Bastos_2020_Neuromuscul.Disord__

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.