A prospective interventional single-center study will be conducted. The study includes clinically diagnosed Intramuros PCA-patients who underwent a PCA gene panel of 113 genes (see Appendix 1) in the UZ-Brussel since 2021.
Retrospective part:
The following retrospective data from the medical file will be analyzed:
- Informed consents signed before genetic analysis with PCA gene panel (Appendix 2).
- Assessment of cardiac history, cardiac family history, cardiac exams and medical treatment
- Assessment of genetic data and family history.
The PCA gene panel already contains the SCN4A gene since 2021. In case patients consented to scientific research or they consented to a wide genetic testing, additional genetic screening of the CLCN1 gene will be implemented. Those who did not consent previous to the PCA-gene panel analysis, will be contacted to sign a new informed consent if interested before additional screen-ing of the CLCN1 gene.
The prevalence of a class 3, 4 or 5 variant in the SCN4A and CLCN1 gene in the PCA-group will be compared to controls who underwent genetic screening for different causes, in which no associa-tion with muscular channelopathies is expected, without access to their medical file. These con-trols are the parents of patients with a congenital malformation syndrome or patients with a neu-rodevelopmental disorder. This to evaluate whether there's a higher prevalence of skeletal muscle channelopathies in patients with PCA compared to the general population.
Prospective part:
Patients with PCA carrying a variant class 3,4 or 5 in the SCN4A gene or a variant class 3, 4 or 5 in the CLCN1 gene will be invited by the department of Medical Genetics where they already have had a consultation, to the Neurology department for one visit on one day for the following as-sessments:
- Interview to assess the presence, onset and duration of myotonia or episodic weakness. Assessment of medical history, family history and medical treatment.
- Clinical neurological assessment for clinical myotonia.
- Electromyography (EMG) to detect the presence of myotonic discharges and using the Streib and Sun score for quantification(34) (see Appendix 3).
- Short exercise test in case of myotonic discharges on nEMG.
- In case of a diagnosis of a muscular channelopathy, assessment with.a QoL scale (see Ap-pendix 4).
The aim of this second phase is to describe the clinical presentation of patients with concomitant PCA and non-dystrophic myotonia . Since there is a known clinical variability between and within families with NDM, we aim to examine whether certain clinical features or severity of the disorder are linked to cardiac involvement.
Patients of the control group, who consented for scientific research and additional testing and who consented to be informed about incidental discoveries, who carry a variant class 3,4 or 5 in the SCN4A gene or a variant class 3, 4 or 5 in the CLCN1 gene, will be invited to the Neurology de-partment for a clinical evaluation outside of the study.
Patients with a variant class 3,4 or 5 in the SCN4A gene who did beforehand not consent for scien-tific research and/or for additional genetic testing are not additionally tested for variants in the CLCN1 gene but will be invited for a clinical evaluation after consent. If,, after clinical evaluation and EMG, they are diagnosed with myotonia, additional testing for a variant in the CLCN1 gene will be proposed.
