BBDS
MCID: BNT003
MIFTS: 41

Bent Bone Dysplasia Syndrome (BBDS)

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

Aliases & Classifications for Bent Bone Dysplasia Syndrome

MalaCards integrated aliases for Bent Bone Dysplasia Syndrome:

Name: Bent Bone Dysplasia Syndrome 57 53 75 29 13 6 73
Bbds 57 75
Perinatal Lethal Bent Bone Dysplasia 59
Fgfr2-Related Bent Bone Dysplasia 59
Bent Bone Dysplasia -Fgfr2 Type 53
Dysplasia, Bent Bone Syndrome 40

Characteristics:

Orphanet epidemiological data:

59
fgfr2-related bent bone dysplasia
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
bent bone dysplasia syndrome:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Bent Bone Dysplasia Syndrome

NIH Rare Diseases : 53 Bent bone dysplasia syndromeis an often lethal skeletal disorder characterized by poor mineralization of the skull (calvarium), craniosynostosis, underdeveloped (hypoplastic) pubic bone (pubis) and clavicles, osteopenia, and bent long bones.  Unusual facial features include low-set ears, widely spaced eyes (hypertelorism), midface hypoplasia, prematurely erupted fetal teeth, and small chin (micrognathia).  This condition is associated with mutations in the FGFR2 gene.

MalaCards based summary : Bent Bone Dysplasia Syndrome, also known as bbds, is related to breast disease and myeloma, multiple. An important gene associated with Bent Bone Dysplasia Syndrome is FGFR2 (Fibroblast Growth Factor Receptor 2), and among its related pathways/superpathways are Pathways in cancer and Glioma. Affiliated tissues include bone and eye, and related phenotypes are hypertelorism and low-set ears

UniProtKB/Swiss-Prot : 75 Bent bone dysplasia syndrome: A perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Dysmorphic facial features included low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia.

Description from OMIM: 614592

Related Diseases for Bent Bone Dysplasia Syndrome

Diseases related to Bent Bone Dysplasia Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 11)
# Related Disease Score Top Affiliating Genes
1 breast disease 10.2
2 myeloma, multiple 10.0
3 miliary tuberculosis 10.0
4 estrogen-receptor positive breast cancer 9.9 ERBB2 FGFR2
5 endometrial adenocarcinoma 9.9 ERBB2 FGFR2
6 adenocarcinoma 9.8 ERBB2 FGFR2
7 uterine carcinosarcoma 9.8 ERBB2 FGFR2
8 gastric adenocarcinoma 9.8 ERBB2 FGFR2
9 squamous cell carcinoma 9.8 ERBB2 FGFR2
10 glioblastoma 9.8 ERBB2 FGFR2
11 endometrial cancer 9.7 ERBB2 FGFR2

Graphical network of the top 20 diseases related to Bent Bone Dysplasia Syndrome:



Diseases related to Bent Bone Dysplasia Syndrome

Symptoms & Phenotypes for Bent Bone Dysplasia Syndrome

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
megalophthalmos

Head And Neck Face:
micrognathia
midface hypoplasia

Skeletal Hands:
brachydactyly
areas of periosteal reaction
areas of deficient ossification

Chest External Features:
bell-shaped thorax

Head And Neck Mouth:
gingival hyperplasia

Head And Neck Head:
open metopic suture

Abdomen Liver:
hepatosplenomegaly (rare)

Skeletal Pelvis:
narrow acetabular roof
narrowed ischia
decreased mineralization of pubis

Hematology:
hepatosplenomegaly, with extramedullary hematopoiesis (rare)

Head And Neck Ears:
low-set ears
overfolded superior helix
deficient auricle

Skeletal Skull:
coronal craniosynostosis
diminished mineralization of the calvarium

Genitourinary External Genitalia Female:
clitoromegaly

Skin Nails Hair Hair:
hirsutism

Chest Ribs Sternum Clavicles And Scapulae:
hypoplastic clavicles
decreased mineralization of inferior margin of scapula

Head And Neck Teeth:
prenatal teeth

Abdomen Spleen:
hepatosplenomegaly (rare)

Skeletal Limbs:
bending of long bones to varying degrees, particularly femora
prominent periosteum


Clinical features from OMIM:

614592

Human phenotypes related to Bent Bone Dysplasia Syndrome:

59 32 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000316
2 low-set ears 59 32 hallmark (90%) Very frequent (99-80%) HP:0000369
3 osteopenia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000938
4 gingival overgrowth 59 32 hallmark (90%) Very frequent (99-80%) HP:0000212
5 micrognathia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000347
6 megalocornea 59 32 hallmark (90%) Very frequent (99-80%) HP:0000485
7 coronal craniosynostosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0004440
8 brachydactyly 59 32 hallmark (90%) Very frequent (99-80%) HP:0001156
9 midface retrusion 59 32 hallmark (90%) Very frequent (99-80%) HP:0011800
10 congenital stationary night blindness 59 32 hallmark (90%) Very frequent (99-80%) HP:0007642
11 decreased calvarial ossification 59 32 hallmark (90%) Very frequent (99-80%) HP:0005474
12 short clavicles 59 32 hallmark (90%) Very frequent (99-80%) HP:0000894
13 hypoplastic ischia 59 32 hallmark (90%) Very frequent (99-80%) HP:0003175
14 bell-shaped thorax 59 32 hallmark (90%) Very frequent (99-80%) HP:0001591
15 hepatosplenomegaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0001433
16 hirsutism 59 32 hallmark (90%) Very frequent (99-80%) HP:0001007
17 bowing of the legs 59 32 occasional (7.5%) Occasional (29-5%) HP:0002979
18 natal tooth 59 32 hallmark (90%) Very frequent (99-80%) HP:0000695
19 extramedullary hematopoiesis 59 32 hallmark (90%) Very frequent (99-80%) HP:0001978
20 overfolding of the superior helices 59 32 hallmark (90%) Very frequent (99-80%) HP:0004453
21 steep acetabular roof 59 32 hallmark (90%) Very frequent (99-80%) HP:0010455
22 metopic depression 59 32 hallmark (90%) Very frequent (99-80%) HP:0011223
23 incomplete ossification of pubis 59 32 hallmark (90%) Very frequent (99-80%) HP:0030042
24 abnormality of the periosteum 59 32 hallmark (90%) Very frequent (99-80%) HP:0040166
25 malar flattening 32 HP:0000272
26 abnormality of the lower limb 59 Occasional (29-5%)
27 clitoromegaly 59 Very frequent (99-80%)
28 clitoral hypertrophy 32 hallmark (90%) HP:0008665
29 abnormality of the outer ear 59 Very frequent (99-80%)
30 abnormally large globe 32 HP:0001090

GenomeRNAi Phenotypes related to Bent Bone Dysplasia Syndrome according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased focal adhesion (FA) area, decreased FA length, decreased FA mean intensity, increased number of small and round FAs, increased FA abundance GR00210-A 8.62 ERBB2 FGFR2

Drugs & Therapeutics for Bent Bone Dysplasia Syndrome

Search Clinical Trials , NIH Clinical Center for Bent Bone Dysplasia Syndrome

Genetic Tests for Bent Bone Dysplasia Syndrome

Genetic tests related to Bent Bone Dysplasia Syndrome:

# Genetic test Affiliating Genes
1 Bent Bone Dysplasia Syndrome 29 FGFR2

Anatomical Context for Bent Bone Dysplasia Syndrome

MalaCards organs/tissues related to Bent Bone Dysplasia Syndrome:

41
Bone, Eye

Publications for Bent Bone Dysplasia Syndrome

Articles related to Bent Bone Dysplasia Syndrome:

# Title Authors Year
1
FGFR2 mutations in bent bone dysplasia syndrome activate nucleolar stress and perturb cell fate determination. ( 28595297 )
2017
2
Cyclohexenylboration of Aldehydes and Ketones with the Borabicyclo[3.3.2]decanes (BBDs). ( 26284657 )
2015
3
Bent bone dysplasia syndrome reveals nucleolar activity for FGFR2 in ribosomal DNA transcription. ( 24908667 )
2014
4
(E)-2-boryl 1,3-dienes from the 10-TMS-9-BBDs: highly selective reagents for the asymmetric synthesis of anti-α,β-disubstituted β-allenylamines from the allylboration of aldimines. ( 25003976 )
2014
5
(E)-2-boryl-1,3-butadiene derivatives of the 10-TMS-9-BBDs: highly selective reagents for the asymmetric synthesis of anti-1,2-disubstituted 3,4-pentadien-1-ols. ( 19580266 )
2009

Variations for Bent Bone Dysplasia Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Bent Bone Dysplasia Syndrome:

75
# Symbol AA change Variation ID SNP ID
1 FGFR2 p.Tyr381Asp VAR_067977 rs387906678
2 FGFR2 p.Met391Arg VAR_067978 rs387906677

ClinVar genetic disease variations for Bent Bone Dysplasia Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 FGFR2 NM_000141.4(FGFR2): c.1172T> G (p.Met391Arg) single nucleotide variant Pathogenic rs387906677 GRCh37 Chromosome 10, 123274746: 123274746
2 FGFR2 NM_000141.4(FGFR2): c.1172T> G (p.Met391Arg) single nucleotide variant Pathogenic rs387906677 GRCh38 Chromosome 10, 121515232: 121515232
3 FGFR2 NM_000141.4(FGFR2): c.1141T> G (p.Tyr381Asp) single nucleotide variant Pathogenic rs387906678 GRCh37 Chromosome 10, 123274777: 123274777
4 FGFR2 NM_000141.4(FGFR2): c.1141T> G (p.Tyr381Asp) single nucleotide variant Pathogenic rs387906678 GRCh38 Chromosome 10, 121515263: 121515263

Expression for Bent Bone Dysplasia Syndrome

Search GEO for disease gene expression data for Bent Bone Dysplasia Syndrome.

Pathways for Bent Bone Dysplasia Syndrome

Pathways related to Bent Bone Dysplasia Syndrome according to GeneCards Suite gene sharing:

(show all 16)
# Super pathways Score Top Affiliating Genes
1 12.27 ERBB2 FGFR2
2
Show member pathways
12.2 ERBB2 FGFR2
3 12.18 ERBB2 FGFR2
4
Show member pathways
12.16 ERBB2 FGFR2
5
Show member pathways
12.12 ERBB2 FGFR2
6
Show member pathways
11.9 ERBB2 FGFR2
7
Show member pathways
11.83 ERBB2 FGFR2
8
Show member pathways
11.74 ERBB2 FGFR2
9
Show member pathways
11.55 ERBB2 FGFR2
10 11.41 ERBB2 FGFR2
11 11.33 ERBB2 FGFR2
12 11.15 ERBB2 FGFR2
13 10.78 ERBB2 FGFR2
14 10.77 ERBB2 FGFR2
15 10.46 ERBB2 FGFR2
16 10.28 ERBB2 FGFR2

GO Terms for Bent Bone Dysplasia Syndrome

Cellular components related to Bent Bone Dysplasia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 receptor complex GO:0043235 8.62 ERBB2 FGFR2

Biological processes related to Bent Bone Dysplasia Syndrome according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.49 ERBB2 FGFR2
2 MAPK cascade GO:0000165 9.48 ERBB2 FGFR2
3 peptidyl-tyrosine phosphorylation GO:0018108 9.46 ERBB2 FGFR2
4 protein autophosphorylation GO:0046777 9.43 ERBB2 FGFR2
5 positive regulation of protein kinase B signaling GO:0051897 9.4 ERBB2 FGFR2
6 positive regulation of MAPK cascade GO:0043410 9.37 ERBB2 FGFR2
7 negative regulation of signal transduction GO:0009968 9.32 ERBB2 FGFR2
8 phosphatidylinositol phosphorylation GO:0046854 9.26 ERBB2 FGFR2
9 wound healing GO:0042060 9.16 ERBB2 FGFR2
10 positive regulation of epithelial cell proliferation GO:0050679 8.96 ERBB2 FGFR2
11 regulation of ERK1 and ERK2 cascade GO:0070372 8.62 ERBB2 FGFR2

Molecular functions related to Bent Bone Dysplasia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein kinase activity GO:0004672 9.4 ERBB2 FGFR2
2 nucleotide binding GO:0000166 9.37 ERBB2 FGFR2
3 transmembrane signaling receptor activity GO:0004888 9.32 ERBB2 FGFR2
4 protein tyrosine kinase activity GO:0004713 9.26 ERBB2 FGFR2
5 Ras guanyl-nucleotide exchange factor activity GO:0005088 9.16 ERBB2 FGFR2
6 phosphatidylinositol-4,5-bisphosphate 3-kinase activity GO:0046934 8.96 ERBB2 FGFR2
7 transmembrane receptor protein tyrosine kinase activity GO:0004714 8.62 ERBB2 FGFR2

Sources for Bent Bone Dysplasia Syndrome

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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