Abstract: SA-PO590
Liddle Syndrome in a Family Presenting with Early-Onset Hypertension, Sudden Death, and Bilateral Kidney Cysts
Session Information
- Cystic Kidney Diseases: Genetic Causes, Modifiers, and Extrarenal Manifestations
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic
Authors
- Wongboonsin, Janewit, Brigham and Women's Hospital, Boston, United States
- Channaoui, Nadine N., Mass General Brigham Inc, Boston, Massachusetts, United States
- Verwillow, Anna, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Ho, Carolyn, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Onuchic-Whitford, Ana C., Brigham and Women's Hospital, Boston, Massachusetts, United States
Introduction
Liddle syndrome is an autosomal dominant form of monogenic hypertension (HTN). Caused by gain-of-function variants in genes encoding subunits of ENaC, classical presentation includes early-onset HTN, hypokalemia and metabolic alkalosis. Here, we describe a family with early-onset HTN referred for history of sudden death and bilateral kidney cysts, found to have Liddle syndrome.
Case Description
A 40-year-old (yo) female with early-onset HTN presented for evaluation of kidney cysts. Diagnosed with HTN at 18 yo, imaging revealed small bilateral kidney cysts, attributed to polycystic kidney disease (PKD). She was treated with lisinopril, HCTZ and metoprolol, with normal serum potassium (mid-high 3s) and renal function. A prior cystic kidney genetic panel was negative. At our clinic, a broad kidney genetic panel was sent to further explore her cystic disease/HTN, revealing a heterozygous pathogenic variant in SCNN1B c.1853C>T (p.Pro618Leu) consistent with Liddle syndrome (LS). No variants were found in PKD-related genes. 24-hour urine study showed undetectable aldosterone and high potassium. A younger sister with early HTN had sudden death at 37yo, during a high-altitude trip after episodes of vomiting. Autopsy revealed cardiomegaly and hypertrophic cardiac remodeling due to HTN, with multiple small bilateral kidney cysts. Cardiomyopathy gene panel (not inclusive of SCNN1B) was negative, with insufficient DNA for further testing. Their 70 yo father had early HTN, stroke, hypokalemia, bilateral kidney cysts, and found to have the same SCNN1B variant. The patient and father were transitioned to amiloride with excellent control of HTN.
Discussion
LS is a tubulopathy typically characterized by hypokalemic HTN and metabolic alkalosis. Lack of this full triad may result in delayed diagnosis and HTN-associated end-organ damage. Although kidney cysts are not regarded as part of LS, here all affected family members had small bilateral cysts, independent of hypokalemia. Additionally, association of LS with sudden cardiac death was suspected due to hypertensive cardiomyopathy, potassium loss, and likely arrhythmia. Increased genetic testing in nephrology may contribute to phenotypic expansion of Mendelian diseases, enable earlier molecular diagnoses, and support inclusion of relevant genes in phenotype-driven panels.