The syndrome is caused by a DNA change, also called mutation or variant, in the RORA gene. The gene codes for a protein which is important for memory and learning. The RORA mutations found in the original study group of children were either absent from both unaffected parents, or inherited from a parent who had similar clinical symptoms. In the first case, the mutations are considered as de novo and the recurrence risk is very low, which means that there is a minimal chance for future children to have the same RORA mutation and be affected by the same disorder as the older sibling. However, this risk is increased compared to that of the general population, due to possible germline mosaicism of a transmitting parent. By contrast, each child of an affected individual has a 50% risk of being affected dependent on whether or not he or she inherits the mutated or normal copy of the gene from the affected parent.
Prenatal genetic counselling can be offered in families where the diagnosis has been molecularly confirmed.