1. 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 G>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:
* permission given by patients
Department of Pediatrics, University Clinic Salzburg,
UNIVERSITY HOSPITAL SALZBURG - Paracelsus Medical University | Gemeinnützige Salzburger Landeskliniken Betriebsges.m.b.H.