Clinical features
Changes in the SCN2A gene can cause a number of disorders of brain function, otherwise known as neurodevelopmental disorders. An individual diagnosed with an SCN2A-related disorder may have a variety of symptoms, which can include seizures (epilepsy), developmental delay and or intellectual disability (DD/ID), autism spectrum disorders (ASD) and abnormalities of movement and muscle tone. Individuals with SCN2A-disorders may have only some of these symptoms.

SCN2A is estimated to be the most common single gene cause of neurodevelopmental disorders including DD/ID and autism, and is a major cause of severe epilepsy. The incidence has been reported as 1:78,000 individuals, although this is likely an underestimate.

Individuals have a pair of SCN2A genes in most cells in their body. SCN2A-related disorders are caused by a fault in one copy of the SCN2A gene. This is called a heterozygous gene change. A gene change is also known as a ‘pathogenic variant’.

The pathogenic variant may arise for the first time in the affected individual, typically very early in development. This is called a ‘de novo’ variant, and can be confirmed by testing DNA of the affected individual (variant present) and both parents (variant not present). Typically, although not always, a de novo variant is associated with one of the more severe types of SCN2A-related disorder. Parents of a child with an apparently de novo genetic change have a low, but not zero chance, of the condition recurring in a future pregnancy. This is because of the possibility of the SCN2A variant beingpresent in some but not all cells of a parent, including in a patch of eggs or sperm (germline or gonadal mosaicism). 

In other families, especially when the SCN2A variant is associated with milder symptoms, the variant may be inherited from a parent who is heterozygous for the same SCN2A variant and who had similar symptoms. An individual who his heterozygous for a pathogenic variant in the SCN2A gene has a 1 in 2 (50%) chance of passing on the variant in each pregnancy.

An appointment with a clinical genetics service is recommended for all families for up-to-date genetic counselling and advice on the most appropriate genetic testing for parents, especially if more children are planned.