U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Thanatophoric dysplasia, type 2(TD2)

MedGen UID:
226975
Concept ID:
C1300257
Disease or Syndrome
Synonyms: Cloverleaf skull with thanatophoric dwarfism; TD2; Thanatophoric Dysplasia Type II; Thanatophoric dysplasia with Kleeblattschaedel; THANATOPHORIC DYSPLASIA WITH STRAIGHT FEMURS AND CLOVERLEAF SKULL
SNOMED CT: Thanatophoric dysplasia, type 2 (389158007)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): FGFR3 (4p16.3)
 
Monarch Initiative: MONDO:0008547
OMIM®: 187601
Orphanet: ORPHA93274

Disease characteristics

Excerpted from the GeneReview: Thanatophoric Dysplasia
Thanatophoric dysplasia (TD) is a short-limb skeletal dysplasia that is usually lethal in the perinatal period. TD is divided into subtypes: TD type 1 is characterized by micromelia with bowed femurs and, uncommonly, the presence of craniosynostosis of varying severity. TD type 2 is characterized by micromelia with straight femurs and uniform presence of moderate-to-severe craniosynostosis with cloverleaf skull deformity. Other features common to type 1 and type 2 include: short ribs, narrow thorax, relative macrocephaly, distinctive facial features, brachydactyly, hypotonia, and redundant skin folds along the limbs. Most affected infants die of respiratory insufficiency shortly after birth. Rare long-term survivors have been reported. [from GeneReviews]
Authors:
Tegan French  |  Ravi Savarirayan   view full author information

Additional descriptions

From OMIM
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).  http://www.omim.org/entry/187601
From MedlinePlus Genetics
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.

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.

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.  https://medlineplus.gov/genetics/condition/thanatophoric-dysplasia

Clinical features

From HPO
Micromelia
MedGen UID:
10031
Concept ID:
C0025995
Congenital Abnormality
The presence of abnormally small extremities.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Lethal short-limbed short stature
MedGen UID:
388831
Concept ID:
C2674171
Finding
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Temporal lobe dysplasia
MedGen UID:
1814372
Concept ID:
C5676808
Congenital Abnormality
A developmental defect of the temporal lobe of the cerebral cortex that is characterized by prominent sulcations and radially directed gyrations.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Short ribs
MedGen UID:
98094
Concept ID:
C0426817
Finding
Reduced rib length.
Metaphyseal irregularity
MedGen UID:
325478
Concept ID:
C1838662
Finding
Irregularity of the normally smooth surface of the metaphyses.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Flared metaphysis
MedGen UID:
337976
Concept ID:
C1850135
Finding
The presence of a splayed (i.e.,flared) metaphyseal segment of one or more long bones.
Cloverleaf skull
MedGen UID:
348010
Concept ID:
C1860050
Congenital Abnormality
Trilobar skull configuration when viewed from the front or behind.
Wide-cupped costochondral junctions
MedGen UID:
349985
Concept ID:
C1861213
Finding
Small foramen magnum
MedGen UID:
348813
Concept ID:
C1861217
Finding
An abnormal narrowing of the foramen magnum.
Hypoplastic ilia
MedGen UID:
348814
Concept ID:
C1861218
Finding
Underdevelopment of the ilium.
Small abnormally formed scapulae
MedGen UID:
396084
Concept ID:
C1861226
Finding
Short greater sciatic notch
MedGen UID:
401058
Concept ID:
C1866689
Finding
The sacroiliac joint in the bony pelvis connects the sacrum and the ilium of the pelvis, which are joined by strong ligaments. The notch is located directly superior to the joint. This term refers to a reduction in the height of the notch.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Small face
MedGen UID:
343376
Concept ID:
C1855538
Finding
A face that is short and narrow.
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Recent clinical studies

Diagnosis

Chen CP, Huang JP, Huang KS, Chen YY, Wu FT, Pan YT, Chiu CL, Wang W
Taiwan J Obstet Gynecol 2024 May;63(3):387-390. doi: 10.1016/j.tjog.2024.03.005. PMID: 38802203
Chen CP, Chang TY, Lin TW, Chern SR, Chen SW, Lai ST, Chuang TY, Wang W
Taiwan J Obstet Gynecol 2018 Feb;57(1):119-122. doi: 10.1016/j.tjog.2017.12.020. PMID: 29458880
Jung M, Park SH
Exp Mol Pathol 2017 Apr;102(2):290-295. Epub 2017 Feb 27 doi: 10.1016/j.yexmp.2017.02.019. PMID: 28249712
Tonni G, Palmisano M, Ginocchi V, Ventura A, Baldi M, Baffico AM
Congenit Anom (Kyoto) 2014 Nov;54(4):228-32. doi: 10.1111/cga.12056. PMID: 24517215
Chen CP, Chang TY, Lin MH, Chern SR, Su JW, Wang W
Taiwan J Obstet Gynecol 2013 Sep;52(3):420-5. doi: 10.1016/j.tjog.2013.05.003. PMID: 24075385

Therapy

Ota S, Zhou ZQ, Romero MP, Yang G, Hurlin PJ
Hum Mol Genet 2016 Oct 1;25(19):4227-4243. Epub 2016 Aug 9 doi: 10.1093/hmg/ddw255. PMID: 27506979
Jin M, Yu Y, Qi H, Xie Y, Su N, Wang X, Tan Q, Luo F, Zhu Y, Wang Q, Du X, Xian CJ, Liu P, Huang H, Shen Y, Deng CX, Chen D, Chen L
Hum Mol Genet 2012 Dec 15;21(26):5443-55. Epub 2012 Sep 26 doi: 10.1093/hmg/dds390. PMID: 23014564Free PMC Article

Prognosis

Martínez-Frías ML, Egüés X, Puras A, Hualde J, de Frutos CA, Bermejo E, Nieto MA, Martínez S
Am J Med Genet A 2011 Jan;155A(1):197-202. doi: 10.1002/ajmg.a.33765. PMID: 21204232

Clinical prediction guides

Martínez-Frías ML, Egüés X, Puras A, Hualde J, de Frutos CA, Bermejo E, Nieto MA, Martínez S
Am J Med Genet A 2011 Jan;155A(1):197-202. doi: 10.1002/ajmg.a.33765. PMID: 21204232

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...