Hypertrophic cardiomyopathy associated with damaging variants in the ALPK3 gene is a fairly recent discovery, and only a small number of patients have been described thus far. Here we present two additional patients with hypertrophic cardiomyopathy caused by biallelic variants in ALPK3. Genetic investigation was performed using a targeted gene panel consisting of known cardiomyopathy-associated genes and whole exome sequencing. The patients showed a large difference in the age of onset, and both presented with extracardiac features that are often seen in ALPK3 patients. The patient with the later onset showed milder extracardiac symptoms, such as decreased muscle tone and distal muscular dystrophy, but had fast progression of cardiac complications leading to the need of heart transplantation. This study further elucidates the variability of both symptoms and age of onset among these patients.

中文翻译：

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两例与 ALPK3 纯合子和复合杂合子变异相关的肥厚型心肌病和骨骼肌特征的新病例

与 ALPK3 基因中的破坏性变异相关的肥厚型心肌病是一个相当新的发现，迄今为止只描述了少数患者。在这里，我们介绍了另外两名由 ALPK3 中的双等位基因变异引起的肥厚型心肌病患者。使用由已知心肌病相关基因和全外显子组测序组成的靶向基因组进行遗传研究。患者在发病年龄上表现出很大差异，并且都表现出在 ALPK3 患者中常见的心外特征。较晚发病的患者表现出较轻的心外症状，如肌张力下降和远端肌营养不良，但心脏并发症进展迅速，需要进行心脏移植。