Original articlePrevalence and genetic subtypes of congenital myasthenic syndromes in the pediatric population of Slovenia
Introduction
Congenital myasthenic syndromes (CMS) are rare, genetically and phenotypically diverse genetic disorders of neuromuscular transmission. The disease usually presents during the first and second year of life with fluctuating weakness, fatigability and exercise intolerance, typically involving ocular, bulbar, and limb muscles [1,2]. Episodic apneas in neonates, which can be the presenting symptom in certain subtypes, can result in brief resolved unexplained events (BRUE) [3].
Up to the last decade, typical clinical picture, positive family history, abnormal neuro-physiology tests, namely repetitive 3 Hz nerve stimulation (RNS) or single fiber electromyography (SF-EMG) and negative ACh and Musk antibodies have been hallmarks of the diagnosis [4]. In the last few years, next generation sequencing (NGS) and whole exome sequencing have become important and more readily available methods of confirming the diagnosis and the genetic subtype. The genetic landscape of CMS has been expanding fast in the past few years. In 2012, a total of 14 different genes known to cause CMS were reported and to date over 30 genes have been implicated [5].
Correct diagnosis is especially important because of treatment possibilities for certain subtypes [[6], [7], [8]]. Drugs with a positive effects for a specific CMS subtype may worsen other forms of CMS, depending on the underlying genetic defect. That is why the genetic subtyping of CMS is key to rational and optimized pharmacological treatment [2,[9], [10], [11]].
The aim of this study was to identify the prevalence and the genetic subtypes of childhood CMS in Slovenia. Knowledge on the most common genetic subtypes and corresponding phenotypes in our region could assist the physicians with establishing correct diagnosis and management of patients with CMS locally and globally.
Section snippets
Methods
In this retrospective, national, cross sectional study, all pediatric patients with genetically confirmed diagnosis of CMS obtained by December 31, 2018, and referred over a 19 – year period (2000–2018) to the Department of Child, Adolescent and Developmental Neurology, University Medical Centre, Ljubljana, Slovenia, were included. Considering ours is the only tertiary centre for child neurology and the only specialized pediatric centre for treatment of children with neuromuscular diseases in
Prevalence
We have identified 8 children (3 males, 5 females) with a confirmed genetic CMS who were born between January 1, 2000 and December 31, 2018. All 8 children were included in the study and none of the identified children died in the study period.
The population of children (age less than 19 years) in Slovenia at the end of 2018 was obtained from the Statistical Office of the Republic of Slovenia and was 360.161. All eight identified children included in the study were still under 19 years of age
Discussion
Despite the fact that CMS is considered to be a very rare disease, the possibility of effective treatment adds to the importance of early diagnosis of CMS.
Data on prevalence of CMS are scarce, the studies were mostly conducted in non-European regions [9,[15], [16], [17], [18]]. In Europe, the reported prevalence was between 1.8 cases per million total population in Spain to 9.2 per million children in UK [15,17]. Our study revealed the prevalence of 22.2 cases per million children, which
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