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 72
Chondrodysplasia Blomstrand Type 12 53 74 29 6 15
Bocd 57 53 59 74
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:
Clinical modifier stillbirth
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0060387
OMIM 57 215045
MeSH 44 C537914
NCIt 50 C131420
MESH via Orphanet 45 C537914
ICD10 via Orphanet 34 Q78.8
UMLS via Orphanet 73 C1859148
Orphanet 59 ORPHA50945
MedGen 42 C1859148
UMLS 72 C1859148

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: 50945DefinitionBlomstrand 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 heterozygous mutations 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 pseudo-torch syndrome 1 and bladder cancer. 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 eye, 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 : 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 : 74 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:

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

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

Respiratory Larynx:
laryngeal calcification

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

Head And Neck Face:
mandibular hypoplasia
severe midface hypoplasia

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:

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, Tongue, Eye, Lung, Breast, Neutrophil

Publications for Chondrodysplasia, Blomstrand Type

Articles related to Chondrodysplasia, Blomstrand Type:

(show all 16)
# Title Authors PMID Year
1
Novel mutations in the parathyroid hormone (PTH)/PTH-related peptide receptor type 1 causing Blomstrand osteochondrodysplasia types I and II. 38 8 71
17164305 2007
2
A homozygous inactivating mutation in the parathyroid hormone/parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia. 8 71
9745456 1998
3
Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia. 8 71
9649554 1998
4
Familial Blomstrand chondrodysplasia with advanced skeletal maturation: further delineation. 8 71
9268097 1997
5
A case of lethal congenital dwarfism with accelerated skeletal maturation. 8 71
3975110 1985
6
Blomstrand osteochondrodysplasia: three novel cases and histological evidence for heterogeneity. 38 8
10664159 2000
7
A frame-shift mutation in the type I parathyroid hormone (PTH)/PTH-related peptide receptor causing Blomstrand lethal osteochondrodysplasia. 38 71
10523019 1999
8
Absence of functional type 1 parathyroid hormone (PTH)/PTH-related protein receptors in humans is associated with abnormal breast development and tooth impaction. 8
11297619 2001
9
First-trimester diagnosis of Blomstrand lethal osteochondrodysplasia. 8
9415697 1997
10
A lethal skeletal dysplasia with generalised sclerosis and advanced skeletal maturation: Blomstrand chondrodysplasia? 8
8445622 1993
11
Usefulness of fetal autopsy in the diagnosis of blomstrand chondrodysplasia: a report of three cases. 38
27353973 2017
12
Stimulation of Fas signaling down-regulates activity of neutrophils from major trauma patients with SIRS. 38
20832139 2011
13
PTHR1 loss-of-function mutations in familial, nonsyndromic primary failure of tooth eruption. 38
19061984 2008
14
zVAD-fmk, unlike BocD-fmk, does not inhibit caspase-6 acting on 14-3-3/Bad pathway in apoptosis of p815 mastocytoma cells. 38
17202839 2006
15
Capacitation induces cyclic adenosine 3',5'-monophosphate-dependent, but apoptosis-unrelated, exposure of aminophospholipids at the apical head plasma membrane of boar sperm cells. 38
12080038 2002
16
Ectoenzyme activity and bacterial secondary production in nutrient-impoverished and nutrient-enriched freshwater mesocosms. 38
24189811 1993

Variations for Chondrodysplasia, Blomstrand Type

ClinVar genetic disease variations for Chondrodysplasia, Blomstrand Type:

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

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

74
# Symbol AA change Variation ID SNP ID
1 PTH1R p.Pro132Leu VAR_016062 rs121434599

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 PTH IHH
2 adenylate cyclase-activating G protein-coupled receptor signaling pathway GO:0007189 9.46 PTH1R PTH
3 cellular calcium ion homeostasis GO:0006874 9.43 PTH1R PTH
4 ossification GO:0001503 9.4 PTH1R IHH
5 skeletal system development GO:0001501 9.33 PTH1R PTH IHH
6 cell maturation GO:0048469 9.26 PTH1R IHH
7 smoothened signaling pathway GO:0007224 9.07 IHH
8 bone mineralization GO:0030282 9.02 PTH1R
9 positive regulation of inositol phosphate biosynthetic process GO:0060732 8.96 PTH1R PTH
10 bone resorption GO:0045453 8.8 PTH1R PTH IHH

Sources for Chondrodysplasia, Blomstrand Type

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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