RARE DISEASE
Familial long QT syndrome
Familial long QT syndrome
Familial long QT syndrome
Synonyms: Congenital long QT syndrome, LQTS
Synonyms: Congenital long QT syndrome, LQTS
Synonyms: Congenital long QT syndrome, LQTS
Drug discovery
3
drugs
With orphan designations
Overview
Familial long QT syndrome (LQTS) is an inherited cardiac arrhythmia disorder characterized by prolonged ventricular repolarization (QT interval) on ECG, increasing the risk of syncope, torsades de pointes, and sudden cardiac death. Autosomal dominant Romano-Ward syndrome (RWS) accounts for 85% of cases, while autosomal recessive Jervell and Lange-Nielsen syndrome includes congenital deafness. Over 15 genetic subtypes involve ion channel mutations (e.g., KCNQ1, KCNH2, SCN5A), with triggers including exercise, stress, or QT-prolonging medications.
Burden
Therapies
First-line: Non-selective β-blockers (nadolol, propranolol) reduce cardiac events by 53–90% [1][3][13][17].
Adjuncts: Mexiletine (for LQT3), left cardiac sympathetic denervation (LCSD), and implantable cardioverter-defibrillators (ICDs) for high-risk patients [3][5][8].
Lifestyle modifications: Avoid QT-prolonging drugs, strenuous exercise, and electrolyte imbalances [1][6][11].
Categories: rare cardiac diseases, rare genetic diseases
Research Papers
1,682 drug discovery papers about Familial long QT syndrome, with 2 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,682 drug discovery papers about Familial long QT syndrome, with 2 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-06 | Case Report: Overlap of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia in two Chinese children with CALM2-related calmodulinopathy.
Calmodulinopathy is a rare CALM-related hereditary channelopathy presenting with long QT syndrome (LQTS), less commonly with catecholaminergic polymorphic ventricular tachycardia (CPVT) or LQTS/CPVT overlap. It carries high mortality and limited data from Chinese population. We reviewed two Chinese children with CALM2 mutation-related LQTS/CPVT overlap. Clinical data, genetic findings, and treatments were collected; outcomes were obtained via telephone follow-up. A systematic literature review was also performed. Case 1 was a 13-year-old girl with seven exercise-induced syncopal episodes. Sinus rhythm QTc 0.55 s, with bidirectional/polymorphic premature ventricular contractions, and ventricular tachycardia during exercise. A de novo CALM2 p.E140Q mutation was found. She remained event-free on propranolol and propafenone for two years. Case 2 was a 15-year-old boy with onset at 4 years. He experienced > 10 syncopal episodes triggered by recurrent exercise or emotional stress. Initial Holter monitoring revealed sinus bradycardia with a mean heart rate of 70 bpm and a maximum QTc of 0.51 s. A de novo CALM2 p.N98S mutation was found. Despite treatment with propranolol plus mexiletine, syncopal episodes continued, with the QTc interval further prolonged to 0.62 s. The p.E140Q variant is novel, whereas p.N98S has been previously reported. Literature suggests that β-blockers combined with Class Ic drugs may be more effective, and implantable cardioverter defibrillator (ICD) implantation should be considered in cases who respond poorly to medical therapy or survivors of aborted cardiac arrest. Patients who experience recurrent syncope coexisting with significant sinus bradycardia may have more severe phenotypes with higher risk of malignant arrhythmias, warranting earlier or more aggressive evaluation for device therapy. Genetic testing is recommended for suspected pediatric channelopathies with phenotype-guided individualized treatment.
2026-08-04 | Clonidine for ADHD with Comorbid Oppositional Defiant Disorder in a Patient with Congenital Long QT Syndrome
Background: Oppositional defiant disorder (ODD) and attention-deficit/hyperactivity disorder (ADHD) co-occur in roughly half of children with ADHD. Pharmacological management for both disorders typically involves stimulants or antipsychotics. However, in patients with congenital Long QT syndrome (LQTS), the use of stimulants might present an additional clinical risk for ventricular arrhythmias. Alternatives must be sought as the impact of these untreated psychiatric conditions can be significantly limiting to these patients. Case Presentation: A 14-year-old male with ODD and comorbid ADHD was started on risperidone 0.25 mg daily for severe behavioral dysregulation following incidents of serious aggression towards an infant sibling. Electrocardiography demonstrated marked QT prolongation (QTc = 508 ms) and subsequently confirmed a diagnosis of congenital LQTS with a maternal family history over 3 generations. Risperidone was discontinued and nadolol 20 mg daily was initiated by a pediatric cardiologist. After a second psychiatric opinion for persistent ADHD, oppositionality, aggression, and suicide risk, he was started on clonidine, a possible alternative to avoind the use of stimulants or antipsychotics. At the one-month follow-up, parents reported a lessening of impulsivity, physical aggression, and improved emotional self-regulation. He is continuing with psychological and cardiac monitoring. Discussion: This case demonstrated a different approach to treating patients with congenital LQTS and neurodevelopmental disorders when first-line pharmacotherapies present a risk to the patient. Clonidine offered clinical benefits without the risk of arrhythmia that comes with stimulants or antipsychotics. Given the lack of studies done on this population, more controlled studies are needed to study the effects of clonidine on patients with congenital LQTS and ODD with comorbid ADHD. Conclusion: Clonidine may be a promising alternative for treating ADHD and ODD in patients with congenital Long QT syndrome, although further research is needed to confirm its safety and effectiveness.
2026-07-20 | Effects of curcumin and nicorandil on nilotinib-induced QT interval prolongation in rats: A telemetry-based study.
Long QT syndrome (LQTS) is characterized by QT prolongation, ventricular arrhythmias and sudden death. Nilotinib (Nilo), a tyrosine kinase inhibitor used in chronic myeloid leukemia, prolongs QTc mainly through hERG (IKr) channel inhibition. Curcumin (Curc), often co-administered, modulates cardiac ion channels, whereas nicorandil (Nico) acts as a KATP channel opener. This study evaluated the effects of Curc and Nico on Nilo-induced QTc prolongation. Male Sprague-Dawley rats implanted with radiotelemetry transmitters received 10 mg/kg nilotinib (selected as the minimal effective dose based on preliminary dose-finding studies at 10, 30 and 50 mg/kg), 100 mg/kg curcumin, or 10 mg/kg nicorandil, as previously described. Animals were allocated into seven groups: Control, Nilo, Curc, Nico, Nilo+Curc, Nilo+Nico and Nilo+Curc+Nico. ECG, biochemical and histopathological analyses were performed. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test. Nilotinib caused dose-dependent QTc prolongation, with 10 mg/kg as the minimal effective dose (p<0.001). Curcumin further exacerbated QTc prolongation, whereas nicorandil co-administration mitigated this effect. (p<0.001). Nilo also elevated TNF-α and TAS, which were attenuated in combination groups. Nilotinib-induced dose-dependent QTc prolongation was aggravated by curcumin, whereas nicorandil demonstrated a potential protective effect on drug-induced LQTS.
2026-07-16 | Multimodality Risk Stratification in Athletes With Long QT Syndrome.
Long QT syndrome has traditionally led to exercise restriction due to concerns for exertion-triggered arrhythmia and sudden cardiac death. Emerging data, however, support individualized participation guided by genotype and physiologic risk markers. We describe 3 young athletes with distinct genotypes (KCNE1 D85N [long QT syndrome type 5-Lite], KCNQ1 R555H [long QT syndrome type 1], and KCNH2 p.T613M [long QT syndrome type 2]) evaluated through electrocardiography, exercise testing, and echocardiographic assessment of the electromechanical window. The electromechanical window ranged from mildly to severely negative (-11 to -103 ms) and corresponded with phenotypic severity. Personalized management, including selective β-blockade, mexiletine, and device therapy, enabled safe continuation of sports participation in all cases. This case series underscores the role of genotype-specific, multimodality assessment in risk stratifying athletes with long QT syndrome. Integration of individualized therapy, shared decision making, and structured emergency preparedness supports safe athletic participation while maintaining arrhythmic protection and quality of life. Individualized risk assessment including resting and stress electrocardiography, genotype analysis, and electromechanical window measurement provides a more accurate estimate of arrhythmic risk than does resting QTc interval alone. Genotype-guided therapy and structured sports counseling allow most patients with LQTS to safely engage in exercise and even competitive athletics under expert supervision. Shared decision making and emergency preparedness, including automated external defibrillator access and multidisciplinary collaboration, are essential to balancing athletic participation with long-term safety in patients with LQTS.
2026-07-15 | Bisoprolol Treatment and Adherence in Pediatric Patients With Genotype-Positive Long QT Syndrome.
Non-selective beta-blockers, such as propranolol, are highly effective in reducing arrhythmia risk in long QT Syndrome (LQTS). The study aim was to evaluate the use of beta-blockers, especially beta-1-selective bisoprolol, and their efficacy in Finnish children with genotype-positive LQTS type 1 or 2. We retrospectively reviewed the medical records of children with genetically confirmed LQTS1 or LQTS2 diagnosis, who were treated at Tampere University Hospital in Finland between 2006 and 2020. Data on cardiac events, beta-blocker use and adherence, ECG, clinical exercise tests, and genetic testing were collected. Eighty-eight children were diagnosed with a genotype-positive type 1 or 2 LQTS, and 84% of them had a family history of LQTS associated gene mutations. Four Finnish founder mutations accounted for 68% of the cases. At diagnosis, 63% had a normal QTc interval. No cardiac events occurred during follow-up among patients receiving beta-blocker therapy. For children aged 0-7 years, propranolol was the primary medication in 90% of cases, and for > 7-year-olds, bisoprolol was used in 77% of cases. At the last follow-up visit, 87/88 were on beta-blockers, most commonly bisoprolol (66%). Medication adherence was high, with 84% of patients using beta-blockers as prescribed. In clinical exercise tests, maximal heart rate remained < 160 beats per minute in 76% of tests, indicating effective beta-blockade. Cascade screening identified asymptomatic patients, most with normal QTc intervals. Bisoprolol was the most commonly used beta-blocker with good adherence, effective heart rate control, and no cardiac events observed during follow-up among these Finnish children with LQTS.
2026-08-06 | Case Report: Overlap of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia in two Chinese children with CALM2-related calmodulinopathy.
Calmodulinopathy is a rare CALM-related hereditary channelopathy presenting with long QT syndrome (LQTS), less commonly with catecholaminergic polymorphic ventricular tachycardia (CPVT) or LQTS/CPVT overlap. It carries high mortality and limited data from Chinese population. We reviewed two Chinese children with CALM2 mutation-related LQTS/CPVT overlap. Clinical data, genetic findings, and treatments were collected; outcomes were obtained via telephone follow-up. A systematic literature review was also performed. Case 1 was a 13-year-old girl with seven exercise-induced syncopal episodes. Sinus rhythm QTc 0.55 s, with bidirectional/polymorphic premature ventricular contractions, and ventricular tachycardia during exercise. A de novo CALM2 p.E140Q mutation was found. She remained event-free on propranolol and propafenone for two years. Case 2 was a 15-year-old boy with onset at 4 years. He experienced > 10 syncopal episodes triggered by recurrent exercise or emotional stress. Initial Holter monitoring revealed sinus bradycardia with a mean heart rate of 70 bpm and a maximum QTc of 0.51 s. A de novo CALM2 p.N98S mutation was found. Despite treatment with propranolol plus mexiletine, syncopal episodes continued, with the QTc interval further prolonged to 0.62 s. The p.E140Q variant is novel, whereas p.N98S has been previously reported. Literature suggests that β-blockers combined with Class Ic drugs may be more effective, and implantable cardioverter defibrillator (ICD) implantation should be considered in cases who respond poorly to medical therapy or survivors of aborted cardiac arrest. Patients who experience recurrent syncope coexisting with significant sinus bradycardia may have more severe phenotypes with higher risk of malignant arrhythmias, warranting earlier or more aggressive evaluation for device therapy. Genetic testing is recommended for suspected pediatric channelopathies with phenotype-guided individualized treatment.
2026-08-04 | Clonidine for ADHD with Comorbid Oppositional Defiant Disorder in a Patient with Congenital Long QT Syndrome
Background: Oppositional defiant disorder (ODD) and attention-deficit/hyperactivity disorder (ADHD) co-occur in roughly half of children with ADHD. Pharmacological management for both disorders typically involves stimulants or antipsychotics. However, in patients with congenital Long QT syndrome (LQTS), the use of stimulants might present an additional clinical risk for ventricular arrhythmias. Alternatives must be sought as the impact of these untreated psychiatric conditions can be significantly limiting to these patients. Case Presentation: A 14-year-old male with ODD and comorbid ADHD was started on risperidone 0.25 mg daily for severe behavioral dysregulation following incidents of serious aggression towards an infant sibling. Electrocardiography demonstrated marked QT prolongation (QTc = 508 ms) and subsequently confirmed a diagnosis of congenital LQTS with a maternal family history over 3 generations. Risperidone was discontinued and nadolol 20 mg daily was initiated by a pediatric cardiologist. After a second psychiatric opinion for persistent ADHD, oppositionality, aggression, and suicide risk, he was started on clonidine, a possible alternative to avoind the use of stimulants or antipsychotics. At the one-month follow-up, parents reported a lessening of impulsivity, physical aggression, and improved emotional self-regulation. He is continuing with psychological and cardiac monitoring. Discussion: This case demonstrated a different approach to treating patients with congenital LQTS and neurodevelopmental disorders when first-line pharmacotherapies present a risk to the patient. Clonidine offered clinical benefits without the risk of arrhythmia that comes with stimulants or antipsychotics. Given the lack of studies done on this population, more controlled studies are needed to study the effects of clonidine on patients with congenital LQTS and ODD with comorbid ADHD. Conclusion: Clonidine may be a promising alternative for treating ADHD and ODD in patients with congenital Long QT syndrome, although further research is needed to confirm its safety and effectiveness.
2026-07-20 | Effects of curcumin and nicorandil on nilotinib-induced QT interval prolongation in rats: A telemetry-based study.
Long QT syndrome (LQTS) is characterized by QT prolongation, ventricular arrhythmias and sudden death. Nilotinib (Nilo), a tyrosine kinase inhibitor used in chronic myeloid leukemia, prolongs QTc mainly through hERG (IKr) channel inhibition. Curcumin (Curc), often co-administered, modulates cardiac ion channels, whereas nicorandil (Nico) acts as a KATP channel opener. This study evaluated the effects of Curc and Nico on Nilo-induced QTc prolongation. Male Sprague-Dawley rats implanted with radiotelemetry transmitters received 10 mg/kg nilotinib (selected as the minimal effective dose based on preliminary dose-finding studies at 10, 30 and 50 mg/kg), 100 mg/kg curcumin, or 10 mg/kg nicorandil, as previously described. Animals were allocated into seven groups: Control, Nilo, Curc, Nico, Nilo+Curc, Nilo+Nico and Nilo+Curc+Nico. ECG, biochemical and histopathological analyses were performed. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test. Nilotinib caused dose-dependent QTc prolongation, with 10 mg/kg as the minimal effective dose (p<0.001). Curcumin further exacerbated QTc prolongation, whereas nicorandil co-administration mitigated this effect. (p<0.001). Nilo also elevated TNF-α and TAS, which were attenuated in combination groups. Nilotinib-induced dose-dependent QTc prolongation was aggravated by curcumin, whereas nicorandil demonstrated a potential protective effect on drug-induced LQTS.
2026-07-16 | Multimodality Risk Stratification in Athletes With Long QT Syndrome.
Long QT syndrome has traditionally led to exercise restriction due to concerns for exertion-triggered arrhythmia and sudden cardiac death. Emerging data, however, support individualized participation guided by genotype and physiologic risk markers. We describe 3 young athletes with distinct genotypes (KCNE1 D85N [long QT syndrome type 5-Lite], KCNQ1 R555H [long QT syndrome type 1], and KCNH2 p.T613M [long QT syndrome type 2]) evaluated through electrocardiography, exercise testing, and echocardiographic assessment of the electromechanical window. The electromechanical window ranged from mildly to severely negative (-11 to -103 ms) and corresponded with phenotypic severity. Personalized management, including selective β-blockade, mexiletine, and device therapy, enabled safe continuation of sports participation in all cases. This case series underscores the role of genotype-specific, multimodality assessment in risk stratifying athletes with long QT syndrome. Integration of individualized therapy, shared decision making, and structured emergency preparedness supports safe athletic participation while maintaining arrhythmic protection and quality of life. Individualized risk assessment including resting and stress electrocardiography, genotype analysis, and electromechanical window measurement provides a more accurate estimate of arrhythmic risk than does resting QTc interval alone. Genotype-guided therapy and structured sports counseling allow most patients with LQTS to safely engage in exercise and even competitive athletics under expert supervision. Shared decision making and emergency preparedness, including automated external defibrillator access and multidisciplinary collaboration, are essential to balancing athletic participation with long-term safety in patients with LQTS.
2026-07-15 | Bisoprolol Treatment and Adherence in Pediatric Patients With Genotype-Positive Long QT Syndrome.
Non-selective beta-blockers, such as propranolol, are highly effective in reducing arrhythmia risk in long QT Syndrome (LQTS). The study aim was to evaluate the use of beta-blockers, especially beta-1-selective bisoprolol, and their efficacy in Finnish children with genotype-positive LQTS type 1 or 2. We retrospectively reviewed the medical records of children with genetically confirmed LQTS1 or LQTS2 diagnosis, who were treated at Tampere University Hospital in Finland between 2006 and 2020. Data on cardiac events, beta-blocker use and adherence, ECG, clinical exercise tests, and genetic testing were collected. Eighty-eight children were diagnosed with a genotype-positive type 1 or 2 LQTS, and 84% of them had a family history of LQTS associated gene mutations. Four Finnish founder mutations accounted for 68% of the cases. At diagnosis, 63% had a normal QTc interval. No cardiac events occurred during follow-up among patients receiving beta-blocker therapy. For children aged 0-7 years, propranolol was the primary medication in 90% of cases, and for > 7-year-olds, bisoprolol was used in 77% of cases. At the last follow-up visit, 87/88 were on beta-blockers, most commonly bisoprolol (66%). Medication adherence was high, with 84% of patients using beta-blockers as prescribed. In clinical exercise tests, maximal heart rate remained < 160 beats per minute in 76% of tests, indicating effective beta-blockade. Cascade screening identified asymptomatic patients, most with normal QTc intervals. Bisoprolol was the most commonly used beta-blocker with good adherence, effective heart rate control, and no cardiac events observed during follow-up among these Finnish children with LQTS.
Access all drug discovery papers and probability of success in trials forecasts:
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Drug Discovery Landscape
3 orphan drug designations for Familial long QT syndrome.
3 orphan drug designations for Familial long QT syndrome.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
recombinant self-complementary AAV9 containing a base editor encoding human SCN5A | gene editing enzymes | FDA | 2025-04-15 | — | Hangzhou Rongze Biotechnology Group Co., Ltd. |
N-(4-(4-((2-(dimethylamino)ethyl)amino)-3-methyl-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-2-fluorophenyl)-2,5-difluorobenzenesulfonamide hydrochloride salt | small molecules | FDA | 2024-09-20 | — | Thryv Therapeutics Inc. |
4-(pyrimidin-2-ylmethyl)-7-[4-(trifluoromethoxy)phenyl]-3,4-dihydro-1,4-benzoxazepin-5(2H)-one | small molecules | FDA | 2015-05-04 | — | Gilead Sciences, Inc. |
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