Pathogenic variants in the POLG gene are one of the most common causes of primary mitochondrial disease. Patients may present with differing features, depending on the age of onset.

Mitochondrial encephalopathy lactic acidosis and stroke-like episodes is a common genetic diagnosis in patients with a suspected mitochondrial condition.

For some adults with epilepsy, there will be an underlying genetic cause.

Tuberous sclerosis complex (TSC) is a rare, variable, autosomal dominant genetic condition caused by pathogenic variants in the tumour suppressor genes TSC1 and TSC2. It is characterised by benign tumour growth and the variable presence of seizures and neurodevelopmental disorders.

Macrocephaly is defined as a head circumference over three standard deviations (3SD) above the mean for the patient’s age. In some affected children, there may be an underlying genomic cause.

Genomic testing should be considered for infants or young children presenting with early onset epilepsy or epileptic encephalopathy because there are numerous genetic causes with overlapping clinical features, and genomic testing may identify appropriate gene-directed precision therapies.

Autism spectrum disorders (ASDs) are typically multifactorial, with a strong genetic component influenced by environmental factors. A smaller proportion of patients will have ASD as a feature of an underlying defined genetic condition, such as fragile X or Rett syndromes.