We here present the case of a patient with a congenital myasthenic syndrome (CMS) due pathogenic variants in the RAPSN gene. During childhood he experienced recurrent episodes of respiratory failure during respiratory infections. This and other cases were reported as isolated dystrophy of the diaphragmatic musculature. In adulthood, whole exome sequencing revealed two heterozygous pathogenic variants in the RAPSN gene. This led to the revision of the diagnosis to rapsyn CMS11 (OMIM:616326, MONDO:0014588). EMG, muscle ultrasound and the revision of muscle biopsies taken in childhood support this diagnosis. After the revision of the diagnosis, treatment with pyridostigmine was started. This resulted in a reduction of fatigability and an improvement in functional abilities and quality of life.
Background: The slow channel syndrome is a rare hereditary disorder caused by a dominant gain-of-function variant in one of the subunits of the acetylcholine receptor at the neuromuscular junction. Patients typically experience axial, limb and particularly extensor finger muscle weakness. Objective: Age at diagnosis is variable and although the long-term prognosis is important for newly diagnosed patients, extensive follow-up studies are rare. We aim to provide answers and perspective for this patient group by presenting an elaborate description of the lifetime follow-up of two slow channel syndrome patients. Methods: We describe 40 years follow-up in two, genetically confirmed cases (CHRNA1; c.866G > T p.(Ser289Ile)(legacy Ser269Ile) and CHRNE; c.721C > T p.(Leu241Phe)(legacy Leu221Phe) variants). Results: We find that the disease course has a fluctuating pattern and is only mildly progressive. However, hormonal imbalances, (psychological) stress or excessive hot or cold environments are often aggravating factors. Quinidine and fluoxetine are helpful, but ephedrine and salbutamol may also improve symptoms. Conclusion: Slow channel syndrome is mildly progressive with a fluctuating pattern. The observations reported here provide a lifespan perspective and answers to the most pressing questions about prognosis and treatment options for newly diagnosed patients.
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