Other areas of the body are also affected by malformations, such as the face, skull, reproductive organs, anus, lungs and pelvis.

The syndrome causes severe malformations of various parts of the body, including the face and head, heart, nervous system, skeleton, and genitalia.

Researchers have found loss-of-function mutations in the WNT3 or the RSPO2 genes in people with tetra-amelia syndrome from several consanguineous families.

Mutations in the WNT3 or RSPO2 genes prevent cells from producing functional WNT3 and RSPO2 proteins, which disrupts normal limb formation and leads to the other serious birth defects associated with tetra-amelia syndrome.

According to a 2018 study by Bruno Reversade, the loss of RSPO2, unlike WNT3, also prevents formation of the lungs causing a lethal syndrome of tetra-amelia.