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Genetics Home Reference: your guide to understanding genetic conditions
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Thanatophoric dysplasia

Reviewed October 2012

What is thanatophoric dysplasia?

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.

How common is thanatophoric dysplasia?

This condition occurs in 1 in 20,000 to 50,000 newborns. Type I thanatophoric dysplasia is more common than type II.

What genes are related to thanatophoric dysplasia?

Mutations in the FGFR3 gene cause thanatophoric dysplasia. Both types of this condition result from mutations in the FGFR3 gene. This gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. Mutations in this gene cause the FGFR3 protein to be overly active, which leads to the severe disturbances in bone growth that are characteristic of thanatophoric dysplasia. It is not known how FGFR3 mutations cause the brain and skin abnormalities associated with this disorder.

Related Gene(s)

Changes in this gene are associated with thanatophoric dysplasia.

  • FGFR3

How do people inherit thanatophoric dysplasia?

Thanatophoric dysplasia is considered an autosomal dominant disorder because one mutated copy of the FGFR3 gene in each cell is sufficient to cause the condition. Virtually all cases of thanatophoric dysplasia are caused by new mutations in the FGFR3 gene and occur in people with no history of the disorder in their family. No affected individuals are known to have had children; therefore, the disorder has not been passed to the next generation.

Where can I find information about diagnosis or management of thanatophoric dysplasia?

These resources address the diagnosis or management of thanatophoric dysplasia and may include treatment providers.

  • Gene Review: Thanatophoric Dysplasia (http://www.ncbi.nlm.nih.gov/books/NBK1366/)
  • Genetic Testing Registry: Thanatophoric dysplasia, type 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1300257)
  • Genetic Testing Registry: Thanatophoric dysplasia type 1 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1868678)

You might also find information on the diagnosis or management of thanatophoric dysplasia in Educational resources (http://ghr.nlm.nih.gov/condition/thanatophoric-dysplasia/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/thanatophoric-dysplasia/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about thanatophoric dysplasia?

You may find the following resources about thanatophoric dysplasia helpful. These materials are written for the general public.

  • MedlinePlus - Health information

    • Health Topic: Craniofacial Abnormalities (http://www.nlm.nih.gov/medlineplus/craniofacialabnormalities.html)
    • Health Topic: Dwarfism (http://www.nlm.nih.gov/medlineplus/dwarfism.html)
    • Health Topic: Respiratory Failure (http://www.nlm.nih.gov/medlineplus/respiratoryfailure.html)
  • Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/85/resources/resources/1)

  • Educational resources - Information pages

    • Madisons Foundation (http://www.madisonsfoundation.org/index.php?option=com_mpower&task=disease&diseaseID=576)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=2655)

  • Patient support - For patients and families

    • International Skeletal Dysplasia Registry, Cedars-Sinai Medical Center (http://isdr.csmc.edu/)
    • Little People of America, Inc. (http://www.lpaonline.org/)
    • Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/skeldysp.html)
    • The MAGIC Foundation (http://www.magicfoundation.org/)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1366/)

  • Genetic Testing Registry - Repository of genetic test information

    • Genetic Testing Registry: Thanatophoric dysplasia, type 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1300257)
    • Genetic Testing Registry: Thanatophoric dysplasia type 1 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1868678)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22thanatophoric%20dysplasia%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(Thanatophoric%20Dysplasia%5BMAJR%5D)%20AND%20(thanatophoric%20dysplasia%5BTIAB%5D)%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)

  • OMIM - Genetic disorder catalog

    • THANATOPHORIC DYSPLASIA, TYPE I (http://omim.org/entry/187600)
    • THANATOPHORIC DYSPLASIA, TYPE II (http://omim.org/entry/187601)

What other names do people use for thanatophoric dysplasia?

  • Dwarf, thanatophoric
  • thanatophoric dwarfism
  • thanatophoric short stature

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about thanatophoric dysplasia?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding thanatophoric dysplasia?

autosomal ; autosomal dominant ; cell ; dwarf ; dwarfism ; dysplasia ; gene ; protein ; respiratory ; short stature ; stature ; tissue

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Cohen MM Jr. Some chondrodysplasias with short limbs: molecular perspectives. Am J Med Genet. 2002 Oct 15;112(3):304-13. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12357475?dopt=Abstract)
  • Foldynova-Trantirkova S, Wilcox WR, Krejci P. Sixteen years and counting: the current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias. Hum Mutat. 2012 Jan;33(1):29-41. doi: 10.1002/humu.21636. Epub 2011 Nov 16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22045636?dopt=Abstract)
  • Gene Review: Thanatophoric Dysplasia (http://www.ncbi.nlm.nih.gov/books/NBK1366/)
  • Martínez-Frías ML, de Frutos CA, Bermejo E, Nieto MA; ECEMC Working Group. Review of the recently defined molecular mechanisms underlying thanatophoric dysplasia and their potential therapeutic implications for achondroplasia. Am J Med Genet A. 2010 Jan;152A(1):245-55. doi: 10.1002/ajmg.a.33188. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20034074?dopt=Abstract)
  • Pannier S, Martinovic J, Heuertz S, Delezoide AL, Munnich A, Schibler L, Serre V, Legeai-Mallet L. Thanatophoric dysplasia caused by double missense FGFR3 mutations. Am J Med Genet A. 2009 Jun;149A(6):1296-301. doi: 10.1002/ajmg.a.32880. (http://www.ncbi.nlm.nih.gov/pubmed/19449430?dopt=Abstract)
  • Vajo Z, Francomano CA, Wilkin DJ. The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans. Endocr Rev. 2000 Feb;21(1):23-39. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10696568?dopt=Abstract)
  • Waller DK, Correa A, Vo TM, Wang Y, Hobbs C, Langlois PH, Pearson K, Romitti PA, Shaw GM, Hecht JT. The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US. Am J Med Genet A. 2008 Sep 15;146A(18):2385-9. doi: 10.1002/ajmg.a.32485. (http://www.ncbi.nlm.nih.gov/pubmed/18698630?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2012
Published: June 10, 2013