Characterized by the clinical triad of potassium-sensitive periodic paralysis (low, normal, or high potassium levels), ventricular arrhythmias (bigeminy, long QT interval, ectopy, bidirectional ventricular tachycardia), and dysmorphic facial features. Sudden death has been reported. Andersen Syndrome must not be confused with Andersen Disease (Glycogen Storage Disease Type IV).
Andersen Syndrome; Long QT Syndrome Type 7 (LQT7); Cardiodysrhythmic Type of Potassium-Sensitive Periodic Paralysis.
Exact incidence is unknown but probably fewer than 150 cases have been described.
Autosomal dominant condition with clinical features of periodic paralysis and prolonged QT Syndrome but genetically distinct from these conditions. However, sporadic cases have been reported, and the penetrance is highly variable. More than one gene may be involved. Research determined that Andersen Cardiodysrhythmic Periodic Paralysis Syndrome (ACPPS) is caused by mutations in the KCNJ2 gene. This gene has been mapped to 17q23 and encodes the inward rectifier K+ channel Kir2.1, which is expressed in cardiac and skeletal muscle, explaining the combination of cardiac and skeletal muscle involvement.
Other forms of periodic paralysis result from mutations in skeletal muscle-specific Na+, K+, and Ca2+ channels. ACPPS is unique among the channelopathies because of the combination of a skeletal and a cardiac muscle phenotype. The potassium-sensitive periodic paralysis can be associated with hypokalemia, hyperkalemia, or normokalemia. Periodic paralysis occurs with different types of cardiac arrhythmias, most commonly prolonged QT Syndrome and ventricular arrhythmias (ventricular bigeminy, bidirectional ventricular tachydysrhythmia, nonsustained ventricular tachycardia, frequent ventricular ectopy).
Clinical triad of potassium-sensitive periodic paralysis, ventricular ectopy, and dysmorphic features are characteristic and allow for an early diagnosis. To prevent sudden cardiac death, cardiac evaluation with serial EKGs and measurements of QTc interval are essential and should be performed early for all patients undergoing workup for periodic paralysis. A prolonged QTc (QTc = QT/√RR) is present in most patients with ACPPS and is considered by some researchers to be a diagnostic sign. In general, the degree of facial dysmorphism does not correlate with the severity of heart and/or muscle involvement; often the dysmorphic features are mild. The age at onset of periodic paralysis varies from 4 to 18 years. Patients usually have proximal weakness that may exacerbate upon a hypokalemic challenge with intravenous glucose and insulin. However, because fluctuations in serum K+ levels may trigger/exacerbate cardiac arrhythmias in these patients, provocative testing for hypokalemic or hyperkalemic periodic paralysis is contraindicated in ACPPS patients.
Dysmorphic features may include short stature, low-set ears (40%), hypertelorism (36%), broad nasal root, micrognathia (50%), prognathism, cleft palate or high arched palate (10%), clinodactyly (70%), syndactyly (11%), and scoliosis (11%). The main neurologic sign is ...