RESUMEN
Pathogenic variants in the cyclin-dependent kinase-like 5 (CDKL5) gene are associated with CDKL5 deficiency disorder (CDD), a severe X-linked developmental and epileptic encephalopathy. Deletions affecting the 5' untranslated region (UTR) of CDKL5, which involve the noncoding exon 1 and/or alternatively spliced first exons (exons 1a-e), are uncommonly reported. We describe genetic and phenotypic characteristics for 15 individuals with CDKL5 partial gene deletions affecting the 5' UTR. All individuals presented characteristic features of CDD, including medically refractory infantile-onset epilepsy, global developmental delay, and visual impairment. We performed RNA sequencing on fibroblast samples from three individuals with small deletions involving exons 1 and/or 1a/1b only. Results demonstrated reduced CDKL5 mRNA expression with no evidence of expression from alternatively spliced first exons. Our study broadens the genotypic spectrum for CDD by adding to existing evidence that deletions affecting the 5' UTR of the CDKL5 gene are associated with the disorder. We propose that smaller 5' UTR deletions may require additional molecular testing approaches such as RNA sequencing to determine pathogenicity.
RESUMEN
Medical cannabis (MC) may offer therapeutic benefits for children with complex neurological conditions and chronic diseases. In Canada, parents, and caregivers frequently report encountering barriers when accessing MC for their children. These include negative preconceived notions about risks and benefits, challenges connecting with a knowledgeable healthcare provider (HCP), the high cost of MC products, and navigating MC product shortages. In this manuscript, we explore several of these barriers and provide recommendations to decision-makers to enable a family-centered and evidence-based approach to MC medicine and research for children.
RESUMEN
Vasculitis of the central nervous system presenting as a mass lesion is a relatively uncommon occurrence. Even more uncommon is a vasculitis mimicking a demyelinating lesion. We present here an interesting case of a 15-year-old boy who was found to have a mass-like lesion on neuroimaging involving the left subcortical white matter and deep gray matter. The differential diagnosis for this lesion was primary demyelination versus a glial tumor, the former being more favored over the latter. Biopsy of this lesion however revealed findings compatible with a vasculitis, which was unexpected given the neuroimaging findings. To the authors' knowledge, case reports in the English literature of a vasculitic lesion mimicking demyelination are scarce. This case also serves as a reminder of the diagnostic difficulty that arises in a pediatric patient with an initial presentation of mass-like lesion.