Chung-Jansen Syndrome is caused by a defect in the PHIP gene encoding the pleckstrin homology domain-interacting protein. The PHIP gene is located on chromosome 6 (6q14.1). Individuals normally have two chromosomes 6 with two copies of the PHIP gene. Individuals with Chung-Jansen syndrome have a defect in one of the two copies, called a heterozygous variant. This can be a variant in the coding sequence of the gene or a deletion of (part of) the gene. This is called autosomal dominant inheritance.
Most individuals with Chung-Jansen syndrome are the first one in the family and their parents do not have the variant. The variant had arisen de novo during the formation of reproductive cells (eggs and sperm) or in early fetal development. Sometimes the variant was not de novo in the child, but inherted from a parent.
Often, if the variant is inherited, parents do not know they are a carrier. This becomes clear when they got their blood tested after the child has been diagnosed. In case of inheritance there is a 50 % chance that children get the disorder.
How the defect in PHIP causes neurodevelopmental problems and overweight is currently not known.