KCNK9 imprinting syndrome is caused by an alteration in the maternal copy of the KCNK9 gene. The alteration in the KCNK9 gene that causes this disorder is usually a de novo alteration in the maternal copy of the gene. This means that the change in the gene occurred randomly and was not passed on from a parent, so the likelihood of another child in the family having the disorder is extremely low. This disorder involves genetic imprinting. Everyone has two copies of every gene – one received from the father and one received from the mother. In most cases, both genes are “turned on” or active. However, some genes are preferentially silenced or “turned off” based upon which parent that gene was inherited from (genetic imprinting). Genetic imprinting is controlled by chemical switches through a process called methylation. Proper genetic imprinting is necessary for normal development. Defective imprinting has been associated with several disorders. With the KCNK9 gene, the copy received from the father is turned off or silenced. An alteration in this gene from the father is not associated with any consequences to the child, but it can be passed to his daughters, who would then be at risk to have affected children. The copy received from the mother is normally turned on. An alteration to the maternal copy of this gene leads to KCNK9 imprinting syndrome.
The KCNK9 gene encodes a specialized protein, which is important for the proper function of the TASK3 ion channel. Ion channels are pores in cell membranes that regulate the movement of electrically-charged particles (e.g. potassium and sodium ions) into neurons and other cells. These ions carry electrical impulses necessary for the normal function of the cells involved. TASK3 ion channels are found throughout the body, particularly in the brain. Alterations in the maternal copy of the KCNK9 gene result in lack of activity of this ion channel and, in turn, affect the proper function and development of neurons.