MCID: THN010
MIFTS: 46

Thanatophoric Dysplasia, Type Ii malady

Genetic diseases, Rare diseases, Bone diseases, Fetal diseases categories

Summaries for Thanatophoric Dysplasia, Type Ii

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OMIM:45 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 thanatophoric dysplasia type ii, is related to dwarfism and thanatophoric dysplasia, type i, and has symptoms including macrocephaly, malar flattening and narrow chest. An important gene associated with Thanatophoric Dysplasia, Type Ii is FGFR3 (fibroblast growth factor receptor 3), and among its related pathways are PI-3K cascade and Endochondral Ossification. The compounds imatinib and phenylalanine have been mentioned in the context of this disorder. Affiliated tissues include bone, lung and skin, and related mouse phenotypes are limbs/digits/tail and vision/eye.

Aliases & Classifications for Thanatophoric Dysplasia, Type Ii

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Sources:
45OMIM, 10diseasecard, 63Wikipedia, 41NIH Rare Diseases, 20GeneTests, 47Orphanet, 22GTR, 60UMLS, 26ICD10 via Orphanet
See all sources

Thanatophoric Dysplasia, Type Ii, Aliases & Descriptions:

Name: Thanatophoric Dysplasia, Type Ii 45 10
Thanatophoric Dysplasia Type Ii 41 20 22
Thanatophoric Dysplasia Type 2 63 41 47
Cloverleaf Skull with Thanatophoric Dwarfism 63 41
Td2 41 47
Thanatophoric Dysplasia with Kleeblattschaedel 41
 
Td with Straight Femurs and Cloverleaf Skull 63
Cloverleaf Skull - Micromelic Bone Dysplasia 47
Thanatophoric Dwarfism - Cloverleaf Skull 47
Thanatophoric Dysplasia, Type 2 60
Thanatophoric Dwarfism Type 2 47


Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Rare diseases, Fetal diseases
Anatomical: Bone diseases


Characteristics (Orphanet epidemiological data):

47
thanatophoric dysplasia type 2:
Inheritance: Autosomal dominant,Not applicable; Age of onset: Infancy,Neonatal; Age of death: early childhood


External Ids:

OMIM45 187601
Orphanet47 93274
ICD10 via Orphanet26 Q77.1

Related Diseases for Thanatophoric Dysplasia, Type Ii

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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 14)
idRelated DiseaseScoreTop Affiliating Genes
1dwarfism30.4FGFR3, STAT1
2thanatophoric dysplasia, type i30.1FGFR3, STAT1
3encephalocele10.5
4micromelic bone dysplasia with cloverleaf skull10.4
5achondroplasia10.3
6holoprosencephaly10.3
7hydrocephalus10.3
8choroiditis10.3
9skeletal dysplasias10.3
10semilobar holoprosencephaly10.3
11agenesis of the corpus callosum10.3
12skeletal dysplasia multi-gene panels10.0FGFR3, STAT1
13myeloma10.0FGFR3, STAT1
14cervical cancer, somatic9.8FGFR3, STAT1

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



Diseases related to thanatophoric dysplasia, type ii

Symptoms for Thanatophoric Dysplasia, Type Ii

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Symptoms by clinical synopsis from OMIM:

187601

Clinical features from OMIM:

187601

Symptoms:

 47 (show all 36)
  • macrocephaly/macrocrania/megalocephaly/megacephaly
  • cloverleaf skull
  • flat face
  • depressed nasal bridge
  • narrow rib cage/thorax
  • short rib cage/thorax
  • platyspondyly
  • rhizomelic micromelia
  • short hand/brachydactyly
  • loose skin/skin relaxation/excess skin/creases
  • hypoplastic lungs/pulmonary hypoplasia/agenesis
  • respiratory distress/dyspnea/respiratory failure/lung volume reduction
  • hypotonia
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • dysostosis/chondrodysplasia/osteodysplasia/osteochondrosis/skeletal dysplasia
  • metaphyseal anomaly
  • autosomal dominant inheritance
  • short stature/dwarfism/nanism
  • stillbirth/neonatal death
  • frontal bossing/prominent forehead
  • proptosis/exophthalmos
  • hearing loss/hypoacusia/deafness
  • kyphosis
  • dilated cerebral ventricles without hydrocephaly
  • seizures/epilepsy/absences/spasms/status epilepticus
  • increased nuchal translucency
  • polyhydramnios
  • acanthosis nigricans
  • atrial septal defect/interauricular communication
  • patent ductus arteriosus
  • renal/kidney anomalies
  • encephalocele/exencephaly
  • holoprosencephaly/arhinencephaly/unique lateral ventricle
  • hydrocephaly
  • agyria/micro/pachy/macrogyria/lissencephaly/gyration/neuronal migration defect
  • restricted joint mobility/joint stiffness/ankylosis

HPO human phenotypes related to Thanatophoric Dysplasia, Type Ii:

(show all 51)
id Description Frequency HPO Source Accession
1 macrocephaly hallmark (90%) HP:0000256
2 malar flattening hallmark (90%) HP:0000272
3 narrow chest hallmark (90%) HP:0000774
4 platyspondyly hallmark (90%) HP:0000926
5 abnormality of the metaphyses hallmark (90%) HP:0000944
6 cutis laxa hallmark (90%) HP:0000973
7 brachydactyly syndrome hallmark (90%) HP:0001156
8 muscular hypotonia hallmark (90%) HP:0001252
9 respiratory insufficiency hallmark (90%) HP:0002093
10 skeletal dysplasia hallmark (90%) HP:0002652
11 cloverleaf skull hallmark (90%) HP:0002676
12 short stature hallmark (90%) HP:0004322
13 depressed nasal bridge hallmark (90%) HP:0005280
14 aplasia/hypoplasia of the lungs hallmark (90%) HP:0006703
15 limb undergrowth hallmark (90%) HP:0009826
16 short thorax hallmark (90%) HP:0010306
17 cognitive impairment hallmark (90%) HP:0100543
18 hearing impairment typical (50%) HP:0000365
19 proptosis typical (50%) HP:0000520
20 seizures typical (50%) HP:0001250
21 polyhydramnios typical (50%) HP:0001561
22 frontal bossing typical (50%) HP:0002007
23 ventriculomegaly typical (50%) HP:0002119
24 kyphosis typical (50%) HP:0002808
25 increased nuchal translucency typical (50%) HP:0010880
26 abnormality of the kidney occasional (7.5%) HP:0000077
27 hydrocephalus occasional (7.5%) HP:0000238
28 acanthosis nigricans occasional (7.5%) HP:0000956
29 holoprosencephaly occasional (7.5%) HP:0001360
30 limitation of joint mobility occasional (7.5%) HP:0001376
31 defect in the atrial septum occasional (7.5%) HP:0001631
32 patent ductus arteriosus occasional (7.5%) HP:0001643
33 encephalocele occasional (7.5%) HP:0002084
34 abnormality of neuronal migration occasional (7.5%) HP:0002269
35 autosomal dominant inheritance HP:0000006
36 small face HP:0000274
37 short ribs HP:0000773
38 narrow chest HP:0000774
39 wide-cupped costochondral junctions HP:0000910
40 platyspondyly HP:0000926
41 flared irregular metaphyses HP:0000945
42 hypoplastic ilia HP:0000946
43 brachydactyly syndrome HP:0001156
44 decreased fetal movement HP:0001558
45 polyhydramnios HP:0001561
46 respiratory insufficiency HP:0002093
47 cloverleaf skull HP:0002676
48 small foramen magnum HP:0002677
49 small sacroiliac notches HP:0003185
50 small abnormally formed scapulae HP:0006584
51 lethal short-limbed short stature HP:0008909

Drugs & Therapeutics for Thanatophoric Dysplasia, Type Ii

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Drug clinical trials:

Search ClinicalTrials for Thanatophoric Dysplasia, Type Ii

Search NIH Clinical Center for Thanatophoric Dysplasia, Type Ii

Genetic Tests for Thanatophoric Dysplasia, Type Ii

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Genetic tests related to Thanatophoric Dysplasia, Type Ii:

id Genetic test Affiliating Genes
1 Thanatophoric Dysplasia Type Ii20 FGFR3
2 Thanatophoric Dysplasia, Type 222

Anatomical Context for Thanatophoric Dysplasia, Type Ii

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

31
Bone, Lung, Skin, Kidney

Animal Models for Thanatophoric Dysplasia, Type Ii or affiliated genes

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MGI Mouse Phenotypes related to Thanatophoric Dysplasia, Type Ii:

35
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053718.5FGFR3, STAT1, SPRY2
2MP:00053918.5FGFR3, STAT1, SPRY2
3MP:00020068.4FGFR3, STAT1, SPRY2
4MP:00053818.2SPRY2, STAT1, FGFR3

Publications for Thanatophoric Dysplasia, Type Ii

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Articles related to Thanatophoric Dysplasia, Type Ii:

(show all 11)
idTitleAuthorsYear
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
Thanatophoric dysplasia type II with encephalocele and aortic hypoplasia diagnosed in an anatomical specimen. (12605444)
2003
8
A central nervous system specific mouse model for thanatophoric dysplasia type II. (12966031)
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

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

62
id Symbol AA change Variation ID SNP ID
1FGFR3p.Lys650GluVAR_004160

Clinvar genetic disease variations for Thanatophoric Dysplasia, Type Ii:

6
id Gene Variation Type Significance SNP ID Assembly Location
1FGFR3NM_000142.4(FGFR3): c.1948A> G (p.Lys650Glu)single nucleotide variantPathogenicrs78311289GRCh37Chr 4, 1807889: 1807889

Expression for genes affiliated with Thanatophoric Dysplasia, Type Ii

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

Pathways for genes affiliated with Thanatophoric Dysplasia, Type Ii

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

(show all 16)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.3STAT1, FGFR3
29.3STAT1, FGFR3
3
Show member pathways
9.3FGFR3, STAT1
49.3FGFR3, STAT1
5
Show member pathways
9.3FGFR3, STAT1
6
Show member pathways
9.3FGFR3, STAT1
79.1STAT1, SPRY2
8
Show member pathways
Type III interferon signaling36
9.1SPRY2, STAT1
99.1STAT1, SPRY2
10
Show member pathways
Prostate Cancer36
Integrated Cancer pathway36
Steroid Biosynthesis36
9.1STAT1, SPRY2
11
Show member pathways
Signaling Pathways in Glioblastoma36
9.0FGFR3, SPRY2
12
Show member pathways
9.0SPRY2, FGFR3
139.0FGFR3, SPRY2
14
Show member pathways
8.5FGFR3, STAT1, SPRY2
15
Show member pathways
8.5FGFR3, STAT1, SPRY2
168.5FGFR3, STAT1, SPRY2

Compounds for genes affiliated with Thanatophoric Dysplasia, Type Ii

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Sources:
43Novoseek, 49PharmGKB, 12DrugBank
See all sources

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

idCompoundScoreTop Affiliating Genes
1imatinib43 49 1211.4FGFR3, STAT1
2phenylalanine439.3STAT1, FGFR3
3lysine439.3FGFR3, STAT1
4phosphotyrosine439.2FGFR3, STAT1
5doxorubicin43 49 1211.0FGFR3, STAT1
6tyrosine438.6FGFR3, STAT1, SPRY2

GO Terms for genes affiliated with Thanatophoric Dysplasia, Type Ii

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

idNameGO IDScoreTop Affiliating Genes
1JAK-STAT cascadeGO:00072599.3FGFR3, STAT1
2epidermal growth factor receptor signaling pathwayGO:00071739.0FGFR3, SPRY2
3positive regulation of ERK1 and ERK2 cascadeGO:00703748.9FGFR3, SPRY2
4fibroblast growth factor receptor signaling pathwayGO:00085438.7FGFR3, SPRY2

Products for genes affiliated with Thanatophoric Dysplasia, Type Ii

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  • Antibodies
  • Proteins
  • Lysates
  • Antibodies
  • Proteins
  • Kits and Assays

Sources for Thanatophoric Dysplasia, Type Ii

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
33MeSH
34MESH via Orphanet
35MGI
38NCIt
39NDF-RT
42NINDS
43Novoseek
45OMIM
46OMIM via Orphanet
50PubMed
51QIAGEN
56SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet