High Prevalence of Neurodevelopmental Disorders in Pediatric Long QT
Syndrome: A Single Centre Experience
Abstract
Background: Long QT Syndrome (LQTS) is a rare familial ion
channelopathy that may result in syncope, cardiac arrest and sudden
death. Ion channel gene variants have been implicated in
neurodevelopmental disorders (NDDs), however the link between LQTS and
NDDs in children is not well characterized. Methods: This
retrospective observational cohort study included patients diagnosed
with LQTS at <19 years of age with an NDD diagnosis,
prospectively enrolled in an inherited arrhythmia registry at a tertiary
hospital between April 2015- June 2021. Patients with hypoxic ischemic
injury were excluded. Demographics, genetics, therapy and outcomes were
evaluated. Results: Among 106 LQTS patients in the registry, we
identified 15 (14%) with NDDs. Eleven (73%) of 15 patients were male
compared with 4 (27%) females (p=0.02). Thirteen (87%) were
KCNQ1-positive, with mean age at LQTS diagnosis of 6.6 years (SD:
4.3) and baseline QTc of 446ms (SD: 24). Eight (53%) patients had
attention deficit hyperactivity disorder, followed by 4 (27%) with
learning/communication disorder, 3 (20%) with autism spectrum disorder
and 2 (13%) with motor disorder. Nine of 15 (60%) patients received an
NDD diagnosis 4.4 (SD: 2.1) years post-LQTS diagnosis; 4 (27%) pre-LQTS
diagnosis, and 2 (13%) were unknown. Thirteen (87%) patients were
treated with Nadolol monotherapy, 1 (7%) with flecainide and 1 (7%)
with lifestyle modifications only. Five (33%) patients were taking a
concomitant psychostimulant for their NDD, and none experienced
arrhythmic events on therapy. LQTS-related event was experienced by 1
(7%) patient over a mean follow-up of 5.7 (SD: 3.9) years.
Conclusion: The prevalence of NDD in LQTS patients (14%) was
higher compared to the general population (4.5-9%). Larger studies
investigating the link between KCNQ1, other LQTS-related genes
and NDDs are warranted.