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
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