From the Guidelines
No, Liddle syndrome is not autosomal recessive; it is an autosomal dominant disorder. This means that a person only needs to inherit one copy of the mutated gene from one parent to develop the condition. Liddle syndrome is a rare genetic disorder characterized by early-onset hypertension (high blood pressure), hypokalemia (low potassium levels), and metabolic alkalosis, despite having low levels of aldosterone. The condition results from mutations in the genes encoding the epithelial sodium channel (ENaC) subunits, particularly the SCNN1B and SCNN1G genes, as listed in the genetic testing recommendations for Bartter syndrome and other related disorders 1. These mutations lead to increased sodium reabsorption in the distal nephron of the kidney, causing fluid retention and hypertension.
Treatment typically involves potassium-sparing diuretics like amiloride or triamterene, which specifically block these sodium channels, rather than traditional antihypertensive medications. Spironolactone and eplerenone are not effective because the condition is not related to aldosterone excess. Genetic counseling is important for affected individuals since each child of an affected person has a 50% chance of inheriting the mutation. The genetic basis of Liddle syndrome is also discussed in the context of monogenic forms of hypertension in children and adolescents 1, and as part of the broader discussion on genetic predisposition to hypertension in adults 1.
Key points about Liddle syndrome include:
- Autosomal dominant inheritance pattern
- Early-onset hypertension
- Hypokalemia and metabolic alkalosis
- Low aldosterone levels
- Mutations in SCNN1B and SCNN1G genes
- Treatment with potassium-sparing diuretics
- Importance of genetic counseling for affected individuals and their families.
From the Research
Inheritance Pattern of Liddle Syndrome
- Liddle syndrome is an inherited form of low-renin hypertension, transmitted with an autosomal dominant pattern 2, 3, 4.
- The molecular basis of Liddle syndrome resides in germline mutations of the SCNN1A, SCNN1B, and SCNN1G genes, encoding the α, β, and γ-subunits of the epithelial Na⁺ channel (ENaC), respectively 2, 3, 5.
- There is no evidence to suggest that Liddle syndrome is autosomal recessive, as all the studies indicate an autosomal dominant pattern of inheritance.
Clinical Presentation and Diagnosis
- The most common clinical presentation of the disease is early onset hypertension, hypokalemia, metabolic alkalosis, suppressed plasma renin activity, and low plasma aldosterone 2, 6, 4, 5.
- Genetic testing can confirm the diagnosis of Liddle syndrome, and it is essential for identifying patients with this condition 2, 3, 4, 5.
Treatment and Management
- The treatment of Liddle syndrome is based on the administration of ENaC blockers, such as amiloride and triamterene 2, 6, 3, 4, 5.
- Potassium-sparing diuretics can reduce ENaC activity, and in combination with a reduced sodium diet, can restore normotension and electrolyte imbalance in Liddle's syndrome patients 5.