neonatal-onset encephalopathy with rigidity and seizures and neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures

[galyea123]

Hi! I wanted to notice that both of these conditions are caused by mutations in the BRAT1 gene (there are some publications about BRAT1 related disorders and Orphanet links both OMIM entries in their page).

"Biallelic BRAT1 variants were first described by Puffenberger et al. in 2012, after sequencing the exome of two individuals from an endogamous population of Amish origin in Pennsylvania. These individuals had a combination of severe drug-resistant epilepsy, limb rigidity, brain injury, and early death [5]. In 2015, Hanes et al. reported a patient with compound heterozygous BRAT1 variants and a less severe clinical phenotype characterized by global developmental delay and cerebellar atrophy [6]. Biallelic BRAT1 variants have therefore been associated with two distinct clinical pictures: BRAT1-related rigidity and multifocal seizure syndrome (RMFSL; MIM 614498) and BRAT1-related neurodevelopmental disorder associating cerebellar atrophy with or without seizures syndrome (NEDCAS; MIM 618056). A correlation between the severity of the disorder and the type of BRAT1 mutations has been suggested, with biallelic truncating variants appearing to be associated with the more severe phenotype" Source: https://www.nature.com/articles/s41431-023-01410-z

I think it will be useful to make clear the relation among these conditions.

Thank you! Gioconda