Clinical trial NCT00521794: Characteristics of Andersen-Tawil Syndrome
Official title: Andersen-Tawil Syndrome: Genotype-Phenotype Correlation and Longitudinal Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Andersen-Tawil Syndrome
Andersen Syndrome
Keywords: Arrhythmia
Muscle Weakness
Periodic Paralysis
Channelopathy
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: Office of Rare Diseases (ORD)
name: Rare Diseases Clinical Research Network
name: National Center for Research Resources (NCRR)
First posted: 2007-08-28
Enrollment: 28
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

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

Primary outcomes:
measure: Collect prospective standardized data from participants to help better define the clinical phenotype of ATS.
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Rochester
country: United States
facility: University of Rochester School of Medicine and Dentistry
state: New York
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Milan
country: Italy
facility: University of Milan
city: London
country: United Kingdom
facility: Institute of Neurology and National Hospital for Neurology
Study officials:
affiliation: University of Rochester
name: Emma Ciafaloni, MD
role: STUDY_CHAIR
affiliation: University of Rochester
name: Robert C. Griggs, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.