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Thanatophoric Dysplasia

Last updated Jan. 16, 2019

Approved by: Maulik P. Purohit MD, MPH

Thanatophoric Dysplasia is a severe skeletal disorder characterized by extremely short limbs and folds of extra skin on the arms and legs.


What are the other Names for this Condition? (Also known as/Synonyms)

  • Dwarfism Thanatophoric
  • Thanatophoric Dwarfism

What is Thanatophoric Dysplasia? (Definition/Background Information)

  • 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

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
  • (Source: Thanatophoric Dysplasia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Thanatophoric Dysplasia? (Age and Sex Distribution)

  • Thanatophoric Dysplasia is a rare congenital disorder. The presentation of symptoms may occur at birth
  • Both males and females may be affected
  • Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Thanatophoric Dysplasia? (Predisposing Factors)

  • Currently, no risk factors have been clearly identified for Thanatophoric Dysplasia

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Thanatophoric Dysplasia? (Etiology)

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

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
  • No affected individuals are known to have had children, so the disorder has not been passed to the next generation

(Source: Thanatophoric Dysplasia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

What are the Signs and Symptoms of Thanatophoric Dysplasia?

The signs and symptoms of Thanatophoric Dysplasia may include:

  • Bowing of the long bones
  • Decreased fetal movement
  • Flared metaphysis
  • Hypoplastic ilia
  • Metaphyseal irregularity
  • Severe platyspondyly
  • Severe short stature
  • Short long bone
  • Short ribs
  • Short sacroiliac notch
  • Small abnormally formed scapulae
  • Small face
  • Small foramen magnum
  • Wide-cupped costochondral junctions

Very frequently present symptoms in 80-99% of the cases:

  • Abnormality of the metaphysis
  • Disproportionate short-limb short stature
  • Flat face
  • Increased nuchal translucency
  • Intellectual disability, profound
  • Macrocephaly
  • Micromelia
  • Muscular hypotonia
  • Narrow chest 
  • Platyspondyly
  • Pulmonary hypoplasia
  • Redundant skin
  • Short thorax
  • Skeletal dysplasia

Frequently present symptoms in 30-79% of the cases:

  • Brachydactyly
  • Frontal bossing
  • Hearing impairment
  • Heterotopia
  • Intrauterine growth retardation
  • Midface retrusion
  • Proptosis
  • Ventriculomegaly

Occasionally present symptoms in 5-29% of the cases:

  • Abnormality of the kidney
  • Abnormality of the sacroiliac joint
  • Acanthosis nigricans
  • Atrial septal defect
  • Cloverleaf skull
  • Down Slanted palpebral fissures
  • Hip dysplasia
  • Hydrocephalus
  • Joint hyperflexibility
  • Joint stiffness
  • Kyphosis
  • Low-set ears
  • Patent ductus arteriosus
  • Polyhydramnios
  • Respiratory insufficiency
  • Seizures

(Source: Thanatophoric Dysplasia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Thanatophoric Dysplasia Diagnosed?

Thanatophoric Dysplasia is diagnosed on the basis of the following information:

  • Complete physical examination
  • Thorough medical history evaluation
  • Assessment of signs and symptoms
  • Laboratory tests
  • Imaging studies
  • Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the Possible Complications of Thanatophoric Dysplasia?

The complications of Thanatophoric Dysplasia may include:

  • Severe physical deformities
  • Dysfunction of vital organs such as the kidney, heart, lungs, and brain

Lethal short-limbed short stature and neonatal death are known to occur.

How is Thanatophoric Dysplasia Treated?

There is no cure for Thanatophoric Dysplasia, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can Thanatophoric Dysplasia be Prevented?

Currently, Thanatophoric Dysplasia may not be preventable, since it is a genetic disorder.

  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Thanatophoric Dysplasia? (Outcomes/Resolutions)

  • 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

(Source: Thanatophoric Dysplasia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Additional and Relevant Useful Information for Thanatophoric Dysplasia:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/diseases-conditions/rare-disorders/

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


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Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Dec. 4, 2017
Last updated: Jan. 16, 2019