MCID: BRC003
MIFTS: 36

Brachyolmia

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

Aliases & Classifications for Brachyolmia

MalaCards integrated aliases for Brachyolmia:

Name: Brachyolmia 12 20 58 36 6 15 39 70
Brachyrachia 12

Characteristics:

Orphanet epidemiological data:

58
brachyolmia
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Childhood; Age of death: normal life expectancy;

Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0050690
KEGG 36 H00522
MESH via Orphanet 45 C537098
ICD10 via Orphanet 33 Q76.3
UMLS via Orphanet 71 C0432228
Orphanet 58 ORPHA1293
SNOMED-CT via HPO 68 249670005
UMLS 70 C0432228

Summaries for Brachyolmia

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1293 Definition Brachyolmia is a rare, clinically and genetically heterogeneous group of bone disorders characterized by short trunk, mild short stature, scoliosis and generalized platyspondyly without significant abnormalities in the long bones. Epidemiology The prevalence of brachyolmia is not known, but the disorder is probably under-recognized. Fewer than 100 cases have been reported to date. Cases have been reported in various ethnic groups. However, most cases with the Hobaek/Toledo type reported so far were of Turkish origin. Clinical description Four types of brachyolmia have been described: autosomal recessive brachyolmia, Hobaek/Toledo type, autosomal recessive brachyolmia-amelogenesis imperfecta syndrome, autosomal dominant brachyolmia, and autosomal recessive brachyolmia, Maroteaux type (see these terms). The age of onset is generally in childhood with short stature becoming more evident with age. The clinical manifestations are generally mild to moderate, with minor physical functional repercussions. Some patients report non-specific back pain. The disorder is not associated with intellectual disability. AR brachyolmia, Hobaek/Toledo type is characterized by short-trunked short stature with platyspondyly and scoliosis. Corneal opacities and precocious calcification of costal cartilage occur in rare cases. In AR brachyolmia-amelogenesis imperfecta syndrome, short-trunked short stature is associated with platyspondyly and enamel abnormalities. AD brachyolmia is a more severe form with significant short-trunked short stature, platyspondyly and kyphoscoliosis. Lastly, presumably autosomal recessive brachyolmia, Maroteaux type is a vague entity that has not been well characterized but may involve short trunk/short stature, generalized platyspondyly and rounding vertebral bodies. Etiology Mutations in the PAPSS2 gene (10q24) have been found in patients with AR brachyolmia, Hobaek/Toledo type, and in the TRPV4 gene (12q24.1) in patients with AD brachyolmia. Precise pathogenesis is not well understood. Diagnostic methods Clinical and radiological findings are used to diagnose brachyolmia. Molecular genetic testing can also be used to confirm the diagnosis. Differential diagnosis The differential diagnosis includes other genetic skeletal dysplasia syndromes, particularly mild spondyloepiphyseal dysplasia, including mild type 2 collagenopathy and mild Morquio disease (see this term). Antenatal diagnosis Prenatal diagnosis is available on molecular grounds, when a mutation (or mutations) was ascertained in a familial case. Genetic counseling Brachyolmia follows either an autosomal recessive or rarely an autosomal dominant pattern of inheritance. Genetic counseling based on the mode of inheritance should be provided to affected families. Management and treatment No specific treatment is currently available for this disease. Prognosis The prognosis for patients with brachyolmia is generally very good.

MalaCards based summary : Brachyolmia, also known as brachyrachia, is related to spondyloepiphyseal dysplasia, maroteaux type and osteochondrodysplasia. An important gene associated with Brachyolmia is PAPSS2 (3'-Phosphoadenosine 5'-Phosphosulfate Synthase 2), and among its related pathways/superpathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and CREB Pathway. Affiliated tissues include bone and heart, and related phenotypes are short thorax and mild short stature

Disease Ontology : 12 An osteochondrodysplasia characterized by generalized platyspondyly without significant long bone abnormalities and short stature.

KEGG : 36 Brachyolmia (BCYM) is a heterogeneous group of skeletal dysplasias that primarily affects the spine. To date, four types of brachyolmia are known. Mutations in the TRPV4, a calcium-permeable nonselective cation channel, have been identified in an autosomal dominant form of brachyolmia (BCYM3). And it has been reported that PAPSS2 mutations cause autosomal recessive brachyolmia (BCRM4).

Related Diseases for Brachyolmia

Diseases in the Brachyolmia family:

Brachyolmia Type 3 Brachyolmia Type 2
Autosomal Recessive Brachyolmia

Diseases related to Brachyolmia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 61)
# Related Disease Score Top Affiliating Genes
1 spondyloepiphyseal dysplasia, maroteaux type 31.4 TRPV6 TRPV4 TRPC1 PACSIN3
2 osteochondrodysplasia 30.4 TRPV4 SLC26A2 PAPSS2 COL2A1
3 hereditary motor and sensory neuropathy, type iic 30.1 TRPV4 PACSIN3
4 brachydactyly 29.8 TRPV4 PAPSS2 LTBP2 COL2A1
5 spondyloepiphyseal dysplasia with congenital joint dislocations 29.7 TRPV4 SLC26A2 PAPSS2 COL2A1
6 brachyolmia type 3 11.7
7 brachyolmia type 2 11.6
8 brachyolmia type 4 with mild epiphyseal and metaphyseal changes 11.6
9 brachyolmia type 1, hobaek type 11.6
10 dental anomalies and short stature 11.5
11 autosomal recessive brachyolmia 11.1
12 brachyolmia type 1, toledo type 11.0
13 type ii collagen disorders 10.3 TRPV4 COL2A1
14 familial avascular necrosis of the femoral head 10.3 TRPV4 COL2A1
15 avascular necrosis 10.3 TRPV4 COL2A1
16 parastremmatic dwarfism 10.3 TRPV4 PACSIN3
17 geleophysic dysplasia 3 10.3 LTBP3 LTBP2
18 excessive tearing 10.3 LTBP3 LTBP2
19 geleophysic dysplasia 1 10.3 LTBP3 LTBP2
20 witkop syndrome 10.3 LTBP3 LTBP2
21 geleophysic dysplasia 2 10.2 LTBP3 LTBP2
22 hydrophthalmos 10.2 LTBP3 LTBP2
23 spondyloepimetaphyseal dysplasia 10.2 TRPV4 PAPSS2 COL2A1
24 photoparoxysmal response 1 10.2 TRPV4 TRPV3
25 phacogenic glaucoma 10.2 LTBP3 LTBP2
26 autosomal recessive cutis laxa type i 10.2 LTBP3 LTBP2
27 acromicric dysplasia 10.2 LTBP3 LTBP2
28 scoliosis 10.2
29 megalocornea 10.1 LTBP3 LTBP2
30 hypochondrogenesis 10.1 SLC26A2 COL2A1
31 achondrogenesis, type ib 10.1 SLC26A2 PAPSS2
32 achondrogenesis, type ia 10.1 SLC26A2 COL2A1
33 atelosteogenesis 10.1 SLC26A2 PAPSS2
34 dwarfism 10.1
35 camurati-engelmann disease 10.1 LTBP3 LTBP2
36 desbuquois dysplasia 10.1 SLC26A2 SLC10A7
37 bone development disease 10.0 TRPV4 SLC26A2 COL2A1
38 achondrogenesis, type ii 10.0 SLC26A2 COL2A1
39 iris disease 10.0 LTBP3 LTBP2
40 amelogenesis imperfecta 10.0
41 legg-calve-perthes disease 10.0 SLC26A2 COL2A1
42 clubfoot 10.0 TRPV4 SLC26A2 COL2A1
43 progressive familial heart block 9.9 TRPV4 TRPV3 TRPC1
44 dentin sensitivity 9.9 TRPV3 TRPV2
45 spondylometaphyseal dysplasia, kozlowski type 9.9 TRPV6 TRPV4 PACSIN3 MIR4497
46 strabismus 9.8
47 mucopolysaccharidosis-plus syndrome 9.8
48 autosomal recessive disease 9.8
49 metaphyseal dysplasia 9.8
50 spinal stenosis 9.8

Graphical network of the top 20 diseases related to Brachyolmia:



Diseases related to Brachyolmia

Symptoms & Phenotypes for Brachyolmia

Human phenotypes related to Brachyolmia:

31
# Description HPO Frequency HPO Source Accession
1 short thorax 31 hallmark (90%) HP:0010306
2 mild short stature 31 hallmark (90%) HP:0003502

MGI Mouse Phenotypes related to Brachyolmia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.1 COL2A1 LTBP3 PAPSS2 SLC10A7 SLC26A2 WDR72

Drugs & Therapeutics for Brachyolmia

Search Clinical Trials , NIH Clinical Center for Brachyolmia

Genetic Tests for Brachyolmia

Anatomical Context for Brachyolmia

MalaCards organs/tissues related to Brachyolmia:

40
Bone, Heart

Publications for Brachyolmia

Articles related to Brachyolmia:

(show top 50) (show all 51)
# Title Authors PMID Year
1
Natural history of TRPV4-Related disorders: From skeletal dysplasia to neuromuscular phenotype. 61
33774370 2021
2
Bi-allelic loss-of-function novel variants in LTBP3-related skeletal dysplasia: Report of first patient from India. 61
32432408 2020
3
TRPV4 expresses in bone cell lineages and TRPV4-R616Q mutant causing Brachyolmia in human reveals "loss-of-interaction" with cholesterol. 61
31387748 2019
4
PAPSS2-related brachyolmia: Clinical and radiological phenotype in 18 new cases. 61
31313512 2019
5
Autosomal dominant brachyolmia: transient metaphyseal striations. 61
28601949 2017
6
Somatic mosaicism for a lethal TRPV4 mutation results in non-lethal metatropic dysplasia. 61
27530454 2016
7
Autosomal recessive brachyolmia: early radiological findings. 61
27544198 2016
8
Whole exome sequencing identified a novel COL2A1 mutation that causes mild Spondylo-epiphyseal dysplasia mimicking autosomal dominant brachyolmia. 61
26586363 2016
9
Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta. 61
25669657 2015
10
Mice expressing mutant Trpv4 recapitulate the human TRPV4 disorders. 61
24644033 2014
11
Autosomal dominant brachyolmia in a large Swedish family: phenotypic spectrum and natural course. 61
24677493 2014
12
Follistatin in chondrocytes: the link between TRPV4 channelopathies and skeletal malformations. 61
24577120 2014
13
Autosomal Dominant TRPV4 Disorders 61
24830047 2014
14
Clinical and radiographic features of the autosomal recessive form of brachyolmia caused by PAPSS2 mutations. 61
23824674 2013
15
Human skeletal dysplasia caused by a constitutive activated transient receptor potential vanilloid 4 (TRPV4) cation channel mutation. 61
23143559 2012
16
A Novel Homozygous WDR72 Mutation in Two Siblings with Amelogenesis Imperfecta and Mild Short Stature. 61
23293580 2012
17
TRPV4-associated skeletal dysplasias. 61
22791502 2012
18
PAPSS2 mutations cause autosomal recessive brachyolmia. 61
22791835 2012
19
TRPV4-pathy manifesting both skeletal dysplasia and peripheral neuropathy: a report of three patients. 61
22419508 2012
20
The importance of conventional radiography in the mutational analysis of skeletal dysplasias (the TRPV4 mutational family). 61
21863289 2012
21
Fetal akinesia in metatropic dysplasia: The combined phenotype of chondrodysplasia and neuropathy? 61
21964829 2011
22
TRPV4 related skeletal dysplasias: a phenotypic spectrum highlighted byclinical, radiographic, and molecular studies in 21 new families. 61
21658220 2011
23
Transient receptor potential genes and human inherited disease. 61
21290338 2011
24
New phenotype with generalized platyspondyly, large mandible, hypoplastic teeth, strabismus, hyperopia and low cholesterol levels. 61
21848004 2011
25
Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family. 61
20577006 2010
26
The vanilloid transient receptor potential channel TRPV4: from structure to disease. 61
19835908 2010
27
Wild-type and brachyolmia-causing mutant TRPV4 channels respond directly to stretch force. 61
20605796 2010
28
TRPV4-mediated channelopathies. 61
20676052 2010
29
TRPV4-pathy, a novel channelopathy affecting diverse systems. 61
20505684 2010
30
Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations. 61
20503319 2010
31
Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia. 61
19232556 2009
32
Brachyolmia with amelogenesis imperfecta: further evidence of a distinct entity. 61
19213025 2009
33
Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia. 61
18587396 2008
34
Brachyolmia and spinal stenosis. 61
12833413 2003
35
Short trunk stature, brachydactyly, and platyspondyly in three sibs: a new form of brachyolmia or a new skeletal dysplasia? 61
12784309 2003
36
Two sibs with brachyolmia type Hobaek: five year follow-up through puberty. 61
12476457 2003
37
Familial brachyolmia. 61
10968486 2000
38
A case of brachyolmia. 61
9339123 1997
39
Toledo type brachyolmia. 61
8660094 1996
40
A new form of skeletal dysplasia with amelogenesis imperfecta and platyspondyly. 61
8721563 1996
41
Brachyolmia: a report of two cases. 61
7883917 1995
42
Toledo type brachyolmia. 61
7826119 1994
43
[Brachyolmia at autosomal recessive transmission]. 61
7951838 1994
44
Brachyolmia: an autosomal dominant form. 61
8209891 1994
45
Spondylar dysplasia (SD)/brachyolmia (BO), type I: search for qualitative anomalies in glycosaminoglycans (GAG) 61
1424247 1992
46
Brachyolmia: a skeletal dysplasia with an altered mucopolysaccharide excretion. 61
1836753 1991
47
[Autosome dominant vitreoretinal dystrophy with skeletal dysplasia in one generation]. 61
2056740 1991
48
Brachyolmia: radiographic and genetic evidence of heterogeneity. 61
2669482 1989
49
Brachyolmia, recessive type (Hobaek): a clinical, radiographic, and histochemical study. 61
6650565 1983
50
[Proceedings: Pure spondyloepiphyseal dysplasia or brachyolmia]. 61
811191 1975

Variations for Brachyolmia

ClinVar genetic disease variations for Brachyolmia:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PAPSS2 NM_001015880.2(PAPSS2):c.222C>G (p.Tyr74Ter) SNV Likely pathogenic 505568 rs374379931 GRCh37: 10:89472908-89472908
GRCh38: 10:87713151-87713151
2 TRPV4 NM_021625.4(TRPV4):c.2484C>T (p.Arg828=) SNV Likely benign 307122 rs142656819 GRCh37: 12:110221558-110221558
GRCh38: 12:109783753-109783753
3 TRPV4 , MIR4497 NR_039718.1(MIR4497):n.66C>T SNV Likely benign 368980 rs56079803 GRCh37: 12:110271218-110271218
GRCh38: 12:109833413-109833413

Expression for Brachyolmia

Search GEO for disease gene expression data for Brachyolmia.

Pathways for Brachyolmia

Pathways related to Brachyolmia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.93 TRPV6 TRPV4 TRPV3 TRPV2 TRPC1 SLC26A2
2
Show member pathways
12.78 TRPV6 TRPV4 TRPV3 TRPV2 TRPC1 LTBP3
3
Show member pathways
11.93 TRPV6 TRPV4 TRPV3 TRPV2 TRPC1 MCOLN3
4
Show member pathways
11.78 TRPV4 TRPV3 TRPV2
5 10.5 TRPV6 TRPV4 TRPV3 TRPV2 TRPC1 MCOLN3

GO Terms for Brachyolmia

Cellular components related to Brachyolmia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of plasma membrane GO:0005887 9.1 TRPV6 TRPV4 TRPV3 TRPV2 TRPC1 SLC26A2

Biological processes related to Brachyolmia according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.87 TRPV6 TRPV4 TRPV3 TRPV2 TRPC1 SLC26A2
2 ion transmembrane transport GO:0034220 9.76 TRPV6 TRPV4 TRPV3 MCOLN3
3 ion transport GO:0006811 9.76 TRPV6 TRPV4 TRPV3 TRPV2 TRPC1 SLC26A2
4 skeletal system development GO:0001501 9.69 PAPSS2 LTBP3 COL2A1
5 cellular calcium ion homeostasis GO:0006874 9.65 TRPV4 TMEM165 SLC10A7
6 calcium ion transport GO:0006816 9.65 TRPV6 TRPV4 TRPV3 TRPV2 TRPC1
7 positive regulation of calcium ion import GO:0090280 9.49 TRPV3 TRPV2
8 response to temperature stimulus GO:0009266 9.43 TRPV3 TRPV2
9 cartilage development involved in endochondral bone morphogenesis GO:0060351 9.4 TRPV4 COL2A1
10 3'-phosphoadenosine 5'-phosphosulfate biosynthetic process GO:0050428 9.37 SLC26A2 PAPSS2
11 calcium ion import across plasma membrane GO:0098703 9.26 TRPV6 TRPV4 TRPV3 TRPV2
12 calcium ion transmembrane transport GO:0070588 9.17 TRPV6 TRPV4 TRPV3 TRPV2 TRPC1 TMEM165

Molecular functions related to Brachyolmia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion channel activity GO:0005216 9.55 TRPV6 TRPV4 TRPV3 TRPV2 TRPC1
2 calcium channel activity GO:0005262 9.35 TRPV6 TRPV4 TRPV3 TRPV2 TRPC1
3 cation channel activity GO:0005261 9.02 TRPV4 TRPV3 TRPV2 TRPC1 MCOLN3

Sources for Brachyolmia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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