Hyperkalemic periodic paralysis (HYPP, HyperKPP) is an inherited autosomal dominant disorder that affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood. It is characterized by muscle hyperexcitability or weakness which, exacerbated by potassium, heat or cold, can lead to uncontrolled shaking followed by paralysis. Onset usually occurs in early childhood, but it still occurs with adults. The mutation which causes this disorder is dominant on SCN4A with linkage to the sodium channel expressed in muscle. The mutation causes single amino acid changes in parts of the channel which are important for inactivation. These mutations impair "ball and chain" fast inactivation of SCN4A following an action potential. Signs and symptoms Hyperkalemic periodic paralysis causes episodes of extreme muscle weakness, with attacks often beginning in childhood. Depending on the type and severity of the HyperKPP, it can increase or stabilize until the fourth or fifth decade where attacks may cease, decline, or, depending on the type, continue on into old age. Factors that can trigger attacks include rest after exercise, potassium-rich foods, stress, fatigue, weather changes, certain pollutants (e.g., cigarette smoke) and fasting. Muscle strength often improves between attacks, although many affected people may have increasing bouts of muscle weakness as the disorder progresses (abortive attacks). Sometimes with HyperKPP those affected may experience degrees of muscle stiffness and spasms (myotonia) in the affected muscles. This can be caused by the same things that trigger the paralysis, dependent on the type of myotonia. Some people with hyperkalemic periodic paralysis have increased levels of potassium in their blood (hyperkalemia) during attacks. In other cases, attacks are associated with normal blood potassium levels (normokalemia). Ingesting potassium can trigger attacks in affected individuals, even if blood potassium levels do not rise in response. In contrast to HyperKPP, hypokalemic periodic paralysis (noted in humans) refers to loss-of-function mutations in channels that prevent muscle depolarisation and therefore are aggravated by low potassium ion concentrations. Genetics In humans, the most common underlying genetic cause is one of several possible point mutations in the gene SCN4A. This gene codes for a voltage-gated sodium channel Nav1.4 found at the neuromuscular junction. This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause it. Action potentials from the central nervous system cause end-plate potentials at the NMJ which causes sodium ions to