BDC
MCID: BRC081
MIFTS: 50

Brachydactyly, Type C (BDC)

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

Aliases & Classifications for Brachydactyly, Type C

MalaCards integrated aliases for Brachydactyly, Type C:

Name: Brachydactyly, Type C 57 13 54 39
Brachydactyly Type C 12 73 20 58 29 6 44 15
Bdc 57 12 20 72
Brachydactyly Haws Type 20 72
Brachydactyly, Haws Type 57
Brachydactyly C 72

Characteristics:

Orphanet epidemiological data:

58
brachydactyly type c
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
allelic to grebe syndrome , du pan syndrome , and acromesomelic dysplasia, hunter thompson type


HPO:

31
brachydactyly, type c:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0110970
OMIM® 57 113100
SNOMED-CT 67 389169005
MESH via Orphanet 45 C537093
ICD10 via Orphanet 33 Q73.8
UMLS via Orphanet 71 C1300268 C1862103
Orphanet 58 ORPHA93384
MedGen 41 C1862103
UMLS 70 C1300268 C1862103

Summaries for Brachydactyly, Type C

GARD : 20 Brachydactyly type C is a very rare congenital condition that is characterized by shortening of certain bones in the index, middle and little fingers. The bones of the ring finger are typically normal. Other abnormalities may also be present such as hypersegmentation (extra bones) of the index and middle fingers; ulnar deviation (angled towards the fifth finger) of the index finger; and unusually-shaped bones and/or epiphysis (end of a long bone). Brachydactyly type C is typically caused by changes ( mutations ) in the GDF5 gene and is inherited in an autosomal dominant manner. Treatment varies based on the severity of the condition. Physical therapy and/or plastic surgery may be indicated if the condition affects hand function.

MalaCards based summary : Brachydactyly, Type C, also known as brachydactyly type c, is related to proximal symphalangism and symphalangism, proximal, 1b. An important gene associated with Brachydactyly, Type C is GDF5 (Growth Differentiation Factor 5), and among its related pathways/superpathways are PAK Pathway and Allograft rejection. Affiliated tissues include skin, bone and thymus, and related phenotypes are ulnar deviation of finger and short middle phalanx of finger

Disease Ontology : 12 A brachydactyly characterized by rachymesophalangy of the index, middle and little fingers, hyperphalangy of the index and middle finger, and shortening of the 1st metacarpal that has material basis in heterozygous mutation in the GDF5 gene on chromosome 20q11.

OMIM® : 57 The brachydactyly type C (BDC) phenotype includes brachymesophalangy of fingers 2, 3, and 5. The fourth finger is usually unaffected and thus appears as the longest finger of the hand. Shortening of metacarpal 1 and hyperphalangy in fingers 2 and 3 may occur and can be considered relatively characteristic signs. BDC can be highly variable, ranging from severely affected hands with very short fingers to mildly affected cases with only moderate brachydactyly, most often affecting the middle and proximal phalanges of fingers 2 and 3 (summary by Lehmann et al., 2006). (113100) (Updated 20-May-2021)

UniProtKB/Swiss-Prot : 72 Brachydactyly C: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type C is characterized by deformity of the middle and proximal phalanges of the second and third fingers, sometimes with hypersegmentation of the proximal phalanx. The ring finger may be essentially normal and project beyond the others.

Wikipedia : 73 Brachydactyly (Greek βραχύς = "short" plus δάκτυλος = "finger"), is a medical term which literally means... more...

Related Diseases for Brachydactyly, Type C

Diseases in the Brachydactyly family:

Brachydactyly, Type A1 Brachydactyly, Type A2
Brachydactyly, Type A3 Brachydactyly, Type A4
Brachydactyly, Type B1 Brachydactyly, Type C
Brachydactyly, Type D Brachydactyly, Type E1
Brachydactyly, Type A1, B Brachydactyly, Type B2
Brachydactyly, Type E2 Brachydactyly, Type A1, C
Brachydactyly, Type A1, D Brachydactyly Type A5
Brachydactyly Type A7

Diseases related to Brachydactyly, Type C via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 304)
# Related Disease Score Top Affiliating Genes
1 proximal symphalangism 30.7 GDF5-AS1 GDF5 BMPR1B
2 symphalangism, proximal, 1b 30.6 GDF5-AS1 GDF5
3 du pan syndrome 30.5 GDF5-AS1 GDF5 BMPR1B
4 brachydactyly, type a2 30.5 GDF5-AS1 GDF5 BMPR1B
5 collecting duct carcinoma 11.1
6 angel-shaped phalangoepiphyseal dysplasia 11.1
7 heart-hand syndrome, spanish type 11.1
8 catel-manzke syndrome 11.1
9 brachydactyly 10.6
10 klippel-feil syndrome 1 10.5 GDF5 BMPR1B
11 multiple synostoses syndrome 2 10.5 GDF5-AS1 GDF5
12 cork-handlers' disease 10.5 CD8A CD4
13 sugarman brachydactyly 10.5 GDF5 BMPR1B
14 necrotic uveal melanoma 10.5 CD8A CD4
15 early yaws 10.4 CD8A CD4
16 acromesomelic dysplasia, hunter-thompson type 10.4 GDF5-AS1 GDF5 BMPR1B
17 acromesomelic dysplasia 10.4 GDF5-AS1 GDF5 BMPR1B
18 chondrodysplasia, grebe type 10.4 GDF5-AS1 GDF5 BMPR1B
19 ventilation pneumonitis 10.4 CD8A CD4
20 diffuse infiltrative lymphocytosis syndrome 10.4 CD8A CD4
21 cervical large cell neuroendocrine carcinoma 10.4 PTPRN CHGA
22 latent syphilis 10.4 CD8A CD4
23 autoimmune lymphoproliferative syndrome, type iia 10.4 CD8A CD4
24 caplan's syndrome 10.4 FOXP3 CD4
25 autoimmune atherosclerosis 10.4 FOXP3 CD4
26 suppurative lymphadenitis 10.4 CD4 CCR6
27 adult acute lymphocytic leukemia 10.4 CD8A CD4 CCR6
28 wissler-fanconi syndrome 10.4 PTPRN CD4
29 synostoses, tarsal, carpal, and digital 10.4 GDF5 BMPR1B
30 parapsoriasis 10.4 CD8A CD4
31 brachydactyly, type a1 10.4 GDF5-AS1 GDF5 BMPR1B
32 gastroduodenitis 10.4 CD8A CD4
33 primary syphilis 10.4 CD8A CD4
34 norwegian scabies 10.4 CD8A CD4
35 multiple synostoses syndrome 10.4 GDF5-AS1 GDF5 BMPR1B
36 bird fancier's lung 10.4 CD8A CD4
37 cecal disease 10.4 CHGA CD4 CCR6
38 splenic flexure cancer 10.4 INS GAD2
39 esophageal candidiasis 10.4 CD8A CD4 CCR6
40 toxicodendron dermatitis 10.4 IL2 CD8A
41 pneumonic tularemia 10.4 CD8A CD4 CCR6
42 tularemia 10.4 CD8A CD4 CCR6
43 variola major 10.4 CD8A CD4
44 herpes simplex virus keratitis 10.4 CD4 CCR6
45 iritis 10.4 CD8A CD4 CCR6
46 autoimmune cholangitis 10.4 CD8A CD4 CCR6
47 follicular mucinosis 10.4 CD8A CD4
48 immunodeficiency 16 10.4 CD8A CD4 CCR6
49 viral pneumonia 10.4 CD8A CD4 CCR6
50 tertiary syphilis 10.4 CD8A CD4

Graphical network of the top 20 diseases related to Brachydactyly, Type C:



Diseases related to Brachydactyly, Type C

Symptoms & Phenotypes for Brachydactyly, Type C

Human phenotypes related to Brachydactyly, Type C:

58 31 (show all 41)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ulnar deviation of finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0009465
2 short middle phalanx of finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0005819
3 type c brachydactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0009373
4 pseudoepiphyses of the 2nd finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0009495
5 aplasia/hypoplasia of the 1st metacarpal 58 31 hallmark (90%) Very frequent (99-80%) HP:0010026
6 short 2nd finger 31 hallmark (90%) HP:0009536
7 pseudoepiphyses of the 3rd finger 31 hallmark (90%) HP:0009417
8 short 3rd finger 31 hallmark (90%) HP:0009461
9 cone-shaped epiphyses of the middle phalanges of the hand 31 hallmark (90%) HP:0010259
10 short stature 58 31 frequent (33%) Occasional (29-5%) HP:0004322
11 abnormal fingernail morphology 58 31 frequent (33%) Frequent (79-30%) HP:0001231
12 clinodactyly of the 5th finger 58 31 frequent (33%) Occasional (29-5%) HP:0004209
13 cone-shaped epiphysis 58 31 frequent (33%) Frequent (79-30%) HP:0010579
14 short metatarsal 58 31 frequent (33%) Frequent (79-30%) HP:0010743
15 complete duplication of distal phalanx of the thumb 58 31 frequent (33%) Frequent (79-30%) HP:0009606
16 stippling of the epiphysis of the distal phalanx of the thumb 58 31 frequent (33%) Frequent (79-30%) HP:0009684
17 short 1st metacarpal 31 frequent (33%) HP:0010034
18 ulnar deviation of the 2nd finger 31 frequent (33%) HP:0009464
19 triangular epiphysis of the middle phalanx of the 2nd finger 31 frequent (33%) HP:0009523
20 ulnar deviation of the 3rd finger 31 frequent (33%) HP:0009463
21 triangular shaped middle phalanx of the 2nd finger 31 frequent (33%) HP:0009575
22 enlarged epiphysis of the middle phalanx of the 3rd finger 31 frequent (33%) HP:0009324
23 triangular epiphysis of the middle phalanx of the 3rd finger 31 frequent (33%) HP:0009331
24 enlarged epiphysis of the proximal phalanx of the 3rd finger 31 frequent (33%) HP:0009349
25 triangular epiphysis of the proximal phalanx of the 3rd finger 31 frequent (33%) HP:0009356
26 triangular shaped middle phalanx of the 3rd finger 31 frequent (33%) HP:0009436
27 triangular shaped proximal phalanx of the 3rd finger 31 frequent (33%) HP:0009456
28 enlarged epiphysis of the middle phalanx of the 2nd finger 31 frequent (33%) HP:0009516
29 enlarged epiphysis of the proximal phalanx of the 2nd finger 31 frequent (33%) HP:0009527
30 triangular epiphysis of the proximal phalanx of the 2nd finger 31 frequent (33%) HP:0009534
31 triangular shaped proximal phalanx of the 2nd finger 31 frequent (33%) HP:0009587
32 metatarsus valgus 58 31 occasional (7.5%) Occasional (29-5%) HP:0010508
33 symphalangism affecting the phalanges of the hand 58 31 occasional (7.5%) Occasional (29-5%) HP:0009773
34 delayed skeletal maturation 31 occasional (7.5%) HP:0002750
35 talipes equinovarus 31 occasional (7.5%) HP:0001762
36 talipes equinovalgus 31 occasional (7.5%) HP:0001772
37 madelung deformity 31 HP:0003067
38 brachydactyly 31 HP:0001156
39 polydactyly 31 HP:0010442
40 hypersegmentation of proximal phalanx of second finger 31 HP:0006206
41 hypersegmentation of proximal phalanx of third finger 31 HP:0011929

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skeletal Limbs:
madelung deformity

Skeletal Hands:
brachydactyly
polydactyly
fifth finger clinodactyly
limited flexion in distal interphalangeal joints
disproportionate shortening of 2nd and 3rd fingers
more
Skeletal Feet:
talipes equinovarus
talipes equinovalgus

Clinical features from OMIM®:

113100 (Updated 20-May-2021)

MGI Mouse Phenotypes related to Brachydactyly, Type C:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 10.03 BMPR1B CD4 CD8A CHGA CTLA4 FOXP3
2 immune system MP:0005387 9.97 AOC3 CCR6 CD4 CD69 CD8A CTLA4
3 no phenotypic analysis MP:0003012 9.56 CD4 CD69 CHGA FOXP3 GAD2 IL2
4 normal MP:0002873 9.32 BMPR1B CCR6 CD4 CD8A CTLA4 FOXP3

Drugs & Therapeutics for Brachydactyly, Type C

Search Clinical Trials , NIH Clinical Center for Brachydactyly, Type C

Cochrane evidence based reviews: brachydactyly type c

Genetic Tests for Brachydactyly, Type C

Genetic tests related to Brachydactyly, Type C:

# Genetic test Affiliating Genes
1 Brachydactyly Type C 29 GDF5

Anatomical Context for Brachydactyly, Type C

MalaCards organs/tissues related to Brachydactyly, Type C:

40
Skin, Bone, Thymus, Lung, Bone Marrow, Eye, Lymph Node

Publications for Brachydactyly, Type C

Articles related to Brachydactyly, Type C:

(show all 39)
# Title Authors PMID Year
1
Novel point mutations in GDF5 associated with two distinct limb malformations in Chinese: brachydactyly type C and proximal symphalangism. 54 6 57 61
18283415 2008
2
Brachydactyly type C caused by a homozygous missense mutation in the prodomain of CDMP1. 61 57 6 54
14735582 2004
3
Broad phenotypic spectrum caused by an identical heterozygous CDMP-1 mutation in three unrelated families. 54 57 61 6
12567410 2003
4
The mutational spectrum of brachydactyly type C. 61 57 6 54
12357473 2002
5
Mutations in CDMP1 cause autosomal dominant brachydactyly type C. 61 6 57
9288091 1997
6
Clinical and locus heterogeneity in brachydactyly type C. 61 6 57
9024575 1997
7
Inherited brachydactyly and hypoplasia of the bones of the extremities. 6 57
13953230 1963
8
A novel R486Q mutation in BMPR1B resulting in either a brachydactyly type C/symphalangism-like phenotype or brachydactyly type A2. 61 57
16957682 2006
9
Differences in complexity of isolated brachydactyly type C cannot be attributed to locus heterogeneity alone. 61 57
11169564 2001
10
Intrafamilial clinical variability in type C brachydactyly. 57 61
11837604 2001
11
Brachydactyly type C gene maps to human chromsome 12q24. 61 57
8954778 1996
12
Brachydactyly type C associated with shortening of the hallux. 57 61
1583664 1992
13
Recessively inherited brachydactyly type C. 61 57
6842546 1983
14
Limb alterations in brachypodism mice due to mutations in a new member of the TGF beta-superfamily. 57
8145850 1994
15
Type C brachydactyly transmitted through four generations. 57
3281570 1988
16
Brachydactyly C, short stature, and hip dysplasia. 57
391043 1979
17
Family study of inherited syndrome with multiple congenital deformities: symphalangism, carpal and tarsal fusion, brachydactyly, craniosynostosis, strabismus, hip osteochondritis. 57
1003450 1976
18
Hereditary brachydactyly and hip disease. Unusual radiological and dermatoglyphic findings in a kindred. 57
5647298 1968
19
GDF5 mutation case report and a systematic review of molecular and clinical spectrum: Expanding current knowledge on genotype-phenotype correlations. 61
33333243 2021
20
[Brachydactyly type C due to a nonsense mutation in the GDF5 gene]. 61
28391997 2018
21
Characterization of an acromesomelic dysplasia, Grebe type case: novel mutation affecting the recognition motif at the processing site of GDF5. 61
26275437 2016
22
[Uncommon bone abnormality: non-syndromic brachydactyly type C]. 61
28292173 2016
23
Brachydactyly Type C patient with compound heterozygosity for p.Gly319Val and p.Ile358Thr variants in the GDF5 proregion: benign variants or mutations? 61
25994865 2015
24
Two novel homozygous missense mutations in the GDF5 gene cause brachydactyly type C. 61
25820810 2015
25
Molecular analysis of two novel missense mutations in the GDF5 proregion that reduce protein activity and are associated with brachydactyly type C. 61
25092592 2014
26
Novel indel Mutation in the GDF5 Gene Is Associated with Brachydactyly Type C in a Four-Generation Turkish Family. 61
24715855 2014
27
Characterization of a novel missense mutation in the prodomain of GDF5, which underlies brachydactyly type C and mild Grebe type chondrodysplasia in a large Pakistani family. 61
23812741 2013
28
Identification of a GDF5 mutation in a Korean patient with brachydactyly type C without foot involvement. 61
23483675 2013
29
A novel mutation in CDMP1 causes brachydactyly type C with "angel-shaped phalanx". A genotype-phenotype correlation in the mutational spectrum. 61
22828468 2012
30
Variable hand and foot abnormalities in family with congenital vertical talus and CDMP-1 gene mutation. 61
16005596 2005
31
Angel-shaped phalanges in brachydactyly C: a case report, and speculation on pathogenesis. 61
15565340 2005
32
Modulation of GDF5/BRI-b signalling through interaction with the tyrosine kinase receptor Ror2. 61
15569154 2004
33
Grebe dysplasia and the spectrum of CDMP1 mutations. 61
12687891 2003
34
Severe aplastic anaemia in a child with brachydactyly type C. 61
12542502 2003
35
Brachydactyly type C. 61
11172365 2001
36
Genetics of limb development and congenital hand malformations. 61
9514351 1998
37
Pitfalls of genetic counselling in brachydactyly type C. 61
7856649 1994
38
[C brachydactyly in four generations]. 61
6694344 1984
39
[Study of fingerprints in 12 cases of hereditary brachydactyly type C and E (author's transl)]. 61
599331 1977

Variations for Brachydactyly, Type C

ClinVar genetic disease variations for Brachydactyly, Type C:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GDF5 GDF5, 23-BP INS, NT811 Insertion Pathogenic 8382 GRCh37:
GRCh38:
2 GDF5 NM_000557.5(GDF5):c.517A>G (p.Met173Val) SNV Pathogenic 8384 rs28936397 GRCh37: 20:34025192-34025192
GRCh38: 20:35437412-35437412
3 GDF5 NM_000557.5(GDF5):c.205dup (p.Ala69fs) Duplication Pathogenic 8385 rs753691079 GRCh37: 20:34025503-34025504
GRCh38: 20:35437723-35437724
4 GDF5-AS1 , GDF5 NM_000557.5(GDF5):c.1461T>G (p.Tyr487Ter) SNV Pathogenic 8391 rs121909348 GRCh37: 20:34021752-34021752
GRCh38: 20:35433954-35433954
5 GDF5-AS1 , GDF5 NM_000557.5(GDF5):c.901C>T (p.Arg301Ter) SNV Pathogenic 8378 rs74315386 GRCh37: 20:34022312-34022312
GRCh38: 20:35434514-35434514
6 GDF5-AS1 , GDF5 NM_000557.5(GDF5):c.1397G>A (p.Cys466Tyr) SNV Likely pathogenic 265991 rs886039878 GRCh37: 20:34021816-34021816
GRCh38: 20:35434018-35434018

UniProtKB/Swiss-Prot genetic disease variations for Brachydactyly, Type C:

72
# Symbol AA change Variation ID SNP ID
1 GDF5 p.Met173Val VAR_037978 rs28936397
2 GDF5 p.Thr201Pro VAR_073139
3 GDF5 p.Leu263Pro VAR_073140
4 GDF5 p.Thr203Asn VAR_074161
5 GDF5 p.Val486Met VAR_074162

Expression for Brachydactyly, Type C

Search GEO for disease gene expression data for Brachydactyly, Type C.

Pathways for Brachydactyly, Type C

GO Terms for Brachydactyly, Type C

Cellular components related to Brachydactyly, Type C according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of plasma membrane GO:0005887 9.5 PTPRN2 CTLA4 CD8A CD69 CD4 CCR6
2 external side of plasma membrane GO:0009897 9.1 ITGAX CTLA4 CD8A CD69 CD4 CCR6

Biological processes related to Brachydactyly, Type C according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 immune response GO:0006955 9.8 IL2 CTLA4 CD8A CD4 CCR6
2 negative regulation of immune response GO:0050777 9.48 FOXP3 CTLA4
3 positive regulation of regulatory T cell differentiation GO:0045591 9.46 IL2 FOXP3
4 T cell mediated immunity GO:0002456 9.43 FOXP3 CD8A
5 negative regulation of T-helper 17 cell differentiation GO:2000320 9.37 IL2 FOXP3
6 insulin secretion involved in cellular response to glucose stimulus GO:0035773 9.32 PTPRN2 PTPRN
7 negative regulation of blood vessel diameter GO:0097756 9.26 INS CHGA
8 negative regulation of lymphocyte proliferation GO:0050672 9.16 IL2 FOXP3
9 T cell activation GO:0042110 9.13 FOXP3 CD8A CD4
10 regulation of regulatory T cell differentiation GO:0045589 8.8 IL2 FOXP3 CTLA4

Sources for Brachydactyly, Type C

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
Content
Loading form....