Gordon syndrome

Overview

Gordon syndrome, also known as familial hyperkalemic hypertension or pseudohypoaldosteronism type II (PHAII), is a rare genetic disorder characterized by high blood pressure (hypertension), elevated levels of potassium in the blood (hyperkalemia), and metabolic acidosis. Unlike many forms of hypertension, Gordon syndrome often presents at a young age, including in childhood or adolescence. The condition is treatable and, with proper management, affected individuals can lead healthy lives.

Causes

Gordon syndrome is caused by mutations in genes that regulate salt and potassium balance in the kidneys. The most commonly affected genes include:

• WNK1

• WNK4

• KLHL3

• CUL3

These genes influence the activity of sodium-chloride transporters in the distal tubules of the kidneys. Mutations lead to increased reabsorption of sodium (causing hypertension) and impaired secretion of potassium (causing hyperkalemia). Gordon syndrome follows an autosomal dominant pattern of inheritance, meaning one copy of the mutated gene from an affected parent is sufficient to cause the disorder.

Symptoms

The presentation of Gordon syndrome varies depending on the age and severity, but common symptoms and findings include:

• High blood pressure (hypertension): Often diagnosed in childhood or adolescence

• Hyperkalemia: Elevated potassium levels, which may be asymptomatic or cause muscle weakness and fatigue

• Metabolic acidosis: A condition in which there is too much acid in the body fluids

• Normal or low levels of renin and aldosterone: Despite electrolyte abnormalities

• Muscle cramps or palpitations: In more severe cases of hyperkalemia

Some individuals may be asymptomatic and diagnosed incidentally during routine blood pressure or electrolyte testing.

Diagnosis

Diagnosis of Gordon syndrome involves a combination of clinical evaluation, laboratory tests, and genetic studies:

• Blood pressure measurement: Confirms hypertension, often at a young age

• Blood tests: Show elevated potassium (hyperkalemia) and metabolic acidosis (low bicarbonate)

• Renin and aldosterone levels: Inappropriately low or normal despite electrolyte imbalances

• Genetic testing: Identifies mutations in WNK1, WNK4, KLHL3, or CUL3 genes to confirm diagnosis

It is important to differentiate Gordon syndrome from other causes of hyperkalemia and hypertension, such as chronic kidney disease or medication side effects.

Treatment

Gordon syndrome responds well to specific medications that correct the underlying electrolyte and blood pressure abnormalities. Treatment options include:

• Thiazide diuretics: The mainstay of treatment; they help lower blood pressure and reduce potassium levels by increasing its excretion

• Dietary management: Restriction of potassium intake may be helpful in some cases

• Regular monitoring: Ongoing assessment of blood pressure, serum electrolytes, and renal function

With proper treatment, the metabolic abnormalities are usually completely reversible, and blood pressure can be well controlled.

Prognosis

The prognosis for individuals with Gordon syndrome is excellent when the condition is recognized and managed appropriately. Early diagnosis and treatment with thiazide diuretics typically lead to normalization of blood pressure and potassium levels, preventing complications. The condition does not usually lead to kidney failure or other serious outcomes if treated. Genetic counseling is recommended for affected families due to the autosomal dominant inheritance pattern, allowing for early detection and treatment in at-risk relatives.