Geller syndrome is a rare, autosomal dominant genetic disorder characterized by hypertension (high blood pressure) and hypokalemia (low potassium levels) that worsens during pregnancy. This condition results from a specific missense mutation (S810L) in the mineralocorticoid receptor (MR) gene.
Here's a breakdown of key aspects:
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Genetic Basis: The root cause is a mutation in the gene that codes for the mineralocorticoid receptor. This receptor plays a critical role in regulating sodium and potassium balance in the kidneys. Specifically, the S810L mutation refers to a change at position 810 in the receptor protein sequence, where serine (S) is replaced by leucine (L). This seemingly small change dramatically alters the receptor's function.
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Autosomal Dominant Inheritance: This means that only one copy of the mutated gene is needed to cause the syndrome. If one parent has Geller syndrome, there is a 50% chance their child will inherit the condition.
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Mineralocorticoid Receptor Upregulation by Progesterone: During pregnancy, progesterone levels increase significantly. Progesterone, normally considered a hormone involved in pregnancy maintenance, can bind to and activate the mutated mineralocorticoid receptor. This activation leads to increased sodium retention and potassium excretion by the kidneys, exacerbating hypertension and hypokalemia. In essence, the mutated receptor becomes abnormally sensitive to progesterone.
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Clinical Manifestations:
- Hypertension: High blood pressure, often significantly elevated, particularly during pregnancy.
- Hypokalemia: Low potassium levels in the blood, which can lead to muscle weakness, cramps, and heart rhythm abnormalities.
- Exacerbation During Pregnancy: Symptoms worsen significantly during pregnancy due to the increased levels of progesterone.
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Diagnosis: Diagnosis typically involves:
- Suspecting the condition based on clinical presentation (hypertension and hypokalemia, especially during pregnancy).
- Biochemical testing to confirm hypokalemia and assess hormone levels (including progesterone).
- Genetic testing to identify the S810L mutation in the mineralocorticoid receptor gene.
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Treatment:
- Potassium supplementation: To correct hypokalemia.
- Antihypertensive medications: To manage high blood pressure. Spironolactone, a mineralocorticoid receptor antagonist, is often ineffective due to the increased progesterone activation of the mutant receptor. Other antihypertensive agents may be necessary.
- Careful monitoring during pregnancy: Due to the potential for severe complications.
In summary, Geller syndrome is a genetic disorder resulting from a mutated mineralocorticoid receptor that is abnormally activated by progesterone, leading to hypertension and hypokalemia, especially during pregnancy.
