The estimated incidence is around 1:25,000-50,000 3.
It results from a mutation coding for the fibroblast growth receptor 3 (FGFR3) located on chromosome 4p16.3. The type of receptor mutation is different from the FGFR mutation in achondroplasia. Inheritance is thought to be sporadic.
There are two recognised subtypes:
- type I: marked underdevelopment of skeleton, telephone handle femurs more pronounced
- the presence of a cloverleaf skull may be a distinctive feature
- limb shortening milder and bowing is not a feature 3
It may be difficult to accurately diagnose before the 3rd trimester (≈22 weeks) 4. Before that time it can be in included in the differential if there is a short femur length measurement.
Sonographically-detectable features may include:
- relatively narrow thoracic cavity 4
- short, thick, bowed tubular bones, especially lower extremity 4
- thickened soft tissues of extremities 4
- comparatively large head with frontal bossing
- a cloverleaf skull appearance may also be seen: type II (see case 3)
Plain films are usually done post-mortem if done at all. Features include:
- proximal portions of the long limbs are small, giving a rhizomelic appearance
- long bones (typically humeri and femora) have a typical "telephone handle" bowing with metaphyseal flaring
- narrow chest
- short horizontal ribs
- small scapulae
Skull and face
- relative macrocephaly
- frontal bossing
- nasal bridge flattening
- kleeblattschaedel, or cloverleaf skull (with type II) 2-4
- platyspondyly: flattening of vertebral bodies
- normal trunk length
Treatment and prognosis
The condition is uniformly fatal within a few hours of birth either from respiratory failure or from brainstem compression from a narrow foramen magnum.
History and etymology
The term thanatophoric derives from the Greek words "thanatos" (θάνατος) meaning "death" 2 and "phoros" meaning "bearing/carrying/bringing".
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- 3. Miller E, Blaser S, Shannon P et-al. Brain and bone abnormalities of thanatophoric dwarfism. AJR Am J Roentgenol. 2009;192 (1): 48-51. doi:10.2214/AJR.08.1524 - Pubmed citation
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- 5. Fink AM, Hingston T, Sampson A et-al. Malformation of the fetal brain in thanatophoric dysplasia: US and MRI findings. Pediatr Radiol. 2010;40 Suppl 1 : S134-7. doi:10.1007/s00247-010-1697-4 - Pubmed citation
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