W. Sperl1 / S. Wortmann-Hagemann1,3 Highly effective treatment in mild symptomatic adolescent twins with Congenital Myasthenic Syndrome (CMS) J. Spenger1 / J. Lotte2 / J. Mayr1 / M. Preisel1 / J. Koch1 / C. Rauscher1 / T. Haack4,(3) / B. Alhaddad3 / W. Sperl1 / S. Wortmann-Hagemann1,3 Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), Salzburg, Austria,1 Clinic for Neuropediatrics and Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schön-Klinik Vogtareuth, Germany2 Institute of Human Genetics, Technische Universität München, Munich, Germany3 (prev. position) Institute of Medical Genetics and Applied Genomics, University of Tübingen, Germany 4 Background Congenital myasthenic syndrome (CMS) is a genetically and clinically diverse entity of diseases which present with fatigable weakness of skeletal muscle (e.g., ocular, bulbar, limb muscles). Onset is mostly at birth, shortly after birth or in early childhood. The course and severity of the disease are highly variable, ranging from minor symptoms to progressive disabling weakness. While there is no Genotype-Phenotype correlation, treatment choice and effect depends on Genotype. Case report Course Both children showed striking amelioration of symptoms increase in physical exercise tolerance 5 sec faster in 60 m-sprint after-lunch nap no more needed correction of ptosis and eye movement higher concentration capacity in school better school-grades (female) increase in everyday fitness improvement of walking distance in 6-min-walking test adolescent twins, male and female male twin at the age of 6 years muscle pain slight weakness in exercise at the age of 10 years bilateral ptosis, impaired eye movement exercise fatigue concentration deficits in school. female twin mild exercise fatigue both: adapted to quality of life (QoL) Investigations CK unremarkable EMG unremarkable Echocardiography unremarkable Bicycle Ergometry: no pathologic lactate peak eye-muscle biopsy: normal respiratory chain, no mtDNA deletion at the age of 13 years: whole exome sequencing homozygous CHRNE mutation (c.1326+1G>A) previously unreported splicing variant CHRNE: ε-subunit of the acetylcholine receptor (ACh-R) PIC.1 bilateral ptosis* (male) Start Pyridostigmine male twin female twin PIC.2 mild bilateral ptosis* (female) FIG.1 6-minutes-walking-test: clear improvement in walking distance Treatment Acetylcholine-Esterase (AChE) inhibitor pyridostigmine is ad-ministered orally increasing the dosage up to 3.7 mg/kg/d (male twin) and 3.3 mg/kg/d (female twin). After 15 months of treatment no side effects ocurred and no additional medication (3, 4-diaminopyridine, albuterol) is needed. Video 1 eye movements pre-medication (female)* Video 2 eye movements on medication (female)* Conclusion In mild course of CMS late treatment start with AChE inhibitor significantly improves associated symptoms. References Schara U, Della Marina A, Abicht A: Congenital Myasthenic Syndromes: Current Diagnostic and Therapeutic Approaches. Neuropediatrics, 2012; 43:184–93 Eymard B et al: Syndromes myasthéniques congenitaux – L‘expérience française. Bull. Acad. Natle Méd 2014; 198: 257-71 * permission given by patients Department of Pediatrics, University Clinic Salzburg, j.spenger@salk.at UNIVERSITY HOSPITAL SALZBURG - Paracelsus Medical University | Gemeinnützige Salzburger Landeskliniken Betriebsges.m.b.H.