Characteristics of Andersen-Tawil Syndrome

• ClinicalTrials.gov Identifier: NCT00521794
• Recruitment Status: Completed
• First Posted: August 28, 2007
• Last Update Posted: January 16, 2013
• Sponsor: University of Rochester
• Collaborators: Office of Rare Diseases (ORD); Rare Diseases Clinical Research Network; National Center for Research Resources (NCRR)
• Information provided by (Responsible Party): Robert Griggs, MD, University of Rochester

Study Description

Brief Summary:

Andersen-Tawil Syndrome (ATS) is a rare, genetic disorder that causes episodes of muscle weakness, potentially life-threatening changes in heart rhythm, and developmental abnormalities. Disease symptoms can vary, the cause of some ATS cases remains unknown, and no specific treatment has been identified. The purpose of this multi-site study is to better characterize ATS, establish whether symptoms change over time, and determine if symptoms are related to a mutation in the KCNJ2 gene.

Condition or disease
Andersen-Tawil Syndrome; Andersen Syndrome

Detailed Description:

ATS is an ion channel disorder that causes episodes of muscle weakness and potentially life-threatening heart arrhythmias for which no treatment has been identified. The majority of ATS cases are caused by a mutation in the KCNJ2 gene; other cases result from unknown causes. The KCNJ2 gene mutation alters potassium channels in such a way that it disrupts the flow of potassium ions in skeletal and heart muscle. This can lead to the characteristic periodic paralysis and irregular heart rhythms. The purpose of this study is to better define the genetic basis, clinical features, and disease progression of ATS. The study will also establish clinically relevant endpoints for use in future clinical studies.

This observational study will last 2 years and will involve three study visits. The first visit will entail a 1.5- to 3.5-day inpatient stay; the length of stay will depend on whether a participant has been taking medications for their symptoms of weakness. Participants will be asked to discontinue use of such medications during the inpatient stay. Participants will not be asked to stop any medications that they may be taking for heart symptoms. This first study visit will include a medical history, a quality of life questionnaire, a physical exam, and muscle strength testing. Nerve, muscle, and heart activity will also be measured, and blood will be drawn for laboratory tests and optional DNA analysis. The second and third study visits will take place 1 and 2 years after the initial study visit and will include the same evaluations. During the 8 weeks following each study visit, participants will record in a telephone diary any muscle and heart symptoms that they experience. During the 1 week after both yearly visits, participants will also undergo an outpatient heart rhythm evaluation. A study coordinator will contact participants once a month by phone over the course of the study to review symptoms.

Study Design

• Study Type: Observational
• Actual Enrollment: 28 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Andersen-Tawil Syndrome: Genotype-Phenotype Correlation and Longitudinal Study
• Study Start Date: November 2007
• Actual Primary Completion Date: October 2012
• Actual Study Completion Date: October 2012

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Collect prospective standardized data from participants to help better define the clinical phenotype of ATS. [ Time Frame: 2 years ]

Biospecimen Retention:   Samples With DNA

Blood samples

Eligibility Criteria

• Ages Eligible for Study: 10 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Individuals with a clinically confirmed diagnosis of Andersen-Tawil Syndrome (ATS) enrolled across seven sites in the United States, England, Italy and Canada

Criteria

Inclusion Criteria:

• Clinically confirmed diagnosis of ATS as defined by at least two of the following three criteria:

  1. Presence of clear-cut episodes of transient muscle weakness with or without a fixed deficit, typically following exertion or prolonged rest OR atypical history with otherwise typical exam findings (absent reflexes with normal sensation during an episode) OR unexplained hypokalemia between episodes OR abnormal long-exercise nerve conduction study
  2. Heart conduction defects: prolonged QTc interval on 12-lead electrocardiogram OR ventricular ectopy, including uniform or multifocal PVCs, polymorphic VT, or bidirectional VT
  3. Presence of two or more of the following physical features: low set ears, hypertelorism, small mandible, clinodactyly, syndactyly, micromelia of hands or feet --OR--
• Meets one of the above three criteria and has at least one family member with two of the criteria --OR--
• Does not meet the above three criteria, but possesses a mutation in the KCNJ2 gene

Exclusion Criteria:

• Less than 10 years of age

Contacts and Locations

Locations

United States, California

University of California, San Francisco

San Francisco, California, United States, 94143

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

United States, New York

University of Rochester School of Medicine and Dentistry

Rochester, New York, United States, 14642

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

Canada, Ontario

London Health Sciences Centre

London, Ontario, Canada, N6A 5A5

Italy

University of Milan

Milan, Italy

United Kingdom

Institute of Neurology and National Hospital for Neurology

London, United Kingdom

Sponsors and Collaborators

University of Rochester

Office of Rare Diseases (ORD)

Rare Diseases Clinical Research Network

National Center for Research Resources (NCRR)

Investigators

• Study Chair: Emma Ciafaloni, MD; University of Rochester
• Principal Investigator: Robert C. Griggs, MD; University of Rochester

More Information

Publications:

Tawil R, Ptacek LJ, Pavlakis SG, DeVivo DC, Penn AS, Ozdemir C, Griggs RC. Andersen's syndrome: potassium-sensitive periodic paralysis, ventricular ectopy, and dysmorphic features. Ann Neurol. 1994 Mar;35(3):326-30.

Sansone V, Griggs RC, Meola G, Ptácek LJ, Barohn R, Iannaccone S, Bryan W, Baker N, Janas SJ, Scott W, Ririe D, Tawil R. Andersen's syndrome: a distinct periodic paralysis. Ann Neurol. 1997 Sep;42(3):305-12.

Tristani-Firouzi M, Jensen JL, Donaldson MR, Sansone V, Meola G, Hahn A, Bendahhou S, Kwiecinski H, Fidzianska A, Plaster N, Fu YH, Ptacek LJ, Tawil R. Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest. 2002 Aug;110(3):381-8.

• Responsible Party: Robert Griggs, MD, Professor of Neurology, Medicine, Pediatrics, Pathology & Laboratory Medicine, and Center for Human Experimental Therapeutics, University of Rochester
• ClinicalTrials.gov Identifier: NCT00521794
• Other Study ID Numbers: RDCRN 5301; 5U54RR019482-02 ( U.S. NIH Grant/Contract )
• First Posted: August 28, 2007
• Last Update Posted: January 16, 2013
• Last Verified: January 2013

Keywords provided by Robert Griggs, MD, University of Rochester:

Arrhythmia; Muscle Weakness; Periodic Paralysis; Channelopathy

Additional relevant MeSH terms:

Andersen Syndrome; Syndrome; Disease; Pathologic Processes; Long QT Syndrome; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities