MCID: BRC078
MIFTS: 47

Brachydactyly, Type A1

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

Aliases & Classifications for Brachydactyly, Type A1

MalaCards integrated aliases for Brachydactyly, Type A1:

Name: Brachydactyly, Type A1 54 13 52 69
Brachydactyly Type A1 12 50 24 56 29
Bda1 12 50 24 71
Farabee Type Brachydactyly 12 24
Brachydactyly 42 69
Brachydactyly, Farabee Type 56
Brachydactyly Farabee Type 50
Farabee-Type Brachydactyly 71
Brachydactyly A1 71

Characteristics:

Orphanet epidemiological data:

56
brachydactyly type a1
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity
allelic to acrocapitofemoral dysplasia


HPO:

32
brachydactyly, type a1:
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



External Ids:

OMIM 54 112500
Disease Ontology 12 DOID:0110964
Orphanet 56 ORPHA93388
MESH via Orphanet 43 C537088
UMLS via Orphanet 70 C1862151
ICD10 via Orphanet 34 Q73.8
MedGen 40 C1862151
MeSH 42 D059327

Summaries for Brachydactyly, Type A1

UniProtKB/Swiss-Prot : 71 Brachydactyly A1: 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 A1 is characterized by middle phalanges of all the digits rudimentary or fused with the terminal phalanges. The proximal phalanges of the thumbs and big toes are short. BDA1 inheritance is autosomal dominant.

MalaCards based summary : Brachydactyly, Type A1, also known as brachydactyly type a1, is related to brachydactyly, type a1, c and brachydactyly, type a1, d, and has symptoms including short stature, scoliosis and talipes equinovarus. An important gene associated with Brachydactyly, Type A1 is IHH (Indian Hedgehog), and among its related pathways/superpathways are Pathways in cancer and Signaling by Hedgehog. Affiliated tissues include bone, and related phenotypes are craniofacial and endocrine/exocrine gland

NIH Rare Diseases : 50 this condition doesn't have a summary yet. please see our page(s) on brachydactyly.

OMIM : 54
In the classification of the brachydactylies, the analysis by Bell (1951) proved highly useful. The type A brachydactylies of Bell have the shortening confined mainly to the middle phalanges. In the A1 type, the middle phalanges of all the digits are rudimentary or fused with the terminal phalanges. The proximal phalanges of the thumbs and big toes are short. (112500)

Disease Ontology : 12 A brachydactyly characterized by rudimentary or fused middle phalanges of all the digits and shortened proximal phalanges of the thumbs and big toes.

Related Diseases for Brachydactyly, Type A1

Diseases in the Brachydactyly family:

Brachydactyly, Type D Brachydactyly, Type A1
Brachydactyly, Type A2 Brachydactyly, Type A1, D
Brachydactyly, Type A1, B Brachydactyly, Type B1
Brachydactyly, Type E2 Brachydactyly, Type B2
Brachydactyly, Type C Brachydactyly, Type A1, C
Brachydactyly, Type E Brachydactyly, Type A4
Brachydactyly Type A3 Brachydactyly Type A5
Brachydactyly Type A7 Hoxd13-Related Brachydactyly
Brachydactyly of Toes

Diseases related to Brachydactyly, Type A1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 36)
id Related Disease Score Top Affiliating Genes
1 brachydactyly, type a1, c 12.4
2 brachydactyly, type a1, d 12.3
3 brachydactyly, type a1, b 12.3
4 brachydactyly, type a2 12.2
5 thumbs, stiff, with brachydactyly type a1 and developmental delay 12.0
6 thumb stiff brachydactyly mental retardation 11.0
7 brachydactyly 10.4
8 symphalangism, proximal, 1b 10.3 BMPR1B GDF5
9 multiple synostoses syndrome 2 10.3 BMPR1B GDF5
10 thrombophilia due to heparin cofactor ii deficiency 10.3 BMPR1B GDF5
11 acromesomelic dysplasia, demirhan type 10.2 BMPR1B GDF5
12 short qt syndrome 10.2 BMPR1B GDF5
13 cri-du-chat syndrome 10.2 GNAS IHH
14 charcot-marie-tooth disease type 7 10.1 BMPR1B GDF5
15 bladder cancer, somatic 10.0 IHH PTCH1
16 inflammatory bowel disease 21 9.9 IHH SHH
17 cerebral creatine deficiency syndrome 9.9 BMPR1B GDF5 IHH
18 scoliosis 9.8
19 sporadic pheochromocytoma 9.8 PTCH1 SHH
20 celosomia 9.8 PTCH1 SHH
21 pelizaeus-merzbacher disease in female carriers 9.7 PTCH1 SHH
22 laryngotracheoesophageal cleft type 2 9.7 PTCH1 SHH
23 laryngotracheoesophageal cleft type 4 9.7 PTCH1 SHH
24 isolated facial myokymia 9.7 PTCH1 SHH
25 oral antidiabetic drugs toxicity or dose selection 9.7 PTCH1 SHH
26 childhood medulloblastoma 9.7 PTCH1 SHH
27 macular dystrophy, patterned, 3 9.6 PTCH1 SHH
28 skin hemangioma 9.6 PTCH1 SHH
29 benign shuddering attacks 9.6 GNAS PTCH1
30 heavy chain disease 9.6 PTCH1 SHH
31 basal cell nevus syndrome 9.5 PTCH1 SHH
32 small cell sarcoma 9.4 PTCH1 SHH
33 y-linked disease 9.4 PTCH1 SHH
34 congenital generalized lipodystrophy 9.4 BMPR1B GDF5 GNAS IHH
35 hydrocephalus 9.1 PTCH1 SHH
36 epilepsy, juvenile myoclonic 9 7.5 BDA1B BMPR1B GDF5 GNAS IHH PTCH1

Graphical network of the top 20 diseases related to Brachydactyly, Type A1:



Diseases related to Brachydactyly, Type A1

Symptoms & Phenotypes for Brachydactyly, Type A1

Symptoms via clinical synopsis from OMIM:

54

Growth- Height:
short stature

Skeletal- Hands:
absent distal interphalangeal creases
short broad hands
short to absent middle phalanges
short distal phalanges
thin metacarpals with broad epiphyses
more
Skin Nails & Hair- Skin:
absent distal interphalangeal creases

Skeletal- Feet:
short proximal phalanx of halluces


Clinical features from OMIM:

112500

Human phenotypes related to Brachydactyly, Type A1:

56 32 (show all 29)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short stature 56 32 hallmark (90%) Very frequent (99-80%) HP:0004322
2 scoliosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0002650
3 talipes equinovarus 56 32 occasional (7.5%) Occasional (29-5%) HP:0001762
4 short thumb 56 32 hallmark (90%) Very frequent (99-80%) HP:0009778
5 short hallux 56 32 hallmark (90%) Very frequent (99-80%) HP:0010109
6 broad metacarpals 56 32 occasional (7.5%) Occasional (29-5%) HP:0001230
7 cone-shaped epiphysis 56 32 frequent (33%) Frequent (79-30%) HP:0010579
8 short foot 56 32 hallmark (90%) Very frequent (99-80%) HP:0001773
9 clinodactyly of the 5th finger 56 32 occasional (7.5%) Occasional (29-5%) HP:0004209
10 hypoplasia of the ulna 56 32 occasional (7.5%) Occasional (29-5%) HP:0003022
11 short middle phalanx of finger 56 32 hallmark (90%) Very frequent (99-80%) HP:0005819
12 brachydactyly 32 HP:0001156
13 absent distal interphalangeal creases 32 HP:0001032
14 proportionate shortening of all digits 32 HP:0006165
15 short metacarpal 32 HP:0010049
16 short palm 32 HP:0004279
17 short distal phalanx of finger 32 HP:0009882
18 broad palm 32 HP:0001169
19 radial deviation of the 2nd finger 32 HP:0009467
20 slender metacarpals 32 HP:0006236
21 distal symphalangism (hands) 56 Occasional (29-5%)
22 distal symphalangism of hands 32 occasional (7.5%) HP:0001204
23 flattened metatarsal heads 32 HP:0005194
24 broad metacarpal epiphyses 32 HP:0006146
25 thin proximal phalanges with broad epiphyses of the hand 32 HP:0006213
26 radial deviation of the 4th finger 32 HP:0009279
27 radial deviation of the 3rd finger 32 HP:0009462
28 short proximal phalanx of thumb 32 HP:0009638
29 short proximal phalanx of hallux 32 HP:0010107

MGI Mouse Phenotypes related to Brachydactyly, Type A1:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.72 BMPR1B GNAS IHH PTCH1 SHH
2 endocrine/exocrine gland MP:0005379 9.65 BMPR1B GNAS IHH PTCH1 SHH
3 growth/size/body region MP:0005378 9.63 PTCH1 SHH BMPR1B GDF5 GNAS IHH
4 limbs/digits/tail MP:0005371 9.43 BMPR1B GDF5 GNAS IHH PTCH1 SHH
5 skeleton MP:0005390 9.1 BMPR1B GDF5 GNAS IHH PTCH1 SHH

Drugs & Therapeutics for Brachydactyly, Type A1

Search Clinical Trials , NIH Clinical Center for Brachydactyly, Type A1

Cochrane evidence based reviews: brachydactyly

Genetic Tests for Brachydactyly, Type A1

Genetic tests related to Brachydactyly, Type A1:

id Genetic test Affiliating Genes
1 Brachydactyly Type A1 29 24 IHH

Anatomical Context for Brachydactyly, Type A1

MalaCards organs/tissues related to Brachydactyly, Type A1:

39
Bone

Publications for Brachydactyly, Type A1

Articles related to Brachydactyly, Type A1:

(show all 19)
id Title Authors Year
1
Severe Form of Brachydactyly Type A1 in a Child with a c.298Ga88>a88A Mutation in IHH Gene. ( 28794911 )
2017
2
Identification of p.Glu131Lys Mutation in the IHH Gene in a Korean Patient With Brachydactyly Type A1. ( 25932455 )
2015
3
Two novel disease-causing variants in BMPR1B are associated with brachydactyly type A1. ( 25758993 )
2015
4
Prenatal diagnosis of a family affected by brachydactyly type A1 with a mutation in IHH: a useful lesson. ( 22406540 )
2012
5
Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels. ( 21537345 )
2011
6
Missense mutations in IHH impair Indian Hedgehog signaling in C3H10T1/2 cells: Implications for brachydactyly type A1, and new targets for Hedgehog signaling. ( 20024692 )
2010
7
Brachydactyly type A1 with short humerus and associated skeletal features. ( 21077205 )
2010
8
[Clinical investigation of a family with brachydactyly type A1 and the identification of the disease gene]. ( 19504437 )
2009
9
Retraction: Clinical features study of a brachydactyly type A1 family and the disease-causing gene location. ( 19806586 )
2009
10
Brachydactyly type A1 associated with unusual radiological findings and a novel Arg158Cys mutation in the Indian hedgehog (IHH) gene. ( 19464397 )
2009
11
Recurrence of the D100N mutation in a Chinese family with brachydactyly type A1: evidence for a mutational hot spot in the Indian hedgehog gene. ( 17486609 )
2007
12
A novel heterozygous mutation in the Indian hedgehog gene (IHH) is associated with brachydactyly type A1 in a Chinese family. ( 16871364 )
2006
13
Answering a century old riddle: brachydactyly type A1. ( 15225411 )
2004
14
Identification of a mutation in the Indian Hedgehog (IHH) gene causing brachydactyly type A1 and evidence for a third locus. ( 12525541 )
2003
15
Mild brachydactyly type A1 maps to chromosome 2q35-q36 and is caused by a novel IHH mutation in a three generation family. ( 12566523 )
2003
16
A novel locus for brachydactyly type A1 on chromosome 5p13.3-p13.2. ( 11897820 )
2002
17
A novel mutation in the IHH gene causes brachydactyly type A1: a 95- year-old mystery resolved. ( 12384778 )
2002
18
Clinical and radiological assessment of a family with mild brachydactyly type A1: the usefulness of metacarpophalangeal profiles. ( 10745048 )
2000
19
Brachydactyly type A1 with abnormal menisci and scoliosis in three generations. ( 9546827 )
1998

Variations for Brachydactyly, Type A1

UniProtKB/Swiss-Prot genetic disease variations for Brachydactyly, Type A1:

71
id Symbol AA change Variation ID SNP ID
1 IHH p.Glu95Lys VAR_015982 rs121917852
2 IHH p.Asp100Glu VAR_015983 rs121917854
3 IHH p.Asp100Asn VAR_015984 rs28936377
4 IHH p.Glu131Lys VAR_015985 rs121917853

ClinVar genetic disease variations for Brachydactyly, Type A1:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 IHH NM_002181.3(IHH): c.284A> G (p.Glu95Gly) single nucleotide variant Pathogenic rs121917859 GRCh37 Chromosome 2, 219924906: 219924906
2 IHH NM_002181.3(IHH): c.283G> A (p.Glu95Lys) single nucleotide variant Pathogenic rs121917852 GRCh37 Chromosome 2, 219924907: 219924907
3 IHH NM_002181.3(IHH): c.391G> A (p.Glu131Lys) single nucleotide variant Pathogenic rs121917853 GRCh37 Chromosome 2, 219922341: 219922341
4 IHH NM_002181.3(IHH): c.300C> A (p.Asp100Glu) single nucleotide variant Pathogenic rs121917854 GRCh37 Chromosome 2, 219924890: 219924890
5 IHH NM_002181.3(IHH): c.298G> A (p.Asp100Asn) single nucleotide variant Pathogenic rs121917855 GRCh37 Chromosome 2, 219924892: 219924892
6 IHH NM_002181.3(IHH): c.461C> T (p.Thr154Ile) single nucleotide variant Pathogenic rs121917861 GRCh37 Chromosome 2, 219922271: 219922271
7 IHH IHH, 3-BP DEL, 283GAG deletion Pathogenic
8 IHH NM_002181.3(IHH): c.383G> A (p.Arg128Gln) single nucleotide variant Pathogenic rs267606873 GRCh37 Chromosome 2, 219922349: 219922349
9 IHH NM_002181.3(IHH): c.389C> A (p.Thr130Asn) single nucleotide variant Pathogenic rs267606872 GRCh37 Chromosome 2, 219922343: 219922343
10 GNAS NM_001077488.3(GNAS): c.85C> T (p.Gln29Ter) single nucleotide variant Pathogenic rs1057518907 GRCh37 Chromosome 20, 57466866: 57466866

Expression for Brachydactyly, Type A1

Search GEO for disease gene expression data for Brachydactyly, Type A1.

Pathways for Brachydactyly, Type A1

Pathways related to Brachydactyly, Type A1 according to GeneCards Suite gene sharing:

(show all 13)
id Super pathways Score Top Affiliating Genes
1 12.27 GNAS PTCH1 SHH
2
Show member pathways
12.1 GNAS IHH PTCH1 SHH
3
Show member pathways
11.99 GNAS PTCH1 SHH
4 11.92 IHH PTCH1 SHH
5
Show member pathways
11.86 GNAS IHH PTCH1 SHH
6 11.82 BMPR1B PTCH1 SHH
7
Show member pathways
11.65 IHH PTCH1 SHH
8 11.45 BMPR1B GDF5
9 11.32 IHH PTCH1
10 11.16 GDF5 SHH
11
Show member pathways
10.61 IHH PTCH1 SHH
12 10.52 GNAS IHH PTCH1 SHH
13 10.22 PTCH1 SHH

GO Terms for Brachydactyly, Type A1

Biological processes related to Brachydactyly, Type A1 according to GeneCards Suite gene sharing:

(show all 46)
id Name GO ID Score Top Affiliating Genes
1 cell-cell signaling GO:0007267 9.85 GDF5 IHH SHH
2 skeletal system development GO:0001501 9.74 BMPR1B GNAS IHH
3 regulation of growth GO:0040008 9.7 IHH PTCH1
4 negative regulation of epithelial cell proliferation GO:0050680 9.69 GDF5 PTCH1
5 heart looping GO:0001947 9.69 IHH SHH
6 embryonic digit morphogenesis GO:0042733 9.69 IHH SHH
7 positive regulation of osteoblast differentiation GO:0045669 9.68 BMPR1B GNAS
8 cell development GO:0048468 9.68 GDF5 SHH
9 positive regulation of cell differentiation GO:0045597 9.68 BMPR1B SHH
10 skin development GO:0043588 9.67 GNAS SHH
11 branching involved in ureteric bud morphogenesis GO:0001658 9.67 PTCH1 SHH
12 chondrocyte differentiation GO:0002062 9.67 BMPR1B GDF5
13 embryonic organ development GO:0048568 9.66 PTCH1 SHH
14 developmental growth GO:0048589 9.66 GNAS SHH
15 branching involved in blood vessel morphogenesis GO:0001569 9.65 IHH SHH
16 positive regulation of mesenchymal cell proliferation GO:0002053 9.65 IHH SHH
17 embryonic hindlimb morphogenesis GO:0035116 9.65 GNAS SHH
18 smoothened signaling pathway GO:0007224 9.65 IHH PTCH1 SHH
19 embryonic pattern specification GO:0009880 9.64 IHH SHH
20 pancreas development GO:0031016 9.64 IHH SHH
21 positive regulation of smoothened signaling pathway GO:0045880 9.63 IHH SHH
22 limb morphogenesis GO:0035108 9.62 BMPR1B PTCH1
23 renal system development GO:0072001 9.62 PTCH1 SHH
24 spinal cord motor neuron differentiation GO:0021522 9.61 PTCH1 SHH
25 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007178 9.61 BMPR1B GDF5
26 embryonic digestive tract morphogenesis GO:0048557 9.6 IHH SHH
27 positive regulation of chondrocyte differentiation GO:0032332 9.59 BMPR1B GDF5
28 cell fate specification GO:0001708 9.58 IHH SHH
29 embryonic limb morphogenesis GO:0030326 9.58 GDF5 PTCH1 SHH
30 dorsal/ventral neural tube patterning GO:0021904 9.56 PTCH1 SHH
31 negative regulation of multicellular organism growth GO:0040015 9.55 GNAS PTCH1
32 hindlimb morphogenesis GO:0035137 9.54 GDF5 PTCH1
33 positive regulation of alpha-beta T cell differentiation GO:0046638 9.52 IHH SHH
34 positive regulation of T cell differentiation in thymus GO:0033089 9.51 IHH SHH
35 negative regulation of mesenchymal cell apoptotic process GO:2001054 9.49 GDF5 SHH
36 camera-type eye development GO:0043010 9.46 BMPR1B SHH
37 response to mechanical stimulus GO:0009612 9.43 GDF5 PTCH1
38 dorsal/ventral pattern formation GO:0009953 9.43 BMPR1B PTCH1 SHH
39 negative regulation of cell differentiation GO:0045596 9.39 SHH
40 pattern specification process GO:0007389 9.37 PTCH1 SHH
41 vasculature development GO:0001944 9.33 SHH
42 negative regulation of alpha-beta T cell differentiation GO:0046639 9.32 IHH SHH
43 prostate gland development GO:0030850 9.27 SHH
44 intein-mediated protein splicing GO:0016539 9.16 IHH SHH
45 somite development GO:0061053 9.13 IHH PTCH1 SHH
46 cartilage development GO:0051216 8.8 BMPR1B GDF5 GNAS

Molecular functions related to Brachydactyly, Type A1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 patched binding GO:0005113 8.8 IHH PTCH1 SHH

Sources for Brachydactyly, Type A1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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