BCYM3
MCID: BRC045
MIFTS: 31

Brachyolmia Type 3 (BCYM3)

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

Aliases & Classifications for Brachyolmia Type 3

MalaCards integrated aliases for Brachyolmia Type 3:

Name: Brachyolmia Type 3 56 52 58 13
Brachyrachia 56 52 73 29 6
Autosomal Dominant Brachyolmia 52 58 73
Bcym3 56 73
Brachyolmia, Autosomal Dominant 56
Brachyolmia Autosomal Dominant 52
Brachyolmia, Type 3 39
Brachyolmia 3 73

Characteristics:

Orphanet epidemiological data:

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

OMIM:

56
Inheritance:
autosomal dominant


HPO:

31
brachyolmia type 3:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

OMIM 56 113500
MeSH 43 D010009
ICD10 via Orphanet 33 Q76.3
UMLS via Orphanet 72 C0432227
Orphanet 58 ORPHA93304
MedGen 41 C0432227

Summaries for Brachyolmia Type 3

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 93304 Definition A relatively severe form of brachyolmia, a group of rare genetic skeletal disorders, characterized by short-trunked short stature , platyspondyly and kyphoscoliosis. Degenerative joint disease (osteoarthropathy) in the spine, large joints and interphalangeal joints becomes manifest in adulthood. Epidemiology The precise prevalence of this form of brachyolmia is not known. About 30 cases have been reported. Clinical description Patients with Brachyolmia type 3 generally have a normal birth weight and length. Affected individuals present with moderately short trunk/short stature and mildly short limbs in childhood. Kyphoscoliosis is common and sometimes severe. Adult patients develop degenerative joint disease in the spine, large joints and small joints of the hands and feet, which may cause significant musculoskeletal morbidity, such as chronic pain in the extremities and spine, and paresthesia. Final adult height is reported to be 155-168 cm (males) and 136-150 cm (females). The radiographic features include severe platyspondyly particularly in the cervical spine, elongated vertebral bodies (overfaced pedicles), broad ilia, and mild metaphyseal irregularity in the proximal femora. Carpal ossification may be mildly delayed, and mild brachydactyly may exist. Etiology Heterozygous mutations in the TRPV4 gene (12q24.11) are responsible for autosomal dominant brachyolmia. TRPV4 mutations are associated with other skeletal dysplasias, including lethal and nonlethal metatropic dysplasia, spondyloepiphyseal dysplasia Maroteaux type, and spondylometaphyseal dysplasia Kozlowski type (see these terms). Autosomal dominant brachyolmia falls into the mildest end of the TRPV4 -associated skeletal dysplasia group. TRPV4 encodes a Ca-permeable, non-selective cation channel that participates in the regulation of osmotic sensitivity and mechanosensitivity. It remains to be explained how dysregulation of the cation channel causes the skeletal abnormalities. Genetic counseling Genetic counseling should be provided to affected families, in consideration of the autosomal dominant mode of inheritance. Visit the Orphanet disease page for more resources.

MalaCards based summary : Brachyolmia Type 3, also known as brachyrachia, is related to brachyolmia type 1, hobaek type and brachyolmia. An important gene associated with Brachyolmia Type 3 is TRPV4 (Transient Receptor Potential Cation Channel Subfamily V Member 4). Affiliated tissues include bone and spinal cord, and related phenotypes are short stature and short thorax

OMIM : 56 Type 3 brachyolmia is an autosomal dominant skeletal dysplasia affecting the spine characterized by severe kyphoscoliosis and flattened, irregular cervical vertebrae (summary by Rock et al., 2008). For a discussion of heterogeneity of brachyolmia, see 271530. (113500)

UniProtKB/Swiss-Prot : 73 Brachyolmia 3: A form of brachyolmia, a clinically and genetically heterogeneous skeletal dysplasia primarily affecting the spine and characterized by a short trunk, short stature, and platyspondyly. BCYM3 is an autosomal dominant form with severe scoliosis with or without kyphosis, and flattened irregular cervical vertebrae.

Related Diseases for Brachyolmia Type 3

Diseases in the Brachyolmia family:

Brachyolmia Type 3 Brachyolmia Type 2
Autosomal Recessive Brachyolmia

Diseases related to Brachyolmia Type 3 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 brachyolmia type 1, hobaek type 11.2
2 brachyolmia 11.2
3 scoliosis 10.3
4 skeletal dysplasias 10.3
5 trpv4-associated disorders 10.2
6 chronic pain 10.2

Graphical network of the top 20 diseases related to Brachyolmia Type 3:



Diseases related to Brachyolmia Type 3

Symptoms & Phenotypes for Brachyolmia Type 3

Human phenotypes related to Brachyolmia Type 3:

58 31 (show all 17)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
2 short thorax 58 31 hallmark (90%) Very frequent (99-80%) HP:0010306
3 kyphoscoliosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002751
4 platyspondyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000926
5 increased vertebral height 58 31 hallmark (90%) Very frequent (99-80%) HP:0004570
6 abnormality of the metaphysis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000944
7 short neck 31 HP:0000470
8 scoliosis 31 HP:0002650
9 kyphosis 31 HP:0002808
10 radial deviation of finger 31 HP:0009466
11 hypermetropia 31 HP:0000540
12 spinal cord compression 31 HP:0002176
13 short femoral neck 31 HP:0100864
14 clinodactyly 31 HP:0030084
15 barrel-shaped chest 31 HP:0001552
16 proximal femoral metaphyseal irregularity 31 HP:0003411
17 childhood-onset short-trunk short stature 31 HP:0008922

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Neck:
short neck

Neurologic Central Nervous System:
spinal cord compression
normal intelligence

Skeletal Hands:
clinodactyly

Growth Height:
normal birth length
short stature, disproportionate (short trunk), identifiable in childhood

Skeletal Spine:
scoliosis
kyphosis
gibbus
marked platyspondyly

Skeletal Pelvis:
short femoral neck
irregular proximal femoral metaphyses

Chest External Features:
barrel-shaped chest

Head And Neck Eyes:
hyperopia

Clinical features from OMIM:

113500

Drugs & Therapeutics for Brachyolmia Type 3

Search Clinical Trials , NIH Clinical Center for Brachyolmia Type 3

Genetic Tests for Brachyolmia Type 3

Genetic tests related to Brachyolmia Type 3:

# Genetic test Affiliating Genes
1 Brachyrachia (short Spine Dysplasia) 29 TRPV4

Anatomical Context for Brachyolmia Type 3

MalaCards organs/tissues related to Brachyolmia Type 3:

40
Bone, Spinal Cord

Publications for Brachyolmia Type 3

Articles related to Brachyolmia Type 3:

# Title Authors PMID Year
1
Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia. 56 6
18587396 2008
2
TRPV4-Associated Disorders 6
24830047 2014
3
Brachyolmia: an autosomal dominant form. 56
8209891 1994
4
Brachyolmia: radiographic and genetic evidence of heterogeneity. 56
2669482 1989
5
Osteochondrodystrophy (Morquio's disease) in three generations. 56
14418038 1959
6
Autosomal dominant brachyolmia in a large Swedish family: phenotypic spectrum and natural course. 61
24677493 2014
7
Human skeletal dysplasia caused by a constitutive activated transient receptor potential vanilloid 4 (TRPV4) cation channel mutation. 61
23143559 2012

Variations for Brachyolmia Type 3

ClinVar genetic disease variations for Brachyolmia Type 3:

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# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TRPV4 NM_021625.4(TRPV4):c.1847G>A (p.Arg616Gln)SNV Pathogenic 4992 rs121912632 12:110230212-110230212 12:109792407-109792407
2 TRPV4 NM_021625.4(TRPV4):c.1858G>A (p.Val620Ile)SNV Pathogenic/Likely pathogenic 4993 rs121912633 12:110230201-110230201 12:109792396-109792396
3 TRPV4 NM_021625.4(TRPV4):c.806G>A (p.Arg269His)SNV Pathogenic/Likely pathogenic 5000 rs267607144 12:110238470-110238470 12:109800665-109800665
4 TRPV4 NM_021625.5(TRPV4):c.742C>T (p.Arg248Cys)SNV Conflicting interpretations of pathogenicity 881173 12:110238534-110238534 12:109800729-109800729
5 TRPV4 NM_021625.4(TRPV4):c.1584C>T (p.Asn528=)SNV Conflicting interpretations of pathogenicity 578089 rs142749412 12:110231735-110231735 12:109793930-109793930
6 TRPV4 NM_021625.4(TRPV4):c.1729G>A (p.Val577Met)SNV Conflicting interpretations of pathogenicity 582636 rs140535889 12:110230552-110230552 12:109792747-109792747
7 TRPV4 NM_021625.4(TRPV4):c.650C>T (p.Ala217Val)SNV Conflicting interpretations of pathogenicity 307138 rs548909101 12:110240858-110240858 12:109803053-109803053
8 TRPV4 NM_021625.4(TRPV4):c.963C>A (p.Gly321=)SNV Conflicting interpretations of pathogenicity 307134 rs148534854 12:110236608-110236608 12:109798803-109798803
9 TRPV4 NM_021625.4(TRPV4):c.2605G>A (p.Ala869Thr)SNV Conflicting interpretations of pathogenicity 216733 rs138396764 12:110221437-110221437 12:109783632-109783632
10 TRPV4 NM_021625.4(TRPV4):c.1825-15C>GSNV Conflicting interpretations of pathogenicity 307126 rs200602134 12:110230249-110230249 12:109792444-109792444
11 TRPV4 NM_021625.4(TRPV4):c.1038C>T (p.Tyr346=)SNV Conflicting interpretations of pathogenicity 386671 rs750086412 12:110236533-110236533 12:109798728-109798728
12 TRPV4 NM_021625.4(TRPV4):c.523A>G (p.Thr175Ala)SNV Conflicting interpretations of pathogenicity 448711 rs146304351 12:110246137-110246137 12:109808332-109808332
13 TRPV4 NM_021625.4(TRPV4):c.958C>T (p.Arg320Ter)SNV Conflicting interpretations of pathogenicity 469047 rs142902080 12:110236613-110236613 12:109798808-109798808
14 TRPV4 NM_021625.4(TRPV4):c.2304G>C (p.Ser768=)SNV Conflicting interpretations of pathogenicity 499138 rs138986228 12:110224547-110224547 12:109786742-109786742
15 TRPV4 NM_021625.4(TRPV4):c.651G>A (p.Ala217=)SNV Conflicting interpretations of pathogenicity 517843 rs371280831 12:110240857-110240857 12:109803052-109803052
16 TRPV4 NM_021625.4(TRPV4):c.1700A>T (p.Tyr567Phe)SNV Conflicting interpretations of pathogenicity 521669 rs763889344 12:110230581-110230581 12:109792776-109792776
17 TRPV4 NM_021625.4(TRPV4):c.2320C>T (p.Arg774Cys)SNV Conflicting interpretations of pathogenicity 536854 rs145102919 12:110224531-110224531 12:109786726-109786726
18 TRPV4 NM_021625.4(TRPV4):c.1465G>A (p.Ala489Thr)SNV Conflicting interpretations of pathogenicity 583175 rs758280554 12:110232160-110232160 12:109794355-109794355
19 TRPV4 NM_021625.4(TRPV4):c.2439C>T (p.Thr813=)SNV Conflicting interpretations of pathogenicity 682229 12:110222140-110222140 12:109784335-109784335
20 TRPV4 NM_021625.4(TRPV4):c.205A>C (p.Met69Leu)SNV Conflicting interpretations of pathogenicity 307143 rs200199102 12:110252397-110252397 12:109814592-109814592
21 TRPV4 NM_021625.4(TRPV4):c.1211G>A (p.Arg404His)SNV Conflicting interpretations of pathogenicity 307132 rs377257364 12:110234451-110234451 12:109796646-109796646
22 TRPV4 NM_021625.4(TRPV4):c.1491+10C>TSNV Conflicting interpretations of pathogenicity 282949 rs201815805 12:110232124-110232124 12:109794319-109794319
23 TRPV4 NM_021625.4(TRPV4):c.402C>A (p.Ser134Arg)SNV Conflicting interpretations of pathogenicity 246556 rs201241092 12:110246258-110246258 12:109808453-109808453
24 TRPV4 NM_021625.4(TRPV4):c.1139C>T (p.Thr380Met)SNV Conflicting interpretations of pathogenicity 245915 rs764949536 12:110236432-110236432 12:109798627-109798627
25 TRPV4 NM_021625.4(TRPV4):c.1390C>T (p.Arg464Cys)SNV Conflicting interpretations of pathogenicity 246534 rs373049874 12:110232235-110232235 12:109794430-109794430
26 TRPV4 NM_021625.4(TRPV4):c.2560G>A (p.Asp854Asn)SNV Uncertain significance 246571 rs368963822 12:110221482-110221482 12:109783677-109783677
27 TRPV4 NM_021625.4(TRPV4):c.1352C>T (p.Ala451Val)SNV Uncertain significance 307131 rs886048940 12:110232273-110232273 12:109794468-109794468
28 TRPV4 NM_021625.4(TRPV4):c.*405G>ASNV Uncertain significance 307114 rs886048937 12:110221021-110221021 12:109783216-109783216
29 TRPV4 NM_021625.4(TRPV4):c.37G>T (p.Gly13Trp)SNV Uncertain significance 245716 rs763302555 12:110252565-110252565 12:109814760-109814760
30 TRPV4 NM_021625.4(TRPV4):c.1601T>C (p.Met534Thr)SNV Uncertain significance 307128 rs775011025 12:110231389-110231389 12:109793584-109793584
31 TRPV4 NM_021625.4(TRPV4):c.1796C>G (p.Thr599Arg)SNV Uncertain significance 307127 rs769225216 12:110230485-110230485 12:109792680-109792680
32 TRPV4 NC_000012.12:g.109833410C>ASNV Uncertain significance 881447 12:110271215-110271215 12:109833410-109833410
33 TRPV4 NM_021625.4(TRPV4):c.184G>A (p.Asp62Asn)SNV Uncertain significance 575960 rs770149544 12:110252418-110252418 12:109814613-109814613
34 TRPV4 NM_021625.4(TRPV4):c.1376T>G (p.Leu459Arg)SNV Uncertain significance 521109 rs201132615 12:110232249-110232249 12:109794444-109794444
35 TRPV4 NM_021625.4(TRPV4):c.569C>T (p.Thr190Met)SNV Uncertain significance 424209 rs1031096826 12:110240939-110240939 12:109803134-109803134
36 TRPV4 NM_021625.4(TRPV4):c.2425G>A (p.Gly809Ser)SNV Uncertain significance 448709 rs375851168 12:110222154-110222154 12:109784349-109784349
37 TRPV4 NM_021625.4(TRPV4):c.*212G>ASNV Uncertain significance 307118 rs886048938 12:110221214-110221214 12:109783409-109783409
38 TRPV4 NM_021625.4(TRPV4):c.*99C>TSNV Uncertain significance 307119 rs552478250 12:110221327-110221327 12:109783522-109783522
39 TRPV4 NM_021625.4(TRPV4):c.*51G>ASNV Uncertain significance 307120 rs886048939 12:110221375-110221375 12:109783570-109783570
40 TRPV4 NM_021625.4(TRPV4):c.-74G>ASNV Uncertain significance 307145 rs886048942 12:110271197-110271197 12:109833392-109833392
41 TRPV4 NM_021625.4(TRPV4):c.622G>A (p.Asp208Asn)SNV Uncertain significance 307139 rs769445973 12:110240886-110240886 12:109803081-109803081
42 TRPV4 NM_021625.4(TRPV4):c.2236C>G (p.Arg746Gly)SNV Uncertain significance 307123 rs375189134 12:110224615-110224615 12:109786810-109786810
43 TRPV4 NM_021625.4(TRPV4):c.1976C>T (p.Ser659Leu)SNV Uncertain significance 409288 rs779715512 12:110226437-110226437 12:109788632-109788632
44 TRPV4 NM_021625.4(TRPV4):c.171T>C (p.Pro57=)SNV Uncertain significance 307144 rs886048941 12:110252431-110252431 12:109814626-109814626
45 TRPV4 NM_021625.4(TRPV4):c.427C>A (p.Pro143Thr)SNV Uncertain significance 307142 rs201642486 12:110246233-110246233 12:109808428-109808428
46 TRPV4 NM_021625.4(TRPV4):c.2162C>G (p.Thr721Arg)SNV Uncertain significance 567260 rs1423138633 12:110226251-110226251 12:109788446-109788446
47 TRPV4 NM_021625.5(TRPV4):c.797C>T (p.Ala266Val)SNV Uncertain significance 881124 12:110238479-110238479 12:109800674-109800674
48 TRPV4 NM_021625.5(TRPV4):c.812G>A (p.Arg271His)SNV Uncertain significance 882712 12:110238464-110238464 12:109800659-109800659
49 TRPV4 NM_021625.5(TRPV4):c.2258G>A (p.Arg753Lys)SNV Uncertain significance 880695 12:110224593-110224593 12:109786788-109786788
50 TRPV4 NM_021625.5(TRPV4):c.2433G>A (p.Ser811=)SNV Uncertain significance 882031 12:110222146-110222146 12:109784341-109784341

UniProtKB/Swiss-Prot genetic disease variations for Brachyolmia Type 3:

73
# Symbol AA change Variation ID SNP ID
1 TRPV4 p.Arg616Gln VAR_054805 rs121912632
2 TRPV4 p.Val620Ile VAR_054806 rs121912633

Expression for Brachyolmia Type 3

Search GEO for disease gene expression data for Brachyolmia Type 3.

Pathways for Brachyolmia Type 3

GO Terms for Brachyolmia Type 3

Sources for Brachyolmia Type 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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