What Causes the Syndrome

SATB2-associated syndrome (SAS) is caused by changes in the SATB2 gene. This gene is on chromosome 2 at position q33.1 and makes a protein called SATB2 (See Understanding Genetic Testing Results and Background Information). The SATB2 protein works as a transcription factor for some other genes. A transcription factor works by controlling which genes are turned on or off in the genome. The SATB2 protein has important roles in how organs and systems in the human body develop. Animal studies, for example, have shown that the same/similar gene for other species (Satb2) is involved in jaw growth, brain development, and proper bone formation and even small changes of the gene can result in many birth defects.
In humans, there are different ways that the SATB2 gene can be changed and not work properly (See Understanding Genetic Testing Results). The leading theory is that the change in one of the copies of SATB2 (we all have 2 copies of each gene) results in its haploinsufficiency (the “good” copy of SATB2 can’t produce enough SATB2 protein to do all the functions of the gene). Other effects or causes that could play a role for patients with mutations (misspellings) of SATB2 are currently being studied. It is unclear if there are any other reasons for a person to be more or less likely to have SATB2 changes or symptoms.