TY - JOUR
T1 - International Triadin Knockout Syndrome Registry
T2 - The Clinical Phenotype and Treatment Outcomes of Patients with Triadin Knockout Syndrome
AU - Clemens, Daniel J.
AU - Tester, David J.
AU - Giudicessi, John R.
AU - Bos, J. Martijn
AU - Rohatgi, Ram K.
AU - Abrams, Dominic J.
AU - Balaji, Seshadri
AU - Crotti, Lia
AU - Faure, Julien
AU - Napolitano, Carlo
AU - Priori, Silvia G.
AU - Probst, Vincent
AU - Rooryck-Thambo, Caroline
AU - Roux-Buisson, Nathalie
AU - Sacher, Frederic
AU - Schwartz, Peter J.
AU - Silka, Michael J.
AU - Walsh, Mark A.
AU - Ackerman, Michael J.
N1 - Publisher Copyright:
© 2019 American Heart Association, Inc.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Background: Triadin knockout syndrome (TKOS) is a rare, inherited arrhythmia syndrome caused by recessive null mutations in TRDN-encoded cardiac triadin. Based previously on 5 triadin null patients, TKOS has been characterized by extensive T-wave inversions, transient QT prolongation, and severe disease expression of exercise-induced cardiac arrest in early childhood refractory to conventional therapy. Methods: We have established the International Triadin Knockout Syndrome Registry to include patients who have genetically proven homozygous/compound heterozygous TRDN null mutations. Clinical/genetic data were collected using an online survey generated through REDCap. Results: Currently, the International Triadin Knockout Syndrome Registry includes 21 patients (11 males, average age of 18 years) from 16 families. Twenty patients (95%) presented with either cardiac arrest (15, 71%) or syncope (5, 24%) at an average age of 3 years. Mild skeletal myopathy/proximal muscle weakness was noted in 6 (29%) patients. Of the 19 surviving patients, 16 (84%) exhibit T-wave inversions, and 10 (53%) have transient QT prolongation > 480 ms. Eight of 9 patients had ventricular ectopy on exercise stress testing. Thirteen (68%) patients have received implantable defibrillators. Despite various treatment strategies, 14 (74%) patients have had recurrent breakthrough cardiac events. Conclusion: TKOS is a potentially lethal disease characterized by T-wave inversions in the precordial leads, transient QT prolongation in some, and recurrent ventricular arrhythmias at a young age despite aggressive treatment. Patients displaying this phenotype should undergo TRDN genetic testing as TKOS may be a cause for otherwise unexplained cardiac arrest in young children. As gene therapy advances, enrollment into the International Triadin Knockout Syndrome Registry is encouraged to better understand TKOS and to ready a well-characterized cohort for future TRDN gene therapy trials.
AB - Background: Triadin knockout syndrome (TKOS) is a rare, inherited arrhythmia syndrome caused by recessive null mutations in TRDN-encoded cardiac triadin. Based previously on 5 triadin null patients, TKOS has been characterized by extensive T-wave inversions, transient QT prolongation, and severe disease expression of exercise-induced cardiac arrest in early childhood refractory to conventional therapy. Methods: We have established the International Triadin Knockout Syndrome Registry to include patients who have genetically proven homozygous/compound heterozygous TRDN null mutations. Clinical/genetic data were collected using an online survey generated through REDCap. Results: Currently, the International Triadin Knockout Syndrome Registry includes 21 patients (11 males, average age of 18 years) from 16 families. Twenty patients (95%) presented with either cardiac arrest (15, 71%) or syncope (5, 24%) at an average age of 3 years. Mild skeletal myopathy/proximal muscle weakness was noted in 6 (29%) patients. Of the 19 surviving patients, 16 (84%) exhibit T-wave inversions, and 10 (53%) have transient QT prolongation > 480 ms. Eight of 9 patients had ventricular ectopy on exercise stress testing. Thirteen (68%) patients have received implantable defibrillators. Despite various treatment strategies, 14 (74%) patients have had recurrent breakthrough cardiac events. Conclusion: TKOS is a potentially lethal disease characterized by T-wave inversions in the precordial leads, transient QT prolongation in some, and recurrent ventricular arrhythmias at a young age despite aggressive treatment. Patients displaying this phenotype should undergo TRDN genetic testing as TKOS may be a cause for otherwise unexplained cardiac arrest in young children. As gene therapy advances, enrollment into the International Triadin Knockout Syndrome Registry is encouraged to better understand TKOS and to ready a well-characterized cohort for future TRDN gene therapy trials.
KW - genetics
KW - human
KW - long QT syndrome
KW - pediatrics
KW - phenotype
UR - http://www.scopus.com/inward/record.url?scp=85061859306&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061859306&partnerID=8YFLogxK
U2 - 10.1161/CIRCGEN.118.002419
DO - 10.1161/CIRCGEN.118.002419
M3 - Article
C2 - 30649896
AN - SCOPUS:85061859306
SN - 1942-325X
VL - 12
SP - 65
EP - 75
JO - Circulation: Genomic and Precision Medicine
JF - Circulation: Genomic and Precision Medicine
IS - 2
M1 - e002419
ER -