Medicine · 2025
Unusual catecholaminergic polymorphic ventricular tachycardia and bradycardia caused by a novel triadin variant in 2 siblings from a Malian family.
СтатьяКлинический случайНазвание и аннотация: Перевод в очереди
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Diakité Mamadou, Samassékou Oumar, Sanni Koudoussou O, Bamba Salia, Dembélé Bouréma, Traoré Oumou, Goita Modibo K, Maiga Alassane Baneye, Diarra Salimata, Sacko Abdoul Karim, Ba Hamidou O, Coulibaly Souleymane, Menta Ichaka, Landouré Guida
Аннотация
RATIONALE: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a hereditary arrhythmia syndrome that can cause sudden cardiac death, particularly in young individuals. CPVT is often linked to triadin (TRDN) variants that disrupt calcium regulation in the cardiac muscle. Although TRDN-associated CPVT is well documented, its association with resting sinus bradycardia is rarely reported. We describe 2 siblings from a consanguineous Malian family presenting with exertional syncope and bradycardia, in whom a novel homozygous pathogenic TRDN variant was identified.
PATIENT CONCERNS: The probands, a 17-year-old male and his 11-year-old sister, presented with recurrent exertional syncope beginning at ages 7 and 11, respectively. After obtaining informed consent and assent, a detailed clinical evaluation was performed, including physical examination, electrocardiography, echocardiography, and exercise stress testing. Whole-exome sequencing and segregation analysis were conducted, and variant pathogenicity was assessed using in silico prediction tools.
DIAGNOSES: Both patients presented sinus bradycardia on electrocardiography and exercise-induced ventricular arrhythmias consistent with a diagnosis of CPVT. Exome sequencing revealed a novel homozygous 5-bp deletion in TRDN (NM_006073.4: c.613_617delCAGAA; p.Gln205GlufsTer3), which was classified as pathogenic according to American College of Medical Genetics and Genomics (ACMG) criteria (PVS1, PP5, PM2). The variant co-segregated with the disease in the family.
INTERVENTIONS: The patients were treated with the nonselective β-blocker nadolol.
OUTCOMES: Therapy effectively resolved exertional syncope and reduced the frequency of arrhythmic episodes during follow-up.
LESSONS: This report highlights an uncommon presentation of bradycardia-associated CPVT caused by a novel TRDN variant. To our knowledge, this is the first genetically confirmed case of a TRDN variant in sub-Saharan Africa. These findings expand the clinical spectrum of TRDN-related cardiac disorders and emphasize the need for genetic exploration of arrhythmic disorders in sub-Saharan Africa, especially for actionable genes.
PATIENT CONCERNS: The probands, a 17-year-old male and his 11-year-old sister, presented with recurrent exertional syncope beginning at ages 7 and 11, respectively. After obtaining informed consent and assent, a detailed clinical evaluation was performed, including physical examination, electrocardiography, echocardiography, and exercise stress testing. Whole-exome sequencing and segregation analysis were conducted, and variant pathogenicity was assessed using in silico prediction tools.
DIAGNOSES: Both patients presented sinus bradycardia on electrocardiography and exercise-induced ventricular arrhythmias consistent with a diagnosis of CPVT. Exome sequencing revealed a novel homozygous 5-bp deletion in TRDN (NM_006073.4: c.613_617delCAGAA; p.Gln205GlufsTer3), which was classified as pathogenic according to American College of Medical Genetics and Genomics (ACMG) criteria (PVS1, PP5, PM2). The variant co-segregated with the disease in the family.
INTERVENTIONS: The patients were treated with the nonselective β-blocker nadolol.
OUTCOMES: Therapy effectively resolved exertional syncope and reduced the frequency of arrhythmic episodes during follow-up.
LESSONS: This report highlights an uncommon presentation of bradycardia-associated CPVT caused by a novel TRDN variant. To our knowledge, this is the first genetically confirmed case of a TRDN variant in sub-Saharan Africa. These findings expand the clinical spectrum of TRDN-related cardiac disorders and emphasize the need for genetic exploration of arrhythmic disorders in sub-Saharan Africa, especially for actionable genes.