Late diagnosis of RAPSN mutation-associated congenital myasthenic syndrome with obstructive sleep apnea in a 5-year-old girl.

backgroundCongenital myasthenic syndromes represent a heterogenous group of rare genetic disorders that affect the neuromuscular junction. They present with variable combinations of extraocular, facial, bulbar, and limb muscle weakness with typical diurnal fluctuations of symptoms, with increased risk of sleep-related disorders. Due to the variable course, clinical diagnosis can be challenging and delayed, sometimes for decades. CASE PRESENTATION: We present the case of a 5-year-old girl presumed to have benign infantile hypotonia, who exhibited head drop during intercurrent illnesses and increased evening fatigue. Intermittent bilateral ptosis, initially unreported by the family and not observed during early morning examinations, became evident during a late afternoon visit. Given the clinical suspicion of a congenital myasthenic syndrome, genetic testing was performed and identified a homozygous pathogenic variant in the RAPSN gene responsible for a post-synaptic form of congenital myasthenia. Due to the complaints of excessive night-time snoring, overnight polygraphies (PG) were performed, revealing obstructive sleep-apnoea secondary to oropharyngeal muscle weakness. Symptomatic treatment with pyridostigmine, including a night-time dose, was followed by drastic improvement and near-complete resolution of nocturnal symptoms.

conclusionCongenital myasthenia may be more prevalent than recognised, with milder phenotypes still frequently overlooked or misdiagnosed. Sleep apnea is an important comorbidity that should be actively investigated. Optimised pyridostigmine therapy, including nocturnal dosing, can significantly alleviate symptoms and improve quality of life.