2.1 Robinow Syndrome

At least four mutations in the FZD2 gene have been found to cause autosomal dominant Robinow syndrome, a condition that affects the development of many parts of the body, particularly the skeleton. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. FZD2 gene mutations cause a form of the condition that can have a wide variety of features. These include short stature, a particular pattern of facial characteristics, shortening of the long bones in the arms and legs, and short fingers and toes (brachydactyly). This combination of features has been described as autosomal omodysplasia, but researchers now believe that it actually represents a subtype of autosomal dominant Robinow syndrome.

Three of the known mutations change a single protein building block (amino acid) at position 434 in the FZD2 protein. Another mutation leads to the production of an abnormally short version of the FZD2 protein. These mutations are thought to alter or remove a region of the protein that is needed for its interaction with DVL proteins, which impairs Wnt signaling. Problems with Wnt signaling pathways disrupt the development of many organs and tissues before birth, leading to Robinow syndrome.