Fibroblast Growth Factor Receptor 2 (FGFR2), a New Gene Involved in the Genesis of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a long-known complex neurodevelopmental disorder, and over the past decades, with the enhancement of the research genomic techniques, has been the object of intensive research activity, and many genes involved in the development and functioning of the central nervous system have been related to ASD genesis. Herein, we report a patient with severe ASD carrying a G > A de novo variant in the FGFR2 gene, determining a missense mutation. FGFR2 encodes for the ubiquitous fibroblast growth factor receptor (FGFR) type 2, a tyrosine kinase receptor implicated in several biological processes. The mutated version of this protein is known to be responsible for several variable overlapping syndromes. Even if there still is only sparse and anecdotal data, recent research highlighted a potential role of FGFR2 on neurodevelopment. Our findings provide new insights into the potential causative role of FGFR2 gene in complex neurodevelopmental disorders.

KCNQ2-Related Neonatal Epilepsy Treated With Vitamin B6: A Report of Two Cases and Literature Review.

Potassium Voltage-Gated Channel Subfamily Q Member 2 (KCNQ2) gene has been initially associated with "Benign familial neonatal epilepsy" (BFNE). Amounting evidence arising by next-generation sequencing techniques have led to the definition of new phenotypes, such as neonatal epileptic encephalopathy (NEE), expanding the spectrum of KCNQ2-related epilepsies. Pyridoxine (PN) dependent epilepsies (PDE) are a heterogeneous group of autosomal recessive disorders associated with neonatal-onset seizures responsive to treatment with vitamin B6 (VitB6). Few cases of neonatal seizures due to KCNQ2 pathogenic variants have been reported as successfully responding to VitB6. We reported two cases of KCNQ2-related neonatal epilepsies involving a 5-year-old male with a paternally inherited heterozygous mutation (c.1639C>T; p.Arg547Trp), and a 10-year-old female with a de novo heterozygous mutation (c.740C>T; p.Ser247Leu). Both children benefited from VitB6 treatment. Although the mechanisms explaining the efficacy of VitB6 in such patients remain unclear, this treatment option in neonatal-onset seizures is easily taken into account in Neonatal Intensive Care Units (NICUs). Further studies should be conducted to better define clinical guidelines and treatment protocols.

Synaptopathies in Developmental and Epileptic Encephalopathies: A Focus on Pre-synaptic Dysfunction.

The proper connection between the pre- and post-synaptic nervous cells depends on any element constituting the synapse: the pre- and post-synaptic membranes, the synaptic cleft, and the surrounding glial cells and extracellular matrix. An alteration of the mechanisms regulating the physiological synergy among these synaptic components is defined as "synaptopathy." Mutations in the genes encoding for proteins involved in neuronal transmission are associated with several neuropsychiatric disorders, but only some of them are associated with Developmental and Epileptic Encephalopathies (DEEs). These conditions include a heterogeneous group of epilepsy syndromes associated with cognitive disturbances/intellectual disability, autistic features, and movement disorders. This review aims to elucidate the pathogenesis of these conditions, focusing on mechanisms affecting the neuronal pre-synaptic terminal and its role in the onset of DEEs, including potential therapeutic approaches.

Treatment of multiple sclerosis in children: A brief overview.

Multiple sclerosis (MS) is the most common autoimmune, chronic inflammatory demyelinating disorder of the central nervous system. Pediatric-onset MS (POMS), as opposed to adult-onset MS (AOMS), is a rare condition, presenting similar clinical features to AOMS, but a more active course of the disease, with higher relapse rates and greater white and grey matter damage. To date, the therapeutic approaches to treat POMS have been extrapolated from observational studies and data from trials conducted on adults, raising concerns about their efficacy and safety in the pediatric population. Herein, we discuss the most common therapeutic strategies used in POMS management, basing on the individual clinical practice and experience.

Neonatal Seizures: An Overview of Genetic Causes and Treatment Options.

Seizures are the most frequent neurological clinical symptoms of the central nervous system (CNS) during the neonatal period. Neonatal seizures may be ascribed to an acute event or symptomatic conditions determined by genetic, metabolic or structural causes, outlining the so-called 'Neonatal Epilepsies'. To date, three main groups of neonatal epilepsies are recognised during the neonatal period: benign familial neonatal epilepsy (BFNE), early myoclonic encephalopathy (EME) and 'Ohtahara syndrome' (OS). Recent advances showed the role of several genes in the pathogenesis of these conditions, such as KCNQ2, KCNQ3, ARX, STXBP1, SLC25A22, CDKL5, KCNT1, SCN2A and SCN8A. Herein, we reviewed the current knowledge regarding the pathogenic variants most frequently associated with neonatal seizures, which should be considered when approaching newborns affected by these disorders. In addition, we considered the new possible therapeutic strategies reported in these conditions.