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Disease Profile

Thanatophoric dysplasia type 1

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.

Unknown

Age of onset

Antenatal

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)

Thanatophoric dwarfism 1; Thanatophoric dysplasia type I; TD1;

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 1860

Definition
Thanatophoric dysplasia type 1 (TD1) is a form of TD (see this term) characterized by short, bowed femurs, micromelia, narrow thorax, and brachydactyly.

Epidemiology
The prevalence is unknown but it is more common than TD 2 (see this term).

Clinical description
TD1 presents in the prenatal period (in the first to second trimester) with growth deficiency of the limbs of less than 5%, bowed femurs (like a telephone receiver), shortened ribs, and platyspondyly of the vertebrae. Distinctive facial features include macrocephaly, large anterior fontanel, frontal bossing, proptosis and low nasal bridge. Neonates usually die shortly after birth due to respiratory insufficiency and/or spinal cord/brain stem compression. Platyspondylic lethal skeletal dysplasia, San Diego type (PTSD-SD) is now thought to be an earlier fetal phenotype of TD1, and is no longer characterized as a distinct dysplasia.

Etiology
TD1 is caused by one of several distinct missense mutations in the fibroblast growth factor receptor 3 (FGFR3) gene, located to chromosome 4p16.3.

Genetic counseling
TD1 is inherited autosomal dominantly but the majority of cases are due to a de novo mutation in the proband. Genetic counseling allows families who have already had one child with TD1 to know that recurrence rate is about 2%, so their chance of having a healthy child is high.

Visit the Orphanet disease page for more resources.

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
Abnormality of the sacroiliac joint
0100781
Brachydactyly
Short fingers or toes
0001156
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
Femoral bowing
Bowed thighbone
0002980
Flat face
Flat facial shape
0012368
Hypoplastic ilia
0000946
Intellectual disability, profound
IQ less than 20
0002187
Lethal short-limbed short stature
0008909
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
Redundant skin
Loose redundant skin
Redundant skin folds
Sagging, redundant skin

[ more ]

0001582
Respiratory insufficiency
Respiratory impairment
0002093
Short femur
Short thighbone
0003097
Short greater sciatic notch
0003185
Skeletal dysplasia
0002652
Split hand
Claw hand
Claw hand deformities
Claw hands
Claw-hand deformities
Split-hand

[ more ]

0001171
30%-79% of people have these symptoms
Aplasia/Hypoplasia of the lungs
Absent/small lungs
Absent/underdeveloped lungs

[ more ]

0006703
Excessive wrinkled skin
0007392
Frontal bossing
0002007
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Increased nuchal translucency
0010880
Kyphosis
Hunched back
Round back

[ more ]

0002808
Polyhydramnios
High levels of amniotic fluid
0001561
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

0000520
Ventriculomegaly
0002119
Wide anterior fontanel
Wider-than-typical soft spot of skull
0000260
5%-29% of people have these symptoms
Abnormality of the kidney
Abnormal kidney
0000077
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
Gray matter heterotopia
0002282
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Joint stiffness
Stiff joint
Stiff joints

[ more ]

0001387
Patent ductus arteriosus
0001643
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
Less than 10 fetal movements in 12 hours
0001558
Flared metaphysis
Flared wide portion of long bone
0003015
Global developmental delay
0001263
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
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

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.

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 type 1. 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 type 1. Click on the link to view a sample search on this topic.