Anatomo-Electro-Clinical Phenotypes in Children With Epilepsy and DYNC1H1 Mutations

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Pathogenic variants in DYNC1H1, encoding cytoplasmic dynein 1 heavy chain 1, are associated with diverse neurological disorders.
• DYNC1H1 plays a crucial role in neuronal development and function.

Purpose of the Study:

• To characterize the clinical, neuroimaging, and neurophysiological features of patients with pathogenic DYNC1H1 variants.
• To identify distinct phenotypes associated with DYNC1H1 mutations.

Main Methods:

• Analysis of clinical data from four patients.
• Review of video-electroencephalography (vEEG) and neuroimaging findings.
• Genetic analysis to identify pathogenic variants in DYNC1H1.

Main Results:

• Distinct neuroimaging and neurophysiological hallmarks were identified.
• Three patients presented with lissencephaly spectrum malformations, developmental and epileptic encephalopathy, focal seizures, and epileptic spasms.
• One patient exhibited bifrontal polymicrogyria, developmental and epileptic encephalopathy, and spike-and-wave activation during sleep.

Conclusions:

• Two distinct phenotypes associated with DYNC1H1 pathogenic variants were identified.
• The study reports the first case of polymicrogyria and epileptic encephalopathy with spike-and-wave activation in sleep linked to a genetic disorder.
• Recognizing these specific phenotypes can aid in the diagnosis of DYNC1H1-related neurological conditions.