Andersen Cardiodysrhythmic Periodic Paralysis Syndrome

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 periodic paralysis, which is not necessarily related to hyperkalemia or hypokalemia and usually presents with proximal muscle weakness (and not myotonia). Cardiac manifestations most often are prolonged QT syndrome and symptomatic or asymptomatic ventricular tachycardias. Patients have a higher risk for sudden cardiac death, although the incidences of syncope and cardiac arrest are significantly lower than in patients with type 1 and 2 long QT syndrome. Long QT Syndrome is present in more than 70% of Andersen syndrome patients with the KCNJ2 mutation, and ventricular arrhythmias occur in 64%. Triggers for periodic paralysis are inconsistent but may include rest after activities, periods of inactivity, and sleep. Fasting, but also eating a large meal, and becoming chilled are other common triggers. Chemical fumes and vapors containing hydrocarbons (paint, gasoline, car exhaustion) have been described as triggers in some patients. Even for an individual patient, potassium shifts during attacks of weakness are inconsistent. This finding indicates that at one point paralysis may be caused by hypokalemia (most common form 55%), but the next time it may be triggered by hyperkalemia (22%). Potassium-sensitive ACPPS patients may become weak and develop QTc prolongation when they are hypokalemic. Carbonic anhydrase inhibitors are used in this form of periodic paralysis to reduce the frequency and severity of the attacks.

Careful history and examination to determine the presence and potential triggers of proximal weakness. Determine association of K+ level and weakness (which may be variable) if possible. Complete cardiovascular evaluation and consultation with a cardiologist should be obtained, including ECG to calculate the QTc interval. Consider continuation of all cardiac medications, particularly beta blockers. Preoperative blood workup should include electrolyte (K+, Ca2+) and blood glucose levels. Carefully evaluate the airway in view of micrognathia, prognathia, and high arched palate because they may result in difficult airway management. If scoliosis is severe (but most often is mild), lung function tests and echocardiography may be indicated, and arrangements for postoperative mechanical ventilation may be required. Pulmonary, hepatic, and thyroid function tests are recommended if the patient has been receiving amiodarone treatment for more than 1 year or shows specific symptoms.

Judicious sedative premedication may be useful to reduce sympathetic output and prevent QT interval prolongation. Avoid histamine-releasing drugs and halothane. Ensure the patient is deeply anesthetized prior to intubation and consider extubation while the patient still is under deep anesthesia (assuming no anatomical considerations or difficulties with airway management). Beta blockers to treat tachyarrhythmias should be available. Check serum electrolytes (K+) frequently in the perioperative period. Although no reports about anesthetic management have been published, based upon knowledge from other forms of periodic paralysis, not administering succinylcholine in order to prevent rapid changes in the K+ serum level and malignant hyperthermia seems prudent.

Consider possible interactions between anesthetic drugs and cardiac medications. Patients may be receiving amiodarone and acetazolamide treatment. Appropriate drugs must be available for management of arrhythmias, particularly beta blockers (e.g., esmolol). See Long QT Syndrome for an extensive list of drugs that affect the QT interval.

Long QT Syndrome: Congenital or acquired adrenergic-induced ventricular arrhythmias.

Periodic Paralysis (PP): Congenital abnormality in membrane electrolyte conductance leading to episodic muscle weakness.

Thyrotoxic Periodic Paralysis: Acquired disorder characterized by intermittent episodes of muscle weakness alternating with periods of normal muscular function. Occurs during hyperthyroidism and thyrotoxicosis. Hypokalemia is present during attacks. May be precipitated by low plasma concentration of insulin. Occurs predominantly in Asian males but also has been found in Latin American males.