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 53 13
Td2 53 49 55 71
Thanatophoric Dysplasia with Kleeblattschaedel 53 49 71
Cloverleaf Skull with Thanatophoric Dwarfism 53 49 71
Thanatophoric Dysplasia with Straight Femurs and Cloverleaf Skull 53 71
Cloverleaf Skull-Micromelic Bone Dysplasia Syndrome 49 55
Thanatophoric Dwarfism-Cloverleaf Skull Syndrome 49 55
Thanatophoric Dysplasia Type Ii 49 71
Thanatophoric Dysplasia Type 2 49 55
Thanatophoric Dwarfism Type 2 49 55
Thanatophoric Dwarfism - Cloverleaf Skull 49
Thanatophoric Dysplasia, Type 2 28
Thanatophoric Dysplasia 2 71

Characteristics:

Orphanet epidemiological data:

55
thanatophoric dysplasia type 2
Inheritance: Autosomal dominant,Not applicable; Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
death in majority of infants soon after birth


HPO:

31
thanatophoric dysplasia, type ii:
Mortality/Aging neonatal death
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Thanatophoric Dysplasia, Type Ii

NIH Rare Diseases : 49 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 td2, is related to thanatophoric dysplasia, type i and blood group, i system, 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 Negative regulation of FGFR3 signaling and MicroRNAs in cancer. The drugs Linagliptin and Benzocaine 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 : 53 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 13)
# Related Disease Score Top Affiliating Genes
1 thanatophoric dysplasia, type i 29.9 FGFR3 STAT1
2 blood group, i system 10.3
3 kleeblattschaedel 10.1
4 encephalocele 10.1
5 achondroplasia 9.9
6 hydrocephalus, nonsyndromic, autosomal recessive 1 9.9
7 hydrocephalus, nonsyndromic, autosomal recessive 2 9.9
8 holoprosencephaly 9.9
9 hydrocephalus 9.9
10 choroiditis 9.9
11 dwarfism 9.9
12 skeletal dysplasias 9.9
13 semilobar holoprosencephaly 9.9

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:

53
Respiratory Lung:
respiratory insufficiency

Skeletal Hands:
brachydactyly

Head And Neck Face:
small face

Chest External Features:
narrow thorax

Growth Height:
dwarfism, lethal micromelic

Skeletal Pelvis:
short and small iliac bones
small sacroiliac notches

Prenatal Manifestations:
prenatal diagnosis by ultrasound

Skeletal Spine:
platyspondyly

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

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

Prenatal Manifestations Movement:
decreased fetal activity

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:

55 31 (show all 46)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 55 31 frequent (33%) Frequent (79-30%) HP:0001250
2 macrocephaly 55 31 hallmark (90%) Very frequent (99-80%) HP:0000256
3 frontal bossing 55 31 frequent (33%) Frequent (79-30%) HP:0002007
4 hydrocephalus 55 31 occasional (7.5%) Occasional (29-5%) HP:0000238
5 muscular hypotonia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001252
6 respiratory insufficiency 55 31 hallmark (90%) Very frequent (99-80%) HP:0002093
7 kyphosis 55 31 frequent (33%) Frequent (79-30%) HP:0002808
8 hearing impairment 55 31 frequent (33%) Frequent (79-30%) HP:0000365
9 skeletal dysplasia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002652
10 depressed nasal bridge 55 31 hallmark (90%) Very frequent (99-80%) HP:0005280
11 short stature 55 31 hallmark (90%) Very frequent (99-80%) HP:0004322
12 cognitive impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0100543
13 acanthosis nigricans 55 31 occasional (7.5%) Occasional (29-5%) HP:0000956
14 cloverleaf skull 55 31 hallmark (90%) Very frequent (99-80%) HP:0002676
15 abnormality of the metaphysis 55 31 hallmark (90%) Very frequent (99-80%) HP:0000944
16 narrow chest 55 31 hallmark (90%) Very frequent (99-80%) HP:0000774
17 platyspondyly 55 31 hallmark (90%) Very frequent (99-80%) HP:0000926
18 patent ductus arteriosus 55 31 occasional (7.5%) Occasional (29-5%) HP:0001643
19 micromelia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002983
20 joint hyperflexibility 55 31 hallmark (90%) Very frequent (99-80%) HP:0005692
21 limitation of joint mobility 55 31 occasional (7.5%) Occasional (29-5%) HP:0001376
22 short thorax 55 31 hallmark (90%) Very frequent (99-80%) HP:0010306
23 flat face 55 31 hallmark (90%) Very frequent (99-80%) HP:0012368
24 atrial septal defect 55 31 occasional (7.5%) Occasional (29-5%) HP:0001631
25 ventriculomegaly 55 31 frequent (33%) Frequent (79-30%) HP:0002119
26 abnormality of neuronal migration 55 31 occasional (7.5%) Occasional (29-5%) HP:0002269
27 abnormality of the kidney 55 31 occasional (7.5%) Occasional (29-5%) HP:0000077
28 brachydactyly 55 31 hallmark (90%) Very frequent (99-80%) HP:0001156
29 polyhydramnios 55 31 frequent (33%) Frequent (79-30%) HP:0001561
30 redundant skin 55 31 hallmark (90%) Very frequent (99-80%) HP:0001582
31 increased nuchal translucency 55 31 frequent (33%) Frequent (79-30%) HP:0010880
32 proptosis 55 31 frequent (33%) Frequent (79-30%) HP:0000520
33 holoprosencephaly 55 31 occasional (7.5%) Occasional (29-5%) HP:0001360
34 aplasia/hypoplasia of the lungs 55 31 hallmark (90%) Very frequent (99-80%) HP:0006703
35 encephalocele 55 31 occasional (7.5%) Occasional (29-5%) HP:0002084
36 decreased fetal movement 31 HP:0001558
37 small abnormally formed scapulae 31 HP:0006584
38 small face 31 HP:0000274
39 hypoplastic ilia 31 HP:0000946
40 short sacroiliac notch 31 HP:0003185
41 lethal short-limbed short stature 31 HP:0008909
42 short ribs 31 HP:0000773
43 flared metaphysis 31 HP:0003015
44 metaphyseal irregularity 31 HP:0003025
45 wide-cupped costochondral junctions 31 HP:0000910
46 small foramen magnum 31 HP:0002677

MGI Mouse Phenotypes related to Thanatophoric Dysplasia, Type Ii:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.5 SPRY2 STAT1 FGFR3
2 limbs/digits/tail MP:0005371 9.43 SPRY2 STAT1 FGFR3
3 neoplasm MP:0002006 9.33 SPRY2 STAT1 FGFR3
4 skeleton MP:0005390 9.13 SPRY2 STAT1 FGFR3
5 vision/eye MP:0005391 8.8 SPRY2 STAT1 FGFR3

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)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Linagliptin Approved Phase 4 668270-12-0 10096344
2
Benzocaine Approved, Investigational 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 2767 441203 84093
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, Investigational Phase 1, Phase 2 53608-75-6
35
Glipizide Approved, Investigational Phase 2 29094-61-9 3478
36
Metformin Approved Phase 2 657-24-9 4091 14219
37
Emtricitabine Approved, Investigational Phase 2 143491-57-0 60877
38
Nevirapine Approved Phase 2 129618-40-2 4463
39
Zidovudine Approved Phase 2 30516-87-1 35370
40
Nicotine Approved Phase 2 54-11-5 89594 942
41 Albumin-Bound Paclitaxel Phase 1, Phase 2
42 Anti-Infective Agents Phase 1, Phase 2
43 Antimetabolites Phase 1, Phase 2
44 Antimetabolites, Antineoplastic Phase 1, Phase 2
45 Antimitotic Agents Phase 1, Phase 2
46 Antineoplastic Agents, Phytogenic Phase 1, Phase 2
47 Antiviral Agents Phase 1, Phase 2
48 Immunosuppressive Agents Phase 1, Phase 2
49 pancreatin Phase 1, Phase 2
50 Anti-HIV Agents Phase 2

Interventional clinical trials:

(show all 14)

# 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 Evaluation of Ruxolitinib in Combination With PU-H71 for Treatment of Myelofibrosis Recruiting NCT03373877 Phase 1 PU-H71;Ruxolitinib
10 Phase 1 Clinical Trial of Metastasis Inhibitor NP-G2-044 in Patients With Advanced or Metastatic Solid Tumors (Including Lymphoma) 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 Recruiting NCT03129139 Phase 1 Minnelide™Capsules
12 A Study of TRK-950 in Patients With Advanced Solid Tumors Recruiting NCT02990481 Phase 1
13 HIIE and Abdominal Fat Mass in DT2 Postmenopausal Women Unknown status NCT02352246
14 Genetic Markers and Proliferative Diabetic Retinopathy Recruiting NCT02879422

Search NIH Clinical Center for Thanatophoric Dysplasia, Type Ii

Genetic Tests for Thanatophoric Dysplasia, Type Ii

Genetic tests related to Thanatophoric Dysplasia, Type Ii:

# Genetic test Affiliating Genes
1 Thanatophoric Dysplasia, Type 2 28 FGFR3

Anatomical Context for Thanatophoric Dysplasia, Type Ii

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

38
Bone, Brain, Spinal Cord, Lung, Skin, Kidney

Publications for Thanatophoric Dysplasia, Type Ii

Articles related to Thanatophoric Dysplasia, Type Ii:

(show all 11)
# 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
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
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
# Symbol AA change Variation ID SNP ID
1 FGFR3 p.Lys650Glu VAR_004160 rs78311289

ClinVar genetic disease variations for Thanatophoric Dysplasia, Type Ii:

6
# 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:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of ERK1 and ERK2 cascade GO:0070374 8.96 FGFR3 SPRY2
2 positive regulation of protein kinase B signaling GO:0051897 8.62 FGFR3 SPRY2

Sources for Thanatophoric Dysplasia, Type Ii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 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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