Etiology (What causes it?)

As a fetus develops the location of each cell and its surroundings determine how
the cells and tissues develop. The process is called morphogenesis. If something goes wrong in morphogenesis, the time at which it occurs influences the occurance and type of effect. If something occurs at a primary stage it is called a "malformation." (As opposed to a "deformation" which is usually at a later stage and arises from mechanical factors. )

graph Limb buds on the fetus develop at about 28-32 days into pregnancy and at 33-36 days the foot plate is visible. If something affects the growth of the fetus around this critical limb-formation time (4 - 6 weeks) it can lead to PFFD. A teratogen" is the term given to the agent that causes a malformation in an embryo or fetus.
(image from http: // Module10KFetaExposure/Module10K.html )

The teratogen for PFFD is unknown. PFFD is not genetic. Some have proposed that it is caused by anoxia (oxygen deficiency), ischemia (temporary blood supply deficiency), chemicals, hypothermia, radiation, bacterial toxins, viral infections, enzyme and hormone changes.

The only definite cause is the drug Thalidomide which was marketed as a sedative, sleeping pill, and for morning-sickness (unfortunately) before being discontinued in the United States in the early 1960's.[Abdel-Mota'al] , [ Panting AL, 1978 ]