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 58 60 13 45 41 74
Chondrodysplasia Blomstrand Type 12 54 76 30 6 15
Bocd 58 54 60 76
Blomstrand Lethal Chondrodysplasia 12 60
Blomstrand Lethal Osteochondrodysplasia 54
Blomstrand's Lethal Chondrodysplasia 54
Blomstrand Osteochondrodysplasia 60
Blomstrand Chondrodysplasia 60
Blc 60

Characteristics:

Orphanet epidemiological data:

60
blomstrand lethal chondrodysplasia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: embryofetal,infantile,stillbirth;

OMIM:

58
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:

33
chondrodysplasia, blomstrand type:
Clinical modifier stillbirth
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Chondrodysplasia, Blomstrand Type

NIH Rare Diseases : 54 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, tongue and lung, and related phenotypes are malar flattening and low-set ears

Disease Ontology : 12 An osteochondrodysplasia that is characterized by rapid endochondral bone maturation, short limbs, dwarfism and prenatal lethality, has material basis in autosomal recessive inheritance of mutation in the PTH1R gene.

OMIM : 58 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 : 76 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

Human phenotypes related to Chondrodysplasia, Blomstrand Type:

60 33 (show all 44)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 malar flattening 60 33 hallmark (90%) Very frequent (99-80%) HP:0000272
2 low-set ears 60 33 hallmark (90%) Very frequent (99-80%) HP:0000369
3 abnormality of epiphysis morphology 60 33 hallmark (90%) Very frequent (99-80%) HP:0005930
4 cataract 60 33 hallmark (90%) Very frequent (99-80%) HP:0000518
5 depressed nasal bridge 60 33 hallmark (90%) Very frequent (99-80%) HP:0005280
6 short nose 60 33 hallmark (90%) Very frequent (99-80%) HP:0003196
7 micrognathia 60 33 hallmark (90%) Very frequent (99-80%) HP:0000347
8 narrow chest 60 33 hallmark (90%) Very frequent (99-80%) HP:0000774
9 platyspondyly 60 33 hallmark (90%) Very frequent (99-80%) HP:0000926
10 short thorax 60 33 hallmark (90%) Very frequent (99-80%) HP:0010306
11 telecanthus 60 33 hallmark (90%) Very frequent (99-80%) HP:0000506
12 rhizomelia 60 33 hallmark (90%) Very frequent (99-80%) HP:0008905
13 polyhydramnios 60 33 hallmark (90%) Very frequent (99-80%) HP:0001561
14 increased bone mineral density 60 33 hallmark (90%) Very frequent (99-80%) HP:0011001
15 neonatal short-limb short stature 60 33 hallmark (90%) Very frequent (99-80%) HP:0008921
16 proptosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0000520
17 premature birth 60 33 hallmark (90%) Very frequent (99-80%) HP:0001622
18 accelerated skeletal maturation 60 33 hallmark (90%) Very frequent (99-80%) HP:0005616
19 pulmonary hypoplasia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002089
20 mesomelia 60 33 hallmark (90%) Very frequent (99-80%) HP:0003027
21 lethal skeletal dysplasia 60 33 hallmark (90%) Very frequent (99-80%) HP:0005716
22 short ribs 60 33 hallmark (90%) Very frequent (99-80%) HP:0000773
23 flared metaphysis 60 33 hallmark (90%) Very frequent (99-80%) HP:0003015
24 protuberant abdomen 60 33 hallmark (90%) Very frequent (99-80%) HP:0001538
25 broad clavicles 60 33 hallmark (90%) Very frequent (99-80%) HP:0000916
26 metaphyseal cupping 60 33 hallmark (90%) Very frequent (99-80%) HP:0003021
27 distal shortening of limbs 60 33 hallmark (90%) Very frequent (99-80%) HP:0006402
28 aplastic clavicle 33 hallmark (90%) HP:0006660
29 bowing of the long bones 60 33 frequent (33%) Frequent (79-30%) HP:0006487
30 synostosis of joints 60 33 frequent (33%) Frequent (79-30%) HP:0100240
31 anteverted nares 60 33 frequent (33%) Frequent (79-30%) HP:0000463
32 long philtrum 60 33 frequent (33%) Frequent (79-30%) HP:0000343
33 hydrops fetalis 60 33 frequent (33%) Frequent (79-30%) HP:0001789
34 protruding tongue 60 33 frequent (33%) Frequent (79-30%) HP:0010808
35 short metacarpal 60 33 frequent (33%) Frequent (79-30%) HP:0010049
36 natal tooth 60 33 frequent (33%) Frequent (79-30%) HP:0000695
37 coarctation of aorta 60 33 occasional (7.5%) Occasional (29-5%) HP:0001680
38 generalized osteosclerosis 33 HP:0005789
39 micromelia 33 HP:0002983
40 squared iliac bones 33 HP:0003177
41 aplastic clavicles 60 Very frequent (99-80%)
42 advanced tarsal ossification 33 HP:0008108
43 laryngeal calcification 33 HP:0008754
44 advanced ossification of carpal bones 33 HP:0004233

Symptoms via clinical synopsis from OMIM:

58
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

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

27
# 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:

47
# 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 30 PTH1R

Anatomical Context for Chondrodysplasia, Blomstrand Type

MalaCards organs/tissues related to Chondrodysplasia, Blomstrand Type:

42
Bone, Tongue, Lung, Eye, Kidney

Publications for Chondrodysplasia, Blomstrand Type

Articles related to Chondrodysplasia, Blomstrand Type:

# Title Authors Year
1
Novel mutations in the parathyroid hormone (PTH)/PTH-related peptide receptor type 1 causing Blomstrand osteochondrodysplasia types I and II. ( 17164305 )
2007
2
A frame-shift mutation in the type I parathyroid hormone (PTH)/PTH-related peptide receptor causing Blomstrand lethal osteochondrodysplasia. ( 10523019 )
1999
3
Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia. ( 9649554 )
1998
4
A homozygous inactivating mutation in the parathyroid hormone/parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia. ( 9745456 )
1998
5
First-trimester diagnosis of Blomstrand lethal osteochondrodysplasia. ( 9415697 )
1997
6
Familial Blomstrand chondrodysplasia with advanced skeletal maturation: further delineation. ( 9268097 )
1997
7
Blomstrand lethal osteochondrodysplasia. ( 8723092 )
1996
8
A case of lethal congenital dwarfism with accelerated skeletal maturation. ( 3975110 )
1985

Variations for Chondrodysplasia, Blomstrand Type

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

76
# 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 cell maturation GO:0048469 9.26 IHH PTH1R
8 bone mineralization GO:0030282 9.02 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 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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