A novel mutation in the DYNC1H1 gene causing developmental and epileptic encephalopathy treated with ketogenic diet:...

DYNC1H1 variants are associated with a spectrum of neurodevelopmental disorders, such as spinal muscular atrophy, severe intellectual disability, and epileptic encephalopathies, with the majority of observed cases attributed to de novo variants.

A 1-year-old Chinese boy presented with frequent seizures and developmental delay.

Cranial magnetic resonance imaging revealed malformations of cortical development. EEG indicated epileptic spasms and focal to bilateral tonic-clonic seizures. Trio-WES identified a de novo missense variant (c.3371A > G) located in exon 14 of the DYNC1H1 gene, which was confirmed by Sanger sequence. The final diagnoses were "DYNC1H1-related developmental and epileptic encephalopathy; malformations of cortical development."

Initial treatment with various ASMs proved ineffective. Finally, ketogenic diet treatment was introduced.

The patient had achieved significant seizure control, and the follow-up EEG discharges were reduced.

This report expanded the genotypic spectrum of DYNC1H1 gene, and highlights the potential therapeutic option of ketogenic diet for DYNC1H1-related developmental and epileptic encephalopathy, particularly in cases refractory to ASMs. These findings contribute valuable insights for the precision medicine approach in treating such patients.