目的 探讨1例非典型症状起病的结蛋白病患者的临床特点与基因变异情况。 方法 选取2021年2月24日于上海市静安区中心医院神经内科就诊的1例男性结蛋白病患者为研究对象，分析患者的临床资料、实验室检查、肌肉病理、肌肉MRI特点及基因变异情况。 结果 患者以下肢活动后肌痛起病，逐渐出现下肢不对称肌无力、肌肉萎缩，心脏检查提示房室传导阻滞和左室舒张功能减退。肌肉MRI提示除半腱肌、缝匠肌、股薄肌、腓骨肌及腓肠肌受累外，前臂旋后肌早期出现选择性受累。肌肉活检证实为结蛋白阳性肌原纤维病病理改变。基因检测发现DES基因第6外显子存在c.1024A>G错义变异，导致氨基酸p.N342D改变。根据美国医学遗传学与基因组学学会(ACMG)相关指南，该变异评定为可能致病性(PS4_Moderate＋PM2_Supporting＋PP3_Moderate＋PP1)。 结论 结蛋白病有较大临床异质性，下肢运动后肌痛无力是N342D携带者少见的一种临床表型，心脏受累较为隐匿，临床中易被忽视，及时进行肌肉MRI、肌肉活检及基因检测将有助于该病的早期诊断。 Objective To explore the clinical characteristics and genetic variant of a patient with desminopathy manifesting with atypical symptoms. Methods A patient who was admitted to the Department of Neurology of Jing′an District Central Hospital on February 24, 2021 was selected as the study subject. Clinical data, laboratory tests, muscle pathology, muscle magnetic resonance imaging (MRI) and genetic testing of the patient were retrospectively analyzed. Results The patient had developed myalgia after lower limb activity, and gradually developed asymmetrical muscle weakness and atrophy of the lower limbs. Cardiac examination revealed atrioventricular block and decreased left ventricular diastolic function. Muscle MRI showed that semitendinosus, sartorius, gracilis, fibula, gastronemius and supinator muscles were selectively involved at the early stage. Muscle biopsy confirmed pathological changes of desmin positive myofibrils. Genetic testing revealed that the patient has harbored a c. 1024A>G (p.n342d) missense variant in exon 6 of theDES gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PS4_moderate+ PM2_supporting+ PP3_moderate+ PP1). Conclusion Desmin disease has a great clinical heterogeneity. Postexercise myalgia of lower limbs is a rare clinical phenotype. For patients harboring the c. 1024A>G (p.n342d) variant of theDES gene, in addition to semitendinosus and fibula, Cardiac involvement is relatively insidious and easy to be ignored in clinic. Timely muscle MRI, muscle biopsy and gene detection will help the early diagnosis of the disease.
Clinical and genetic analysis of a patient with Desminopathy manifesting initially with myalgia after lower limb activity
Objective To explore the clinical characteristics and genetic variant of a patient with desminopathy manifesting with atypical symptoms. Methods A patient who was admitted to the Department of Neurology of Jing′an District Central Hospital on February 24, 2021 was selected as the study subject. Clinical data, laboratory tests, muscle pathology, muscle magnetic resonance imaging (MRI) and genetic testing of the patient were retrospectively analyzed. Results The patient had developed myalgia after lower limb activity, and gradually developed asymmetrical muscle weakness and atrophy of the lower limbs. Cardiac examination revealed atrioventricular block and decreased left ventricular diastolic function. Muscle MRI showed that semitendinosus, sartorius, gracilis, fibula, gastronemius and supinator muscles were selectively involved at the early stage. Muscle biopsy confirmed pathological changes of desmin positive myofibrils. Genetic testing revealed that the patient has harbored a c. 1024A>G (p.n342d) missense variant in exon 6 of theDES gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PS4_moderate+ PM2_supporting+ PP3_moderate+ PP1). Conclusion Desmin disease has a great clinical heterogeneity. Postexercise myalgia of lower limbs is a rare clinical phenotype. For patients harboring the c. 1024A>G (p.n342d) variant of theDES gene, in addition to semitendinosus and fibula, Cardiac involvement is relatively insidious and easy to be ignored in clinic. Timely muscle MRI, muscle biopsy and gene detection will help the early diagnosis of the disease.
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