MCID: THN010
MIFTS: 51

Thanatophoric Dysplasia, Type Ii

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

Aliases & Classifications for Thanatophoric Dysplasia, Type Ii

MalaCards integrated aliases for Thanatophoric Dysplasia, Type Ii:

Name: Thanatophoric Dysplasia, Type Ii 54 13
Thanatophoric Dysplasia Type Ii 50 24 71
Td2 50 56 71
Cloverleaf Skull-Micromelic Bone Dysplasia Syndrome 50 56
Thanatophoric Dwarfism-Cloverleaf Skull Syndrome 50 56
Thanatophoric Dysplasia with Kleeblattschaedel 50 71
Cloverleaf Skull with Thanatophoric Dwarfism 50 71
Thanatophoric Dysplasia Type 2 50 56
Thanatophoric Dwarfism Type 2 50 56
Thanatophoric Dysplasia with Straight Femurs and Cloverleaf Skull 71
Micromelic Bone Dysplasia with Cloverleaf Skull 29
Thanatophoric Dwarfism - Cloverleaf Skull 50
Thanatophoric Dysplasia, Type 2 29
Thanatophoric Dysplasia 2 71
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;

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
death in majority of infants soon after birth


HPO:

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


Classifications:



Summaries for Thanatophoric Dysplasia, Type Ii

NIH Rare Diseases : 50 the following summary is from orphanet, a european reference portal for information on rare diseases and orphan drugs.orpha number: 93274disease definitionthanatophoric dysplasia, type 2 (td2) is a form of td (see this term) characterized by micromelia, straight long-bones, macrocephaly, brachydactyly, shortened ribs and a clover-leaf skull (kleeblattschaedel).epidemiologythe prevalence is unknown but it is less common than td1 (see this term).clinical descriptiontd2 presents in the prenatal period (in the first to second trimester) with micromelia, long-bones (femurs) that are straight and not as short as those seen in td type 1, platyspondyly of the vertebrae, narrow thorax, and a cloverleaf (trilobed) skull. distinctive facial features include macrocephaly, frontal bossing, low nasal bridge, large anterior fontanel and proptosis. polyhydramnios is common. neonates usually die shortly after birth due to respiratory insufficiency and/or spinal cord/brain stem compression.etiologytd2 is caused by a single missense mutation (k650e) in the fibroblast growth factor receptor 3 (fgfr3) gene, located to chromosome 4p16.3.genetic counselingtd2 is inherited autosomal dominantly but the majority of cases are due to a de novo mutation in the proband. genetic counseling allows families who have already had one child with td2 to know that recurrence rate is about 2%, so their chance of having a healthy child is high. expert reviewers: dr. michael bober and ms. angie dukervisit the orphanet disease page for more resources. last updated: 10/1/2013

MalaCards based summary : Thanatophoric Dysplasia, Type Ii, also known as thanatophoric dysplasia type ii, is related to thanatophoric dysplasia, type i and encephalocele, and has symptoms including short stature, ventriculomegaly and cognitive impairment. 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 Dopamine and Olanzapine have been mentioned in the context of this disorder. Affiliated tissues include bone, brain and spinal cord, and related phenotypes are digestive/alimentary and limbs/digits/tail

OMIM : 54
Thanatophoric dysplasia is a severe short-limb dwarfism syndrome that is usually lethal in the perinatal period. Norman et al. (1992) classified cases of TD into subtypes based on the presence of curved as opposed to straight femurs; patients with straight, relatively long femurs always had associated severe cloverleaf skull and were designated TD type II (TD2), whereas TD cases with curved, short femurs with or without cloverleaf skull were designated TD type I (TD1; 187600) (Langer et al., 1987). (187601)

UniProtKB/Swiss-Prot : 71 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 achondroplasia 9.9
4 holoprosencephaly 9.9
5 hydrocephalus 9.9
6 choroiditis 9.9
7 dwarfism 9.9
8 skeletal dysplasias 9.9
9 skeletal dysplasia 9.9
10 semilobar holoprosencephaly 9.9
11 crouzon syndrome with acanthosis nigricans 9.7 FGFR3 STAT1
12 saddan 8.6 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 via clinical synopsis from OMIM:

54

Skeletal- Hands:
brachydactyly

Prenatal Manifestations- Movement:
decreased fetal activity

Chest- Ribs Sternum Clavicles And Scapulae:
short ribs
wide-cupped costochondral junctions
small abnormally formed scapula

Chest- External Features:
narrow thorax

Head And Neck- Face:
small face

Skeletal- Pelvis:
short and small iliac bones
small sacroiliac notches

Prenatal Manifestations:
prenatal diagnosis by ultrasound

Skeletal- Spine:
platyspondyly

Prenatal Manifestations- Amniotic Fluid:
polyhydramnios

Respiratory- Lung:
respiratory insufficiency

Growth- Height:
dwarfism, lethal micromelic

Skeletal- Skull:
small foramen magnum
severe cloverleaf skull (kleeblattschaedel)

Skeletal- Limbs:
flared and irregular metaphyses
straight femurs

Head And Neck- Head:
clover leaf head


Clinical features from OMIM:

187601

Human phenotypes related to Thanatophoric Dysplasia, Type Ii:

56 32 (show all 49)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short stature 56 32 hallmark (90%) Very frequent (99-80%) HP:0004322
2 ventriculomegaly 56 32 frequent (33%) Frequent (79-30%) HP:0002119
3 cognitive impairment 56 32 hallmark (90%) Very frequent (99-80%) HP:0100543
4 seizures 56 32 frequent (33%) Frequent (79-30%) HP:0001250
5 hydrocephalus 56 32 occasional (7.5%) Occasional (29-5%) HP:0000238
6 depressed nasal bridge 56 32 hallmark (90%) Very frequent (99-80%) HP:0005280
7 proptosis 56 32 frequent (33%) Frequent (79-30%) HP:0000520
8 platyspondyly 56 32 hallmark (90%) Very frequent (99-80%) HP:0000926
9 kyphosis 56 32 frequent (33%) Frequent (79-30%) HP:0002808
10 patent ductus arteriosus 56 32 occasional (7.5%) Occasional (29-5%) HP:0001643
11 polyhydramnios 56 32 frequent (33%) Frequent (79-30%) HP:0001561
12 frontal bossing 56 32 frequent (33%) Frequent (79-30%) HP:0002007
13 narrow chest 56 32 hallmark (90%) Very frequent (99-80%) HP:0000774
14 macrocephaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0000256
15 respiratory insufficiency 56 32 hallmark (90%) Very frequent (99-80%) HP:0002093
16 flat face 56 32 hallmark (90%) Very frequent (99-80%) HP:0012368
17 joint hyperflexibility 56 32 hallmark (90%) Very frequent (99-80%) HP:0005692
18 holoprosencephaly 56 32 occasional (7.5%) Occasional (29-5%) HP:0001360
19 micromelia 56 32 hallmark (90%) Very frequent (99-80%) HP:0002983
20 muscular hypotonia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001252
21 acanthosis nigricans 56 32 occasional (7.5%) Occasional (29-5%) HP:0000956
22 encephalocele 56 32 occasional (7.5%) Occasional (29-5%) HP:0002084
23 skeletal dysplasia 56 32 hallmark (90%) Very frequent (99-80%) HP:0002652
24 redundant skin 56 32 hallmark (90%) Very frequent (99-80%) HP:0001582
25 hearing impairment 56 32 frequent (33%) Frequent (79-30%) HP:0000365
26 cloverleaf skull 56 32 hallmark (90%) Very frequent (99-80%) HP:0002676
27 short thorax 56 32 hallmark (90%) Very frequent (99-80%) HP:0010306
28 limitation of joint mobility 56 32 occasional (7.5%) Occasional (29-5%) HP:0001376
29 abnormality of neuronal migration 56 32 occasional (7.5%) Occasional (29-5%) HP:0002269
30 abnormality of the kidney 56 32 occasional (7.5%) Occasional (29-5%) HP:0000077
31 increased nuchal translucency 56 32 frequent (33%) Frequent (79-30%) HP:0010880
32 aplasia/hypoplasia of the lungs 56 32 hallmark (90%) Very frequent (99-80%) HP:0006703
33 brachydactyly 32 hallmark (90%) HP:0001156
34 atrial septal defect 32 occasional (7.5%) HP:0001631
35 short ribs 32 HP:0000773
36 hypoplastic ilia 32 HP:0000946
37 decreased fetal movement 32 HP:0001558
38 small face 32 HP:0000274
39 wide-cupped costochondral junctions 32 HP:0000910
40 small abnormally formed scapulae 32 HP:0006584
41 small foramen magnum 32 HP:0002677
42 metaphyseal irregularity 32 HP:0003025
43 abnormality of the metaphyses 56 Very frequent (99-80%)
44 atria septal defect 56 Occasional (29-5%)
45 brachydactyly syndrome 56 Very frequent (99-80%)
46 short sacroiliac notch 32 HP:0003185
47 lethal short-limbed short stature 32 HP:0008909
48 flared metaphysis 32 HP:0003015
49 abnormality of the metaphysis 32 hallmark (90%) HP:0000944

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 FGFR3 SPRY2 STAT1
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
Dopamine Approved Phase 4 51-61-6, 62-31-7 681
2
Olanzapine Approved, Investigational Phase 4 132539-06-1 4585
3
Benzocaine Approved Phase 4 1994-09-7, 94-09-7 2337
4
Linagliptin Approved Phase 4 668270-12-0 10096344
5 tannic acid Approved, Nutraceutical Phase 4
6 sultopride Phase 4
7
Serotonin Phase 4 50-67-9 5202
8
protease inhibitors Phase 4
9 Central Nervous System Depressants Phase 4
10 Serotonin Agents Phase 4
11 Serotonin Uptake Inhibitors Phase 4
12 Gastrointestinal Agents Phase 4
13 Glucagon-Like Peptide 1 Phase 4
14 Neurotransmitter Agents Phase 4,Phase 2
15 Neurotransmitter Uptake Inhibitors Phase 4
16 HIV Protease Inhibitors Phase 4
17 Hormone Antagonists Phase 4
18 Tranquilizing Agents Phase 4
19 Hormones Phase 4
20 Dipeptidyl-Peptidase IV Inhibitors Phase 4
21 Dopamine Agents Phase 4
22 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 4
23 Dopamine Antagonists Phase 4
24 Peripheral Nervous System Agents Phase 4,Phase 2
25 Hypoglycemic Agents Phase 4,Phase 2
26 Incretins Phase 4
27 Antiemetics Phase 4
28 Psychotropic Drugs Phase 4
29 Antipsychotic Agents Phase 4
30 Autonomic Agents Phase 4,Phase 2
31
Paclitaxel Approved, Vet_approved Phase 1, Phase 2 33069-62-4 36314
32
Cisplatin Approved Phase 1, Phase 2 15663-27-1 84093 441203 2767
33
Gemcitabine Approved Phase 1, Phase 2 95058-81-4 60750
34
Pancrelipase Approved Phase 1, Phase 2 53608-75-6
35
Nicotine Approved Phase 2 54-11-5 942 89594
36
Nevirapine Approved Phase 2 129618-40-2 4463
37
Zidovudine Approved Phase 2 30516-87-1 35370
38
Glipizide Approved Phase 2 29094-61-9 3478
39
Metformin Approved Phase 2 657-24-9 14219 4091
40
Emtricitabine Approved, Investigational Phase 2 143491-57-0 60877
41 pancreatin Phase 1, Phase 2
42 Albumin-Bound Paclitaxel Phase 1, Phase 2
43 Anti-Infective Agents Phase 1, Phase 2
44 Immunosuppressive Agents Phase 1, Phase 2
45 Antimetabolites Phase 1, Phase 2
46 Antimetabolites, Antineoplastic Phase 1, Phase 2
47 Antimitotic Agents Phase 1, Phase 2
48 Antineoplastic Agents, Phytogenic Phase 1, Phase 2
49 Antiviral Agents Phase 1, Phase 2
50
Tenofovir Phase 2 147127-20-6 464205

Interventional clinical trials:

(show all 13)

id Name Status NCT ID Phase Drugs
1 Effects of Linagliptin on Active GLP-1 Concentrations in Subjects With Renal Impairment Completed NCT01903070 Phase 4 Linagliptin
2 Tardive Dyskinesia and Cognitive Function Completed NCT00926965 Phase 4 amisulpride;Olanzapine;Conventional antipsychotics
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 nab-paclitaxel;Cisplatin;gemcitabine
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 AZD1656;Placebo;Glipizide
6 Maternal TDF and FTC to Reduce NNRTI Resistance Mutations After Intrapartum NVP Completed NCT00204308 Phase 2 Combination tenofovir-emtricitabine
7 Nicotine Patch Safety Study Completed NCT01655082 Phase 2 V0116 transdermal patch;Nicotine transdermal patch
8 Study of Minnelide™ in Patients With Advanced GI Tumors Completed NCT01927965 Phase 1 Minnelide™ 001
9 A Study of TRK-950 in Patients With Advanced Solid Tumors Recruiting NCT02990481 Phase 1
10 Phase 1 Clinical Trial of Metastasis Inhibitor NP-G2-044 in Patients With Advanced or Metastatic Solid Tumors (Including Lymphoma) Not yet recruiting NCT03199586 Phase 1 NP-G2-044
11 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 Minnelide™Capsules
12 Genetic Markers and Proliferative Diabetic Retinopathy Recruiting NCT02879422
13 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, Brain, Spinal Cord, Lung, Kidney, Skin

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
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
7
A central nervous system specific mouse model for thanatophoric dysplasia type II. ( 12966031 )
2003
8
Thanatophoric dysplasia type II with encephalocele and aortic hypoplasia diagnosed in an anatomical specimen. ( 12605444 )
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:

71
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 HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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