TD2
MCID: THN010
MIFTS: 49

Thanatophoric Dysplasia, Type Ii (TD2) malady

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

Aliases & Classifications for Thanatophoric Dysplasia, Type Ii

Aliases & Descriptions for Thanatophoric Dysplasia, Type Ii:

Name: Thanatophoric Dysplasia, Type Ii 54 13
Cloverleaf Skull-Micromelic Bone Dysplasia Syndrome 50 56 29
Thanatophoric Dysplasia Type Ii 50 24 66
Td2 50 56 66
Thanatophoric Dwarfism-Cloverleaf Skull Syndrome 50 56
Thanatophoric Dysplasia with Kleeblattschaedel 50 66
Cloverleaf Skull with Thanatophoric Dwarfism 50 66
Thanatophoric Dysplasia Type 2 50 56
Thanatophoric Dwarfism Type 2 50 56
Thanatophoric Dysplasia 2 66 29
Thanatophoric Dysplasia with Straight Femurs and Cloverleaf Skull 66
Thanatophoric Dwarfism - Cloverleaf Skull 50
Tdii 24

Characteristics:

Orphanet epidemiological data:

56
thanatophoric dysplasia type 2
Inheritance: Autosomal dominant,Not applicable; Age of onset: Infancy,Neonatal; Age of death: early childhood;

HPO:

32
thanatophoric dysplasia, type ii:
Mortality/Aging neonatal death
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 54 187601
Orphanet 56 ORPHA93274
ICD10 via Orphanet 34 Q77.1
MedGen 40 C1300257
MeSH 42 D013796

Summaries for Thanatophoric Dysplasia, Type Ii

OMIM : 54 Thanatophoric dysplasia is a severe short-limb dwarfism syndrome that is usually lethal in the perinatal period. Norman... (187601) more...

MalaCards based summary : Thanatophoric Dysplasia, Type Ii, also known as cloverleaf skull-micromelic bone dysplasia syndrome, is related to thanatophoric dysplasia, type i and encephalocele, and has symptoms including seizures, macrocephaly and frontal bossing. An important gene associated with Thanatophoric Dysplasia, Type Ii is FGFR3 (Fibroblast Growth Factor Receptor 3), and among its related pathways/superpathways are Pathways in cancer and Negative regulation of FGFR1 signaling. The drugs Linagliptin and Benzocaine have been mentioned in the context of this disorder. Affiliated tissues include bone, lung and skin, and related phenotypes are digestive/alimentary and limbs/digits/tail

UniProtKB/Swiss-Prot : 66 Thanatophoric dysplasia 2: A neonatal lethal skeletal dysplasia causing severe shortening of the limbs, narrow thorax and short ribs. Patients with thanatophoric dysplasia type 2 have straight femurs and cloverleaf skull.

Related Diseases for Thanatophoric Dysplasia, Type Ii

Diseases in the Thanatophoric Dysplasia, Type I family:

Thanatophoric Dysplasia, Type Ii

Diseases related to Thanatophoric Dysplasia, Type Ii via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
id Related Disease Score Top Affiliating Genes
1 thanatophoric dysplasia, type i 10.8
2 encephalocele 10.0
3 muenke syndrome 9.9 FGFR3 STAT1
4 dwarfism 9.9
5 skeletal dysplasias 9.9
6 skeletal dysplasia 9.9
7 semilobar holoprosencephaly 9.9
8 achondroplasia 9.9
9 holoprosencephaly 9.9
10 hydrocephalus 9.9
11 choroiditis 9.9
12 huntington disease 9.5 FGFR3 SPRY2 STAT1

Graphical network of the top 20 diseases related to Thanatophoric Dysplasia, Type Ii:



Diseases related to Thanatophoric Dysplasia, Type Ii

Symptoms & Phenotypes for Thanatophoric Dysplasia, Type Ii

Symptoms by clinical synopsis from OMIM:

187601

Clinical features from OMIM:

187601

Human phenotypes related to Thanatophoric Dysplasia, Type Ii:

56 32 (show all 47)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 56 32 Frequent (79-30%) HP:0001250
2 macrocephaly 56 32 Very frequent (99-80%) HP:0000256
3 frontal bossing 56 32 Frequent (79-30%) HP:0002007
4 hydrocephalus 56 32 Occasional (29-5%) HP:0000238
5 muscular hypotonia 56 32 Very frequent (99-80%) HP:0001252
6 respiratory insufficiency 56 32 Very frequent (99-80%) HP:0002093
7 kyphosis 56 32 Frequent (79-30%) HP:0002808
8 hearing impairment 56 32 Frequent (79-30%) HP:0000365
9 skeletal dysplasia 56 32 Very frequent (99-80%) HP:0002652
10 depressed nasal bridge 56 32 Very frequent (99-80%) HP:0005280
11 short stature 56 32 Very frequent (99-80%) HP:0004322
12 cognitive impairment 56 32 Very frequent (99-80%) HP:0100543
13 acanthosis nigricans 56 32 Occasional (29-5%) HP:0000956
14 cloverleaf skull 56 32 Very frequent (99-80%) HP:0002676
15 abnormality of the metaphyses 56 32 Very frequent (99-80%) HP:0000944
16 narrow chest 56 32 Very frequent (99-80%) HP:0000774
17 platyspondyly 56 32 Very frequent (99-80%) HP:0000926
18 patent ductus arteriosus 56 32 Occasional (29-5%) HP:0001643
19 micromelia 56 32 Very frequent (99-80%) HP:0002983
20 joint hyperflexibility 56 32 Very frequent (99-80%) HP:0005692
21 limitation of joint mobility 56 32 Occasional (29-5%) HP:0001376
22 short thorax 56 32 Very frequent (99-80%) HP:0010306
23 flat face 56 32 Very frequent (99-80%) HP:0012368
24 ventriculomegaly 56 32 Frequent (79-30%) HP:0002119
25 abnormality of neuronal migration 56 32 Occasional (29-5%) HP:0002269
26 abnormality of the kidney 56 32 Occasional (29-5%) HP:0000077
27 brachydactyly syndrome 56 32 Very frequent (99-80%) HP:0001156
28 polyhydramnios 56 32 Frequent (79-30%) HP:0001561
29 redundant skin 56 32 Very frequent (99-80%) HP:0001582
30 increased nuchal translucency 56 32 Frequent (79-30%) HP:0010880
31 proptosis 56 32 Frequent (79-30%) HP:0000520
32 holoprosencephaly 56 32 Occasional (29-5%) HP:0001360
33 aplasia/hypoplasia of the lungs 56 32 Very frequent (99-80%) HP:0006703
34 encephalocele 56 32 Occasional (29-5%) HP:0002084
35 atria septal defect 56 Occasional (29-5%)
36 decreased fetal movement 32 HP:0001558
37 small abnormally formed scapulae 32 HP:0006584
38 small face 32 HP:0000274
39 hypoplastic ilia 32 HP:0000946
40 short sacroiliac notch 32 HP:0003185
41 lethal short-limbed short stature 32 HP:0008909
42 short ribs 32 HP:0000773
43 flared metaphysis 32 HP:0003015
44 metaphyseal irregularity 32 HP:0003025
45 atrial septal defect 32 HP:0001631
46 small foramen magnum 32 HP:0002677
47 wide-cupped costochondral junctions 32 HP:0000910

MGI Mouse Phenotypes related to Thanatophoric Dysplasia, Type Ii:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.43 STAT1 FGFR3 SPRY2
2 limbs/digits/tail MP:0005371 9.33 FGFR3 SPRY2 STAT1
3 neoplasm MP:0002006 9.13 FGFR3 SPRY2 STAT1
4 vision/eye MP:0005391 8.8 FGFR3 SPRY2 STAT1

Drugs & Therapeutics for Thanatophoric Dysplasia, Type Ii

Drugs for Thanatophoric Dysplasia, Type Ii (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 59)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Linagliptin Approved Phase 4 668270-12-0 10096344
2
Benzocaine Approved Phase 4 1994-09-7, 94-09-7 2337
3
Dopamine Approved Phase 4 51-61-6, 62-31-7 681
4
Olanzapine Approved, Investigational Phase 4 132539-06-1 4585
5 tannic acid Approved, Nutraceutical Phase 4
6 Dipeptidyl-Peptidase IV Inhibitors Phase 4
7 Glucagon-Like Peptide 1 Phase 4
8 HIV Protease Inhibitors Phase 4
9 Hormone Antagonists Phase 4
10 Hormones Phase 4
11 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 4
12 Hypoglycemic Agents Phase 4,Phase 2
13 Incretins Phase 4
14
protease inhibitors Phase 4
15 Antiemetics Phase 4
16 Antipsychotic Agents Phase 4
17 Autonomic Agents Phase 4,Phase 2
18 Central Nervous System Depressants Phase 4
19 Dopamine Agents Phase 4
20 Dopamine Antagonists Phase 4
21 Gastrointestinal Agents Phase 4
22 Neurotransmitter Agents Phase 4,Phase 2
23 Neurotransmitter Uptake Inhibitors Phase 4
24 Peripheral Nervous System Agents Phase 4,Phase 2
25 Psychotropic Drugs Phase 4
26
Serotonin Phase 4 50-67-9 5202
27 Serotonin Agents Phase 4
28 Serotonin Uptake Inhibitors Phase 4
29 sultopride Phase 4
30 Tranquilizing Agents Phase 4
31
Cisplatin Approved Phase 1, Phase 2 15663-27-1 84093 441203 2767
32
Gemcitabine Approved Phase 1, Phase 2 95058-81-4 60750
33
Paclitaxel Approved, Vet_approved Phase 1, Phase 2 33069-62-4 36314
34
Pancrelipase Approved Phase 1, Phase 2 53608-75-6
35
Glipizide Approved Phase 2 29094-61-9 3478
36
Metformin Approved Phase 2 657-24-9 14219 4091
37
Emtricitabine Approved, Investigational Phase 2 143491-57-0 60877
38
Nevirapine Approved Phase 2 129618-40-2 4463
39
Tenofovir Approved, Investigational Phase 2 147127-20-6 464205
40
Zidovudine Approved Phase 2 30516-87-1 35370
41
Nicotine Approved Phase 2 54-11-5 942 89594
42 Albumin-Bound Paclitaxel Phase 1, Phase 2
43 Anti-Infective Agents Phase 1, Phase 2
44 Antimetabolites Phase 1, Phase 2
45 Antimetabolites, Antineoplastic Phase 1, Phase 2
46 Antimitotic Agents Phase 1, Phase 2
47 Antineoplastic Agents, Phytogenic Phase 1, Phase 2
48 Antiviral Agents Phase 1, Phase 2
49 Immunosuppressive Agents Phase 1, Phase 2
50 pancreatin Phase 1, Phase 2

Interventional clinical trials:

(show all 12)
id Name Status NCT ID Phase
1 Effects of Linagliptin on Active GLP-1 Concentrations in Subjects With Renal Impairment Completed NCT01903070 Phase 4
2 Tardive Dyskinesia and Cognitive Function Completed NCT00926965 Phase 4
3 Study to Improve Quality of Care and Patient Health in the Field of Cardiovascular Risk Factors in General Practice Completed NCT00348855 Phase 4
4 Nab-Paclitaxel+Cisplatin+Gemcitabine in Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma (PDA) Unknown status NCT01893801 Phase 1, Phase 2
5 Evaluate Efficacy, Safety and Tolerability of AZD1656 as Add-on Treatment to Metformin in Type 2 Diabetes Mellitus (TD2M) Patients Completed NCT01020123 Phase 2
6 Maternal TDF and FTC to Reduce NNRTI Resistance Mutations After Intrapartum NVP Completed NCT00204308 Phase 2
7 Nicotine Patch Safety Study Completed NCT01655082 Phase 2
8 Study of Minnelide™ in Patients With Advanced GI Tumors Completed NCT01927965 Phase 1
9 A Study of TRK-950 in Patients With Advanced Solid Tumors Recruiting NCT02990481 Phase 1
10 A Phase I, Multicenter, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Minnelide™Capsules in Patients With Advanced Solid Tumors Not yet recruiting NCT03129139 Phase 1
11 Genetic Markers and Proliferative Diabetic Retinopathy Recruiting NCT02879422
12 HIIE and Abdominal Fat Mass in DT2 Postmenopausal Women Not yet recruiting NCT02352246

Search NIH Clinical Center for Thanatophoric Dysplasia, Type Ii

Genetic Tests for Thanatophoric Dysplasia, Type Ii

Genetic tests related to Thanatophoric Dysplasia, Type Ii:

id Genetic test Affiliating Genes
1 Thanatophoric Dysplasia, Type 2 29
2 Micromelic Bone Dysplasia with Cloverleaf Skull 29
3 Thanatophoric Dysplasia Type Ii 24 FGFR3

Anatomical Context for Thanatophoric Dysplasia, Type Ii

MalaCards organs/tissues related to Thanatophoric Dysplasia, Type Ii:

39
Bone, Lung, Skin, Kidney

Publications for Thanatophoric Dysplasia, Type Ii

Articles related to Thanatophoric Dysplasia, Type Ii:

(show all 11)
id Title Authors Year
1
Dysmorphic choroid plexuses and hydrocephalus associated with increased nuchal translucency: Early ultrasound markers of de novo thanatophoric dysplasia type II with cloverleaf skull (Kleeblattschaedel). ( 24517215 )
2014
2
Rapid detection of K650E mutation in FGFR3 using uncultured amniocytes in a pregnancy affected with fetal cloverleaf skull, occipital pseudoencephalocele, ventriculomegaly, straight short femurs, and thanatophoric dysplasia type II. ( 24075385 )
2013
3
Disruption of a Sox9-I^-catenin circuit by mutant Fgfr3 in thanatophoric dysplasia type II. ( 22843502 )
2012
4
Thanatophoric dysplasia type II with encephalocele and semilobar holoprosencephaly: Insights into its pathogenesis. ( 21204232 )
2011
5
Sprouty 2 disturbs FGFR3 degradation in thanatophoric dysplasia type II: a severe form of human achondroplasia. ( 18485666 )
2008
6
A central nervous system specific mouse model for thanatophoric dysplasia type II. ( 12966031 )
2003
7
Thanatophoric dysplasia type II with encephalocele and aortic hypoplasia diagnosed in an anatomical specimen. ( 12605444 )
2003
8
The thanatophoric dysplasia type II mutation hampers complete maturation of fibroblast growth factor receptor 3 (FGFR3), which activates signal transducer and activator of transcription 1 (STAT1) from the endoplasmic reticulum. ( 12624096 )
2003
9
Thanatophoric dysplasia type II: new entity? ( 9481651 )
1998
10
Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism. ( 9069288 )
1997
11
Profound ligand-independent kinase activation of fibroblast growth factor receptor 3 by the activation loop mutation responsible for a lethal skeletal dysplasia, thanatophoric dysplasia type II. ( 8754806 )
1996

Variations for Thanatophoric Dysplasia, Type Ii

UniProtKB/Swiss-Prot genetic disease variations for Thanatophoric Dysplasia, Type Ii:

66
id Symbol AA change Variation ID SNP ID
1 FGFR3 p.Lys650Glu VAR_004160 rs78311289

ClinVar genetic disease variations for Thanatophoric Dysplasia, Type Ii:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 FGFR3 NM_000142.4(FGFR3): c.1948A> G (p.Lys650Glu) single nucleotide variant Pathogenic/Likely pathogenic rs78311289 GRCh37 Chromosome 4, 1807889: 1807889

Expression for Thanatophoric Dysplasia, Type Ii

Search GEO for disease gene expression data for Thanatophoric Dysplasia, Type Ii.

Pathways for Thanatophoric Dysplasia, Type Ii

GO Terms for Thanatophoric Dysplasia, Type Ii

Biological processes related to Thanatophoric Dysplasia, Type Ii according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 positive regulation of ERK1 and ERK2 cascade GO:0070374 8.96 FGFR3 SPRY2
2 JAK-STAT cascade GO:0007259 8.62 FGFR3 STAT1

Sources for Thanatophoric Dysplasia, Type Ii

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 Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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