TD1
MCID: THN009
MIFTS: 59

Thanatophoric Dysplasia, Type I (TD1)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Respiratory diseases, Skin diseases

Aliases & Classifications for Thanatophoric Dysplasia, Type I

MalaCards integrated aliases for Thanatophoric Dysplasia, Type I:

Name: Thanatophoric Dysplasia, Type I 57 13 72
Thanatophoric Dysplasia 57 12 75 24 53 25 59 37 55 44 15
Thanatophoric Dysplasia Type 1 53 59 29 6
Thanatophoric Dwarfism 57 53 25 74
Td1 57 53 59 74
Thanatophoric Dysplasia Type I 53 74
Thanatophoric Dwarfism Type 1 53 59
Thanatophoric Short Stature 25 33
Td 57 59
Lethal Short-Limbed Platyspondylic Dwarfism, San Diego Type 57
Lethal Short-Limbed Platyspondylic Dwarfism San Diego Type 74
Platyspondylic Lethal Skeletal Dysplasia, San Diego Type 57
Platyspondylic Lethal Skeletal Dysplasia San Diego Type 74
Dysplasia, Thanatophoric, Type I 40
Thanatophoric Dysplasia; Td 57
Thanatophoric Dysplasia 1 74
Thanatophoric Dwarfism 1 53
Dwarfism Thanatophoric 53
Dwarf, Thanatophoric 25

Characteristics:

Orphanet epidemiological data:

59
thanatophoric dysplasia
Inheritance: Autosomal dominant,Not applicable; Prevalence: 1-9/100000 (Europe); Age of onset: Antenatal,Neonatal; Age of death: early childhood;
thanatophoric dysplasia type 1
Inheritance: Autosomal dominant,Not applicable; Age of onset: Antenatal,Neonatal; Age of death: stillbirth;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
death in majority of infants soon after birth


HPO:

32
thanatophoric dysplasia, type i:
Clinical modifier neonatal death
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance The penetrance of fgfr3 pathogenic variants is 100%.

Classifications:



External Ids:

Disease Ontology 12 DOID:13481
OMIM 57 187600
KEGG 37 H01750
MeSH 44 D013796
NCIt 50 C85187
SNOMED-CT 68 29352008
ICD10 33 Q77.1
ICD10 via Orphanet 34 Q77.1
UMLS via Orphanet 73 C0039743 C1868678 C2931282
UMLS 72 C0039743 C1868678

Summaries for Thanatophoric Dysplasia, Type I

NIH Rare Diseases : 53 Thanatophoric dysplasia is a severe skeletal disorder characterized by extremely short limbs and folds of extra skin on the arms and legs. Other features of this condition include a narrow chest, short ribs, underdeveloped lungs, and an enlarged head with a large forehead and prominent, wide-spaced eyes. Most infants with thanatophoric dysplasia are stillborn or die shortly after birth from respiratory failure. A few affected individuals have survived into childhood with extensive medical help. Thanatophoric dysplasia is caused by mutations in the FGFR3 gene. While this condition is considered to be autosomal dominant, virtually all cases have occurred in people with no history of the disorder in their family. Two major forms of thanatophoric dysplasia have been described, type I and type II. Type I thanatophoric dysplasia is distinguished by the presence of curved thigh bones and flattened bones of the spine (platyspondyly). Type II thanatophoric dysplasia is characterized by straight thigh bones and a moderate to severe skull abnormality called a cloverleaf skull.

MalaCards based summary : Thanatophoric Dysplasia, Type I, also known as thanatophoric dysplasia, is related to acanthosis nigricans and achondroplasia, severe, with developmental delay and acanthosis nigricans. An important gene associated with Thanatophoric Dysplasia, Type I is FGFR3 (Fibroblast Growth Factor Receptor 3), and among its related pathways/superpathways are TGF-Beta Pathway and Cytokine Signaling in Immune system. Affiliated tissues include bone, skin and lung, and related phenotypes are macrocephaly and muscular hypotonia

Disease Ontology : 12 An osteochondrodysplasia that results in short arms and legs with excess folds of skin.

Genetics Home Reference : 25 Thanatophoric dysplasia is a severe skeletal disorder characterized by extremely short limbs and folds of extra (redundant) skin on the arms and legs. Other features of this condition include a narrow chest, short ribs, underdeveloped lungs, and an enlarged head with a large forehead and prominent, wide-spaced eyes. Researchers have described two major forms of thanatophoric dysplasia, type I and type II. Type I thanatophoric dysplasia is distinguished by the presence of curved thigh bones and flattened bones of the spine (platyspondyly). Type II thanatophoric dysplasia is characterized by straight thigh bones and a moderate to severe skull abnormality called a cloverleaf skull. The term thanatophoric is Greek for "death bearing." Infants with thanatophoric dysplasia are usually stillborn or die shortly after birth from respiratory failure; however, a few affected individuals have survived into childhood with extensive medical help.

OMIM : 57 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), while TD cases with curved, short femurs with or without cloverleaf skull were designated TD type I (TD1) (Langer et al., 1987). (187600)

KEGG : 37
Thanatophoric dysplasia (TD) is a congenital skeletal dysplasia characterized by marked underdevelopment of the skeletal system and short-limb dwarfism. It is the most common form of lethal skeletal dysplasia syndromes. Two types of TD have been described. Type I TD (TDI) is associated with curved and short femurs. The shortness of the bones in type II TD (TDII) is not as significant as in TDI. TDII is characterized by straight femurs and cloverleaf skull deformity. Other features common to type I and type II include short ribs, narrow thorax, macrocephaly, distinctive facial features, brachydactyly, hypotonia, and redundant skin folds along the limbs. Most affected infants die of respiratory insufficiency shortly after birth. Both TDI and TDII are caused by heterozygous fibroblast growth factor receptor 3 (FGFR3) missense mutations. Its incidence is 1 in 20 000 to 50 000 births and it is an autosomal dominant condition. The mutation in most TD cases is de novo.

UniProtKB/Swiss-Prot : 74 Thanatophoric dysplasia 1: A neonatal lethal skeletal dysplasia. Affected individuals manifest severe shortening of the limbs with macrocephaly, narrow thorax, short ribs, and curved femurs.

Wikipedia : 75 Thanatophoric dysplasia (thanatophoric dwarfism) is a severe skeletal disorder characterized by a... more...

GeneReviews: NBK1366

Related Diseases for Thanatophoric Dysplasia, Type I

Diseases in the Thanatophoric Dysplasia, Type I family:

Thanatophoric Dysplasia, Type Ii

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

(show top 50) (show all 107)
# Related Disease Score Top Affiliating Genes
1 acanthosis nigricans 30.9 FGFR3 FGFR2
2 achondroplasia, severe, with developmental delay and acanthosis nigricans 30.7 STAT1 FGFR3
3 thanatophoric dysplasia, type ii 30.6 STAT1 FGFR3
4 hypochondroplasia 30.5 FGFR3 FGFR2
5 chromosome 2q35 duplication syndrome 30.3 FGFR3 FGFR2
6 apert syndrome 30.3 FGFR3 FGFR2
7 acromesomelic dysplasia, maroteaux type 30.2 NPR2 FGFR3
8 crouzon syndrome 30.2 FGFR3 FGFR2
9 skeletal dysplasias 30.0 PTH1R FGFR3 COMP
10 bone disease 29.7 PTH1R FGFR3 FGFR2
11 brittle bone disorder 29.7 PTH1R FGFR3
12 craniosynostosis 29.5 FGFR3 FGFR2 FGF8
13 achondroplasia 29.5 PTH1R FGFR3 FGFR2 COMP
14 kleeblattschaedel 11.7
15 platyspondylic lethal skeletal dysplasia, torrance type 11.5
16 atelosteogenesis, type i 11.3
17 boomerang dysplasia 11.3
18 hydrocephalus 10.5
19 congenital hydrocephalus 10.5
20 dwarfism 10.4
21 hemifacial hyperplasia 10.4 FGFR3 FGFR2
22 achondrogenesis 10.4
23 plagiocephaly 10.4 FGFR3 FGFR2
24 osteoglophonic dysplasia 10.4 FGFR3 FGFR2
25 luteoma 10.4 FGFR3 FGFR2
26 macrocephaly/megalencephaly syndrome, autosomal recessive 10.4
27 polyhydramnios 10.4
28 megalencephaly 10.4
29 beare-stevenson cutis gyrata syndrome 10.3 FGFR3 FGFR2
30 jackson-weiss syndrome 10.3 FGFR3 FGFR2
31 radioulnar synostosis 10.3 FGFR3 FGFR2
32 odontochondrodysplasia 10.3
33 encephalocele 10.3
34 hypertropia 10.3 FGFR3 FGFR2
35 achondrogenesis, type ia 10.3
36 schneckenbecken dysplasia 10.3
37 osteogenesis imperfecta, type ii 10.2
38 brachydactyly 10.2
39 col1a1/2-related osteogenesis imperfecta 10.2
40 skeletal dysplasia, san diego type 10.2
41 exophthalmos 10.2 FGFR3 FGFR2
42 keratosis, seborrheic 10.2
43 respiratory failure 10.2
44 chromosomal triplication 10.2
45 hypotonia 10.2
46 lethal chondrodysplasia 10.2
47 achondrogenesis, type ii 10.1
48 congenital heart defects, hamartomas of tongue, and polysyndactyly 10.1
49 achondrogenesis, type ib 10.1
50 polydactyly 10.1

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



Diseases related to Thanatophoric Dysplasia, Type I

Symptoms & Phenotypes for Thanatophoric Dysplasia, Type I

Human phenotypes related to Thanatophoric Dysplasia, Type I:

59 32 (show top 50) (show all 64)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000256
2 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001252
3 respiratory insufficiency 59 32 hallmark (90%) Occasional (29-5%),Very frequent (99-80%) HP:0002093
4 skeletal dysplasia 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0002652
5 depressed nasal bridge 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0005280
6 abnormality of the metaphysis 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000944
7 narrow chest 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000774
8 platyspondyly 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000926
9 micromelia 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0002983
10 short thorax 59 32 hallmark (90%) Very frequent (99-80%) HP:0010306
11 flat face 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0012368
12 brachydactyly 59 32 hallmark (90%) Frequent (79-30%),Very frequent (99-80%) HP:0001156
13 intellectual disability, profound 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0002187
14 split hand 59 32 hallmark (90%) Very frequent (99-80%) HP:0001171
15 redundant skin 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001582
16 increased nuchal translucency 59 32 frequent (33%) Very frequent (99-80%),Frequent (79-30%) HP:0010880
17 disproportionate short-limb short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0008873
18 pulmonary hypoplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002089
19 femoral bowing 59 32 hallmark (90%) Very frequent (99-80%) HP:0002980
20 hypoplastic ilia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000946
21 short femur 59 32 hallmark (90%) Very frequent (99-80%) HP:0003097
22 short sacroiliac notch 59 32 hallmark (90%) Very frequent (99-80%) HP:0003185
23 lethal short-limbed short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0008909
24 frontal bossing 59 32 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0002007
25 kyphosis 59 32 frequent (33%) Occasional (29-5%),Frequent (79-30%) HP:0002808
26 hearing impairment 59 32 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0000365
27 intrauterine growth retardation 59 32 frequent (33%) Frequent (79-30%) HP:0001511
28 ventriculomegaly 59 32 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0002119
29 polyhydramnios 59 32 frequent (33%) Occasional (29-5%),Frequent (79-30%) HP:0001561
30 proptosis 59 32 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0000520
31 aplasia/hypoplasia of the lungs 59 32 frequent (33%) Frequent (79-30%) HP:0006703
32 midface retrusion 59 32 frequent (33%) Frequent (79-30%) HP:0011800
33 wide anterior fontanel 59 32 frequent (33%) Frequent (79-30%) HP:0000260
34 excessive wrinkled skin 59 32 frequent (33%) Frequent (79-30%) HP:0007392
35 gray matter heterotopia 32 occasional (7.5%) HP:0002282
36 low-set ears 59 32 occasional (7.5%) Occasional (29-5%) HP:0000369
37 hydrocephalus 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0000238
38 seizures 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0001250
39 hip dysplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001385
40 joint stiffness 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0001387
41 acanthosis nigricans 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0000956
42 cloverleaf skull 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0002676
43 patent ductus arteriosus 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0001643
44 joint hyperflexibility 59 32 occasional (7.5%) Occasional (29-5%) HP:0005692
45 atrial septal defect 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0001631
46 abnormality of the kidney 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0000077
47 downslanted palpebral fissures 59 32 occasional (7.5%) Occasional (29-5%) HP:0000494
48 abnormality of the sacroiliac joint 59 32 occasional (7.5%) Occasional (29-5%),Very frequent (99-80%) HP:0100781
49 bowing of the long bones 59 32 Very frequent (99-80%) HP:0006487
50 global developmental delay 32 HP:0001263

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Head:
macrocephaly
frontal bossing

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Head And Neck Face:
small face

Skeletal Spine:
severe platyspondyly

Prenatal Manifestations Movement:
decreased fetal activity

Growth Other:
severe growth deficiency in survivors

Skeletal Pelvis:
short and small iliac bones
small sacroiliac notches

Prenatal Manifestations:
prenatal diagnosis by ultrasound

Neurologic Central Nervous System:
hydrocephalus
temporal lobe heterotopias
profound mental retardation and hypotonia in survivors

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

Skeletal Skull:
small foramen magnum
cloverleaf skull rarely

Chest External Features:
narrow thorax

Growth Height:
dwarfism, lethal micromelic

Respiratory Lung:
respiratory insufficiency/failure

Skeletal Limbs:
marked shortness and bowing of long bones
'french telephone receiver femurs'
flared and irregular metaphyses

Clinical features from OMIM:

187600

GenomeRNAi Phenotypes related to Thanatophoric Dysplasia, Type I according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased substrate adherent cell growth GR00193-A-2 8.92 FGFR2
2 Decreased substrate adherent cell growth GR00193-A-3 8.92 FGFR2 FGFR3 NPR2

MGI Mouse Phenotypes related to Thanatophoric Dysplasia, Type I:

46 (show all 20)
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.19 CBL COMP FGF8 FGFR2 FGFR3 NPR2
2 growth/size/body region MP:0005378 10.14 CBL COMP FGF8 FGFR2 FGFR3 NPR2
3 cardiovascular system MP:0005385 10.13 CBL COMP FGF8 FGFR2 NPR2 PTH1R
4 homeostasis/metabolism MP:0005376 10.1 CBL COMP FGF8 FGFR2 FGFR3 NPR2
5 immune system MP:0005387 10.08 CBL COMP FGF8 FGFR2 FGFR3 NPR2
6 limbs/digits/tail MP:0005371 10.06 CBL COMP FGF8 FGFR2 FGFR3 NPR2
7 cellular MP:0005384 10.05 CBL COMP FGF8 FGFR2 FGFR3 STAT1
8 hematopoietic system MP:0005397 10.05 CBL FGF8 FGFR2 FGFR3 NPR2 PTH1R
9 craniofacial MP:0005382 10.04 CBL FGF8 FGFR2 FGFR3 NPR2 PTH1R
10 digestive/alimentary MP:0005381 10.03 FGF8 FGFR2 FGFR3 NPR2 PTH1R STAT1
11 endocrine/exocrine gland MP:0005379 10.02 CBL FGF8 FGFR2 NPR2 PTH1R STAT1
12 mortality/aging MP:0010768 9.98 CBL FGF8 FGFR2 FGFR3 NPR2 PTH1R
13 muscle MP:0005369 9.88 CBL COMP FGF8 FGFR2 NPR2 STAT1
14 hearing/vestibular/ear MP:0005377 9.83 CBL FGF8 FGFR2 FGFR3
15 nervous system MP:0003631 9.8 FGF8 FGFR2 FGFR3 NPR2 PTH1R STAT1
16 neoplasm MP:0002006 9.67 FGFR2 FGFR3 PTH1R STAT1
17 normal MP:0002873 9.65 COMP FGF8 FGFR2 FGFR3 STAT1
18 respiratory system MP:0005388 9.63 CBL FGF8 FGFR2 FGFR3 NPR2 PTH1R
19 skeleton MP:0005390 9.56 CBL COMP FGF8 FGFR2 FGFR3 NPR2
20 vision/eye MP:0005391 9.02 FGF8 FGFR2 FGFR3 PTH1R STAT1

Drugs & Therapeutics for Thanatophoric Dysplasia, Type I

Search Clinical Trials , NIH Clinical Center for Thanatophoric Dysplasia, Type I

Cochrane evidence based reviews: thanatophoric dysplasia

Genetic Tests for Thanatophoric Dysplasia, Type I

Genetic tests related to Thanatophoric Dysplasia, Type I:

# Genetic test Affiliating Genes
1 Thanatophoric Dysplasia Type 1 29 FGFR3

Anatomical Context for Thanatophoric Dysplasia, Type I

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

41
Bone, Skin, Lung, Eye, Temporal Lobe, Brain, Heart

Publications for Thanatophoric Dysplasia, Type I

Articles related to Thanatophoric Dysplasia, Type I:

(show top 50) (show all 436)
# Title Authors PMID Year
1
Thanatophoric dysplasia caused by double missense FGFR3 mutations. 9 38 4 8 71
19449430 2009
2
Molecular, radiologic, and histopathologic correlations in thanatophoric dysplasia. 9 38 4 8 71
9677066 1998
3
Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I. 9 38 8 71
8589699 1995
4
Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3. 9 38 8 71
7773297 1995
5
Somatic and germline mosaicism for a R248C missense mutation in FGFR3, resulting in a skeletal dysplasia distinct from thanatophoric dysplasia. 9 38 4 71
12833394 2003
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. 9 38 4 71
12624096 2003
7
A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene. 9 38 4 71
10053006 1999
8
Prenatal diagnosis of thanatophoric dysplasia by mutational analysis of the fibroblast growth factor receptor 3 gene and a proposed correction of previously published PCR results. 38 8 71
10073901 1999
9
Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1). 9 8 71
8845844 1996
10
Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations. 38 4 8
10360402 1999
11
Growth and development in thanatophoric dysplasia. 38 4 8
2596513 1989
12
Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors. 9 38 71
19855393 2009
13
Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi. 9 38 71
16841094 2006
14
Thanatophoric dysplasia type I with syndactyly. 9 38 71
9843049 1998
15
Abnormal FGFR 3 expression in cartilage of thanatophoric dysplasia fetuses. 9 38 8
9302269 1997
16
The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US. 38 8
18698630 2008
17
Thanatophoric dysplasia type 2 with encephalocele during the second trimester. 38 71
16752380 2006
18
The cytoplasmic tyrosine kinase Pyk2 as a novel effector of fibroblast growth factor receptor 3 activation. 9 38 4
15105428 2004
19
Thanatophoric Dysplasia 38 71
20301540 2004
20
Overexpression of FGFR3, Stat1, Stat5 and p21Cip1 correlates with phenotypic severity and defective chondrocyte differentiation in FGFR3-related chondrodysplasias. 9 38 4
14751560 2004
21
Occurrence of thanatophoric dysplasia type I (R248C) and hypochondroplasia (N540K) mutations in two patients with achondroplasia phenotype. 9 38 4
11754059 2001
22
Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN): phenotypic analysis of a new skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3. 9 38 4
10377013 1999
23
Fibroblast growth factor receptor 3 mutations promote apoptosis but do not alter chondrocyte proliferation in thanatophoric dysplasia. 9 38 4
9582336 1998
24
Lys650Met substitution in the tyrosine kinase domain of the fibroblast growth factor receptor gene causes thanatophoric dysplasia Type I. Mutations in brief no. 199. Online. 38 71
10671061 1998
25
Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. 9 71
9207791 1997
26
Long-term survival in typical thanatophoric dysplasia type 1. 38 8
9182787 1997
27
Japanese cases of type 1 thanatophoric dysplasia exclusively carry a C to T transition at nucleotide 742 of the fibroblast growth factor receptor 3 gene. 38 71
8858131 1996
28
Antenatal sonographic diagnosis of thanatophoric dysplasia: a report of three cases and a review of the literature with special emphasis on the differential diagnosis. 38 8
8843623 1996
29
Stop codon FGFR3 mutations in thanatophoric dwarfism type 1. 9 71
7647778 1995
30
De novo 1;10 balanced translocation in an infant with thanatophoric dysplasia: a clue to the locus of the candidate gene. 38 8
7643360 1995
31
Thanatophoric dysplasia of the straight-bone type (type 2). 38 8
1345514 1992
32
Thanatophoric dysplasia in monozygotic twins discordant for cloverleaf skull: prenatal diagnosis, clinical and pathological findings. 38 8
1308351 1992
33
Thanatophoric dysplasia in identical twins. 38 8
2585471 1989
34
Thanatophoric dysplasia in identical twins. 38 8
2716037 1989
35
Prevalence of lethal osteochondrodysplasias in Denmark. 38 8
2789000 1989
36
Thanatophoric dysplasia: an autosomal dominant condition? 38 8
3239573 1988
37
Abnormal ossification in thanatophoric dysplasia. 38 8
3132190 1988
38
A boy with thanatophoric dysplasia surviving 212 days. 38 8
3436092 1987
39
The birth prevalence rates for the skeletal dysplasias. 38 8
3746832 1986
40
Thanatophoric dysplasia: fetal manifestations and prenatal diagnosis. 38 8
4073120 1985
41
Lethal neonatal chondrodysplasias in the West of Scotland 1970-1983 with a description of a thanatophoric, dysplasialike, autosomal recessive disorder, Glasgow variant. 38 8
3901754 1985
42
Prenatal diagnosis of thanatophoric dysplasia at 24 weeks. 38 8
6741994 1984
43
Thanatophoric dysplasia of identical twins. 38 8
6538757 1984
44
Neuropathologic findings in thanatophoric dysplasia. 38 8
6464678 1984
45
Neuropathological findings in thanatophoric dysplasia. 38 8
6687528 1983
46
Further heterogeneity within lethal neonatal short-limbed dwarfism: the platyspondylic types. 38 8
448481 1979
47
Molecular Analysis of a Case of Thanatophoric Dysplasia Reveals Two de novo FGFR3 Missense Mutations located in cis. 38 4
23573386 2013
48
Clinical epidemiology of skeletal dysplasias in South America. 38 4
22407836 2012
49
Atypical achondroplasia due to somatic mosaicism for the common thanatophoric dysplasia mutation R248C. 38 4
22106050 2012
50
Anesthetic management of an infant with thanatophoric dysplasia for suboccipital decompression. 38 4
21155935 2011

Variations for Thanatophoric Dysplasia, Type I

ClinVar genetic disease variations for Thanatophoric Dysplasia, Type I:

6 (show all 23)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 FGFR3 NM_000142.4(FGFR3): c.2419T> A (p.Ter807Arg) single nucleotide variant Pathogenic rs121913101 4:1808987-1808987 4:1807260-1807260
2 FGFR3 NM_000142.4(FGFR3): c.2421A> T (p.Ter807Cys) single nucleotide variant Pathogenic rs121913103 4:1808989-1808989 4:1807262-1807262
3 FGFR3 NM_000142.4(FGFR3): c.1620C> A (p.Asn540Lys) single nucleotide variant Pathogenic rs28933068 4:1807371-1807371 4:1805644-1805644
4 FGFR3 NM_000142.4(FGFR3): c.1111A> T (p.Ser371Cys) single nucleotide variant Pathogenic rs121913484 4:1806092-1806092 4:1804365-1804365
5 FGFR3 NM_000142.4(FGFR3): c.2419T> G (p.Ter807Gly) single nucleotide variant Pathogenic rs121913101 4:1808987-1808987 4:1807260-1807260
6 FGFR3 NM_000142.4(FGFR3): c.2419T> C (p.Ter807Arg) single nucleotide variant Pathogenic rs121913101 4:1808987-1808987 4:1807260-1807260
7 FGFR3 NM_000142.4(FGFR3): c.2420G> T (p.Ter807Leu) single nucleotide variant Pathogenic rs397515514 4:1808988-1808988 4:1807261-1807261
8 FGFR3 NM_000142.4(FGFR3): c.2421A> C (p.Ter807Cys) single nucleotide variant Pathogenic rs121913103 4:1808989-1808989 4:1807262-1807262
9 FGFR3 NM_000142.4(FGFR3): c.2421A> G (p.Ter807Trp) single nucleotide variant Pathogenic rs121913103 4:1808989-1808989 4:1807262-1807262
10 FGFR3 NM_000142.4(FGFR3): c.1949A> T (p.Lys650Met) single nucleotide variant Pathogenic rs121913105 4:1807890-1807890 4:1806163-1806163
11 FGFR3 NM_000142.4(FGFR3): c.749C> G (p.Pro250Arg) single nucleotide variant Pathogenic rs4647924 4:1803571-1803571 4:1801844-1801844
12 FGFR3 NM_000142.4(FGFR3): c.746C> G (p.Ser249Cys) single nucleotide variant Pathogenic rs121913483 4:1803568-1803568 4:1801841-1801841
13 FGFR3 NM_000142.4(FGFR3): c.1620C> G (p.Asn540Lys) single nucleotide variant Pathogenic rs28933068 4:1807371-1807371 4:1805644-1805644
14 FGFR3 NM_000142.4(FGFR3): c.742C> T (p.Arg248Cys) single nucleotide variant Pathogenic rs121913482 4:1803564-1803564 4:1801837-1801837
15 FGFR3 NM_000142.4(FGFR3): c.1108G> T (p.Gly370Cys) single nucleotide variant Pathogenic rs121913479 4:1806089-1806089 4:1804362-1804362
16 FGFR3 NM_000142.4(FGFR3): c.1949A> C (p.Lys650Thr) single nucleotide variant Pathogenic rs121913105 4:1807890-1807890 4:1806163-1806163
17 FGFR3 NM_000142.4(FGFR3): c.1138G> A (p.Gly380Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs28931614 4:1806119-1806119 4:1804392-1804392
18 FGFR3 NM_000142.4(FGFR3): c.1118A> G (p.Tyr373Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs121913485 4:1806099-1806099 4:1804372-1804372
19 FGFR3 NM_000142.4(FGFR3): c.1519G> A (p.Val507Met) single nucleotide variant Uncertain significance 4:1807188-1807188 4:1805461-1805461
20 FGFR3 NM_000142.4(FGFR3): c.200G> A (p.Gly67Asp) single nucleotide variant Uncertain significance rs369232922 4:1801071-1801071 4:1799344-1799344
21 FGFR3 NM_000142.4(FGFR3): c.2153A> G (p.Asn718Ser) single nucleotide variant Uncertain significance rs139773438 4:1808395-1808395 4:1806668-1806668
22 FGFR3 NM_000142.4(FGFR3): c.1993G> T (p.Ala665Ser) single nucleotide variant Uncertain significance rs764892330 4:1808017-1808017 4:1806290-1806290
23 FGFR3 NM_000142.4(FGFR3): c.1454A> G (p.Gln485Arg) single nucleotide variant no interpretation for the single variant rs267606808 4:1807123-1807123 4:1805396-1805396

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

74
# Symbol AA change Variation ID SNP ID
1 FGFR3 p.Arg248Cys VAR_004148 rs121913482
2 FGFR3 p.Ser249Cys VAR_004149 rs121913483
3 FGFR3 p.Gly370Cys VAR_004151 rs121913479
4 FGFR3 p.Ser371Cys VAR_004152 rs121913484
5 FGFR3 p.Tyr373Cys VAR_004153 rs121913485
6 FGFR3 p.Lys650Met VAR_004161 rs121913105

Expression for Thanatophoric Dysplasia, Type I

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

Pathways for Thanatophoric Dysplasia, Type I

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

(show all 32)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.25 STAT1 FGFR3 FGFR2 FGF8 CBL
2
Show member pathways
13.09 STAT1 FGFR3 FGFR2 FGF8 CBL
3
Show member pathways
13.01 NPR2 FGFR3 FGFR2 FGF8 CBL
4
Show member pathways
12.78 STAT1 FGFR3 FGFR2 FGF8
5
Show member pathways
12.6 STAT1 FGFR3 FGFR2 FGF8 COMP
6
Show member pathways
12.46 FGFR3 FGFR2 FGF8 CBL
7
Show member pathways
12.43 FGFR3 FGFR2 FGF8 CBL
8 12.39 FGFR3 FGFR2 FGF8
9
Show member pathways
12.3 FGFR3 FGFR2 FGF8 CBL
10 12.28 STAT1 FGFR3 FGFR2 FGF8 CBL
11
Show member pathways
12.18 FGFR3 FGFR2 FGF8
12
Show member pathways
12.17 FGFR3 FGFR2 FGF8
13 12.15 FGFR3 FGFR2 CBL
14
Show member pathways
12.15 FGFR3 FGFR2 FGF8 CBL
15
Show member pathways
12.15 FGFR3 FGFR2 FGF8 CBL
16
Show member pathways
12.01 STAT1 FGFR3 FGFR2 FGF8
17 11.91 FGFR3 FGFR2 CBL
18
Show member pathways
11.85 FGFR3 FGFR2 FGF8 CBL
19 11.69 FGFR3 FGFR2 FGF8
20 11.49 FGFR3 FGFR2
21
Show member pathways
11.46 STAT1 FGFR3 FGFR2 FGF8
22 11.45 FGFR3 FGFR2 FGF8 CBL
23
Show member pathways
11.41 FGFR3 FGF8
24
Show member pathways
11.41 STAT1 CBL
25 11.39 STAT1 PTH1R FGFR3
26 11.38 STAT1 CBL
27 11.37 STAT1 CBL
28 11.28 FGFR3 FGFR2
29 11.26 FGFR3 FGFR2
30 11.17 STAT1 FGFR2 CBL
31
Show member pathways
11.03 STAT1 FGFR3 FGFR2 FGF8 CBL
32 10.9 FGFR3 FGFR2 FGF8

GO Terms for Thanatophoric Dysplasia, Type I

Cellular components related to Thanatophoric Dysplasia, Type I according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 receptor complex GO:0043235 8.8 PTH1R FGFR3 FGFR2

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

(show all 25)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.75 FGFR3 FGFR2 FGF8
2 MAPK cascade GO:0000165 9.74 FGFR3 FGFR2 FGF8
3 apoptotic process GO:0006915 9.73 FGFR3 FGFR2 COMP
4 positive regulation of protein kinase B signaling GO:0051897 9.69 FGFR3 FGFR2 FGF8
5 skeletal system development GO:0001501 9.67 PTH1R FGFR3 COMP
6 inner ear morphogenesis GO:0042472 9.62 FGFR2 FGF8
7 cell fate commitment GO:0045165 9.62 FGFR2 FGF8
8 positive regulation of smooth muscle cell proliferation GO:0048661 9.61 STAT1 FGFR2
9 positive regulation of cell division GO:0051781 9.61 FGFR2 FGF8
10 chondrocyte differentiation GO:0002062 9.6 PTH1R FGFR3
11 odontogenesis GO:0042476 9.59 FGFR2 FGF8
12 bone morphogenesis GO:0060349 9.58 FGFR3 FGFR2
13 outflow tract septum morphogenesis GO:0003148 9.55 FGFR2 FGF8
14 positive regulation of cell proliferation GO:0008284 9.55 STAT1 PTH1R FGFR3 FGFR2 FGF8
15 positive regulation of mesenchymal cell proliferation GO:0002053 9.54 STAT1 FGFR2
16 peptidyl-tyrosine phosphorylation GO:0018108 9.52 FGFR3 FGFR2
17 bone development GO:0060348 9.5 NPR2 FGFR2 FGF8
18 interleukin-6-mediated signaling pathway GO:0070102 9.48 STAT1 CBL
19 branching involved in salivary gland morphogenesis GO:0060445 9.46 FGFR2 FGF8
20 positive regulation of phospholipase activity GO:0010518 9.43 FGFR3 FGFR2
21 negative regulation of apoptotic process GO:0043066 9.43 FGF8 COMP CBL
22 otic vesicle formation GO:0030916 9.4 FGFR2 FGF8
23 endochondral bone growth GO:0003416 9.37 FGFR3 FGFR2
24 bone mineralization GO:0030282 9.13 PTH1R FGFR3 FGFR2
25 fibroblast growth factor receptor signaling pathway GO:0008543 8.92 FGFR3 FGFR2 FGF8 CBL

Molecular functions related to Thanatophoric Dysplasia, Type I according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transmembrane receptor protein tyrosine kinase activity GO:0004714 9.37 FGFR3 FGFR2
2 peptide hormone binding GO:0017046 9.32 PTH1R NPR2
3 fibroblast growth factor binding GO:0017134 9.16 FGFR3 FGFR2
4 transmembrane signaling receptor activity GO:0004888 8.96 PTH1R
5 protein tyrosine kinase activity GO:0004713 8.96 FGFR3 FGFR2
6 fibroblast growth factor-activated receptor activity GO:0005007 8.62 FGFR3 FGFR2

Sources for Thanatophoric Dysplasia, Type I

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
Content
Loading form....