Liddle's Syndrome: Review of the Clinical Disorder and its Molecular Genetic Basis

Abstract

Liddle's syndrome is an inherited form of salt-sensitive hypertension caused by activating mutations in the beta or gamma subunits of the epithelial sodium channel. These mutations truncate or alter the PY motif in the carboxy-terminus of one of these subunits. The PY motif is important in normal channel regulation via interactions with other proteins, and its loss or alteration results in increased sodium reabsorption, extracellular volume expansion and hypertension. The molecular genetics of this disorder has not only advanced our understanding of its pathophysiology, but now allows prospective screening of atrisk members in known Liddle's kindreds. This may lead to more appropriate pharmacologic therapy and provide further insights into the phenotypic expression of this disease. Although Liddle's syndrome is a rare form of hypertension, study of the genes contributing to normal sodium channel regulation may elucidate other potential candidates involved in more common forms of hypertension.