Characteristics of Andersen-Tawil Syndrome

NCT ID: NCT00521794

Last Updated: 2013-01-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 28 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2012-10-31

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.

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.

Conditions

Andersen-Tawil Syndrome; Andersen Syndrome

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility 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

• Minimum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Office of Rare Diseases (ORD)

NIH

Sponsor Role: collaborator

Rare Diseases Clinical Research Network

NETWORK

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Robert Griggs, MD

Professor of Neurology, Medicine, Pediatrics, Pathology & Laboratory Medicine, and Center for Human Experimental Therapeutics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Emma Ciafaloni, MD

Role: STUDY_CHAIR

University of Rochester

Robert C. Griggs, MD

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Locations

University of California, San Francisco

San Francisco, California, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

University of Rochester School of Medicine and Dentistry

Rochester, New York, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

London Health Sciences Centre

London, Ontario, Canada

University of Milan

Milan, , Italy

Institute of Neurology and National Hospital for Neurology

London, , United Kingdom

Countries

United States; Canada; Italy; United Kingdom

References

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. doi: 10.1002/ana.410350313.

Reference Type: BACKGROUND

PMID: 8080508 (View on PubMed)

Sansone V, Griggs RC, Meola G, Ptacek 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. doi: 10.1002/ana.410420306.

Reference Type: BACKGROUND

PMID: 9307251 (View on PubMed)

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. doi: 10.1172/JCI15183.

Reference Type: BACKGROUND

PMID: 12163457 (View on PubMed)

Other Identifiers

5U54RR019482-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

RDCRN 5301

Identifier Type: -

Identifier Source: org_study_id