Thanatophoric Dysplasia Causes & Symptoms

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About 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).

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

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

Thanatophoric dysplasia is characterized by a severe growth deficiency. At birth, children are, on average 40cm 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 and 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 and Spine

  • narrow thorax, owing to the shortened ribs
  • protuberant abdomen
  • short spine with flattened vertebrae

Arms and Legs

  • disproportionately short extremities compared to a relatively average-sized trunk
  • stunted limbs with small fingers
  • bowed long bones in type I

X-Ray Characteristics

  • 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. 
  • Phalanges, metacarpals, and metatarsal bones are characteristically short (3).

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.

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.

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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