Low clinical penetrance in causal mutation carriers for cardiac channelopathies.
OBJECTIVE
Cardiac channelopathies are genetic alterations that can cause sudden death. Long QT syndrome and Brugada syndrome are 2 such conditions. Both are diagnosed according to previously published criteria. Our objective was to determine the sensitivity of these criteria in a consecutive series of patients carrying the mutations that cause them.


METHODS
We enrolled 15 families and 31 causal mutation carriers with a high pathogenic probability of having long QT syndrome and Brugada syndrome. We conducted clinical and electrocardiographic studies to analyze the extent to which these patients fulfilled the diagnostic criteria. Statistical analysis was with SPSS 17.0.


RESULTS
Some 48.3% of the subjects met the criteria indicating a high probability of long QT syndrome or Brugada syndrome. Among those with the mutation for long QT syndrome, only 10 out of 21 had a Schwartz index score ≥ 4. Both the median Schwartz score and the cQT interval were lower in relatives than in probands. Of those with the mutation for Brugada syndrome, 60% failed to meet current diagnostic criteria, which were more frequently fulfilled in relatives. Pharmacological tests with epinephrine and flecainide helped establish the diagnosis in 2 mutation carriers with negative phenotype.


CONCLUSIONS
Current diagnostic criteria for long QT syndrome and Brugada syndrome had low sensitivity in our sample of genetic carriers. Genetic tests supported by pharmacological tests can increase diagnostic sensitivity, especially in asymptomatic relatives.
Servicio de Cardiología, Hospital Universitario Virgen de las Nieves, Granada, Spain. Electronic address: jimenez.jaimez@gmail.com.
Juan
J
Jiménez-Jáimez
Servicio de Cardiología, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Miguel
M
Álvarez
Servicio de Cardiología, Hospital Universitario Virgen de las Nieves, Granada, Spain.
María
M
Algarra
Servicio de Cardiología, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Rosa
R
Macías Ruíz
Servicio de Cardiología, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Rocío
R
Peñas
Servicio de Cardiología, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Francisca
F
Valverde
Servicio de Cardiología, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Gustavo
G
Tortajada
Departamento de Medicina Legal y Toxicología, Universidad de Granada, GENYO-Centro Pfizer-Universidad de Granada-Junta de Andalucía de Genómica y Oncología, Granada, Spain.
Jose Antonio
JA
Lorente
Servicio de Cardiología, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Rafael
R
Melgares
Servicio de Cardiología, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Luis
L
Tercedor
D000328:Adult; D053840:Brugada Syndrome / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D053447:Channelopathies / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D006331:Heart Diseases / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008133:Long QT Syndrome / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019683:Penetrance; D055815:Young Adult