Congenital myasthenic syndromes are disorders of the neuromuscular junction resulting from genetic defects in its components. Clinical presentations are diverse and virtually always of early onset. We report a 67-year-old female patient first presenting with episodes of sudden respiratory failure. A diagnosis of seronegative myasthenia gravis was put forward based on the presence of a limb-girdle pattern of muscle weakness with pathological decremental responses on Repetitive Nerve Stimulation. Lack of response to steroids, intravenous human immunoglobulin and acetylcholinesterase inhibitors lead us to test for classical congenital myasthenic syndrome genes. A c.1378dup heterozygotic mutation in DOK7 was found, classically (albeit not exclusively) described as pathogenic only when inherited in a homozygotic fashion. Patients with such a single, heterozygous mutation have been previously described, but these have been left unexplained. Thus, under certain still poorly understood circumstances, a heterozygotic state may allow for disease manifestation. These patients may benefit from tailored therapies akin to those normally reserved to homozygotic/compound heterozygotic patients. Awareness for and recognition of such conditions are expected to allow for better provided care and improved quality of life.

中文翻译：

---

由杂合 DOK7 突变引起的迟发性先天性肌无力综合征

先天性肌无力综合征是由神经肌肉接头成分的遗传缺陷引起的疾病。临床表现多种多样，几乎总是早发。我们报告了一名 67 岁女性患者，该患者首次出现突发呼吸衰竭。血清阴性重症肌无力的诊断是基于存在肌肉无力的肢带模式，对重复神经刺激有病理性递减反应。对类固醇、静脉注射人免疫球蛋白和乙酰胆碱酯酶抑制剂缺乏反应导致我们测试经典的先天性肌无力综合征基因。发现 DOK7 中的 c.1378dup 杂合突变，经典（尽管不是唯一的）仅在以纯合方式遗传时才被描述为致病性。有这样的单身患者，杂合突变以前已经描述过，但这些都没有得到解释。因此，在某些仍然知之甚少的情况下，杂合状态可能会导致疾病表现。这些患者可能受益于类似于通常保留给纯合子/复合杂合子患者的定制疗法。对此类状况的认识和认可有望提供更好的护理和改善的生活质量。