VAMP-1 associated congenital myasthenic syndrome: a demonstrative case with response to low-dose pyridostigmine (P2-8.003)

Abstract

<h3>Objective:</h3> To report a case of VAMP1-associated congenital myasthenic syndrome with response to low-dose pyridostigmine, adding to an emerging literature describing this condition. <h3>Background:</h3> Biallelic mutations in VAMP1 are associated with a rare pre-synaptic congenital myasthenic syndrome (CMS). VAMP1 encodes a protein involved in synaptic vesicles formation and fusion. <h3>Design/Methods:</h3> Case report and review of literature <h3>Results:</h3> A 15 month-old boy was referred for evaluation of hypotonia and dysphagia since birth at term. The infant was unable to sit or roll. He was unable to feed orally. Examination revealed myopathic facies, fluctuating ptosis, ophthalmoparesis, hypotonia, and areflexia. Cry was weak. Secretion control was poor. Spontaneous movement was minimal; movements were antigravity in the distal extremities. Results of a prior Whole Exome Sequence identified a homozygous pathogenic variant in VAMP1 [ c.103C&lt;T; p.Q35* (NM_014231.3)]. A proactive airway clearance regimen was instituted. Pyridostigmine (0.25 mg/kg per dose) demonstrated immediate benefit, as indicated by antigravity movement of limbs, louder cry and cough, and improved secretion control despite being admitted for respiratory infection at the time of trial. Dose was increased to 0.5 mg/kg every four hours while awake. Parents observed more robust activity at home. Independent sitting was attained at age 17 months. Dysphagia persisted. A polysomnogram was abnormal (max ETCO2 50torr, AHI 9.8). <h3>Conclusions:</h3> This adds to the literature documenting a recessive VAMP1-related CMS. Recent reports have suggested pyridostigmine responsiveness. This case demonstrated motor benefit from low-dose pyridostigmine. Given risk of mucous plugging and aspiration in patients with neuromuscular weakness, an airway clearance regimen (ex: cough assist device) should be considered prior to a trial of therapy. Assessment of nocturnal ventilation and swallow safety remain crucial, as highlighted by this infant’s still abnormal polysomnogram and persistent dysphagia. <b>Disclosure:</b> Dr. Drakou has nothing to disclose. Dr. Delfiner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Delfiner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Gene Therapies. Dr. Delfiner has received personal compensation in the range of $500-$4,999 for serving as a MDA Engage Event Chair and speaker with Muscular Dystrophy Association.