Familial hypokalemic periodic paralysis (HOPP) is an autosomal dominant disorder characterized by episodic muscle weakness with hypokalemia. HOPP is genetically linked to missense mutations at charged residues in either a calcium channel gene (CACNA1S) or a sodium channel gene (SCN4A). The paralytic attacks generally spare the respiratory muscles and the heart. Here, we report an atypical case of HOPP in a family that presented with frequent respiratory insufficiency during severe attacks. A 17-year-old boy was referred to our clinic for evaluation of episodic attacks of flaccid weakness with concomitant respiratory insufficiency over the previous five years. His father and uncle experienced similar paralytic attacks, but the frequency and severity of attacks were decreased with age. An acute crisis would occur after the ingestion of carbohydrate- or sodium-rich meals and vigorous exercise. During severe attacks, the patient frequently required ventilator support. In a provocation test with intravenous injections of glucose and insulin, the patient developed numbness in hands, followed by a severe flaccid paralysis of all extremities and trunk with respiratory distress. There was hypokalemia (1.3mmol/L), blood pH 7.31, PaCO2 52.2mmHg, HCO3 27mmHg and SaO2 85%. He was cyanosed in spite of high flow oxygen supply by mask. He required ventilator support for 18 hours. The patient recovered completely from the paralysis after the injection of intravenous potassium. A combination of spironolactone, amiloride, and oral potassium salts was prescribed for treatment. After beginning this regimen, the frequency and severity of attacks were markedly reduced. Molecular analysis identified a rare mutation, Arg222Trp, in the SCN4A gene. This mutation has not previously been reported in Asian patients with HOPP. The patient\'s aunt with an affected son had the same mutation but never experienced any paralytic attacks in her lifetime. This is the first case of incomplete penetrance of the Arg222Trp SCN4A mutation. Genotype-Phenotype correlations in HOPP patients are of interest and have been reported in a number of previous studies. However, respiratory insufficiency has not previously been reported in association with the Arg222Trp mutation.