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Disease Profile

Thanatophoric dysplasia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Neonatal

ICD-10

Q77.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Dwarfism thanatophoric; Thanatophoric Dwarfism; TD

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]

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.

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
IQ less than 20
0002187
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Micromelia
Smaller or shorter than typical limbs
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
Shorter than typical length between neck and abdomen
0010306
Skeletal dysplasia
0002652
30%-79% of people have these symptoms
Brachydactyly
Short fingers or toes
0001156
Frontal bossing
0002007
Gray matter heterotopia
0002282
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
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
Darkened and thickened skin
0000956
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

0001631
Cloverleaf skull
0002676
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Hip dysplasia
0001385
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Joint hyperflexibility
Joints move beyond expected range of motion
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
High levels of amniotic fluid
0001561
Respiratory insufficiency
Respiratory impairment
0002093
Seizure
0001250

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]

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.

    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

      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

        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.
        • 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.

          References

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

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