PDF(Pubmed)
Abstract：
Pathogenic variants in LMNA have been associated with a wide spectrum of muscular conditions: the laminopathies. LMNA-related congenital muscular dystrophy is a laminopathy characterised by the early onset of symptoms and often leads to a fatal outcome at young ages. Children face a heightened risk of malignant arrhythmias. No established paediatric protocols for managing this condition are available. We review published cases and provide insights into disease progression in two twin sisters with LMNA-related muscular dystrophy. Our objective is to propose a cardiac surveillance and management plan tailored specifically for paediatric patients. We present a family of five members, including two twin sisters with LMNA-related muscular dystrophy. A comprehensive neuromuscular and cardiac work-up was performed in all family members. Genetic analysis using massive sequencing technology was performed in both twins. Clinical assessment showed that only the twins showed diagnoses of LMNA-related muscular dystrophy. Follow-up showed an early onset of symptoms and life-threatening arrhythmias, with differing disease progressions despite both twins passing away. Genetic analysis identified a de novo rare missense deleterious variant in the LMNA gene. Other additional rare variants were identified in genes associated with myasthenic syndrome. Early-onset neuromuscular symptoms could be related to a prognosis of worse life-threatening arrhythmias in LMNA related muscular dystrophy. Being a carrier of other rare variants may be a modifying factor in the progression of the phenotype, although further studies are needed. There is a pressing need for specific cardiac recommendations tailored to the paediatric population to mitigate the risk of malignant arrhythmias.
摘要：
LMNA中的致病变体与广泛的肌肉疾病有关：层蛋白病。LMNA相关的先天性肌营养不良是一种以早期症状为特征的层肌病，通常在年轻时导致致命的结果。儿童面临恶性心律失常的风险增加。没有建立的儿科方案来管理这种情况。我们回顾了已发表的病例，并提供了两个患有LMNA相关肌营养不良的双胞胎姐妹的疾病进展的见解。我们的目标是提出专门为儿科患者量身定制的心脏监测和管理计划。我们介绍了一个有五个成员的家庭，包括两个患有LMNA相关肌营养不良的双胞胎姐妹。对所有家庭成员进行了全面的神经肌肉和心脏检查。使用大规模测序技术对两个双胞胎进行了遗传分析。临床评估显示，只有双胞胎诊断出LMNA相关的肌营养不良。随访显示早期出现症状和危及生命的心律失常，尽管两个双胞胎都去世了，但疾病进展不同。遗传分析确定了LMNA基因中的从头罕见的错义有害变体。在与肌无力综合征相关的基因中发现了其他其他罕见变异。早发性神经肌肉症状可能与LMNA相关肌营养不良中危及生命的心律失常的预后有关。作为其他罕见变体的载体可能是表型进展的修饰因素，虽然还需要进一步的研究。迫切需要针对儿科人群的特定心脏建议，以减轻恶性心律失常的风险。
