Channelopathies and Periodic Paralysis

Educational scope notice: This is a study note for medical students, not medical advice, diagnosis, or treatment guidance. Clinical management should follow local protocols and current guidelines.

Channelopathies are disorders of voltage-gated ion channels in the muscle membrane. Mutations change how sodium, calcium, potassium, or chloride channels open and close, so the fibre cannot hold a stable resting potential. Excessive depolarisation makes the fibre inexcitable and produces episodic paralysis; unstable repolarisation produces myotonia, delayed relaxation after contraction. Because the defect is electrical rather than structural, attacks come and go and often respond to treatment, which sets these disorders apart from the steady progression of muscular dystrophy.

Hypokalaemic periodic paralysis

This form most often comes from calcium-channel mutations, with some cases from sodium-channel variants. A carbohydrate-rich meal releases insulin, drives potassium into cells, and the resulting low serum potassium depolarises vulnerable fibres into inexcitability, so the patient may wake unable to move. Onset is usually in early childhood, reflexes vanish during attacks in a peripheral pattern, and the electrocardiogram flattens its T waves. Potassium replacement restores strength and confirms the physiology.

Hyperkalaemic periodic paralysis

Here sodium-channel mutations make attacks follow raised rather than lowered potassium, after exercise, fasting, or potassium-rich meals. Episodes tend to be briefer, minutes to hours, and the electrocardiogram shows tall peaked T waves instead. The potassium level during the attack and the tracing together separate the two forms. Cardiac arrhythmia is uncommon in either, because the mutant channels sit in skeletal rather than cardiac muscle and the shifts are transient.

Andersen-Tawil syndrome

This distinct channelopathy combines episodic paralysis with cardiac arrhythmia risk and dysmorphic features such as low-set ears, small jaw, and wide-set eyes. Potassium can swing in either direction, and both extremes can provoke ventricular arrhythmia, so regular potassium monitoring and cardiac surveillance are part of care from diagnosis.

The nondystrophic myotonias

Myotonia congenita comes from chloride-channel mutations and produces stiffness that eases with repeated contraction, the warm-up phenomenon. Patients compensate for years, so diagnosis is often delayed into adolescence. Paramyotonia congenita comes from sodium-channel mutations and behaves oppositely: stiffness worsens with repeated exercise and cold, a paradoxical myotonia. Neither carries systemic disease, which is the point of the comparison below.

Myotonia on electromyography plus cataracts, endocrine, or cardiac involvement therefore means myotonic dystrophy, not a simple channelopathy.

Treatment

Acetazolamide, a carbonic anhydrase inhibitor, reduces attack frequency in many patients with either hypo- or hyperkalaemic paralysis. Its effect runs through pH-dependent changes in channel gating rather than direct potassium correction, which explains why one drug helps opposite potassium shifts. GeneReviews-based guidance notes benefit in roughly half of treated hypokalaemic patients, no standardised regimen, and possible worsening in sodium-channel genotypes, so genotype informs the choice. Dosing is individualised, typically in the low-to-moderate daily range in divided doses. Potassium management and trigger avoidance accompany drug therapy, and Andersen-Tawil disease adds cardiac follow-up.

Evidence anchors

• Weber F, Lehmann-Horn F. Hypokalemic periodic paralysis. GeneReviews [Internet]. University of Washington, Seattle. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1338/
• Matthews E, Portaro S, Ke Q, et al. Acetazolamide efficacy in hypokalemic periodic paralysis and the predictive role of genotype. Neurology. 2011;77(21):1960-1964. doi:10.1212/WNL.0b013e31823a0e9e