Molecular characteristics

Disease-causing mutations in the LRP2 gene are responsible for Donnai-Barrow syndrome. Two disease-causing mutations, one on each copy of the LRP2 gene, are necessary for the condition to develop. This type of genetic inheritance is called autosomal recessive.

Individuals carrying only one disease-causing mutation are not affected, and they are referred to as carriers. Both parents of a child with Donnai-Barrow syndrome are usually carriers, and have a 25% risk of having a child with the condition in every pregnancy. A personalized risk assessment can be performed in a genetic counselling session.

The LRP2 protein, also called Megalin, is important during the formation of organs and tissues before birth. When the LRP2 protein cannot be produced because of two altered LRP2 genes, some organs and tissues may not develop correctly.

The exact mechanism leading to the specific pattern of anomalies seen in individuals with Donnai-Barrow syndrome is the object of active research. It is hypothesized that signalling molecules (such as Shh) driving the correct formation of organs and tissues, may not be recognized by cells missing the LRP2 protein.