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