4 p.Ala716Ser VAR_062334 rs121912635
4 TRPV4 p.Glu278Lys VAR_064521 rs267607148
5 TRPV4 p.Leu596Pro VAR_064527 rs515726159
6 TRPV4 p.Gly600Trp VAR_064528 rs515726160
7 TRPV4 p.Met625Ile VAR_064533 rs515726164
8 TRPV4 p.Leu709Met VAR_064534 rs116571438
9 TRPV4 p.Cys777Tyr VAR_064536 rs515726165
10 TRPV4 p.Glu797Lys VAR_064537 rs267607149

ClinVar genetic disease variations for Spondylometaphyseal Dysplasia, Kozlowski Type:

6
(show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 TRPV4 NM_021625.4(TRPV4): c.1781G> A (p.Arg594His) single nucleotide variant Pathogenic rs77975504 GRCh37 Chromosome 12, 110230500: 110230500
2 TRPV4 NM_021625.4(TRPV4): c.1781G> A (p.Arg594His) single nucleotide variant Pathogenic rs77975504 GRCh38 Chromosome 12, 109792695: 109792695
3 TRPV4 NM_021625.4(TRPV4): c.998A> G (p.Asp333Gly) single nucleotide variant Pathogenic rs121912634 GRCh37 Chromosome 12, 110236573: 110236573
4 TRPV4 NM_021625.4(TRPV4): c.998A> G (p.Asp333Gly) single nucleotide variant Pathogenic rs121912634 GRCh38 Chromosome 12, 109798768: 109798768
5 TRPV4 NM_021625.4(TRPV4): c.2146G> T (p.Ala716Ser) single nucleotide variant Pathogenic rs121912635 GRCh37 Chromosome 12, 110226267: 110226267
6 TRPV4 NM_021625.4(TRPV4): c.2146G> T (p.Ala716Ser) single nucleotide variant Pathogenic rs121912635 GRCh38 Chromosome 12, 109788462: 109788462
7 TRPV4 NM_021625.4(TRPV4): c.832G> A (p.Glu278Lys) single nucleotide variant Pathogenic rs267607148 GRCh37 Chromosome 12, 110238444: 110238444
8 TRPV4 NM_021625.4(TRPV4): c.832G> A (p.Glu278Lys) single nucleotide variant Pathogenic rs267607148 GRCh38 Chromosome 12, 109800639: 109800639
9 TRPV4 NM_021625.4(TRPV4): c.2389G> A (p.Glu797Lys) single nucleotide variant Pathogenic rs267607149 GRCh37 Chromosome 12, 110222190: 110222190
10 TRPV4 NM_021625.4(TRPV4): c.2389G> A (p.Glu797Lys) single nucleotide variant Pathogenic rs267607149 GRCh38 Chromosome 12, 109784385: 109784385
11 TRPV4 NM_021625.4(TRPV4): c.2479C> G (p.Pro827Ala) single nucleotide variant Uncertain significance GRCh38 Chromosome 12, 109783758: 109783758
12 TRPV4 NM_021625.4(TRPV4): c.2479C> G (p.Pro827Ala) single nucleotide variant Uncertain significance GRCh37 Chromosome 12, 110221563: 110221563

Expression for Spondylometaphyseal Dysplasia, Kozlowski Type

Search GEO for disease gene expression data for Spondylometaphyseal Dysplasia, Kozlowski Type.

Pathways for Spondylometaphyseal Dysplasia, Kozlowski Type

GO Terms for Spondylometaphyseal Dysplasia, Kozlowski Type

Sources for Spondylometaphyseal Dysplasia, Kozlowski Type

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74 UMLS via Orphanet
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