Are SCN2A-related BFNISs also responsible for seizures in adulthood? A case report opens new scenarios.

Large cohort studies and variant-specific electrophysiology have enabled the delineation of different SCN2A-epilepsy phenotypes, phenotype-genotype correlations, prediction of pharmacosensitivity to sodium channel blockers, and long-term prognostication for clinicians and families. One of the most common clinical presentations of SCN2A pathological variants is benign familial neonatal-infantile seizures (BFNIS), which are characterized by seizure onset between the first day of life and 23 months of age and typically resolve, either spontaneously or with the aid of sodium channel blockers, within the first 2 years of life. In 2004, Berkovic et al. reported the case of a young boy affected by SCN2A-related BFNIS whose mother, who carried the same pathological variant, had also presented with BFNIS in infancy. Our case report focuses on the aforementioned woman who, more than 40 years later, presented two additional seizures, therefore opening the possibility of a role for SCN2A-related seizures in adulthood.

ACOX1 gain-of-function variation in a 10-years-old patient responsive to immunomodulating therapy.

A heterozygous gain-of-function variant in the acyl-CoA oxidase 1 (ACOX1) gene, c.710A>G (p.Asn237Ser), is known to cause Mitchell syndrome, a very rare progressive disorder characterized by episodic demyelination, sensory polyneuropathy, and hearing loss. Only eight patients have been described so far. A single patient has been treated with intravenous immunoglobulin administration, indicating clinical improvement. In this study, we describe a 10-year-old girl carrying the identical mutation, who presented with progressive sensorineural deafness, visual abnormalities, skin ichthyosis, and gait ataxia from infantile age with progressive worsening and loss of walking ability by the age of 10 years. Antioxidant therapies and monthly intravenous immunoglobulin infusions showed excellent clinical results: after 1 year of treatment, the child is now able to walk, run, and jump. We emphasize the importance of early genetic diagnosis since an effective treatment is available for this rare condition.

Children with Cerebral Palsy can imagine actions like their normally developed peers.

The present study aimed at assessing whether children with Cerebral Palsy (CP) can imagine object directed actions similarly to their normally developed peers. We asked children with CP (n = 12) and paired healthy controls (n = 12) to imagine in first person perspective eight daily actions, after observing them through videoclips presented on a computer screen. During motor imagery (MI) children were interrupted at a specific timepoint (e.g., at 2.5 s) from the start. Two frames extracted from the videoclips were then presented on the screen. One of the two depicted the correct timepoint at which the imagined action was interrupted, while the other represented an earlier or later timepoint. Children had to respond by pressing the key associated to the correct frame. Children also underwent VMIQ-2 questionnaire. Both groups performed similarly in the questionnaire and in the requested task, where they showed the same error rate. Errors mainly concerned the later frame, suggesting a similar strategy to solve the task in the two groups. The results support the view that children with CP can imagine actions similarly to their normally developed peers. This encourages the use of MI as a rehabilitative tool in children with motor impairment.

Repetitive and stereotyped behaviors in neurodevelopmental disorders: an observational analysis of four diagnostic groups.

BACKGROUND: Repetitive and Stereotyped Behaviors (ST) are one of the key features of autism spectrum disorder (ASD) and they frequently occur in children with developmental delay/intellectual disability or sensory deprivation, but they are also described in children otherwise typical. This study aims to describe and compare ST in children with different neurodevelopmental disorders and in children having stereotypies but no other medical diagnosis (primary stereotypies). METHODS: The study sample comprised children with autism spectrum disorder (ASD) developmental delay (DD), severe visual impairment (VI) and primary stereotypies (PS), aged between 2 and 12 years old. The characteristics of the ST (age of onset, frequency, duration, triggers, phenomenology) were collected from their clinical history. The children's caregivers completed the Repetitive Behavior Scalerevised (RBS-R) and the Child Behavior Checklist (CBCL) to assess the ST and to screen for behavioral problems, respectively. Data concerning family history and comorbidity were also collected. RESULTS: 87 children (ASD [n=23]; DD [n=21]; VI [n=20]; PS [n=23]) were assessed. Mean age of ST onset was before 24 months in the whole sample. Symptoms usually occurred more than once a day in all groups, but Self-Injurious Behavior (SIB) and ST were reported at higher scores on the RBS-R in Secondary group. Stereotypies lasted less than 5 minutes in all but VI sample, in which lasted longer. Stereotypies of locomotion were mostly reported in ASD, self-injurious behaviors in VI, upper limb stereotypies in PS and DD. Parents reported several repetitive behaviors on the RBS-R, while attention deficit and withdrawn behavior appeared to be the main findings of the sample in the CBCL. Finally, a high number of comorbidities and family history for neurodevelopmental disorders was found in all groups. CONCLUSIONS: The study showed that some specific patterns of stereotypies could be identified in most groups of disorders. At the same time the behavioral profile of children with stereotypies shows a significant overlap among different groups. These preliminary results suggest that stereotypies are strongly linked to neurodevelopmental disorders, but their association needs to be clarified with further studies.

Cerebral folate transporter deficiency syndrome in three siblings: Why genetic testing for developmental and epileptic encephalopathies should be performed early and include the FOLR1 gene.

Cerebral folate transporter deficiency syndrome, caused by FOLR-1 mutations is characterized by late infantile onset, severe developmental regression, epilepsy, and leukodystrophy. An extremely low concentration of 5-methyltetrahydrofolate in the cerebrospinal fluid provides a crucial clue to its diagnosis and is a treatment target. Oral or intravenous folinic acid (5-formyltetrahydrofolate) administration improves clinical symptoms and brain magnetic resonance imaging (MRI) findings. We describe three siblings carrying a novel homozygous FOLR1 nonsense mutation, that were referred due to intractable epilepsy and progressive neurological decline. Brain MRI showed hypomyelination and cerebellar atrophy. Folinic acid (oral and intravenous) supplementation, initiated after over 15 years illness, has failed to result in any sizeable clinical or neurophysiological improvement. Cerebral folate transport deficiency bears overlapping clinical features with many severe developmental encephalopathies. It is crucial to recognize FOLR1 signs and establish an early clinical and molecular diagnosis in order to provide timely folinic acid treatment and improve outcome.

Rett Syndrome as a movement and motor disorder - A narrative review.

Rett syndrome (RTT) is neurodevelopmental disorder affecting approximately 1:10000-15000 live female births, commonly associated with MECP2 gene mutations. Hand stereotypies and gait disturbance, as well as spasticity and dystonia, were noted in RTT since first descriptions. This review aimed to explore the prevalence of reported movement disorders in RTT. DATA SOURCES AND EXTRACTION: Pubmed and Embase databases for papers describing features of movement disorders in RTT. Papers were selected if included description of case report, cohort or case-series of patients with RTT including descriptions of clinical features of their movement disorder. Papers were divided into 3 epochs - i) Pre-1999,ii) 2000-2009, and iii) 2010 onwards. RESULTS: 32 studies (13 in the first, 10 in the second and 9 in the third epochs) reported on movement disorders in RTT. Hand stereotypies were almost universal, diminishing but not disappearing over time. Gait disturbance and ataxia/tremor were also very common (>50% cases). Hypertonia was also often reported, increasing with age. In earlier descriptions spasticity was commonly described, with greater reference to dystonia/rigidity in more recent reports. Myoclonus and choreoathetosis were uncommonly reported. CONCLUSIONS: Movement disorders beyond hand stereotypies are common in RTT, most notably tremor. Hypertonia is frequently seen in RTT, increasing in prevalence with age, with apparent changes in nomenclature over time, (i.e early epoch spasticity, late epoch dystonia). Dystonia was specifically reported in 229/417 cases. Further work is required to explore the relative contribution of dystonia and rigidity to hypertonia in RTT, as well as the impact of these impairments when present.

MeDuSa: a multi-draft based scaffolder.

MOTIVATION: Completing the genome sequence of an organism is an important task in comparative, functional and structural genomics. However, this remains a challenging issue from both a computational and an experimental viewpoint. Genome scaffolding (i.e. the process of ordering and orientating contigs) of de novo assemblies usually represents the first step in most genome finishing pipelines. RESULTS: In this article we present MeDuSa (Multi-Draft based Scaffolder), an algorithm for genome scaffolding. MeDuSa exploits information obtained from a set of (draft or closed) genomes from related organisms to determine the correct order and orientation of the contigs. MeDuSa formalizes the scaffolding problem by means of a combinatorial optimization formulation on graphs and implements an efficient constant factor approximation algorithm to solve it. In contrast to currently used scaffolders, it does not require either prior knowledge on the microrganisms dataset under analysis (e.g. their phylogenetic relationships) or the availability of paired end read libraries. This makes usability and running time two additional important features of our method. Moreover, benchmarks and tests on real bacterial datasets showed that MeDuSa is highly accurate and, in most cases, outperforms traditional scaffolders. The possibility to use MeDuSa on eukaryotic datasets has also been evaluated, leading to interesting results.

PARPST: a PARallel algorithm to find peptide sequence tags.

BACKGROUND: Protein identification is one of the most challenging problems in proteomics. Tandem mass spectrometry provides an important tool to handle the protein identification problem. RESULTS: We developed a work-efficient parallel algorithm for the peptide sequence tag problem. The algorithm runs on the concurrent-read, exclusive-write PRAM in O(n) time using log n processors, where n is the number of mass peaks in the spectrum. The algorithm is able to find all the sequence tags having score greater than a parameter or all the sequence tags of maximum length. Our tests on 1507 spectra in the Open Proteomics Database shown that our algorithm is efficient and effective since achieves comparable results to other methods. CONCLUSIONS: The proposed algorithm can be used to speed up the database searching or to identify post-translational modifications, comparing the homology of the sequence tags found with the sequences in the biological database.