Statistics from Altmetric.com
Sarcolemmal voltage-gated sodium and calcium ion channels are essential for generating action potentials and excitation contraction coupling required for muscle contraction. Autosomal dominant sodium and calcium ion channel gene disorders cause episodic symptoms of periodic paralysis (PP) and myotonia.1 Acetazolamide treatment improves these symptoms.2 Recently, recessive congenital myopathies due to compound heterozygous or homozygous ion channel gene mutations have been described with fixed muscle weakness and disability.3 4
In case series we previously reported, two individuals with ion channel-related congenital myopathy had additional discrete episodic or fluctuant weakness causing added morbidity.3 4 Here, we delineate the long-term benefit of treatment with acetazolamide for these individuals and discuss the implications for genetic diagnosis and management of future cases.
A 16-year-old girl with compound heterozygous SCN4A gene mutations (figure 1B).3 Reduced fetal movements were noted during pregnancy with a breech presentation at birth. Features of congenital myopathy included neonatal hypotonia, weak cry, talipes, thin muscle build and weak suck requiring nasogastric tube feeding for 12 days. With maturity, significant proximal and axial weakness occurred with difficulties running, going upstairs, rising from the floor and walking long distances. Due to respiratory insufficiency, she required nocturnal BiLevel Positive Airway Pressure (BiPAP) from age 6. Progressive scoliosis required surgical fixation at age 12.
Contributors EM: drafting the manuscript for content, analysis or interpretation of data, study concept. LH: revising the manuscript for content, analysis or interpretation of data, study concept. RS: revising the manuscript for content, analysis or interpretation of data. MGH: revising the manuscript for content, analysis or interpretation of data. FM: revising the manuscript for content, analysis or interpretation of data, study concept. PM: revising the manuscript for content, analysis or interpretation of data, study concept.
Funding EM has received funding from an NIHR rare disease TRC postdoctoral fellowship, which is supported via the UCLH NIHR BRC. Part of this work was undertaken at University College London Hospitals/University College London, which received a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme. MGH is supported by a Medical Research Council Centre grant, the UCLH NIHR BRC and receives research funding from the Muscular Dystrophy Campaign. FM is supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London.
Competing interests None declared.
Patient consent Next of kin consent obtained.
Ethics approval The London—West London and GTAC Research Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement This is a letter describing two clinical cases. All data are reported in the letter.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.