To clinically, genetically, and histopathologically characterize patients presenting with an unusual combination of distal myopathy and facial weakness, without involvement of upper limb or shoulder girdle muscles.

Two families with a novel form of actininopathy were identified. Patients had been followed up over 10 years. Their molecular genetic diagnosis was not clear after extensive investigations, including analysis of candidate genes and FSHD1-related D4Z4 repeats.

Patients shared a similar clinical phenotype and a common pattern of muscle involvement. They presented with a very slowly progressive myopathy involving anterior lower leg and facial muscles. Muscle MRI finding showed complete fat replacement of anterolateral compartment muscles of the lower legs with variable involvement of soleus and gastrocnemius but sparing thigh muscles. Muscle biopsy showed internalized nuclei, myofibrillar disorganization, and rimmed vacuoles. High-throughput sequencing identified in each proband a heterozygous single nucleotide deletion (c.2558del and c.2567del) in the last exon of the ACTN2 gene. The deletions are predicted to lead to a novel but unstructured slightly extended C-terminal amino acid sequence.

Our findings indicate an unusual form of actininopathy with specific molecular and clinical features. Actininopathy should be considered in the differential diagnosis of distal myopathy combined with facial weakness.

从临床、遗传和组织病理学上对表现为远端肌病和面部无力的异常组合的患者进行表征，但不累及上肢或肩带肌肉。

确定了两个具有新型放线菌病形式的家庭。患者已被随访超过 10 年。经过广泛调查，包括候选基因和 FSHD1 相关 D4Z4 重复序列的分析，他们的分子遗传学诊断尚不清楚。

患者具有相似的临床表型和常见的肌肉受累模式。他们出现了涉及小腿前部和面部肌肉的非常缓慢进行性肌病。肌肉 MRI 发现显示小腿前外侧隔室肌肉完全脂肪替代，比目鱼肌和腓肠肌受累不同，但大腿肌肉不受影响。肌肉活检显示核内化、肌原纤维解体和边缘空泡。高通量测序在每个先证者中鉴定出ACTN2基因最后一个外显子中的杂合单核苷酸缺失（c.2558del 和 c.2567del）。预计这些缺失会导致新的但非结构化的略微延伸的 C 末端氨基酸序列。

我们的研究结果表明具有特定分子和临床特征的不寻常形式的放线菌病。在远端肌病合并面部无力的鉴别诊断中应考虑放线肌病。