THYP
MCID: TBH001
MIFTS: 47

Tibia, Hypoplasia or Aplasia of, with Polydactyly (THYP)

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

Aliases & Classifications for Tibia, Hypoplasia or Aplasia of, with Polydactyly

MalaCards integrated aliases for Tibia, Hypoplasia or Aplasia of, with Polydactyly:

Name: Tibia, Hypoplasia or Aplasia of, with Polydactyly 56 73 29 6
Hypoplastic or Aplastic Tibia with Polydactyly 56 12 73 15
Absence of Tibia with Polydactyly 12 52 43
Werner Mesomelic Syndrome 12 58 73
Tibial Hemimelia-Polydactyly-Triphalangeal Thumbs with Fibular Dimelia 56 73
Tibial Hemimelia-Polysyndactyly-Triphalangeal Thumb Syndrome 12 58
Hypoplastic Tibiae-Postaxial Polydactyly Syndrome 12 58
Absent Tibia-Polydactyly Syndrome 12 58
Thyp 56 73
Tibia, Hypoplastic or Aplastic, with Polydactyly 39
Hypoplasia or Aplasia of Tibia with Polydactyly 73
Hypoplastic Tibia-Polydactyly Syndrome 58
Tibia, Hypoplasia of, with Polydactyly 71
Polydactyly with Absent Tibia 52
Wms 73

Characteristics:

Orphanet epidemiological data:

58
hypoplastic tibiae-postaxial polydactyly syndrome
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal dominant


HPO:

31
tibia, hypoplasia or aplasia of, with polydactyly:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0111564
OMIM 56 188740
MESH via Orphanet 44 C535564
ICD10 via Orphanet 33 Q74.8 Q87.2
UMLS via Orphanet 72 C1861099
Orphanet 58 ORPHA3332 ORPHA988
UMLS 71 C1861098 C1861099

Summaries for Tibia, Hypoplasia or Aplasia of, with Polydactyly

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 988 Definition Tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome is a rare, genetic dysostosis syndrome, with marked inter- and intra-familial variation, typically characterized by triphalangeal thumbs, hand and/or foot polysyndactyly and/or absent/hypoplastic tibiae (associated with duplication of fibulae in some cases), although isolated triphalangeal thumbs have also been reported. It is often accompanied with remarkable short stature and additional features may include radio-ulnar synostosis and hand oligodactyly, as well as abnormal carpal and metatarsal bones. Visit the Orphanet disease page for more resources.

MalaCards based summary : Tibia, Hypoplasia or Aplasia of, with Polydactyly, also known as hypoplastic or aplastic tibia with polydactyly, is related to tibial hemimelia and hemimelia. An important gene associated with Tibia, Hypoplasia or Aplasia of, with Polydactyly is LMBR1 (Limb Development Membrane Protein 1), and among its related pathways/superpathways are Pathways in cancer and Translation Non-genomic (rapid) action of Androgen Receptor. The drugs Trimetazidine and Vasodilator Agents have been mentioned in the context of this disorder. Affiliated tissues include bone and heart, and related phenotypes are bowing of the long bones and short stature

Disease Ontology : 12 A syndrome characterized by preaxial polydactyly of the hands and feet and hypoplasia or aplasia of the tibia that has material basis in heterozygous mutation in the SHH regulatory region (ZRS) located in intron 5 of LMBR1 on chromosome 7q36.3.

UniProtKB/Swiss-Prot : 73 Hypoplasia or aplasia of tibia with polydactyly: An autosomal dominant disease characterized by hypoplastic or absent tibia, and polydactyly.

More information from OMIM: 188740

Related Diseases for Tibia, Hypoplasia or Aplasia of, with Polydactyly

Diseases related to Tibia, Hypoplasia or Aplasia of, with Polydactyly via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 106)
# Related Disease Score Top Affiliating Genes
1 tibial hemimelia 33.5 ZRS GLI3
2 hemimelia 31.4 ZRS GLI3
3 synostosis 30.5 SHH LMBR1 HOXD13 GLI3
4 syndactyly, type iv 30.2 ZRS SHH LMBR1
5 polydactyly, preaxial ii 30.2 ZRS SHH LMBR1
6 chromosome 2q35 duplication syndrome 29.6 ZP2 SHH LMBR1 HOXD9 HOXD13 HOXD12
7 polydactyly 29.2 ZRS SHH LMBR1 HOXD13 GLI3
8 waldenstroem's macroglobulinemia 12.2
9 hypoplasia of the tibia with polydactyly 12.1
10 lymphoplasmacytic lymphoma 12.0
11 weill-marchesani syndrome 12.0
12 femur bifid with monodactylous ectrodactyly 11.6
13 williams-beuren syndrome 11.5
14 macroglobulinemia, waldenstrom 1 11.5
15 microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma 11.2
16 weill-marchesani syndrome 2 11.2
17 weill-marchesani syndrome 3 11.2
18 polydactyly, preaxial iii 10.6
19 radioulnar synostosis 10.6
20 macroglobulinemia 10.6
21 temporal lobe epilepsy 10.4
22 traumatic brain injury 10.4
23 radial hemimelia 10.3 SHH LMBR1
24 mesomelia 10.3 ZRS LMBR1
25 nephrotic syndrome 10.3
26 monoclonal gammopathy of uncertain significance 10.2
27 split-foot deformity with mandibulofacial dysostosis 10.2
28 holoprosencephaly 3 10.1 ZRS SHH LMBR1
29 lymphoma 10.1
30 amnestic disorder 10.1
31 alcohol use disorder 10.1
32 glomerulonephritis 10.1
33 substance abuse 10.1
34 47,xyy 10.1
35 brain injury 10.1
36 head injury 10.1
37 brachydactyly, type e1 10.1 HOXD13 HOXD12
38 brachydactyly, type d 10.1 HOXD13 HOXD12
39 culler-jones syndrome 10.1 SHH GLI3
40 fibular aplasia or hypoplasia, femoral bowing and poly-, syn-, and oligodactyly 10.0 WNT7A LMBR1
41 vacterl association 10.0 SHH HOXD13
42 amyotrophic lateral sclerosis 1 10.0
43 exudative vitreoretinopathy 1 10.0
44 huntington disease 10.0
45 renal cell carcinoma, nonpapillary 10.0
46 strabismus 10.0
47 autism 10.0
48 lymphoma, hodgkin, classic 10.0
49 wilson disease 10.0
50 anemia, x-linked, with or without neutropenia and/or platelet abnormalities 10.0

Graphical network of the top 20 diseases related to Tibia, Hypoplasia or Aplasia of, with Polydactyly:



Diseases related to Tibia, Hypoplasia or Aplasia of, with Polydactyly

Symptoms & Phenotypes for Tibia, Hypoplasia or Aplasia of, with Polydactyly

Human phenotypes related to Tibia, Hypoplasia or Aplasia of, with Polydactyly:

58 31 (show all 21)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 bowing of the long bones 58 31 hallmark (90%) Very frequent (99-80%) HP:0006487
2 short stature 58 31 occasional (7.5%) Very frequent (99-80%),Occasional (29-5%) HP:0004322
3 clinodactyly of the 5th finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0004209
4 finger syndactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0006101
5 postaxial hand polydactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001162
6 patellar aplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0006443
7 short tibia 58 31 hallmark (90%) Very frequent (99-80%) HP:0005736
8 abnormality of fibula morphology 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0002991
9 aplasia/hypoplasia of the tibia 58 31 hallmark (90%) Very frequent (99-80%) HP:0005772
10 fibular duplication 58 31 hallmark (90%) Very frequent (99-80%) HP:0010503
11 increased fibular diameter 58 31 hallmark (90%) Very frequent (99-80%) HP:0012107
12 preaxial hand polydactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001177
13 synostosis of carpal bones 58 31 frequent (33%) Frequent (79-30%) HP:0005048
14 aplasia/hypoplasia of the thumb 58 31 occasional (7.5%) Frequent (79-30%),Occasional (29-5%) HP:0009601
15 camptodactyly of finger 58 31 occasional (7.5%) Occasional (29-5%) HP:0100490
16 limitation of joint mobility 58 31 occasional (7.5%) Occasional (29-5%) HP:0001376
17 triphalangeal thumb 58 31 occasional (7.5%) Occasional (29-5%) HP:0001199
18 depressed nasal tip 58 31 occasional (7.5%) Occasional (29-5%) HP:0000437
19 abnormal heart morphology 31 HP:0001627
20 absent tibia 31 HP:0009556
21 polydactyly 31 HP:0010442

Symptoms via clinical synopsis from OMIM:

56
Limbs:
absent tibia
polydactyly

Cardiac:
congenital heart defect

Clinical features from OMIM:

188740

MGI Mouse Phenotypes related to Tibia, Hypoplasia or Aplasia of, with Polydactyly:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.87 ETS1 GLI3 HAND2 HOXD13 SHH WNT7A
2 endocrine/exocrine gland MP:0005379 9.86 ETS1 GLI3 HAND2 HOXD13 HOXD9 SHH
3 limbs/digits/tail MP:0005371 9.76 GLI3 HAND2 HOXD12 HOXD13 HOXD9 LMBR1
4 reproductive system MP:0005389 9.5 GLI3 HOXD12 HOXD13 HOXD9 SHH WNT7A
5 skeleton MP:0005390 9.23 GLI3 HAND2 HOXD12 HOXD13 HOXD9 LMBR1

Drugs & Therapeutics for Tibia, Hypoplasia or Aplasia of, with Polydactyly

Drugs for Tibia, Hypoplasia or Aplasia of, with Polydactyly (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Trimetazidine Approved, Investigational Phase 4 5011-34-7
2 Vasodilator Agents Phase 4

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 The Study to Assess the Effect of Trimetazidine on Index of Microcirculatory Resistance (IMR), Measured by Coronary Pressure and Temperature Wire, in Patients With Stable Coronary Artery Disease Unknown status NCT02107144 Phase 4 trimetazidine

Search NIH Clinical Center for Tibia, Hypoplasia or Aplasia of, with Polydactyly

Cochrane evidence based reviews: absence of tibia with polydactyly

Genetic Tests for Tibia, Hypoplasia or Aplasia of, with Polydactyly

Genetic tests related to Tibia, Hypoplasia or Aplasia of, with Polydactyly:

# Genetic test Affiliating Genes
1 Tibia, Hypoplasia or Aplasia of, with Polydactyly 29 LMBR1

Anatomical Context for Tibia, Hypoplasia or Aplasia of, with Polydactyly

MalaCards organs/tissues related to Tibia, Hypoplasia or Aplasia of, with Polydactyly:

40
Bone, Heart

Publications for Tibia, Hypoplasia or Aplasia of, with Polydactyly

Articles related to Tibia, Hypoplasia or Aplasia of, with Polydactyly:

(show all 23)
# Title Authors PMID Year
1
A novel ZRS mutation leads to preaxial polydactyly type 2 in a heterozygous form and Werner mesomelic syndrome in a homozygous form. 6 56 61
24777739 2014
2
ZRS 406A>G mutation in patients with tibial hypoplasia, polydactyly and triphalangeal first fingers. 56 6 61
24965254 2014
3
A specific mutation in the distant sonic hedgehog (SHH) cis-regulator (ZRS) causes Werner mesomelic syndrome (WMS) while complete ZRS duplications underlie Haas type polysyndactyly and preaxial polydactyly (PPD) with or without triphalangeal thumb. 6 56 61
19847792 2010
4
A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. 6 56
12837695 2003
5
Clinical and genetic studies on 12 preaxial polydactyly families and refinement of the localisation of the gene responsible to a 1.9 cM region on chromosome 7q36. 56 6
9950363 1999
6
Absent tibiae--polydactyly--triphalangeal thumbs with fibular dimelia: variable expression of the Werner (McKusick 188770) syndrome? 6 56
7726219 1995
7
Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly. 6
18156157 2008
8
Werner mesomelic dysplasia with Hirschsprung disease. 56
14598345 2003
9
Are triphalangeal thumb-polysyndactyly syndrome (TPTPS) and tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome (THPTTS) identical? A father with TPTPS and his daughter with THPTTS in a Thai family. 56
10869115 2000
10
A hereditable combination of congenital anomalies. 56
8636194 1996
11
Autosomal dominant tibial hemimelia-polysyndactyly-triphalangeal thumbs syndrome: report of a Brazilian family. 56
2333896 1990
12
Hypoplastic tibiae with postaxial polysyndactyly: a new dominant syndrome? 56
3039141 1987
13
Congenital absence of the tibiae and thumbs with polydactyly. A rare genetic disease (Werner's syndrome). 56
3495233 1986
14
Absent tibiae, triphalangeal thumbs and polydactyly: description of a family and prenatal diagnosis. 56
6705252 1984
15
Werner's mesomelic dysplasia with ventricular septal defect and Hirschsprung's disease. 56
7254925 1981
16
A syndrome of polydactyly-syndactyly and triphalangeal thumbs in three generations. 56
4372010 1974
17
Apparent congenital absence of the tibia with lethal congenital cardiac disease. 56
5129538 1971
18
Bilateral aplasia of the tibia, polydactyly and absent thumb in father and daughter. 56
5562375 1971
19
[Agenesia of the tibia, duplication of the fibula and mirror foot (diplopodia) in mother and child]. 56
5096741 1971
20
[An uncommon bone syndrome, associating heptadactylia with tibial aplasia]. 56
5710710 1968
21
BILATERAL ABSENCE OF THE RADIUS AND TIBIA WITH BILATERAL REDUPLICATION OF THE ULNA AND FIBULA. A CASE REPORT. 56
14104303 1964
22
A novel 13 base pair insertion in the sonic hedgehog ZRS limb enhancer (ZRS/LMBR1) causes preaxial polydactyly with triphalangeal thumb. 61
22495965 2012
23
Identification of two novel mutations in Shh long-range regulator associated with familial pre-axial polydactyly. 61
20569257 2011

Variations for Tibia, Hypoplasia or Aplasia of, with Polydactyly

ClinVar genetic disease variations for Tibia, Hypoplasia or Aplasia of, with Polydactyly:

6 ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 LMBR1 NM_022458.4(LMBR1):c.423+4917G>ASNV Pathogenic 4898 rs606231147 7:156584166-156584166 7:156791472-156791472
2 LMBR1 NM_022458.4(LMBR1):c.423+4915C>TSNV Pathogenic 126371 rs587779752 7:156584168-156584168 7:156791474-156791474
3 LMBR1 LMBR1, 404G-CSNV Pathogenic 155921
4 LMBR1 LMBR1, 406A-GSNV Pathogenic 155923

Expression for Tibia, Hypoplasia or Aplasia of, with Polydactyly

Search GEO for disease gene expression data for Tibia, Hypoplasia or Aplasia of, with Polydactyly.

Pathways for Tibia, Hypoplasia or Aplasia of, with Polydactyly

Pathways related to Tibia, Hypoplasia or Aplasia of, with Polydactyly according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 12.18 WNT7A SHH GLI3 ETS1
2
Show member pathways
11.75 WNT7A SHH GLI3
3 10.97 SHH GLI3
4
Show member pathways
10.23 SHH GLI3
5 9.58 SHH GLI3

GO Terms for Tibia, Hypoplasia or Aplasia of, with Polydactyly

Cellular components related to Tibia, Hypoplasia or Aplasia of, with Polydactyly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcription factor complex GO:0005667 9.13 HOXD12 HAND2 ETS1
2 nuclear chromatin GO:0000790 9.02 HOXD9 HOXD13 HOXD12 HAND2 ETS1

Biological processes related to Tibia, Hypoplasia or Aplasia of, with Polydactyly according to GeneCards Suite gene sharing:

(show all 47)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 10.11 SHH HOXD9 HOXD13 HOXD12 HAND2 GLI3
2 multicellular organism development GO:0007275 10.08 WNT7A SHH HOXD9 HOXD13 HOXD12 HAND2
3 positive regulation of transcription, DNA-templated GO:0045893 9.99 WNT7A SHH HAND2 GLI3 ETS1
4 negative regulation of apoptotic process GO:0043066 9.98 WNT7A SHH HAND2 GLI3
5 positive regulation of gene expression GO:0010628 9.96 WNT7A SHH HAND2 ETS1
6 positive regulation of transcription by RNA polymerase II GO:0045944 9.91 WNT7A SHH HOXD9 HOXD13 HAND2 GLI3
7 regulation of cell proliferation GO:0042127 9.86 WNT7A SHH HOXD13 GLI3
8 roof of mouth development GO:0060021 9.75 SHH HAND2 GLI3
9 odontogenesis of dentin-containing tooth GO:0042475 9.72 SHH HAND2 GLI3
10 embryonic skeletal system development GO:0048706 9.7 SHH HOXD9
11 branching involved in ureteric bud morphogenesis GO:0001658 9.7 SHH GLI3
12 positive regulation of protein import into nucleus GO:0042307 9.7 SHH GLI3
13 establishment of cell polarity GO:0030010 9.69 WNT7A SHH
14 metanephros development GO:0001656 9.69 SHH GLI3
15 oligodendrocyte differentiation GO:0048709 9.69 SHH GLI3
16 T cell differentiation in thymus GO:0033077 9.68 SHH GLI3
17 mammary gland development GO:0030879 9.68 HOXD9 GLI3
18 neuron fate commitment GO:0048663 9.68 SHH GLI3
19 developmental growth GO:0048589 9.67 SHH GLI3
20 embryonic hindlimb morphogenesis GO:0035116 9.67 WNT7A SHH
21 branching morphogenesis of an epithelial tube GO:0048754 9.67 SHH GLI3
22 proximal/distal pattern formation GO:0009954 9.66 HOXD9 GLI3
23 limb morphogenesis GO:0035108 9.65 HOXD13 GLI3
24 spinal cord motor neuron differentiation GO:0021522 9.65 SHH GLI3
25 positive regulation of neuroblast proliferation GO:0002052 9.65 SHH GLI3
26 limb development GO:0060173 9.65 WNT7A SHH GLI3
27 embryonic morphogenesis GO:0048598 9.64 SHH GLI3
28 male genitalia development GO:0030539 9.64 SHH HOXD13
29 anatomical structure formation involved in morphogenesis GO:0048646 9.63 SHH GLI3
30 embryonic digestive tract morphogenesis GO:0048557 9.63 SHH GLI3
31 dorsal/ventral pattern formation GO:0009953 9.63 WNT7A SHH GLI3
32 tongue development GO:0043586 9.62 HAND2 GLI3
33 peripheral nervous system neuron development GO:0048935 9.62 HOXD9 HAND2
34 anterior/posterior pattern specification GO:0009952 9.62 SHH HOXD9 HOXD13 GLI3
35 negative thymic T cell selection GO:0045060 9.61 SHH GLI3
36 positive regulation of alpha-beta T cell differentiation GO:0046638 9.6 SHH GLI3
37 artery development GO:0060840 9.58 SHH GLI3
38 embryonic forelimb morphogenesis GO:0035115 9.58 WNT7A SHH HOXD9
39 stem cell development GO:0048864 9.54 WNT7A SHH
40 spinal cord dorsal/ventral patterning GO:0021513 9.52 SHH GLI3
41 mesenchymal cell proliferation GO:0010463 9.51 SHH HAND2
42 hindgut morphogenesis GO:0007442 9.49 SHH GLI3
43 pattern specification process GO:0007389 9.46 SHH HOXD13 HOXD12 GLI3
44 negative regulation of alpha-beta T cell differentiation GO:0046639 9.43 SHH GLI3
45 prostate gland development GO:0030850 9.43 SHH HOXD13 GLI3
46 embryonic limb morphogenesis GO:0030326 9.26 WNT7A SHH HOXD13 GLI3
47 embryonic digit morphogenesis GO:0042733 9.17 WNT7A SHH LMBR1 HOXD13 HOXD12 HAND2

Molecular functions related to Tibia, Hypoplasia or Aplasia of, with Polydactyly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.43 HOXD9 HOXD13 HOXD12 HAND2 GLI3 ETS1
2 histone acetyltransferase binding GO:0035035 9.26 GLI3 ETS1
3 sequence-specific double-stranded DNA binding GO:1990837 9.16 HOXD13 ETS1
4 sequence-specific DNA binding GO:0043565 9.1 HOXD9 HOXD13 HOXD12 HAND2 GLI3 ETS1

Sources for Tibia, Hypoplasia or Aplasia of, with Polydactyly

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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