Because this syndrome is rare, it may only be considered by the treating physician after the child's hypertension does not respond to medications for lowering blood pressure.

[3] This syndrome is caused by dysregulation of the epithelial sodium channel (ENaC) due to a genetic mutation at the 16p13-p12 locus.

Specifically, the PY motif in the protein is deleted or altered so the E3 ligase (Nedd4) no longer recognizes the channel.

This loss of ability to be degraded leads to high amounts of the channel being chronically present on the apical membrane of the epithelial cells that line the collecting ducts of the kidney.

[9] Medical treatment usually corrects both the hypertension and the hypokalemia, and as a result these patients may not require any potassium replacement therapy.

[11] Liddle described the syndrome in a family of people exemplifying a heritable, autosomal dominant hypertension with low potassium, renin, and aldosterone.