Long Term Follow-Up on Pediatric Cases With Congenital Myasthenic Syndromes-A Retrospective Single Centre Cohort Study.

Autor:	Della Marina A; Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, University Children's Hospital Essen, University Duisburg-Essen, Essen, Germany., Wibbeler E; Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany., Abicht A; Medical Genetic Center Munich, Munich, Germany.; Friedrich-Baur Institute, Ludwig Maximilian University, Munich, Germany., Kölbel H; Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, University Children's Hospital Essen, University Duisburg-Essen, Essen, Germany., Lochmüller H; Children's Hospital of Eastern Ontario Research Institute, Division of Neurology, Department of Medicine, The Ottawa Hospital, Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada.; Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany.; Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Spain., Roos A; Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, University Children's Hospital Essen, University Duisburg-Essen, Essen, Germany., Schara U; Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, University Children's Hospital Essen, University Duisburg-Essen, Essen, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in human neuroscience [Front Hum Neurosci] 2020 Dec 07; Vol. 14, pp. 560860. Date of Electronic Publication: 2020 Dec 07 (Print Publication: 2020).
DOI:	10.3389/fnhum.2020.560860
Abstrakt:	Introduction : Congenital myasthenic syndromes (CMS) refer to a heterogenic group of neuromuscular transmission disorders. CMS-subtypes are diverse regarding exercise intolerance and muscular weakness, varying from mild symptoms to life-limiting forms with neonatal onset. Long-term follow-up studies on disease progression and treatment-response in pediatric patients are rare. Patients and Methods : We analyzed retrospective clinical and medication data in a cohort of 32 CMS-patients including the application of a standardized, not yet validated test (CMS-ST) to examine muscular strength and endurance in 21 patients at the last follow-up. Findings obtained in our cohort were compared with long-term follow-up studies of (adult) CMS-cohorts from the literature by considering the underlying molecular mechanisms. Outcomes of CMS-ST were compared to results of normal clinical assessment. Results : Thirty-two pediatric patients with defects in eight different CMS-genes were followed by a median time of 12.8 years. Fifty-nine percentage of patients manifested with first symptoms as neonates, 35% as infants. While 53% of patients presented a reduced walking distance, 34% were wheelchair-bound. Even under adequate therapy with pyridostigmine (PS) and 3,4-diaminopyridine, CHAT -mutations led to the progression of muscular weakness partly in combination with persistent respiratory and bulbar symptoms. RAPSN, CHRND , and CHRNB1 patients with neonatal manifestation, early respiratory problems, and bulbar symptoms showed a good and maintained treatment response. CHAT and CHRNE patients required higher PS dosages, whereas RAPSN patients needed a lower mean dosage at the last follow-up. The benefits of short-term medication and long-term progression of symptoms were highly dependent on the specific genetic defect. CMS-ST was carried out in 17/21 patients, determined affected muscle groups including bulbar and ocular symptoms, some of which were not reported by the patients. Conclusions : Our findings and comparison with the literature- suggest a better treatment-response and less severe progression of symptoms present in patients suffering from mutations in CMS-genes directly associated with receptor deficiency, while patients with defects leading to synaptopathy and presynaptic defects tend to have worse outcomes. Assessment of affected muscular groups and clinical symptoms by CMS-ST may be a useful tool for optimal therapeutic management of the patients, especially for future clinical studies. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2020 Della Marina, Wibbeler, Abicht, Kölbel, Lochmüller, Roos and Schara.)
Databáze:	MEDLINE
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