What question did this study set out to answer?

To explore the implications of a rare CACNA1S variant on hypokalemic periodic paralysis symptoms.

January 18, 2026Open Access

Hypokalemic Periodic Paralysis Associated With a Rare CACNA1S Variant (p.Leu1243Val): Expanding the Mutational Spectrum

Key Result

The CACNA1S variant p.Leu1243Val was identified in a patient with hypokalemic periodic paralysis, highlighting a potential genotype-phenotype link.

Key Points

To explore the implications of a rare CACNA1S variant on hypokalemic periodic paralysis symptoms.
Case presentation of a 30-year-old woman with recurrent paralytic episodes.
Genetic testing revealed heterozygosity for CACNA1S c.3727C > G (p.Leu1243Val).
Treatment included spironolactone and acetazolamide, with monitoring of symptoms and side effects.
The patient experienced reduced episode frequency with treatment.
Transient hypophosphatemia and hypokalemia occurred during hospitalization.
Family history indicated similar electrolyte disturbances.

Structured PICO

Population

30-year-old Caucasian woman with recurrent paralytic episodes and hypokalemia (2.1–2.3 mmol/L), triggered by stress and carbohydrate-rich meals, heterozygous for CACNA1S c.3727C > G (p.Leu1243Val).

Intervention

Spironolactone 25 mg daily, acetazolamide 250 mg four times daily, and 40 mEq KCl twice daily (later approved for dichlorphenamide).

Outcome

Reduction in paralytic episode frequency and stabilization of serum potassium levels.

This case expands the mutational spectrum of hypokalemic periodic paralysis by highlighting a possible genotype-phenotype link involving the rare CACNA1S p.Leu1243Val variant.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Background Hypokalemic periodic paralysis (HypoPP) is a rare skeletal muscle channelopathy, most often caused by mutations in CACNA1S or SCN4A . Most pathogenic CACNA1S mutations affect arginine residues in S4 voltage‐sensor domains, but other variants remain poorly understood. Case Presentation I describe a 30‐year‐old Caucasian woman with recurrent paralytic episodes and hypokalemia (2.1–2.3 mmol/L), triggered by stress and carbohydrate‐rich meals. Genetic testing revealed heterozygosity for CACNA1S c.3727C > G (p.Leu1243Val), a variant of uncertain significance not previously associated with pathogenicity. Her phenotype was consistent with HypoPP. Treatment with spironolactone and acetazolamide reduced episode frequency, although the latter caused intolerable side effects, particularly tachypnea; she was later approved for dichlorphenamide. During one hospitalization, she also developed transient hypophosphatemia and hypokalemia, consistent with her HypoPP picture. Kidney function and imaging were normal. Family history revealed electrolyte disturbances in her grandfather. Conclusions This case highlights a possible genotype–phenotype link involving CACNA1S p.Leu1243Val. Continued reporting of such cases is essential for variant reclassification and for improving recognition of metabolic shifts during HypoPP attacks.