Liddle's syndrome: prospective genetic screening and suppressed aldosterone secretion in an extended kindred

J Clin Endocrinol Metab. 1997 Apr;82(4):1071-4. doi: 10.1210/jcem.82.4.3862.


Liddle's syndrome is an autosomal dominant form of hypertension that resembles primary hyperaldosteronism, is characterized by the early onset of hypertension with hypokalemia and suppression of both PRA and aldosterone, and is caused by mutations in the carboxyl-terminus of the beta- or gamma-subunits of the renal epithelial sodium channel. We describe a kindred (K176) whose distinguishing clinical features were mild hypertension and decreased aldosterone secretion. The index case was a 16-yr-old girl with intermittent mild hypertension and hypokalemia and subnormal PRA, aldosterone, 18-hydroxy-corticosterone, and deoxycortisol levels, but normal cortisol/cortisone metabolite ratio and cortisol half-life. A frameshift mutation in the carboxyl-terminus of the beta-subunit of the epithelial sodium channel was identified in the index case, establishing the diagnosis of Liddle's syndrome. Sixteen at-risk relatives of the index case were tested. Seven new subjects were heterozygous for the mutation found in the index case, and two deceased obligate carriers were identified. All genetically affected adult subjects had a history of mild hypertension, and four had a history of hypokalemia. Basal and postcosyntropin plasma aldosterone and urinary aldosterone levels were significantly suppressed in those positive for the mutation. The family demonstrates variability in the severity of hypertension and hypokalemia in this disease, raising the possibility that this disease may be underdiagnosed among patients with essential hypertension.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aldosterone / blood
  • Aldosterone / metabolism*
  • Blood Pressure
  • Female
  • Frameshift Mutation
  • Genetic Testing*
  • Heterozygote
  • Humans
  • Hypertension / genetics*
  • Hypertension / physiopathology
  • Hypokalemia / genetics*
  • Male
  • Middle Aged
  • Pedigree
  • Prospective Studies
  • Syndrome


  • Aldosterone