Thanatophoric dysplasia, the most common fatal form of skeletal dysplasia, is a condition characterized by a cloverleaf skull, short limbs, short ribs, narrow chest, large head, prominent forehead, central nervous abnormalities, shortened spine, and the underdevelopment of the upper jaw, cheekbones, and eye sockets. The incidence rate of thanatophoric dysplasia ranges from 0.27 in 10,000 to 0.4 in 10,000 live births.
Thanatophoric dysplasia is not associated with aneuploidy or chromosomal abnormalities. Thanatophoric dysplasia is associated premature birth as well as other fetal anomalies such as agenesis of the corpus callosum, hydrocephalus, polyhydramnios, and pulmonary hypoplasia. Thanatophoric dysplasia is uniformly fatal in the perinatal period. In the rare instances when a baby survives beyond the perinatal period, the prognosis is extremely poor.
In 50% of instances of thanatophoric dysplasia, the father’s age was over 35 years old. When the father’s age is between 35 and 39 years old at the time of conception, there is a threefold increase in risk for thanatophoric dysplasia. Thanatophoric dysplasia almost always occurs randomly, meaning the recurrence risk is extremely low; however, there are a small number of familial cases. Parental genetic testing may be indicated prior to subsequent pregnancies.