2026 年 90 巻 1 号 p. 140-
A 38-year-old man was referred to hospital with palpitations and loss of memory. He had a 2-year history of complaining of palpitations and presyncope during exercise. On admission, ECG showed sinus bradycardia (Figure A; 38 beats/min). Holter ECG showed atrial fibrillation and frequent sinus arrest. Echocardiography showed enlargement of the left ventricle and atrium. Doppler echography demonstrated severe mitral regurgitation (MR) due to prolapse of the A2 segment of the mitral anterior leaflet with marked thickening (Figure B; Supplementary Movies 1,2). The MR fraction was 62%. We diagnosed severe MR due to myxomatous mitral valve prolapse (MVP), sick sinus syndrome (SSS) and atrial fibrillation. Mitral valve plasty and maze procedure were performed but because sinus pause remained, pacemaker implantation was performed postoperatively.
(A) Electrocardiography. (B) Echocardiography showing the thickened anterior leaflet and prolapse (red arrowheads) and severe mitral regurgitation. (C) Pedigree of the family. (D) Chest X-rays. (E) Hematoxylin and eosin staining of the mitral valve from the mother. Magnification of inset. (F) Partial-sequence electropherogram of HCN4. (G) Schematic representation of the HCN4 protein with the position of the mutation. Each number represents the amino acid number. MVP, mitral valve prolapse; SSS, sick sinus syndrome.
Surprisingly, the patient’s mother had undergone pacemaker implantation at 33 years old and mitral valve replacement for severe MR at 59 years old (Figure C,D). Pathological examination showed myxomatous changes in her mitral valve tissue (Figure E). She is now fine at 73 years old.
To investigate the underlying molecular pathophysiological mechanisms, whole-exome sequence analysis was performed and revealed a mutation in HCN4, a pacemaker channel gene (NM_005477:c.440dupG, p.Leu148ProfsTer113), as shown in Figure F. This variant is not registered in ClinVar and is classified as Likely pathogenic by ACMG. HCN4 mutation can cause several cardiac pathologies, including sinus bradycardia, valvular heart disease and non-compaction cardiomyopathy.1
We thank Rie Ito for her technical assistance.
Y.S. is a member of the Circulation Journal’s Editorial Team.
Supplementary Movie 1. B-mode ultrasound.
Supplementary Movie 2. Color Doppler ultrasound.
Please find supplementary file(s);
https://doi.org/10.1253/circj.CJ-25-0831
