How is NDM passed on?
NDM is a group of rare hereditary neuromuscular diseases that are caused predominantly by mutations in the genes responsible for producing sodium (Na+) or chloride (Cl–) ion channels in muscle cells. Defects in these ion channels can delay muscles from relaxing after they have been used.
How do genes work?
Genes give our cells instructions to make all the different proteins our body needs to function. We carry two copies of every gene in our cells; we receive one copy of each gene from each of our parents.
What are the mutations that cause NDM?
People with NDM have mutations in the genes that produce two types of ion channels – these channels are called sodium (Na+) and chloride (Cl–) ion channels.1,2 Learn more about ion channels and the causes of NDM. The gene responsible for sodium channels is called SCN4A and the gene responsible for chloride channels is called CLCN1. More than 200 CLCN1 and 65 SCN4A gene mutations have been linked with NDM.3
Various mutations in different ion channels cause several types of NDM. It is important to understand what type of NDM you have, to help manage your symptoms better.
How are NDM genes inherited?
NDM is an autosomal genetic disorder and can be inherited in an “autosomal dominant” or “autosomal recessive” manner.1 If a genetic mutation is classed as autosomal dominant, it only needs one copy of the mutated gene to be present for the mutation to have an effect that causes disease. If a genetic mutation is classed as autosomal recessive, both copies of the gene (one from each parent) must be mutated for disease to be caused.
Thomsen myotonia congenita, paramyotonia congenita, dyskalaemic episodic paralysis and potassium-aggravated myotonia are inherited in an autosomal dominant manner.1,2 Therefore, a parent with one of these types of NDM will carry a single copy of the abnormal gene, and has a 50% (1 in 2) chance of passing on the condition to each of their children.
Autosomal dominant inheritance of Thomsen myotonia congenita, paramyotonia congenita, dyskalaemic episodic paralysis and potassium aggravated myotonia.
Becker myotonia congenita is inherited in an autosomal recessive manner.1,2 This means that for a child to inherit Becker myotonia congenita, he/she will need to receive two copies of the mutated gene, and both parents will need to be carriers. Two parents who are both carriers will have a 25% (1 in 4) chance of each child being affected by the disease.
Autosomal recessive inheritance of Becker myotonia congenita
- Hahn C, Salajegheh MK. Iran J Neurol 2016;15:46–53
- Matthews E et al. Brain 2010;133:9–22
- Morales F and Pusch M. Front Neurol 2020;10:1404