Genetic Epilepsies and Developmental Epileptic Encephalopathies with Early Onset: A Multicenter Study.

The genetic causes of epilepsies and developmental and epileptic encephalopathies (DEE) with onset in early childhood are increasingly recognized. Their outcomes vary from benign to severe disability. In this paper, we wished to retrospectively review the clinical, genetic, EEG, neuroimaging, and outcome data of patients experiencing the onset of epilepsy in the first three years of life, diagnosed and followed up in four Italian epilepsy centres (Epilepsy Centre of San Paolo University Hospital in Milan, Child Neurology and Psychiatry Unit of AUSL-IRCCS di Reggio Emilia, Pediatric Neurology Unit of Vittore Buzzi Children's Hospital, Milan, and Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia). We included 168 patients (104 with monogenic conditions, 45 with copy number variations (CNVs) or chromosomal abnormalities, and 19 with variants of unknown significance), who had been followed up for a mean of 14.75 years. We found a high occurrence of generalized seizures at onset, drug resistance, abnormal neurological examination, global developmental delay and intellectual disability, and behavioural and psychiatric comorbidities. We also documented differing presentations between monogenic issues versus CNVs and chromosomal conditions, as well as atypical/rare phenotypes. Genetic early-childhood-onset epilepsies and DEE show a very wide phenotypic and genotypic spectrum, with a high risk of complex neurological and neuropsychiatric phenotypes.

Guillain-Barrè Syndrome-Retrospective Analysis of Data from a Cohort of Patients Referred to a Tertiary Care Pediatric Neuromuscular Center from 2000 to 2017: Electrophysiological Findings, Outcomes, and a Brief Literature Review.

Background and Objectives: Guillain-Barré syndrome (GBS) is the most frequent cause of acute flaccid paresis in children. The aim of this study was to describe the clinical and electrophysiological findings and outcomes of children with GBS diagnosed in our unit. Moreover, the literature on pediatric GBS cases from the past 5 years was reviewed. In this retrospective study, we reported data on 12 patients (9 male and 3 female patients; mean age: 5 y, 4 mo; range: 9 mo-11 y) clinically diagnosed at the Child Neurology Unit of the AUSL-IRCCS of Reggio Emilia, Italy, between 2000 and 2017 and a brief analysis/comparison with data from the literature. Materials and Methods: Data were collected from medical charts. Results: In our cohort, male patients were more frequent than female ones (9 vs. 3), and upper respiratory tract infection (n = 8, 66.7%) was the most frequent triggering factor. The main clinical symptoms on admission were distal lower limbs' weakness with gait difficulties (83.3%), pain (50%), upper limbs' weakness (50%), and dysphagia for liquids (25%). Peripheral neurophysiological studies revealed acute inflammatory demyelinating polyradiculoneuropathy (AIDP) in 66.6% of the children, acute motor and sensory axonal neuropathy (AMSAN) in 25%, and acute motor axonal neuropathy (AMAN) in 8.3%. Ten individuals (83.3%) received timely treatment with intravenous immunoglobulins (IVIG), and, out of these ten patients, 58% received concomitant treatment with IV methylprednisolone because of a progressive disease course. Complete remission was observed in the majority of individuals (91.6%) within 6 months of symptom onset. Conclusions: Different subtypes of GBS can affect children; however, the outcome is usually positive. Early treatment appears to be important for a favorable outcome.

Improving the phenotype description of Basel-Vanagaite-Smirin-Yosef syndrome, MED25-related: polymicrogyria as a distinctive neuroradiological finding.

Basel-Vanagaite-Smirin-Yosef syndrome (BVSYS) is an extremely rare autosomal recessive genetic disorder caused by variants in the MED25 gene. It is characterized by severe developmental delay and variable craniofacial, neurological, ocular, and cardiac anomalies. Since 2015, through whole exome sequencing, 20 patients have been described with common clinical features and biallelic variants in MED25, leading to a better definition of the phenotype associated with BVSYS. We report two young sisters, born to consanguineous parents, presenting with intellectual disability, neurological findings, and dysmorphic features typical of BVSYS, and also with bilateral perisylvian polymicrogyria. The younger sister died at the age of 1 year without autoptic examination. Whole exome sequencing detected a homozygous frameshift variant in the MED25 gene: NM_030973.3:c.1778_1779delAG, p.(Gln593Argfs). This report further delineates the most common clinical features of BVSYS and points to polymicrogyria as a distinctive neuroradiological feature of this syndrome.

PIGW-related glycosylphosphatidylinositol deficiency: Description of a new patient and review of the literature.

Inherited glycosylphosphatidylinositol (GPI) deficiencies are a group of clinically and genetically heterogeneous conditions belonging to the congenital disorders of glycosylation. PIGW is involved in GPI biosynthesis and modification, and biallelic pathogenic variants in this gene cause autosomal recessive GPI biosynthesis defect 11. Only five patients and two fetuses have been reported in the literature thus far. Here we describe a new patient with a novel homozygous missense variant in PIGW, who presented with hypotonia, severe intellectual disability, early-onset epileptic seizures, brain abnormalities, nystagmus, hand stereotypies, recurrent respiratory infections, distinctive facial features, and hyperphosphatasia. Our report expands the phenotype of GPI biosynthesis defect 11 to include stereotypies and recurrent respiratory infections. A detailed and long-term analysis of the electroclinical characteristics and review of the literature suggest that early-onset epileptic seizures are a key manifestation of GPI biosynthesis defect 11. West syndrome and focal-onset epileptic seizures are the most common seizure types, and the fronto-temporal regions may be the most frequently involved areas in these patients.