Laustsenholme5123

Conclusions Although physician trainees recognize the importance of education related to FSD, the majority report little time being allocated to it in their training programs.Purpose The objective of this study was to delineate the long-term impact of pediatric convulsive status epilepticus (CSE) on health-related quality of life (HRQOL) in children recently diagnosed with epilepsy. Methods Children with newly-diagnosed epilepsy were recruited between 2004-2007 through a Canada-wide population-based study, the Health-Related Quality of Life Study in Children with Epilepsy Study (HERQULES). Eligible children were 4-12 years of age at epilepsy diagnosis; consequently, children with the more catastrophic syndromes and epileptic encephalopathies typically diagnosed at younger ages were ineligible. Participants were followed over 10 years, and neurologists identified those with CSE in the first two years after epilepsy diagnosis. HRQOL was self-reported by adolescents and young adults (AYAs) in the long-term, and reported by parents at multiple time points throughout the 10-year follow-up. Results A total of 204 AYAs were followed over the long-term, 12 of whom had a history of CSE. Parents of those with CSE reported poorer HRQOL in their children two years after the epilepsy diagnosis, (Cohen's d = 0.58, p = .037), though not at the 10-year follow-up (d = 0.28, p = .19). Results from AYAs' self-reports at the 10-year follow-up were similar, such that mean HRQOL scores were poorer for AYAs with CSE, though this difference was not significant (d = 0.39, p = .11). Results were similar when adjusting for HRQOL at the time of epilepsy diagnosis. Conclusion These findings suggest that compromised HRQOL in the short-term after CSE may resolve over the long-term. It will be important for future studies to focus on patient-reported outcomes in reporting the long-term sequelae of CSE.To date 45 autosomal recessive disease-causing variants are reported in the FKBP10 gene. Those variant were found to be associated with Osteogenesis Imperfecta (OI) for which the hallmark phenotype is bone fractuers or Bruck Syndrome (BS) where bone fractures are accompanied with contractures. In addition, a specific homozygous FKBP10 mutation (p.Tyr293del) has been described in Yup'ik Inuit population to cause Kuskokwim syndrome (KS) in which contractures without fractures are observed. Here we present an extended Palestinian family with 10 affected individuals harboring a novel homozygous splice site mutation, c.391+4A > T in intron 2 of the FKBP10 gene, in which the three above mentioned syndromes segregate as a result of skipping of exon 2 and absence of the FKBP65 protein. At the biochemical level, Hydroxylysyl pyridinoline (HP)/lysyl pyridinoline (LP) values were inversely correlated with OI phenotypes, a trend we could confirm in our patients. Our findings illustrate that single familial FKBP10 mutations can result in a phenotypic spectrum, ranging from fractures without contractures, to fractures and contractures and even to only contractures. This broad intra-familial clinical variability within one single family is a new finding in the field of bone fragility.Mutations in the TRIM8 gene have been described in patients with severe developmental delay, intellectual disability and epilepsy. Only six patients have been described to date. All the previous mutations were truncating variants clustered in the C-terminus of the protein. A previous patient with TRIM8-related epileptic encephalopathy was reported to have nephrotic syndrome. Here we describe the clinical, radiological and histological features of an 8-year-old male patient with a TRIM8 mutation who, in contrast to previous patients, had only mild intellectual disability and well-controlled epilepsy. The patient was found to have proteinuria at 2 years of age. Renal biopsy findings were suggestive of focal segmental glomerulosclerosis. His kidney function declined and peritoneal dialysis was started at 5 years of age. He underwent renal transplant at 7 years of age. Trio-based whole genome sequencing identified a novel de novo heterozygous frameshift mutation in TRIM8 (NM_030912.2) c.1198_1220del, p.(Tyr400ArgfsTer2). This patient is further evidence that TRIM8 mutations cause a syndrome with both neurological and renal features. Our findings suggest the spectrum of TRIM8-related disease may be wider than previously thought with the possibility of milder neurodevelopmental problems and/or a more severe, progressive renal phenotype. We highlight the need for proteinuria screening in patients with TRIM8 mutations.Pathogenic variants in AIMP1 gene are rare causes of neurologic disorders. selleck chemicals Homozygous frameshift and nonsense variants in AIMP1 have been described in severe neurodegenerative disease. This is the third report of a homozygous nonsense variant in AIMP1 [c.115 C > T (p.Gln39*)] in a girl with severe neonatal onset epileptic encephalopathy. Like the two other cases reported, our patient is also of Filipino descent. Clinical features include microcephaly, poor visual motor development, shallow breathing, severe hypertonia in extremities, severe global developmental delay, poor gag and suck reflex, failure to thrive in the neonatal period, and early onset intractable seizures. Brain MRI showed hypoplasia of corpus callosum as well as cerebellar vermis, global volume loss and diminished myelination for her age. Electroencephalogram at four months of age showed background consisting of synchronous and asynchronous intervals of burst suppression with intermittent multifocal spikes predominantly in the bi-temporal region, suggestive of Early Onset Epileptic Encephalopathy with Burst Suppression (EOEE-BS) which has not been previously associated with the c.115 C > T variant in AIMP1. Of note, she presented to us in super refractory status epilepticus which was eventually controlled after administration of ketogenic diet and Epidiolex (cannabidiol). This report expands the genetic landscape of EOEE-BS. This is the first case of this specific variant in which Epidiolex was administered, which along with Ketogenic diet aided in controlling patient's super refractory status epilepticus.