Temporal Dynamics of MOG Antibodies in Children With Acquired Demyelinating Syndrome.

Background And Objective: The spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) comprises monophasic diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), and transverse myelitis and relapsing courses of these presentations. Persistently high MOG antibodies (MOG immunoglobulin G [IgG]) are found in patients with a relapsing disease course. Prognostic factors to determine the clinical course of children with a first MOGAD are still lacking.

Variants in the degron of AFF3 are associated with intellectual disability, mesomelic dysplasia, horseshoe kidney, and epileptic encephalopathy.

The ALF transcription factor paralogs, AFF1, AFF2, AFF3, and AFF4, are components of the transcriptional super elongation complex that regulates expression of genes involved in neurogenesis and development. We describe an autosomal dominant disorder associated with de novo missense variants in the degron of AFF3, a nine amino acid sequence important for its binding to ubiquitin ligase, or with de novo deletions of this region. The sixteen affected individuals we identified, along with two previously reported individuals, present with a recognizable pattern of anomalies, which we named KINSSHIP syndrome (KI for horseshoe kidney, NS for Nievergelt/Savarirayan type of mesomelic dysplasia, S for seizures, H for hypertrichosis, I for intellectual disability, and P for pulmonary involvement), partially overlapping the AFF4-associated CHOPS syndrome.

Treatment with Nusinersen - Challenges Regarding the Indication for Children with SMA Type 1.

The natural history of patients with spinal muscular atrophy (SMA) has changed due to advances in standard care and development of targeted treatments. Nusinersen was the first drug approved for the treatment of all SMA patients. The transfer of clinical trial data into a real-life environment is challenging, especially regarding the advice of patients and families to what extent they can expect a benefit from the novel treatment.

Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy.

Rolandic epilepsy (RE) is the most common focal epilepsy in childhood. To date no hypothesis-free exome-wide mutational screen has been conducted for RE and atypical RE (ARE). Here we report on whole-exome sequencing of 194 unrelated patients with RE/ARE and 567 ethnically matched population controls.

Autoimmune phenotype with type I interferon signature in two brothers with ADA2 deficiency carrying a novel CECR1 mutation.

Background: Loss-of-function CECR1 mutations cause polyarteritis nodosa (PAN) with childhood onset, an autoinflammatory disorder without significant signs of autoimmunity. Herein we describe the unusual presentation of an autoimmune phenotype with constitutive type I interferon activation in siblings with adenosine deaminase 2 (ADA2) deficiency.

Case Presentation: We describe two siblings with early-onset recurrent strokes, arthritis, oral ulcers, discoid rash, peripheral vascular occlusive disease and high antinuclear antibody titers.

Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome.

Objective: To assess the prognostic value of MOG antibodies (abs) in the differential diagnosis of acquired demyelinating syndromes (ADS).

Methods: Clinical course, MRI, MOG-abs, AQP4-abs, and CSF cells and oligoclonal bands (OCB) in children with ADS and 24 months of follow-up were reviewed in this observational prospective multicenter hospital-based study.

Results: Two hundred ten children with ADS were included and diagnosed with acute disseminated encephalomyelitis (ADEM) (n = 60), neuromyelitis optica spectrum disorder (NMOSD) (n = 12), clinically isolated syndrome (CIS) (n = 101), and multiple sclerosis (MS) (n = 37) after the first episode.

Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.

Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants.

Antibodies to MOG and AQP4 in children with neuromyelitis optica and limited forms of the disease.

Objective: To determine the frequency and clinical-radiological associations of antibodies to myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) in children presenting with neuromyelitis optica (NMO) and limited forms.

Methods: Children with a first event of NMO, recurrent (RON), bilateral ON (BON), longitudinally extensive transverse myelitis (LETM) or brainstem syndrome (BS) with a clinical follow-up of more than 12 months were enrolled. Serum samples were tested for MOG- and AQP4-antibodies using live cell-based assays.

Mutation screen reveals novel variants and expands the phenotypes associated with DYNC1H1.

Dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) encodes a necessary subunit of the cytoplasmic dynein complex, which traffics cargo along microtubules. Dominant DYNC1H1 mutations are implicated in neural diseases, including spinal muscular atrophy with lower extremity dominance (SMA-LED), intellectual disability with neuronal migration defects, malformations of cortical development, and Charcot-Marie-Tooth disease, type 2O. We hypothesized that additional variants could be found in these and novel motoneuron and related diseases.

Rare variants in γ-aminobutyric acid type A receptor genes in rolandic epilepsy and related syndromes.

Objective: To test whether mutations in γ-aminobutyric acid type A receptor (GABAA -R) subunit genes contribute to the etiology of rolandic epilepsy (RE) or its atypical variants (ARE).

Methods: We performed exome sequencing to compare the frequency of variants in 18 GABAA -R genes in 204 European patients with RE/ARE versus 728 platform-matched controls. Identified GABRG2 variants were functionally assessed for protein stability, trafficking, postsynaptic clustering, and receptor function.

Analysis of ELP4, SRPX2, and interacting genes in typical and atypical rolandic epilepsy.

Rolandic epilepsy (RE) and its atypical variants (atypical rolandic epilepsy, ARE) along the spectrum of epilepsy-aphasia disorders are characterized by a strong but largely unknown genetic basis. Two genes with a putative (ELP4) or a proven (SRPX2) function in neuronal migration were postulated to confer susceptibility to parts of the disease spectrum: the ELP4 gene to centrotemporal spikes and SRPX2 to ARE. To reexamine these findings, we investigated a cohort of 280 patients of European ancestry with RE/ARE for the etiological contribution of these genes and their close interaction partners.

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy.

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.

Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A.

Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures.

Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes.

Idiopathic focal epilepsy (IFE) with rolandic spikes is the most common childhood epilepsy, comprising a phenotypic spectrum from rolandic epilepsy (also benign epilepsy with centrotemporal spikes, BECTS) to atypical benign partial epilepsy (ABPE), Landau-Kleffner syndrome (LKS) and epileptic encephalopathy with continuous spike and waves during slow-wave sleep (CSWS). The genetic basis is largely unknown. We detected new heterozygous mutations in GRIN2A in 27 of 359 affected individuals from 2 independent cohorts with IFE (7.

Left ventricular hypertrabeculation/noncompaction with epilepsy, other heart defects, minor facial anomalies and new copy number variants.

Background: Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology which has been described in children as well as in adults with and without chromosomal aberrations. LVHT has been reported in association with various cardiac and extracardiac abnormalities like epilepsy and facial dysmorphism.

Case Presentation: A unique combination of LVHT, atrial septal defect, pulmonary valve stenosis, aortic stenosis, epilepsy and minor facial anomalies is presented in a 5.

Mutations in SLC33A1 cause a lethal autosomal-recessive disorder with congenital cataracts, hearing loss, and low serum copper and ceruloplasmin.

Low copper and ceruloplasmin in serum are the diagnostic hallmarks for Menkes disease, Wilson disease, and aceruloplasminemia. We report on five patients from four unrelated families with these biochemical findings who presented with a lethal autosomal-recessive syndrome of congenital cataracts, hearing loss, and severe developmental delay. Cerebral MRI showed pronounced cerebellar hypoplasia and hypomyelination.

New mutations in the ATM gene and clinical data of 25 AT patients.

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar degeneration, immunodeficiency, oculocutaneous telangiectasias, chromosomal instability, radiosensitivity, and cancer predisposition. The gene mutated in the patients, ATM, encodes a member of the phosphatidylinositol 3-kinase family proteins. The ATM protein has a key role in the cellular response to DNA damage.

Functional variant in complement C3 gene promoter and genetic susceptibility to temporal lobe epilepsy and febrile seizures.

Background: Human mesial temporal lobe epilepsies (MTLE) represent the most frequent form of partial epilepsies and are frequently preceded by febrile seizures (FS) in infancy and early childhood. Genetic associations of several complement genes including its central component C3 with disorders of the central nervous system, and the existence of C3 dysregulation in the epilepsies and in the MTLE particularly, make it the C3 gene a good candidate for human MTLE.

Methodology/principal Findings: A case-control association study of the C3 gene was performed in a first series of 122 patients with MTLE and 196 controls.

Tick-borne encephalitis in Styrian children from 1981 to 2005: a retrospective study and a review of the literature.

Background: Tick-borne encephalitis in children appears to be more benign than in adults and shows also a more favourable outcome. Only some authors report of sequelae like paralysis, paresis or seizures and behavioural abnormalities. The aim was to describe the clinical features of tick-borne encephalitis in children with special attention to sequelae and to review the literature.