MBOAT7 encephalopathy: Characterizing the neurology and epileptology

Area of Science:

• Genetics
• Neurology
• Developmental Biology

Background:

• Biallelic pathogenic MBOAT7 variants are linked to neurodevelopmental disorders, intellectual disability (ID), and epilepsy.
• These variants are also associated with neuropsychiatric conditions like ADHD and ASD.

Purpose of the Study:

• To characterize the epilepsy phenotype in patients with biallelic MBOAT7 variants.
• To analyze neurodevelopmental outcomes and treatment responses in this cohort.

Main Methods:

• Described epilepsy features, EEG, MRI findings, and treatment response in 15 patients with biallelic MBOAT7 variants.
• Assessed neurodevelopmental status, including ID and developmental delay (DD).

Main Results:

• All 15 patients had ID or DD; 12 experienced epilepsy with diverse seizure types.
• Seizure freedom was achieved in 66.7% of epilepsy patients. Frequent MRI findings included T2/FLAIR hyperintensities in dentate nuclei and globus pallidus.
• Biallelic missense variants correlated with better cognitive and motor outcomes than truncating or in-frame deletion variants.

Conclusions:

• Biallelic MBOAT7 variants are associated with global developmental impairment and epilepsy in the majority of affected individuals.
• Seizure semiology is heterogeneous, with approximately one-third experiencing persistent seizures despite treatment.
• Characteristic MRI findings involve hyperintensities in the dentate nuclei and globus pallidus.