Epileptic Phenotype and Cannabidiol Efficacy in a Williams–Beuren Syndrome Patient With Atypical Deletion: A Case Report

Abstract

Epilepsy is a rare clinical manifestation in Williams–Beuren syndrome patients. However, some studies report the presence of infantile spasms and epilepsy in patients carrying larger deletions. Herein, we describe a 13-year-old female affected by Williams–Beuren syndrome and pharmacoresistant epilepsy reporting a de novo large heterozygous 7q11.21q21 deletion (19.4 Mb) also including the YWHAG gene. Studies indicate that cannabidiol is effective as adjunctive therapy for seizures associated with tuberous sclerosis complex, and it is under investigation also in focal cortical dysplasia. When treated with cannabidiol, our patient showed a significant reduction in seizure frequency and intensity, and improved motor and social skills. We hypothesized that CBD could exert a gene/disease-specific effect.

Genetic Generalized Epilepsy and Intrafamilial Phenotypic Variability with Distal 7q11.23 Deletion

“…Most deletions included HIP1 and YWHAG , with the exception of patient #4 and patient #9 described by Ramocki et al Most patients had considerably larger deletions extending to the centromeric and/or telomeric sides, which could include the region responsible for the Williams-Beuren syndrome and 2 other candidate genes for a phenotype of epilepsy and neurodevelopmental abnormalities, KIAA0442 and MAGI2 . 5 , 10 , 12 , 15 …”

“… 6 Seizures are rarely reported with the common deletion, but are more often described in patients with larger atypical deletions including HIP1 and YWHAG , as well as MAGI2, who present with more pronounced neurological features than typically seen in Williams-Beuren syndrome due to common deletions. 2 , 5 , 12 , 16 …”

“…Better understanding of the roles of HIP1 and YWHAG may eventually offer avenues for rational drug design, including antiseizure agents, in these patients who often present with drug-resistant epilepsy. 5 …”

“…34 patients were identified. 1,2,[5][6][7][8][9][10][11][12][13][14][15] A large majority of these patients also had developmental impairment and/or intellectual disability, and some had reported neurobehavioral abnormalities or dysmorphic features. Most deletions included HIP1 and YWHAG, with the exception of patient #4 and patient #9 described by Ramocki et al Most patients had considerably larger deletions extending to the centromeric and/or telomeric sides, which could include the region responsible for the Williams-Beuren syndrome and 2 other candidate genes for a phenotype of epilepsy and neurodevelopmental abnormalities, KIAA0442 and MAGI2.…”

An overview on the RSV-mediated mechanisms in the onset of non-allergic asthma

“…Specifically, the TRPV family (TRPV1–6) are non-selective cationic ligand-gated channels with high permeability to Ca 2+ . They are commonly expressed by non-neuronal cells, including immune cells and type C sensory nerve fibers of the respiratory tract, and neuronal cells [( 73 – 75 ), Figure 1 ]. TRPV family is triggered by exogenous mediators, such as high temperature, osmolarity, exposure to air pollutants, cigarette smoke, allergens and viral agents, capsaicin (CPS); and endogenous stimuli, such as bioactive pro-inflammatory lipids [thromboxanes, prostaglandins E2 (PGE2), leukotrienes, and arachidonic acid derivatives] ( 73 , 74 ).…”