Liddle syndrome is an autosomal dominant disorder characterized by early, and frequently severe, hypertension associated with low plasma renin activity, metabolic alkalosis due to hypokalemia and low secretion of aldosterone. Liddle syndrome involves abnormal kidney function, with excess reabsorption of sodium and loss of potassium from the renal tubule. It is extremely rare, with fewer than 30 cases reported worldwide as of 2008.
The SCNN1B and SCNN1G genes provide instructions for making one piece, the gamma subunit, of a protein complex called the epithelial sodium channel (ENaC). The channel is composed of alpha, beta, and gamma subunits, each of which is produced from a different gene. These channels are found at the surface of epithelial cells in many tissues of the body, including the kidneys, lungs, and sweat glands. The ENaC channel transports sodium into epithelial cells. Mutations in the SCNN1B and SCNN1G genes lead to increased sodium absorption which result in hypertension and hypokalemia.
Children with Liddle syndrome are frequently asymptomatic. The first indication of the syndrome often is the incidental finding of hypertension during a routine physical exam. Because this syndrome is rare, it may only be considered by the treating physician after the child's hypertension does not respond to antihypertensive agents. Adults could present with nonspecific symptoms of hypokalemia, which can include weakness, fatigue, palpitations or muscular weakness. Additionally, long-standing hypertension could become symptomatic.
||16 known mutations associated with Liddle syndrome.
||5 known mutations in SCNN1G associated with Liddle syndrome.
Methodology: Sequencing of entire coding region
Purpose: Confirmation of Clinical Diagnosis
ICD-10 Code I15.8
Test Requisition: Sequencing Requisition
SCNN1B CPT Code: 81406 Cost: $957.00
SCNN1G CPT Code: 81406 Cost: $858.00
Panel CPT Code: 81406x2 Cost: $1815.00
Turn-around-time: 5-6 weeks each test
1. Online Mendelian Inheritance in Man (OMIM) 177200
2. Rossier BC, Schild L (October 2008). "Epithelial sodium channel: mendelian versus essential hypertension". Hypertension 52 (4): 595–601
3. Brenner and Rector's The Kidney, 8th ed. CHAPTER 40 – Inherited Disorders of the Renal Tubule. Section on Liddle Syndrome. Accessed via MDConsult.
4. Liddle Syndrome. Fact File. British Hypertension Society. 02/2006.