Objectives

To report a case of adult-onset non-dystrophic myotonia complicated by recurrent episodes of laryngospasm.

Methods

The patient is a 35-year-old man who was admitted to our hospital for recurrent episodes of apnea requiring endotracheal intubation with mechanical ventilation. He underwent extensive evaluation, including EMG, laryngoscopy, muscle biopsy, and genetic testing, which revealed a diagnosis of non-dystrophic myotonia.

Results

His myotonic disorder was due to the synergistic effects of a pathogenic CLCN1 variant and a newly reported SCN4A variant. His muscle biopsy demonstrated myofibrillar disorganization with Z-band streaming, which may reflect the severity of his clinical and electrographic myotonia. Treatment with mexiletine resulted in resolution of his episodes of laryngospasm and symptoms of myotonia in the extremities.

Discussion

Our case adds to the literature on the potentiating effects of chloride channelopathies on sodium channel myotonia. This is the first reported case of an adult-onset sodium channelopathy manifesting with respiratory failure due to laryngospasm. In addition, we present muscle biopsy findings that have not been described in the recent literature. This case also highlights that a myotonic disorder should be considered in the differential diagnosis for recurrent episodes of mixed hypoxic and hypercarbic respiratory failure.

Ligand receptor interactions instruct axon guidance during development. How dendrites are guided to specific targets is less understood. The C. elegans PVD sensory neuron innervates muscle-skin interface with its elaborate dendritic branches. Here, we found that LECT-2, the ortholog of leukocyte cell-derived chemotaxin-2 (LECT2), is secreted from the muscles and required for muscle innervation by PVD. Mosaic analyses showed that LECT-2 acted locally to guide the growth of terminal branches. Ectopic expression of LECT-2 from seam cells is sufficient to redirect the PVD dendrites onto seam cells. LECT-2 functions in a multi-protein receptor-ligand complex that also contains two transmembrane ligands on the skin, SAX-7/L1CAM and MNR-1, and the neuronal transmembrane receptor DMA-1. LECT-2 greatly enhances the binding between SAX-7, MNR-1 and DMA-1. The activation of DMA-1 strictly requires all three ligands, which establishes a combinatorial code to precisely target and pattern dendritic arbors.