ANDERSENS-SYNDROME - A DISTINCT PERIODIC PARALYSIS

A previous study of 4 patients defined Andersen's syndrome (AS) as a t riad of potassium-sensitive periodic paralysis, ventricular dysrhythmi as, and dysmorphic features. AS appears to be distinct in terms of its genetic defect from the alpha-subunit of skeletal muscle sodium chann el and the cardiac potassium channel responsible for most long QT synd romes (LQT1). We studied Ii additional patients with AS from 5 kindred s. Spontaneous attacks of paralysis were associated with hypokalemia, normokalemia, or hyperkalemia. All 11 patients had similar dysmorphic features. The QT interval was prolonged in all patients although only 4 were symptomatic. Genetic linkage studies excluded linkage to the a- subunit of the skeletal muscle sodium channel and to four distinct LQT loci. In addition, none of the common dihydropyridine receptor mutati ons responsible for hypokalemic periodic paralysis were present. We co nclude that (1) AS is a genetically unique channelopathy affecting bot h cardiac and skeletal membrane excitability, (2) attacks of paralysis may be either hypokalemic or hyperkalemic, (3) a prolonged QT interva l is an integral feature of this syndrome, and (4) a prolonged QT inte rval may be the only sign in an individual from an otherwise typical A S kindred. This may be confused with more common, potentially lethal L QT syndromes.