New Technological Approach for the Evaluation of Postural Control Abilities in Children with Developmental Coordination Disorder

Background: Developmental Coordination Disorder (DCD) causes difficulties in postural control which are crucial to assess due to their impact on everyday life. There is a lack of suitable tools to acquire quantitative data and deeply analyze postural control, especially during the developmental age. The aim of this study is to investigate postural control skills in children with DCD and typically developing children (TD) using the Virtual Reality Rehabilitation System (VRRS). Methods: 18 children with DCD and 30 TD children (mean age 9.12 +/- 2.65 and 7.12 +/- 2.77 years, respectively) were tested by using the Movement Assessment Battery for Children Second Edition (MABC-2) and a VRRS stabilometric balance platform. A t-test was performed to identify differences in the VRRS parameters between the two groups. Furthermore, we investigated whether a correlation exists between the VRRS data and the MABC-2. Results: Significant differences (p < 0.05) in mean distance and frequency of the COP are found in the two groups. These parameters also correlate with the MABC-2 total score (p <= 0.05) and balance subscales (p <= 0.05). Conclusions: This study opens a new frontier for the assessment of postural skills in children with DCD and represents a potential basis for a tailored rehabilitation program, from which their postural stability and, consequently, their everyday life will benefit

NOTCH1-related leukoencephalopathy: a novel variant and literature review

Background: NOTCH1-related leukoencephalopathy is a new diagnostic entity linked to heterozygous gain-of-function variants in NOTCH1 that neuroradiologically shows some overlap with the inflammatory microangiopathy Aicardi-Goutières syndrome (AGS). Aim: To report a 16-year-old boy harbouring a novel NOTCH1 mutation who presented neuroradiological features suggestive of enhanced type I interferon signalling. We describe 5-years of follow-up and review the current literature on NOTCH1-related leukoencephalopathy. Methods: Clinical evaluation, standardized scales (SPRS, SARA, CBCL, CDI-2:P, WISCH-IV and VABS-2) and neuroradiological studies were performed, as well as blood DNA analysis. For the literature review, a search was performed on Pubmed, Scopus and Web of Science, up to December 2023 using the following text word search strategy: (NOTCH1) AND (leukoencephalopathy). Results: Our patient presents clinical features consistent with other reported cases with NOTCH1 mutations but is among the minority of patients with an onset after infancy. During the 5-year follow-up, we observed an increase in the severity of spasticity and ataxia. However, at the age of 16 years, our proband is still ambulatory. As for other reported patients, he manifests psychiatric features, ranging from hyperactivity during childhood, to anxiety and depression during adolescence. The neuroradiological picture remained essentially stable over 5 years. In addition to the typical findings of leukoencephalopathy with cysts and calcifications already described, we report the presence of T2-hyperintensity and T1-hypotensity of the transverse pontine fibres, enhancement in the periventricular white matter after gadolinium administration, and decreased NAA and Cho peaks in the periventricular white matter on MRS. We identified a novel heterozygous variant in NOTCH1 (c.4788_4799dup), a frame insertion located in extracellular negative regulatory region (NRR)-domain as in previously published cases. Blood interferon signalling was not elevated compared to controls. Conclusions: This case provides further data on a new diagnostic entity i.e. NOTCH1-related leukoencephalopathy. By describing a standardized 5-year follow-up in one case, and reviewing the other patients described to date, we outline recommendations relating to monitoring in this illness, emphasizing the importance of psychiatric and gastroenterological surveillance alongside neurological and neuropsychological management. Studies are needed to better understand the factors influencing disease onset and severity, which are heterogeneous

Arginine : glycine amidinotransferase (AGAT) deficiency in a newborn: Early treatment can prevent phenotypic expression of the disease

Arginine:glycine amidinotransferase deficiency is a treatable inborn error of creatine synthesis, characterized by mental retardation, language impairment, and behavioral disorders. We describe a patient in whom arginine:glycine amidinotransferase was diagnosed at birth and treated at 4 months with creatine supplementation. In contrast with his 2 older sisters, he had normal psychomotor development at 18 months

Further characterization of NFIB-associated phenotypes: Report of two new individuals

Nuclear Factor I B (NFIB) haploinsufficiency has recently been identified as a cause of intellectual disability (ID) and macrocephaly. Here we report on two new individuals carrying a microdeletion in the chromosomal region 9p23-p22.3 containing NFIB. The first is a 7-year 9-month old boy with developmental delays, ID, definite facial anomalies, and brain and spinal cord magnetic resonance imaging findings including periventricular nodular heterotopia, hypoplasia of the corpus callosum, arachnoid cyst in the left middle cranial fossa, syringomyelia in the thoracic spinal cord and distal tract of the conus medullaris, and a stretched appearance of the filum terminale. The second is a 32-year-old lady (the proband' mother) with dysmorphic features, and a history of learning disability, hypothyroidism, poor growth, left inguinal hernia, and panic attacks. Her brain magnetic resonance imaging findings include a dysmorphic corpus callosum, and a small cyst in the left choroidal fissure that marks the hippocampal head. Array-based comparative genomic hybridization identified, in both, a 232 Kb interstitial deletion at 9p23p22.3 including several exons of NFIB and no other known genes. Our two individuals add to the knowledge of this rare disorder through the addition of new brain and spinal cord MRI findings and dysmorphic features. We propose that NFIB haploinsufficiency causes a clinically recognizable malformation-ID syndrome

Parental Practices and Environmental Differences among Infants Living in Upper-Middle and High-Income Countries: A Cross-Sectional Study

Parental practices and environmental factors can impact a child's development and, consequently, functionality. The objective is to assess the parental practices and environmental differences in healthy and at-risk infants at 3-6 months of age living in upper-middle (Brazil) and high-income (Italy) countries. A total group of 115 infants was identified and classified into four groups: healthy Italian infants (H_IT); Italian infants exposed to biological risk factors (R_IT); healthy Brazilian infants (H_BR); and Brazilian infants exposed to environmental risk factors (L_BR). The dependent variables were parental practices and environmental factors, which were assessed through a semi-structured interview and the "variety of stimulation dimension" from the Affordances in the Home Environment for Motor Development-Infant Scale (AHEMD-IS) questionnaire. Descriptive analyses, a multivariate analysis of variance (MANOVA), and correlation tests were applied. Regarding the environment and parental practices, the mother's age, maternal and paternal education, civil status, and variety of stimulation showed significant differences among the infants living in Brazil or in Italy. There were strong dissimilarities in parental practices and environmental factors among infants living in low/upper-middle and high-income countries. Since the home environment is the main stimulus for infant growth and development, our results are meaningful for providing knowledge about these two different cultures

Expanding the natural history of CASK-related disorders to the prenatal period

Aim To assess whether microcephaly with pontine and cerebellar hypoplasia (MICPCH) could manifest in the prenatal period in patients with calcium/calmodulin-dependent serine protein kinase (CASK) gene disorders. Method In this international multicentre retrospective study, we contacted a CASK parents' social media group and colleagues with expertise in cerebellar malformations and asked them to supply clinical and imaging information. Centiles and standard deviations (SD) were calculated according to age by nomograms. Results The study consisted of 49 patients (44 females and 5 males). Information regarding prenatal head circumference was available in 19 patients; 11 out of 19 had a fetal head circumference below -2SD (range -4.1SD to -2.02SD, mean gestational age at diagnosis 20 weeks). Progressive prenatal deceleration of head circumference growth rate was observed in 15 out of 19. At birth, 20 out of 42 had a head circumference below -2SD. A total of 6 out of 15 fetuses had a TCD z-score below -2 (range -5.88 to -2.02). Interpretation This study expands the natural history of CASK-related disorders to the prenatal period, showing evidence of progressive deceleration of head circumference growth rate, head circumference below -2SD, or small TCD. Most cases will not be diagnosed according to current recommendations for fetal central nervous system routine assessment. Consecutive measurements and genetic studies are advised in the presence of progressive deceleration of head circumference growth rates or small TCD

Lung ultrasound in young children with neurological impairment: A proposed integrative clinical tool for deaeration-detection related to feeding

Infants and children with neurological impairment, such as cerebral palsy (CP), often experience abnormal ingestion functions, including oropharyngeal dysphagia and gastroesophageal reflux disease, which led to aspiration-related respiratory complications, morbidity, hospitalization, or death. There is a lack of evidence-based, repeatable, infant-friendly instrumental procedures to assess aspiration-risk in infants with CP or other neurological disorders, with also a lack of clinical assessment measures to support the use of more invasive diagnostic techniques. To this purpose, in the current study we explore the feasibility of lung ultrasound (LUS), to assess lung deaeration possibly related to aspiration during meal, in a cohort of 35 subjects affected by CP or other encephalopathies, and 10 controls in the same age-range. We coupled LUS procedure with meal caregiver administration for each child. Our results support the feasibility of this innovative approach in the clinical setting. Exploratory findings revealed a number of lung abnormalities likely related to abnormal ingestion function in subjects. Subgroup analyses revealed possible differences in LUS abnormalities between CP and other encephalopathies, possibly related to different mechanism of disease or dysfunction. Also, some evidences arose about the possible relationship between such LUS abnormalities and feeding and swallowing abilities in CP or other encephalopathies. LUS showed preliminarily feasibility and effectiveness in detecting meal-related LUS abnormalities in a dynamic manner in the clinical setting. This approach demonstrated usefulness as a potential tool for improving assessment and management in complex care of infants and young children with severe neurological disorders

Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy

To continue evaluation of the long-term efficacy and safety of eteplirsen, a phosphorodiamidate morpholino oligomer designed to skip DMD exon 51 in patients with Duchenne muscular dystrophy (DMD). Three-year progression of eteplirsen-treated patients was compared to matched historical controls (HC). METHODS: Ambulatory DMD patients who were 657 years old and amenable to exon 51 skipping were randomized to eteplirsen (30/50mg/kg) or placebo for 24 weeks. Thereafter, all received eteplirsen on an open-label basis. The primary functional assessment in this study was the 6-Minute Walk Test (6MWT). Respiratory muscle function was assessed by pulmonary function testing (PFT). Longitudinal natural history data were used for comparative analysis of 6MWT performance at baseline and months 12, 24, and 36. Patients were matched to the eteplirsen group based on age, corticosteroid use, and genotype. RESULTS: At 36 months, eteplirsen-treated patients (n = 12) demonstrated a statistically significant advantage of 151m (p < 0.01) on 6MWT and experienced a lower incidence of loss of ambulation in comparison to matched HC (n = 13) amenable to exon 51 skipping. PFT results remained relatively stable in eteplirsen-treated patients. Eteplirsen was well tolerated. Analysis of HC confirmed the previously observed change in disease trajectory at age 7 years, and more severe progression was observed in patients with mutations amenable to exon skipping than in those not amenable. The subset of patients amenable to exon 51 skipping showed a more severe disease course than those amenable to any exon skipping. INTERPRETATION: Over 3 years of follow-up, eteplirsen-treated patients showed a slower rate of decline in ambulation assessed by 6MWT compared to untreated matched HC. Ann Neurol 2016;79:257-271

Expanding the clinical and genetic heterogeneity of SPAX5

Mutations in the ATPase family 3-like gene (AFG3L2) have been linked to autosomal-dominant spinocerebellar ataxia type 28 and autosomal recessive spastic ataxia-neuropathy syndrome. Here, we describe the case of a child carrying bi-allelic mutations in AFG3L2 and presenting with ictal paroxysmal episodes associated with neuroimaging suggestive of basal ganglia involvement. Studies in skin fibroblasts showed a significant reduction of AFG3L2 expression. The relatively mild clinical presentation and the benign course, in spite of severe neuroimaging features, distinguish this case from data reported in the literature, and therefore expand the spectrum of neurological and neuroradiological features associated with AFG3L2 mutations