title: Intrafamilial phenotypic variability in Andersen-Tawil syndrome: A diagnostic challenge in a potentially treatable condition.
abstract: Andersen-Tawil syndrome (ATS) is a rare autosomal dominant channelopathy characterized by periodic paralysis, cardiac dysrhythmias, and distinct facial and skeletal characteristics, that may be variably present in the affected members. Mutations in the KCNJ2 and KCNJ5 gene have been associated with this disorder. We describe a family in which several members presented with different ATS phenotypes. The proband, a 4-year-old boy, presented with recurrent episodes of muscle weakness from an early age; two siblings suffered cardiac arrhythmia but had never experienced episodes of paralysis; their mother reported occasional muscle pain after exercise and unspecified cardiac arrhythmias. The analysis of KCNJ2 gene in the proband disclosed the presence of a pathogenic mutation (p.R218W), that was subsequently confirmed in the other affected subjects. Our results underline the possible intrafamilial phenotypic variability, ranging from full clinical triad to exclusive cardiac or muscular involvement, representing a diagnostic challenge that may also delay adequate management. There are still limited data on the treatment of ATS; in our patient there was clinical improvement with dichlorphenamide.
authors.affiliation: Child Neurology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy. Electronic address: anna.ardissone@istituto-besta.it.
authors.forename: A
authors.initials: A
authors.lastname: Ardissone
authors.affiliation: Neurorehabilitation Unit, University of Milan, NEuroMuscularOmnicenter, NEMO Clinical Center, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Sansone
authors.affiliation: Neuromuscular and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Colleoni
authors.affiliation: Neuromuscular and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Bernasconi
authors.affiliation: Child Neurology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Moroni
mesh_terms: D050030:Andersen Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D002675:Child, Preschool; D006801:Humans; D008297:Male; D010375:Pedigree
keywords: Andersen–Tawil syndrome; Cardiac dysrhythmias; Dichlorphenamide; KCNJ2; Periodic paralysis