Liddle syndrome Type 1 Sequencing

Liddle syndrome, pseudoaldosteronism, 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 pedigrees or isolated cases having been reported worldwide as of 2008.

This syndrome is caused by disregulation of an epithelial sodium channel (ENaC) due to a genetic mutation of the SCNN1B or SCNN1G genes chromosome locus 16p13-p12. The SCNN1B and SCNN1G genes each provide instructions for making one piece, of a protein complex called the epithelial sodium channel (ENaC). The channel is composed of alpha, beta, and gamma subunits. These channels are found at the surface of certain cells called epithelial cells in many tissues of the body, including the kidneys, lungs, and sweat glands. The ENaC channel transports sodium into cells.

The mutations change a domain in the channel so it is no longer degraded correctly by the ubiquitin proteasome system. Specifically the PY motif in the protein is deleted or altered so the E3 ligase (Nedd4) no longer recognizes the channel. Therefore, there is increased activity of this channel leading to increased sodium reabsorption. The increased sodium reabsorption leads to hypertension due to an increase in extracellular volume.

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.

We provide sequencing for SCNN1B and SCNN1G.

Methodology: Sequencing of entire coding region

Purpose: Confirmation of Clinical Diagnosis

ICD-9 Code 405.99

Test Requisition: Sequencing Requisition

CPT Code: 81479 Cost: $1193.00 each test. If sequencing both genes total cost $2343.00.

Turn-around-time: 5-6 weeks each test