Refining the electroclinical spectrum of NPRL3-related epilepsy: A novel multiplex family and literature review.

Objective: NPRL3-related epilepsy (NRE) is an emerging condition set within the wide GATOR-1 spectrum with a particularly heterogeneous and elusive phenotypic expression. Here, we delineated the genotype-phenotype spectrum of NRE, reporting an illustrative familial case and reviewing pertinent literature.

Methods: Through exome sequencing (ES), we investigated a 12-year-old girl with recurrent focal motor seizures during sleep, suggestive of sleep-related hypermotor epilepsy (SHE), and a family history of epilepsy in siblings.

Refining the mutational spectrum and gene-phenotype correlates in pontocerebellar hypoplasia: results of a multicentric study.

Background: Pontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders characterised by concurrent hypoplasia of the pons and the cerebellum and variable clinical and imaging features. The current classification includes 13 subtypes, with ~20 known causative genes. Attempts have been made to delineate the phenotypic spectrum associated to specific PCH genes, yet clinical and neuroradiological features are not consistent across studies, making it difficult to define gene-specific outcomes.

Pathogenic variants in EP300 and ANKRD11 in patients with phenotypes overlapping Cornelia de Lange syndrome.

Cornelia de Lange syndrome (CdLS), Rubinstein-Taybi syndrome (RSTS), and KBG syndrome are three distinct developmental human disorders. Variants in seven genes belonging to the cohesin pathway, NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11, and BRD4, were identified in about 80% of patients with CdLS, suggesting that additional causative genes remain to be discovered. Two genes, CREBBP and EP300, have been associated with RSTS, whereas KBG results from variants in ANKRD11.

14q12 duplication including FOXG1: is there a common age-dependent epileptic phenotype?

Introduction: Duplications of 14q12 encompassing FOXG1 gene have been recently associated with developmental delay, severe speech impairment, epilepsy, aspecific neuroimaging findings and minor dysmorphisms.

Aim And Methods: In order to refine the epileptic phenotype associated with 14q12 duplications, we have performed a review of the electroclinical picture of the patients reported to date in the literature, adding a new personal case. A comprehensive set of clinical and instrumental data (with a particular focus on the electroclinical aspects including seizure type, age of onset, EEG at onset and after antiepileptic therapy, drug efficacy) has been taken into account.

Pathogenic role of the X-linked cyclin-dependent kinase-like 5 and aristaless-related homeobox genes in epileptic encephalopathy of unknown etiology with onset in the first year of life.

Two genes causally involved in refractory epilepsy with mental retardation, cyclin-dependent kinase-like 5 and aristaless-related homeobox, could account for at least some forms of early onset epileptic encephalopathy that still lack etiological explanation. With the aim of investigating the specific pathogenic involvement of the 2 genes, we have conducted a clinical and molecular study in 80 patients with epileptic encephalopathy of unknown etiology and onset within the first year of life, regardless of the presence of other clinical features or the definition of a precise epileptologic syndrome. A total of 8 different disease-causing mutations were detected in our population, confirming the pivotal role of these genes in the pathogenesis of the epileptic encephalopathies in infancy.