Bernard, Geneviève

Abstract Objective Biallelic pathogenic MBOAT7 variants are associated with neurodevelopmental disorders, intellectual disability (ID), epilepsy, and neuropsychiatric disorders such as attention‐deficit/hyperactivity disorder and autism spectrum disorders. We aimed to characterize the epilepsy phenotype in a cohort of patients affected by this syndrome. Methods We describe epilepsy features, electroencephalography, magnetic resonance imaging (MRI) findings, antiseizure treatment response, and neurodevelopment of 15 patients with biallelic MBOAT7 variants. Results All 15 patients had ID or developmental delay (DD). Twelve suffered from epilepsy, with mean age at seizure onset of 36 months (range = 2 months–6.5 years) and 10 of 12 showing signs of DD before seizure onset. Patients with epilepsy presented with focal motor seizures with impaired awareness ( n = 3), focal tonic–clonic seizures and epileptic spasms ( n = 1), focal to bilateral tonic–clonic seizures ( n = 1), unknown onset bilateral tonic–clonic seizures ( n = 2), myoclonic seizures ( n = 4), myoclonic–atonic seizures ( n = 1), atonic seizures ( n = 1), tonic seizures ( n = 1), and myoclonic absences ( n = 2). Seizure freedom was achieved in 66.7% (8/12), with variable antiseizure treatment regimes. We reviewed electroencephalograms of the patients with epilepsy. Background activity was normal in 64%, whereas 36% had either a generalized or a focal slowing. Interictal epileptiform discharges (IEDs) were reported in 83%. Generalized spikes/polyspikes were found in 53%, multifocal IEDs in 23%, and parasagittal focal IEDs in 26%. The most frequent abnormal brain MRI findings, reported in 58% of patients, included high‐intensity signal in T2 and fluid‐attenuated inversion recovery (FLAIR) sequences in dentate nuclei and globus pallidus. Biallelic missense variants seemed to be associated with better cognitive and motor outcomes compared to truncating variants and in‐frame deletions. Significance Biallelic MBOAT7 variants are associated with global developmental impairment in all affected patients and epilepsy in the majority. The seizure semiology is heterogenous. One third of our cohort had persistent seizures despite treatment. The most frequent MRI findings were hyperintensities in T2/FLAIR sequences in dentate nuclei and globus pallidus.

Background: RNA polymerase III (POLR3)-related leukodystrophy is a rare, neurodegenerative disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. Despite the challenges of caring for a child with POLR3-related leukodystrophy, few studies have examined parents’ disease burden. We sought to investigate quality of life and stress levels amongst parents of children with POLR3-related leukodystrophy. Methods: 43 parents of 32 children completed questionnaires on demographics, stress, quality of life, coping mechanisms, and experience of injustice. Detailed clinical data was collected from all patients. Results: Mothers ( t[27] = –8.66, P < .001) and fathers (t[16] = –4.47, P < .001) had lower quality of life scores compared to the normative population, yet 80% of parents’ stress scores fell within the normal stress range. Parents’ experience of injustice scores were high (>60). Correlations were found between and within parents’ scores. Years since disease onset and certain life circumstances correlated to mothers’ quality of life scores; however, no correlation was found between modifiable factors and fathers’ quality of life scores. Helpful coping mechanisms included those that allowed parents to be involved in their child's life. Conclusions: This is the first study to assess stress and quality of life in this population. These results shed light on the importance of implementing services and social support to improve the well-being of parents.