HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yoon, G. Articles by Ptácek, L. J. Search for Related Content PubMed PubMed Citation Articles by Yoon, G. Articles by Ptácek, L. J. Related Collections Muscle disease Oscillopsia All Neuropsychology/Behavior

Andersen–Tawil syndrome

Definition of a neurocognitive phenotype

G. Yoon, MD, L. Quitania, BA, J. H. Kramer, PsyD, Y. H. Fu, PhD, B. L. Miller, MD and L. J. Ptáek, MD

From the Department of Pediatrics, Division of Medical Genetics (G.Y.), Memory and Aging Center (L.Q., J.H.K., B.L.M.), Department of Neurology (G.Y., Y.H.F., L.J.P.), and Howard Hughes Medical Institute (L.J.P.), University of California, San Francisco.

Address correspondence and reprint requests to Dr Ptáek, Howard Hughes Medical Institute, Department of Neurology, 548F Rock Hall, Box 2922, University of California, San Francisco, 1550 4th Street, San Francisco, CA 94158; e-mail: ljp{at}ucsf.edu

Background: The Andersen–Tawil syndrome (ATS) is a potassium ion channelopathy caused by mutations in the KCNJ2 gene. It is characterized by periodic paralysis, cardiac arrhythmias, and distinctive features; the effect of KCNJ2 mutations on the CNS has never been studied.

Objective: To define a potential CNS phenotype in ATS using standardized methods.

Methods: Ten subjects with KCNJ2 mutations and their unaffected siblings were evaluated at the University of California San Francisco General Clinical Research Center. A comprehensive battery of neurocognitive tests was administered to ATS subjects and their unaffected siblings, followed by pairwise analysis of the resultant differences in scores. An EEG was obtained for all ATS subjects.

Results: There was no EEG evidence of subclinical seizure activity in any subject. ATS subjects universally had more school difficulties than their siblings, despite similar IQ between the two groups. On formal neurocognitive testing, there was no difference between ATS subjects and their siblings on tests of verbal and visual memory. Assessment of executive functioning revealed ATS subjects scored 1.93 points lower than their siblings on tests of Design Fluency (95% CI –3.46, 0.01; p = 0.052) and made 1.9 more errors (95% CI 0.46, 2.54; p = 0.005). Subjects with ATS scored an average of 5 points lower than their siblings on tests of matrix reasoning (95% CI –8.67, –1.33; p = 0.008). On tests of general ability, ATS subjects achieved much lower scores than their siblings, with an average difference of 9.13 points for reading (95% CI –12.46, 3.21; p = 0.056) and 23.4 points for mathematics (95% CI –42.53, –4.22; p = 0.017).

Conclusion: Mutations in KCNJ2 are associated with a distinct neurocognitive phenotype, characterized by deficits in executive function and abstract reasoning.

Supported by grants from the Sandler Neurogenetics Center (Y.H.F.), the Muscular Dystrophy Association (L.J.P), and the NIH (5 U54 RR019482-03, Nervous System Channelopathies: Pathogenesis and Treatment). L.J.P. is an investigator of the Howard Hughes Medical Institute. These studies were carried out in part in the General Clinical Research Center, Moffitt Hospital, University of California, San Francisco, with funds provided by the National Center for Research Resources (5 M01 RR-00079), U.S. Public Health Service.

Disclosure: The authors report no financial or nonfinancial conflicts of interest.

Received December 1, 2005. Accepted in final form February 22, 2006.