HSMR syndrome is caused by genetic defects in the Cyclin M2 (CNNM2) gene. Loss-of-function of the CNNM2 gene results in the disease. Some patients have an inherited form of HSMR syndrome, meaning that at least one parent also has a genetic defect in CNNM2, while others have de novo mutations (no familial history).
About the function of CNNM2 is still little known, but it is known that it plays an important role in maintaining magnesium (Mg2+) levels within our body. This salt plays an important role in many physiological processes, such as muscle contraction and brain function. Loss of CNNM2 function results in Mg2+ loss via the urine. This results in lowered Mg2+ levels in the blood, a condition called hypomagnesemia. How CNNM2 is involved in brain function and development has yet to be determined.