Sex-related differences in reading achievement.

Over the last 40 years, ever-growing interest in sex-related differences in the human brain has led to a vast amount of literature on the subject, a small part of which relates to studies of differences in the ability to read. The data concerning typically developing children mainly come from school-based screening projects (Programme for International Student Assessment, INVALSI) and partially from the standardization of reading tests. These have revealed the existence of a gap in favor of females that primarily appears during adolescence and in situations of sociocultural disadvantage, usually explained on the basis of environmental factors such as socioeconomic status and gender-based education. Dyslexia is a neurodevelopmental disorder that is significantly more prevalent among males, a difference that neuroimaging and genetic studies have attributed to the presence of hormone-related protective factors in females, although it has been hypothesized that a different neurocognitive substrate may also be involved. However, the literature on the subject is still limited, and further studies of the interactions between genetic risk, environmental factors, and brain phenotypes are needed to clarify why females are better at performing reading tasks and less susceptible to dyslexia, regardless of their language or the educational system in the country in which they live. The aim of this mini-review was to describe the studies that have investigated sex-related differences in reading ability in both typically and atypically developing subjects.

A Missense De Novo Variant in the CASK-interactor KIRREL3 Gene Leading to Neurodevelopmental Disorder with Mild Cerebellar Hypoplasia.

KIRREL3 is a gene important for the central nervous system development-in particular for the process of neuronal migration, axonal fasciculation, and synaptogenesis-and colocalizes and cooperates in neurons with CASK gene. Alterations of KIRREL3 have been linked to neurodevelopmental disorders, ranging from developmental delay, to autism spectrum disorder, to attention deficit/hyperactivity disorder. The underlying mechanism is not yet fully understood, as it has been hypothesized a fully dominant effect, a risk factor role of KIRREL3 partially penetrating variants, and a recessive inheritance pattern. We report a novel and de novo KIRREL3 mutation in a child affected by severe neurodevelopmental disorder and with brain magnetic resonance imaging evidence of mega cisterna magna and mild cerebellar hypoplasia. This case strengthens the hypothesis that dominant KIRREL3 variants may lead to neurodevelopmental disruption; furthermore, given the strong interaction between KIRREL3 and CASK, we discuss as posterior fossa anomalies may also be part of the phenotype of KIRREL3-related syndrome.

22q13.33 duplication involving SHANK3 gene: a boy and his mother with "persistent" language and speech sound disorder.

Patients carrying 22q13.33 duplication present variable neurodevelopmental phenotype. Among these, patients with genetic alteration disrupting SHANK3 gene are very rare and they also present neurodevelopmental disorder such as autism spectrum disorder and intellectual disability. The real incidence is unknown because mild and variable phenotype could cause reduction in diagnosed cases. We describe the first case of 22q13.33 microduplication disrupting SHANK3 gene, inherited from mother to son, that presents a "persistent" language and speech sound disorder as main symptom without intellectual disability and autism spectrum disorder. More clinical reports with accurate phenotype description are needed to better define the profile of carriers of this genetic alteration.

Identifying the risk of dyslexia in bilingual children: The potential of language-dependent and language-independent tasks.

This study investigates the linguistic processing and non-linguistic cognitive abilities of monolingual and bilingual children with and without reading difficulties and examines the relationship between these skills and reading. There were 72 Italian-speaking children: 18 monolingual good readers (MONO-GR, Mage = 10;4), 19 monolingual poor readers (MONO-PR, Mage = 10;3), 21 bilingual good readers (BI-GR, Mage = 10;6), and 16 bilingual poor readers (BI-PR, Mage = 10;6). All bilingual children spoke Italian as their L2. Children completed a battery of standardized Italian reading tests, language-dependent tasks: nonword repetition (NWR), sentence repetition (SR), and phonological awareness (PA), and language-independent tasks: timing anticipation, beat synchronization, inhibition control, auditory reaction time, and rapid automatized naming (RAN). Poor readers scored below good readers on the language-dependent tasks, including NWR, PA, and SR. Beat synchronization was the only language-independent task sensitive to reading ability, with poor readers showing greater variability than good readers in tapping to fast rhythms. SR was the only task influenced by language experience as bilinguals underperformed monolinguals on the task. Moreover, there were weak to moderate correlations between performance on some language-dependent tasks (NWR, PA), language-independent tasks (inhibition control, RAN), and reading measures. Performance on the experimental tasks (except for RAN) was not associated with the length of exposure to Italian. The results highlight the potential of NWR, PA, SR, and beat synchronization tasks in identifying the risk of dyslexia in bilingual populations. Future research is needed to validate these findings and to establish the tasks' diagnostic accuracy.

Evaluation of oro-phonatory development and articulatory diadochokinesis in a sample of Italian children using the protocol of Robbins & Klee.

PURPOSE: The Italian version (Granocchio et al., 2019) of the protocol proposed by Robbins and Klee (1987) allows the assessment of structure of the vocal tract, oromotor and oro-phonatory ability, and articulatory diadochokinesis in children. The aim of this study was to collect the first normative sample of Italian children. METHODS: We measured the total structural score (TSS), total functional score (TFS), oral function score (OFS), phonatory function score (PFS), maximum phonation time (MPT), speed of monosyllable repetition (SMR), and speed of polysyllable repetition (SPR) in 191 typically developing Italian children aged 2.6-6.11 years. RESULTS: Like the finding observed in the original protocol, there were no significant age-related changes in TSS, but the correlation was observed for TFS, OFS, PFS, MPT, SMR and SPR. The Inter-observer agreement was "good" or "excellent" for all scores except for SPR that was "moderate". CONCLUSIONS: The increase in oro-motor, oro-phonatory and diadochokinetic abilities confirmed the progressive maturation of these functions with age. The protocol can therefore be considered a useful instrument to classify speech sound disorders (SSDs) by excluding alterations in anatomical structures and evaluate the motor impairment. This normative sample of Italian children allows to use these measures for diagnostic purposes in young Italian speakers.

Telerehabilitation and Wellbeing Experience in Children with Special Needs during the COVID-19 Pandemic.

Social distancing due to the COVID-19 pandemic represented a golden opportunity to implement telerehabilitation for clinical groups of children. The present study aims to show the impact that telerehabilitation had on the experience of well-being of children with special needs being treated at the Foundation IRCCS Neurological Institute 'C. Besta' in Milan (Specific Learning Disorders and Cerebral Palsy diagnosis); it aims to do so by comparing it with experiences of those who did not undertake telerehabilitation despite the diagnosis during the pandemic, and with typically developing children. Results show that the three groups differed in the Support, Respect and Learning dimensions of well-being experience. Post hoc comparisons revealed that children with Specific Learning Disorders and Cerebral Palsy scored higher than normotypical children in Support and in Respect scales. Furthermore, children who experienced telerehabilitation showed the highest scores on the Learning scale in comparison with the other two groups. These results support the importance of reorganizing care and assistance by integrating telemedicine, which seems to have fostered a positive experience of well-being in people with special needs, particularly in the perception of a supportive environment that respects psychological needs.

Dyslexia Telerehabilitation during the COVID-19 Pandemic: Results of a Rhythm-Based Intervention for Reading.

The COVID-19 outbreak necessitated a reorganization of the rehabilitation practices for Learning Disorders (LDs). During the lockdown phase, telerehabilitation offered the possibility to continue training interventions while enabling social distancing. Given such an advantage of telerehabilitation methods for LDs, clinical research is still needed to test the effectiveness of diverse teletraining approaches by comparing their outcomes with those of face-to-face interventions. To compare the effectiveness of telerehabilitation vs. in-presence rehabilitation of dyslexia, a rhythm-based intervention for reading, called Rhythmic Reading Training (RRT), was tested in a small-scale clinical trial during the lockdown phase of the COVID-19 pandemic. Thirty children aged 8-13 with a diagnosis of developmental dyslexia were assigned to either a telerehabilitation or an in-presence rehabilitation setting and received RRT for 10 biweekly sessions of 45 min, supervised by a trained practitioner. The results showed that both telerehabilitation and in-presence rehabilitation were effective in improving reading and rapid automatized naming in children with dyslexia and that the effects were comparable between settings. Therefore, RRT was found to be effective in spite of the administration method (remote or in-presence). These results confirm the potential of telemedicine for the rehabilitation of LDs. Clinical Trial ID: NCT04995471.

Timing anticipation in adults and children with Developmental Dyslexia: evidence of an inefficient mechanism.

Developmental Dyslexia (DD) is a learning disorder characterized by specific difficulties in learning to read accurately and fluently, which has been generally explained in terms of phonological deficits. Recent research has shown that individuals with DD experience timing difficulties in the domains of language, music perception and motor control, probably due to impaired rhythmic perception, suggesting that timing deficit might be a key underlying factor to explain such a variety of difficulties. The present work presents two experiments aimed at assessing the anticipatory ability on a given rhythm of 9-year old Italian children and Italian adults with and without DD. Both adults and children with DD displayed a greater timing error and were more variable than controls in high predictable stimuli. No difference between participants with and without DD was found in the control condition, in which the uncertain timing of the beat did not permit the extraction of regularities. These results suggest that both children and adults with DD are unable to exploit temporal regularities to efficiently anticipate the next sensory event whereas control participants easily are. By showing that the anticipatory timing system of individuals with Developmental Dyslexia appears affected, this study adds another piece of evidence to the multifaceted reality of Developmental Dyslexia.

A Novel WAC Loss of Function Mutation in an Individual Presenting with Encephalopathy Related to Status Epilepticus during Sleep (ESES).

WAC (WW Domain Containing Adaptor With Coiled-Coil) mutations have been reported in only 20 individuals presenting a neurodevelopmental disorder characterized by intellectual disability, neonatal hypotonia, behavioral problems, and mildly dysmorphic features. Using targeted deep sequencing, we screened a cohort of 630 individuals with variable degrees of intellectual disability and identified five WAC rare variants: two variants were inherited from healthy parents; two previously reported de novo mutations, c.1661_1664del (p.Ser554*) and c.374C>A (p.Ser125*); and a novel c.381+2T>C variant causing the skipping of exon 4 of the gene, inherited from a reportedly asymptomatic father with somatic mosaicism. A phenotypic evaluation of this individual evidenced areas of cognitive and behavioral deficits. The patient carrying the novel splicing mutation had a clinical history of encephalopathy related to status epilepticus during slow sleep (ESES), recently reported in another WAC individual. This first report of a WAC somatic mosaic remarks the contribution of mosaicism in the etiology of neurodevelopmental and neuropsychiatric disorders. We summarized the clinical data of reported individuals with WAC pathogenic mutations, which together with our findings, allowed for the expansion of the phenotypic spectrum of WAC-related disorders.

Motor impairment on awakening in a patient with an EEG pattern of "unilateral, continuous spikes and waves during slow sleep".

Movement disorders are rarely described in association with the "continuous spikes and waves during slow sleep (CSWS)" EEG pattern. We report the case of a young girl affected by an epileptic encephalopathy who, from the age of seven years and four months, has twice presented a movement disorder affecting the right arm, manifesting on awakening and disappearing by early afternoon. Sleep EEG during these periods showed continuous, high-amplitude, diphasic spikes and slow waves over the left hemisphere. Association of clobazam, valproic acid and, on the second occasion, ethosuccimide led to disappearance of the above-described EEG picture and associated motor symptoms. Neurophysiological investigations excluded other possible aetiologies. In view of this, and of the close relationship between the EEG picture and clinical course, we interpret the patient's impairment as "motor neglect" secondary to the continuous electrical activity recorded during sleep over the left hemisphere and involving the associative areas. This electrical activity in sleep, may be regarded as a "functional lesion" whose clinical consequences can be correlated with the site of the abnormalities.[Published with video sequences].

Dyslexic children fail to comply with the rhythmic constraints of handwriting.

In this study, we sought to demonstrate that deficits in a specific motor activity, handwriting, are associated to Developmental Dyslexia. The linguistic and writing performance of children with Developmental Dyslexia, with and without handwriting problems (dysgraphia), were compared to that of children with Typical Development. The quantitative kinematic variables of handwriting were collected by means of a digitizing tablet. The results showed that all children with Developmental Dyslexia wrote more slowly than those with Typical Development. Contrary to typically developing children, they also varied more in the time taken to write the individual letters of a word and failed to comply with the principles of isochrony and homothety. Moreover, a series of correlations was found among reading, language measures and writing measures suggesting that the two abilities may be linked. We propose that the link between handwriting and reading/language deficits is mediated by rhythm, as both reading (which is grounded on language) and handwriting are ruled by principles of rhythmic organization.

Early-onset occipital idiopathic epilepsy: a syndrome to be treated?

The purpose of this study was to evaluate prognostic factors in early-onset childhood epilepsy with occipital paroxysms. We studied retrospectively a population of 46 patients, which was divided into three groups according to seizure frequency group 1, patients experiencing a single seizure (3396); group 2, patients experiencing two to six seizures (48%); and group 3, patients experiencing more than six seizures (20%). The mean follow-up period was about 5 years in the three groups. At the end of the first 6 months of this retrospective follow-up, the average number of seizures was higher in group 3 (2.9 seizures) than in groups 2 and 1 (1.8 and 1 seizure, respectively). We suggest that low seizure frequency in the first 6 months of follow-up could have prognostic value. We propose that the introduction of anti-epilepsy drugs be delayed for 6 months following epilepsy onset and be subsequently limited to patients with frequent seizure recurrence.

Long-term neuropsychological follow-up and nosological considerations in five patients with continuous spikes and waves during slow sleep.

Continuous spikes and waves during slow sleep (CSWSS) is a well-known EEG pattern that can be associated with cognitive and behavioural deterioration. We present the long-term neuropsychological follow-up and nosological considerations of five patients who developed CSWSS during childhood. All five of our patients presented CSWSS, although the duration and severity of this pattern varied. The outcome was of three basic types: acquired frontal dementia, language deficits and normal. Four of our patients were initially diagnosed with Landau-Kleffner syndrome but have had markedly diverse outcomes in terms of the severity and type of compromise. Our data suggest that the initial diagnosis, according to current nosological categories, has almost no prognostic significance, while the length and the age of onset of CSWSS, the site of epileptiform activity and the individual neuropsychological profile are more useful for identifying the long-term outcome of patients with CSWSS.