Thanatophoric Dysplasia

“Thanatophoric” is a Greek term meaning “death-bringing.” There are two distinct forms of this dysplasia: Type 1 and Type 2. Thanatophoric Dwarfism is one of the most common lethal skeletal dysplasias. Its incidence is approximately 2 to 5 in 100,000 births (2).

 
How Thanatophoric Dysplasia Is Inherited

Thanatophoric dysplasia follows an autosomal dominant inheritance pattern. All cases are a result of spontaneous gene mutations (1).

 
Causes of Thanatophoric Dysplasia

A mutation in the fibroblast growth factor receptor-3 (FGFR3) gene is responsible for causing Thanatophoric Dysplasia (1).

 
Physical Characteristics

Thanatophoric dysplasia is characterized by a severe growth deficiency. At birth, children are, on average 40 cm long. Thanatophoric dysplasia type 1 is more common and is characterized by curved long bones, especially the femur, and flat vertebral bodies. A straight femur, taller vertebral bodies, and a cloverleaf skull are typical of Thanatophoric dysplasia type 2.

Face & Skull
Type I:
  • Large cranium and fontanelle
  • Disproportionately full and pronounced forehead
  • Protruding eyes
  • Depressed nasal bridge
Type II:
  • Cloverleaf skull
  • Secondary skull deformities due to premature closure of cranial sutures
Trunk, Chest, & Spine:
  • Narrow thorax, owing to the shortened ribs
  • Protuberant abdomen
  • Short spine with flattened vertebrae
Arms & Legs:
  • Disproportionatly short extremities compared to a relatively average-sized trunk
  • Stunted limbs with small fingers
  • Bowed long bones in type I
What are the X-ray characteristics?

The major radiographic feature of infants with Thanatophoric dysplasia is a narrow thorax. Ribs are short with the rib ends appearing wide and cupped. Vertebral bodies are flat with a wide intervertebral disk space. The interpediculate distances narrow in the lumbar spine.

The pelvis has a short and square configuration. A small sciatic notch and medial spurs are typical. The long bones of the extremities are characteristically short and broad. The metaphyses exhibit cupped, spur-like flaring. Marked bowing of the femur is characteristic in Thanatophoric dysplasia, type I. Fibulae are markedly shorter than the tibiae. The phalanges, metacarpals, and metatarsal bones are characteristically short (3).

 
Making the Diagnosis

Thanatophoric dysplasia can be recognized in utero via ultrasound. Indicators include markedly short limbs and a narrow thorax. After birth, physical and radiographic examination can provide a diagnosis. Molecular testing of the FGFR-3 gene can be done to confirm the diagnosis either prenatally via an amniocentesis sample or postnatally from a blood sample.

 
Associated Medical Problems

Thanatophoric Dysplasia is a type of lethal short-limb platyspondylic dysplasia in which patients usually die shortly after birth, due mostly to respiratory insufficiency. Patients who survive the perinatal period are ventilator-dependent and have severe developmental delay.

 
Problems Elsewhere in Body

Long-term survival is rare, albeit three Thanatophoric children, between the ages of 9 and 10, have been reported. All have severe developmental delay, growth deficiency, and are ventilator-dependent (3).

 
References
  1. Jones, Kenneth L. Recognizable Patterns of Human Malformation. Philadelphia, PA: Elsevier Saunders. 2006.
  2. Orioli, IM. Castilla EE. Barbosa-Neto JG. The birth prevalence rates for the skeletal dysplasias. J Med Genetics. 23: 328-332
  3. Spranger, Jurgen W. Brill, Paula W. Poznanski, Andrew. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2002.

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