Hypertrophic cardiomyopathy (HCM) is a genetic disorder mostly caused by sarcomeric gene mutations, but almost 10% of cases are attributed to inherited metabolic and neuromuscular disorders. First described in 2008 in an American-Italian family with scapuloperoneal myopathy, FHL1 gene encodes four-and-a-half LIM domains 1 proteins which are involved in sarcomere formation, assembly and biomechanical stress sensing both in cardiac and skeletal muscle, and its mutations are responsible for a large spectrum of neuromuscular disorders (mostly myopathies) and cardiac disease, represented by HCM, either isolated, or in conjunction with neurologic and skeletal muscle impairment. We thereby report a novel mutation variant in FHL1 structure, associated with HCM and type 6 Emery-Dreifuss muscular dystrophy (EDMD). We describe the case of a 40 year old male patient, who was referred to our department for evaluation in the setting of NYHA II heart failure symptoms and was found to have HCM. The elevated muscular enzymes raised the suspicion of a neuromuscular disease. Rigid low spine and wasting of deltoidus, supraspinatus, infraspinatus and calf muscles were described by the neurological examination. Electromyography and muscle biopsy found evidence of chronic myopathy. Diagnosis work-up was completed by next-generation sequencing genetic testing which found a likely pathogenic mutation in the FHL1 gene (c.157-1G > A, hemizygous) involved in the development of X-linked EDMD type 6. This case report highlights the importance of multimodality diagnostic approach in a patient with a neuromuscular disorder and associated hypertrophic cardiomyopathy by identifying a novel mutation variant in FHL1 gene. Raising awareness of non-sarcomeric gene mutations which can lead to HCM is fundamental, because of diagnostic and clinical risk stratification challenges.

中文翻译：

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在非阻塞性肥厚型心肌病和肌病患者中鉴定出新型FHL1突变变异体–病例报告

肥厚型心肌病（HCM）是一种遗传性疾病，主要由肌节基因突变引起，但几乎有10％的病例归因于遗传性代谢和神经肌肉疾病。FHL1基因于2008年首次在美国-意大利患有肩my骨肌病的家庭中进行描述，其编码四个半LIM域1蛋白，它们参与心肌和骨骼肌的肌节形成，组装和生物力学应力感测及其突变。它们是由HCM代表的广泛的神经肌肉疾病（主要是肌病）和心脏疾病的原因，既可以是单独发生的，也可以是神经系统和骨骼肌损伤的结合。因此，我们报告了与HCM和6型金刚砂-Dreifuss肌营养不良症（EDMD）相关的FHL1结构的新型突变变异。我们描述了一名40岁男性患者的病例，该患者被转诊至我科以评估NYHA II心力衰竭症状并被发现患有HCM。升高的肌肉酶增加了对神经肌肉疾病的怀疑。通过神经系统检查，可以观察到僵硬的低脊椎和三角肌，上棘，下斜肌和小腿肌肉的消瘦。肌电图和肌肉活检发现了慢性肌病的证据。通过下一代测序基因测试完成了诊断工作，该测试发现了X连锁EDMD 6型的发展中FHL1基因（c.157-1G> A，半合子）可能存在致病突变。该病例报告通过鉴定FHL1基因中的新型突变变体，突出了多模式诊断方法在神经肌肉疾病和相关性肥厚性心肌病患者中的重要性。由于诊断和临床风险分层方面的挑战，提高对可能导致HCM的非肌型基因突变的认识至关重要。