[Andersen syndrome: a particular form of paralysis with cardiac dysrhythmia].
Andersen syndrome includes a clinical triad with periodic paralysis, cardiac arrhythmia and dysmorphic features most often mild but relevant. It is a potassium channelopathy due to mutation of KCJN2 gene coding for Kir 2.1 protein. We report a familial case with mutation R218W of Kir 2.1 and discuss the main phenotypic and genetic aspects of Andersen syndrome. Muscle manifestations are essentially a periodic paralysis most often of hypokaliemic type. Muscle biopsy reveals tubular aggregates but can be normal as it is shown in the same patient in our kindred. Our proband complained of paralytic attacks since childhood and at adult age she demonstrated a mild permanent deficit of pelvic girdle muscles as it has been described in other types of periodic paralysis after a long duration course. Cardiac manifestations may include in a variable manner a long QT syndrome, premature ventricular contractions, complex ventricular ectopy, polymorphic or bidirectional ventricular tachycardia. Imipramine had a positive effect on arrhythmia in our case. Dysmorphic features are often mild and have to be cautiously looked for as a clue to the diagnosis of Andersen syndrome. They can be easily overlooked if not systematically looked for. Clinical expressivity is variable including in the same family. In our observation, the daughter showed a complete triad, early expressed, which allowed the diagnosis. Her father was late diagnosed on ventricular dysrhytmia but without muscle manifestations and dysmorphic features. Since KCJN2 gene mutation identification, locus heterogeneity of Andersen syndrome was shown. Andersen syndrome kindreds without mutations in KCNJ2 were clinically indistinguishable from KCNJ2-associated subjects. KCNJ2 gene encodes the inward rectifier K+ channel Kir2.1 which plays an important role in maintaining membrane potential and during the terminal phase of cardiac action potential repolarization. Several studies showed a dominant negative effect of the mutation on Kir 2.1 channel function.
Pouget
J
J
Service de neurologie et maladies neuromusculaires, Hôpital de La Timone, 264 rue Saint-Pierre, 13005 Marseille, France. jpouget@ap-hm.fr
Philip
N
N
Faugere
G
G
Pellissier
J F
JF
D000293:Adolescent; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D004562:Electrocardiography; D005147:Facial Bones / Q000002:abnormalities; D005260:Female; D006011:Glycogen Storage Disease Type IV / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D010243:Paralysis / Q000503:physiopathology*; D015221:Potassium Channels / Q000235:genetics
D015221:Potassium Channels