Thanatophoric dysplasia

Title

Other Names:

Dwarfism thanatophoric; Thanatophoric Dwarfism

Summary Summary

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.^[1]

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.^[1]

Last updated: 12/13/2012

Symptoms Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormality of the metaphysis	Abnormality of the wide portion of a long bone	0000944
Depressed nasal bridge	Depressed bridge of nose Flat bridge of nose Flat nasal bridge Flat, nasal bridge Flattened nasal bridge Low nasal bridge Low nasal root [ more ]	0005280
Disproportionate short-limb short stature	Short limb dwarfism, disproportionate Short-limbed dwarfism [ more ]	0008873
Flat face	Flat facial shape	0012368
Increased nuchal translucency		0010880
Intellectual disability, profound		0002187
Macrocephaly	Increased size of skull Large head Large head circumference [ more ]	0000256
Micromelia		0002983
Muscular hypotonia	Low or weak muscle tone	0001252
Narrow chest	Low chest circumference Narrow shoulders [ more ]	0000774
Platyspondyly	Flattened vertebrae	0000926
Pulmonary hypoplasia	Small lung Underdeveloped lung [ more ]	0002089
Redundant skin	Loose redundant skin Redundant skin folds Sagging, redundant skin [ more ]	0001582
Short thorax		0010306
Skeletal dysplasia		0002652
30%-79% of people have these symptoms
Brachydactyly		0001156
Frontal bossing		0002007
Hearing impairment	Deafness Hearing defect [ more ]	0000365
Heterotopia		0002282
Intrauterine growth retardation	Prenatal growth deficiency Prenatal growth retardation [ more ]	0001511
Midface retrusion	Decreased size of midface Midface deficiency Underdevelopment of midface [ more ]	0011800
Proptosis	Bulging eye Eyeballs bulging out Prominent eyes Prominent globes Protruding eyes [ more ]	0000520
Ventriculomegaly		0002119
5%-29% of people have these symptoms
Abnormality of the kidney	Abnormal kidney	0000077
Abnormality of the sacroiliac joint		0100781
Acanthosis nigricans		0000956
Atrial septal defect		0001631
Cloverleaf skull		0002676
Downslanted palpebral fissures	Downward slanting of the opening between the eyelids	0000494
Hip dysplasia		0001385
Hydrocephalus		0000238
Joint hyperflexibility		0005692
Joint stiffness	Stiff joint Stiff joints [ more ]	0001387
Kyphosis	Hunched back Round back [ more ]	0002808
Low-set ears	Low set ears Lowset ears [ more ]	0000369
Patent ductus arteriosus		0001643
Polyhydramnios		0001561
Respiratory insufficiency	Respiratory impairment	0002093
Seizures	Seizure	0001250
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance		0000006
Bowing of the long bones	Bowed long bones Bowing of long bones [ more ]	0006487
Decreased fetal movement		0001558
Flared metaphysis	Flared wide portion of long bone	0003015
Global developmental delay		0001263
Hypoplastic ilia		0000946
Lethal short-limbed short stature		0008909
Metaphyseal irregularity	Irregular wide portion of a long bone	0003025
Neonatal death	Neonatal lethal	0003811
Severe platyspondyly		0004565
Severe short stature	Dwarfism Proportionate dwarfism Short stature, severe [ more ]	0003510
Short long bone	Long bone shortening	0003026
Short ribs		0000773
Short sacroiliac notch		0003185
Small abnormally formed scapulae	Small abnormally formed shoulder blade	0006584
Small face	Short and narrow face Small facies [ more ]	0000274
Small foramen magnum	Little foramen magnum Narrow foramen magnum [ more ]	0002677
Wide-cupped costochondral junctions		0000910

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 5/1/2018

Cause Cause

Thanatophoric dysplasia is caused by 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 problems with bone growth that are seen in thanatophoric dysplasia. It is not known how FGFR3 mutations cause the brain and skin abnormalities associated with this disorder.^[1]

Last updated: 6/5/2014

Inheritance Inheritance

Thanatophoric dysplasia is considered an autosomal dominant disorder because one mutated copy of the FGFR3 gene in each cell causes the condition. However, almost 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.^[1]^[2] No affected individuals are known to have had children, so the disorder has not been passed to the next generation.^[1]

Last updated: 6/5/2014

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

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Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Patient Registry

International Skeletal Dysplasia Registry
UCLA-OHRC
Attn: Alisa Zargaryan
615 Charles E. Young Drive
South, Room 410
Los Angeles, CA 90095-7358
Telephone: 310-825-8998
E-mail: AZargaryan@mednet.ucla.edu
Web site: http://ortho.ucla.edu/isdr

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Compassionate Friends
P.O. Box 3696
Oak Brook, IL 60522-3696
Toll-free: 877-969-0010
Telephone: 630-990-0010
Fax: 630-990-0246
E-mail: nationaloffice@compassionatefriends.org
Website: http://www.compassionatefriends.org
European Skeletal Dysplasia Network
Wellcome Trust Centre for Cell-Matrix Research
Faculty of Life Sciences
University of Manchester
Michael Smith Building
Oxford Road
Manchester M13 9PT
United Kingdom
Telephone: 0161 276 3202
Fax: 0161 276 4058
E-mail: info@esdn.org
Website: http://www.esdn.org/eug/Home
Helping After Neonatal Death (HAND)
Los Gatos, CA 95031
Telephone: 888-908-4263
E-mail: info@handonline.org
Website: http://www.handonline.org/resources/handgroups.html

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Thanatophoric dysplasia. This website is maintained by the National Library of Medicine.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Thanatophoric dysplasia. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I was pregnant with twins who were diagnosed with thanatophoric dysplasia. What are the chances that I will have another pregnancy affected by this condition? See answer

Have a question? Contact a GARD Information Specialist.

References References

Thanatophoric dysplasia. Genetics Home Reference (GHR). October 2012; http://ghr.nlm.nih.gov/condition/thanatophoric-dysplasia.
Karczeski B, Cutting GR. Thanatophoric Dysplasia. GeneReviews. September 12, 2013; http://www.ncbi.nlm.nih.gov/books/NBK1366/.

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