BOCD
MCID: CHN054
MIFTS: 45

Chondrodysplasia, Blomstrand Type (BOCD)

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

Aliases & Classifications for Chondrodysplasia, Blomstrand Type

MalaCards integrated aliases for Chondrodysplasia, Blomstrand Type:

Name: Chondrodysplasia, Blomstrand Type 57 59 13 44 40 73
Chondrodysplasia Blomstrand Type 12 53 75 29 6 15
Bocd 57 53 59 75
Blomstrand Lethal Chondrodysplasia 12 59
Blomstrand Lethal Osteochondrodysplasia 53
Blomstrand's Lethal Chondrodysplasia 53
Blomstrand Osteochondrodysplasia 59
Blomstrand Chondrodysplasia 59
Blc 59

Characteristics:

Orphanet epidemiological data:

59
blomstrand lethal chondrodysplasia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: embryofetal,infantile,stillbirth;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
die at birth or shortly after birth
caused by inactivating mutations in the parathyroid hormone receptor 1 gene, in contrast to jansen type metaphyseal chondrodysplasia,


HPO:

32
chondrodysplasia, blomstrand type:
Mortality/Aging stillbirth
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Chondrodysplasia, Blomstrand Type

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 50945Disease definitionBlomstrand lethal chondrodysplasia (BLC) is a neonatal osteosclerotic dysplasia (see this term) characterized by advanced endochondral bone maturation, very short limbs, dwarfism and prenatal lethality.EpidemiologyTo date, less than 10 cases have been described in the literature.Clinical descriptionBLC is a congenital disorder characterized by a low birth weight, facial dysmorphism (widely spaced and protruding eyes (which typically show cataract), depressed nasal bridge, short columella, long philtrum, macroglossia, protruding tongue, severe micrognathia), short trunk, narrow thorax and severe rhizo-meso-acromelic shortness of the limbs. Other anomalies also observed include tooth and mammary gland development defects, hypoplastic lungs, aorta coarctation (see this term), and bowel malrotation. Two forms of BCL, have been described: type I which is the severe, classical form and type II which has less severe features (such as absence of short trunk or, severely shortened arms but moderately shortened legs).EtiologyBLC is caused by inactivating homozygous or compound heterozygousmutations in PTH1R (3p22-p21.1) which encodes the parathyroid hormone (PTH)/parathyroid-hormone-related peptide (PTHrP) receptor (PTH1R). These mutations result in the decrease in binding or response to PTH and PTHrP.Diagnostic methodsDiagnosis is based on the clinical and radiological characteristics which show generalized increase in bone density with advanced ossification, severe shortness of the long bones with wide metaphyses and club-shaped distal ends, long narrow thorax, calcified hyoid bone and laryngeal cartilage and underdeveloped viscerocranium. Histopathological examination shows an important acceleration of the endochondral ossification in tubular bones, narrow cartilages of the epiphyses and large epiphyseal ossification centers. Diagnosis is confirmed by the genetic screening of PTH1R.Differential diagnosisDifferential diagnosis includes primary failure of tooth eruption (see this term) and other lethal short limbed dwarfisms.Antenatal diagnosisPrenatal diagnosis is achieved by sonographic examination showing polyhydramnios, hydrops fetalis (see this term) and a fetus with very short limbs, nuchale dema, macroglossia, a protuberant abdomen, internal anomalies and markedly advanced endochondral bone formation.Genetic counselingTransmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% chance of having an affected child.PrognosisBoth forms of BLC are lethal either prenatally or shortly after birth.Visit the Orphanet disease page for more resources.

MalaCards based summary : Chondrodysplasia, Blomstrand Type, also known as chondrodysplasia blomstrand type, is related to bladder cancer and pseudo-torch syndrome 1. An important gene associated with Chondrodysplasia, Blomstrand Type is PTH1R (Parathyroid Hormone 1 Receptor), and among its related pathways/superpathways are Presynaptic function of Kainate receptors and G alpha (s) signalling events. Affiliated tissues include bone, eye and tongue, and related phenotypes are malar flattening and low-set ears

OMIM : 57 Blomstrand chondrodysplasia is an autosomal recessive disorder characterized by short limbs, polyhydramnios, hydrops fetalis, facial anomalies, increased bone density, and advanced skeletal maturation (summary by Loshkajian et al., 1997). (215045)

UniProtKB/Swiss-Prot : 75 Chondrodysplasia Blomstrand type: Severe skeletal dysplasia.

Related Diseases for Chondrodysplasia, Blomstrand Type

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



Diseases related to Chondrodysplasia, Blomstrand Type

Symptoms & Phenotypes for Chondrodysplasia, Blomstrand Type

Symptoms via clinical synopsis from OMIM:

57
Skeletal Limbs:
micromelia
marked metaphyseal flaring of long bones

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Chest Ribs Sternum Clavicles And Scapulae:
short ribs
anterior rib widening

Head And Neck Face:
mandibular hypoplasia
severe midface hypoplasia

Skeletal:
generalized sclerosis
advanced skeletal maturation

Skeletal Pelvis:
square ilia

Prenatal Manifestations:
hydrops fetalis

Prenatal Manifestations Delivery:
premature birth
die at birth or shortly after birth

Skeletal Feet:
advanced tarsal ossification

Respiratory Larynx:
laryngeal calcification

Skeletal Spine:
normal vertebrae

Skeletal Hands:
advanced carpal ossification


Clinical features from OMIM:

215045

Human phenotypes related to Chondrodysplasia, Blomstrand Type:

59 32 (show all 44)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 malar flattening 59 32 hallmark (90%) Very frequent (99-80%) HP:0000272
2 low-set ears 59 32 hallmark (90%) Very frequent (99-80%) HP:0000369
3 abnormality of epiphysis morphology 59 32 hallmark (90%) Very frequent (99-80%) HP:0005930
4 cataract 59 32 hallmark (90%) Very frequent (99-80%) HP:0000518
5 depressed nasal bridge 59 32 hallmark (90%) Very frequent (99-80%) HP:0005280
6 bowing of the long bones 59 32 frequent (33%) Frequent (79-30%) HP:0006487
7 synostosis of joints 59 32 frequent (33%) Frequent (79-30%) HP:0100240
8 short nose 59 32 hallmark (90%) Very frequent (99-80%) HP:0003196
9 anteverted nares 59 32 frequent (33%) Frequent (79-30%) HP:0000463
10 long philtrum 59 32 frequent (33%) Frequent (79-30%) HP:0000343
11 micrognathia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000347
12 narrow chest 59 32 hallmark (90%) Very frequent (99-80%) HP:0000774
13 platyspondyly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000926
14 short thorax 59 32 hallmark (90%) Very frequent (99-80%) HP:0010306
15 hydrops fetalis 59 32 frequent (33%) Frequent (79-30%) HP:0001789
16 coarctation of aorta 59 32 occasional (7.5%) Occasional (29-5%) HP:0001680
17 telecanthus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000506
18 rhizomelia 59 32 hallmark (90%) Very frequent (99-80%) HP:0008905
19 protruding tongue 59 32 frequent (33%) Frequent (79-30%) HP:0010808
20 polyhydramnios 59 32 hallmark (90%) Very frequent (99-80%) HP:0001561
21 increased bone mineral density 59 32 hallmark (90%) Very frequent (99-80%) HP:0011001
22 neonatal short-limb short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0008921
23 proptosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000520
24 short metacarpal 59 32 frequent (33%) Frequent (79-30%) HP:0010049
25 premature birth 59 32 hallmark (90%) Very frequent (99-80%) HP:0001622
26 accelerated skeletal maturation 59 32 hallmark (90%) Very frequent (99-80%) HP:0005616
27 pulmonary hypoplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002089
28 mesomelia 59 32 hallmark (90%) Very frequent (99-80%) HP:0003027
29 natal tooth 59 32 frequent (33%) Frequent (79-30%) HP:0000695
30 lethal skeletal dysplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0005716
31 short ribs 59 32 hallmark (90%) Very frequent (99-80%) HP:0000773
32 flared metaphysis 59 32 hallmark (90%) Very frequent (99-80%) HP:0003015
33 protuberant abdomen 59 32 hallmark (90%) Very frequent (99-80%) HP:0001538
34 broad clavicles 59 32 hallmark (90%) Very frequent (99-80%) HP:0000916
35 metaphyseal cupping 59 32 hallmark (90%) Very frequent (99-80%) HP:0003021
36 distal shortening of limbs 59 32 hallmark (90%) Very frequent (99-80%) HP:0006402
37 generalized osteosclerosis 32 HP:0005789
38 micromelia 32 HP:0002983
39 squared iliac bones 32 HP:0003177
40 aplastic clavicles 59 Very frequent (99-80%)
41 advanced tarsal ossification 32 HP:0008108
42 laryngeal calcification 32 HP:0008754
43 aplastic clavicle 32 hallmark (90%) HP:0006660
44 advanced ossification of carpal bones 32 HP:0004233

GenomeRNAi Phenotypes related to Chondrodysplasia, Blomstrand Type according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased NF-kappaB reporter expression GR00312-A 8.92 HHIP IHH PTH PTH1R

MGI Mouse Phenotypes related to Chondrodysplasia, Blomstrand Type:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.67 HHIP IHH PTH PTH1R
2 endocrine/exocrine gland MP:0005379 9.56 HHIP IHH PTH PTH1R
3 digestive/alimentary MP:0005381 9.5 HHIP IHH PTH1R
4 growth/size/body region MP:0005378 9.46 HHIP IHH PTH PTH1R
5 limbs/digits/tail MP:0005371 9.13 IHH PTH PTH1R
6 respiratory system MP:0005388 8.8 HHIP IHH PTH1R

Drugs & Therapeutics for Chondrodysplasia, Blomstrand Type

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

Cochrane evidence based reviews: chondrodysplasia, blomstrand type

Genetic Tests for Chondrodysplasia, Blomstrand Type

Genetic tests related to Chondrodysplasia, Blomstrand Type:

# Genetic test Affiliating Genes
1 Chondrodysplasia Blomstrand Type 29 PTH1R

Anatomical Context for Chondrodysplasia, Blomstrand Type

MalaCards organs/tissues related to Chondrodysplasia, Blomstrand Type:

41
Bone, Eye, Tongue, Lung, Kidney

Publications for Chondrodysplasia, Blomstrand Type

Articles related to Chondrodysplasia, Blomstrand Type:

# Title Authors Year
1
A frame-shift mutation in the type I parathyroid hormone (PTH)/PTH-related peptide receptor causing Blomstrand lethal osteochondrodysplasia. ( 10523019 )
1999
2
First-trimester diagnosis of Blomstrand lethal osteochondrodysplasia. ( 9415697 )
1997
3
Blomstrand lethal osteochondrodysplasia. ( 8723092 )
1996

Variations for Chondrodysplasia, Blomstrand Type

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

75
# Symbol AA change Variation ID SNP ID
1 PTH1R p.Pro132Leu VAR_016062 rs121434599

ClinVar genetic disease variations for Chondrodysplasia, Blomstrand Type:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PTH1R NM_000316.2(PTH1R): c.1148G> A (p.Arg383Gln) single nucleotide variant Pathogenic rs398122843 GRCh37 Chromosome 3, 46943287: 46943287
2 PTH1R NM_000316.2(PTH1R): c.1148G> A (p.Arg383Gln) single nucleotide variant Pathogenic rs398122843 GRCh38 Chromosome 3, 46901797: 46901797
3 PTH1R NM_000316.2(PTH1R): c.395C> T (p.Pro132Leu) single nucleotide variant Pathogenic rs121434599 GRCh37 Chromosome 3, 46939426: 46939426
4 PTH1R NM_000316.2(PTH1R): c.395C> T (p.Pro132Leu) single nucleotide variant Pathogenic rs121434599 GRCh38 Chromosome 3, 46897936: 46897936
5 PTH1R PTH1R, 1-BP DEL, 1122G deletion Pathogenic
6 PTH1R NM_000316.2(PTH1R): c.310C> T (p.Arg104Ter) single nucleotide variant Pathogenic rs121434604 GRCh37 Chromosome 3, 46937356: 46937356
7 PTH1R NM_000316.2(PTH1R): c.310C> T (p.Arg104Ter) single nucleotide variant Pathogenic rs121434604 GRCh38 Chromosome 3, 46895866: 46895866
8 PTH1R PTH1R, IVSM4, C-T, +27 single nucleotide variant Pathogenic

Expression for Chondrodysplasia, Blomstrand Type

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

Pathways for Chondrodysplasia, Blomstrand Type

GO Terms for Chondrodysplasia, Blomstrand Type

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

# Name GO ID Score Top Affiliating Genes
1 cell-cell signaling GO:0007267 9.48 IHH PTH
2 adenylate cyclase-activating G protein-coupled receptor signaling pathway GO:0007189 9.46 PTH PTH1R
3 cellular calcium ion homeostasis GO:0006874 9.43 PTH PTH1R
4 ossification GO:0001503 9.4 IHH PTH1R
5 smoothened signaling pathway GO:0007224 9.37 HHIP IHH
6 skeletal system development GO:0001501 9.33 IHH PTH PTH1R
7 bone mineralization GO:0030282 9.32 PTH PTH1R
8 cell maturation GO:0048469 9.26 IHH PTH1R
9 positive regulation of inositol phosphate biosynthetic process GO:0060732 8.96 PTH PTH1R
10 bone resorption GO:0045453 8.8 IHH PTH PTH1R

Sources for Chondrodysplasia, Blomstrand Type

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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