CHR2 encodes the delta subunit of the nicotinic acetylcholine receptor (AChR), a pentameric ion channel complex at the neuromuscular junction 1. Upon acetylcholine binding, CHR2 undergoes conformational changes that facilitate opening of an ion-conducting channel, enabling depolarization and skeletal muscle contraction 2. This component is essential for neuromuscular signal transmission and synaptic transmission. Pathogenic CHR2 variants cause congenital myasthenic syndromes (CMS), a group of heterogeneous neuromuscular disorders characterized by impaired neuromuscular transmission 23. CMS associated with CHR2 variants typically present with ocular symptoms, feeding difficulties, and bulbar dysfunction with earlier symptom onset compared to variants in other AChR subunits 1. In a Belgian cohort, CHR2 variants represented one of multiple genes associated with CMS phenotypes 4. Treatment responses are largely predictable based on CHR2 genotypes, with cholinesterase inhibitors and sympathomimetics showing efficacy in most patients 2. Rare CHR2 variants have also been associated with familial esophageal atresia and tracheoesophageal fistula, suggesting potential pleiotropic effects 5. Long-term prognosis for CMS patients with CHR2 variants is generally favorable with appropriate pharmacological intervention 3.