Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity

Background The SYNGAP1 gene encodes for a small GTPase-regulating protein critical to dendritic spine maturation and synaptic plasticity. Mutations have recently been identified to cause a breadth of neurodevelopmental disorders including autism, intellectual disability, and epilepsy. The purpose of this work is to define the phenotypic spectrum of SYNGAP1 gene mutations and identify potential biomarkers of clinical severity and developmental progression. Methods A retrospective clinical data analysis of individuals with SYNGAP1 mutations was conducted. Data included genetic diagnosis, clinical history and examinations, neurophysiologic data, neuroimaging, and serial neurodevelopmental/behavioral assessments. All patients were seen longitudinally within a 6-year period; data analysis was completed on June 30, 2018. Records for all individuals diagnosed with deleterious SYNGAP1 variants (by clinical sequencing or exome sequencing panels) were reviewed. Results Fifteen individuals (53% male) with seventeen unique SYNGAP1 mutations are reported. Mean age at genetic diagnosis was 65.9 months (28–174 months). All individuals had epilepsy, with atypical absence seizures being the most common semiology (60%). EEG abnormalities included intermittent rhythmic delta activity (60%), slow or absent posterior dominant rhythm (87%), and epileptiform activity (93%), with generalized discharges being more common than focal. Neuroimaging revealed nonspecific abnormalities (53%). Neurodevelopmental evaluation revealed impairment in all individuals, with gross motor function being the least affected. Autism spectrum disorder was diagnosed in 73% and aggression in 60% of cases. Analysis of biomarkers revealed a trend toward a moderate positive correlation between visual-perceptual/fine motor/adaptive skills and language development, with posterior dominant rhythm on electroencephalogram (EEG), independent of age. No other neurophysiology-development associations or correlations were identified. Conclusions A broad spectrum of neurologic and neurodevelopmental features are found with pathogenic variants of SYNGAP1 . An abnormal posterior dominant rhythm on EEG correlated with abnormal developmental progression, providing a possible prognostic biomarker. Electronic supplementary material The online version of this article (10.1186/s11689-019-9276-y) contains supplementary material, which is available to authorized users.

Background The objective of this study was to describe the case literature of human coronavirus infections in the nervous system of children, including from SARS-CoV-2, and to provide guidance to pediatric providers for managing the potential long-term effects on neurodevelopment of human coronavirus infections in the nervous system. Methods Using a structured strategy, the PubMed and Ovid:Embase databases were queried for articles about the clinical presentation and pathophysiology of coronavirus infections in the nervous system of children and young adults, aged 0 to 24 years. Results Of 2302 articles reviewed, 31 described SARS-CoV-2 infections in the nervous system of children and 21 described other human coronaviruses: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1. Excepting MERS-CoV, we found cases of neurological disease in children from each human coronavirus. Children with non-SARS-CoV-2 infections have suffered acute flaccid paralysis, acute disseminated encephalomyelitis, encephalitis, and seizures. In addition, cases of ischemic, hemorrhagic, and microvascular strokes have occurred in children with SARS-CoV-2. Patients with multisystem inflammatory syndrome in children have suffered encephalitis, stroke, pseudotumor cerebri syndrome, and cytotoxic lesions of deep brain structures. Despite these reports, few articles evaluated the impact of human coronavirus infections on long-term neurodevelopmental domains including cognitive, language, academic, motor, and psychosocial outcomes. Conclusions Neurological manifestations of human coronavirus infections can cause severe disease in children. The case literature suggests a critical gap in knowledge of the long-term effects on child neurodevelopment of these infections. As the current SARS-CoV-2 pandemic continues, this gap must be filled to facilitate optimal outcomes in recovering children.

Trauma is the most common cause of death and significant morbidity in childhood; abusive head trauma (AHT) is a prominent cause of significant morbidity and mortality in children younger than 2 years old. Correctly diagnosing AHT is challenging both clinically and radiologically. The primary diagnostic challenges are that the abused children are usually too young to provide an adequate history, perpetrators are unlikely to provide truthful account of trauma, and clinicians may be biased in their assessment of potentially abused children. The main radiological challenge is that there is no single imaging finding that is independently specific for or diagnostic of AHT. The radiological evaluation should be based on the multiplicity and severity of findings and an inconsistency with the provided mechanism of trauma. While the most common neuroimaging finding in AHT is subdural hemorrhage, other less well‐known magnetic resonance imaging (MRI) findings such as the “lollipop sign” or “tadpole sign,” parenchymal or cortical lacerations, subpial hemorrhage, cranio‐cervical junction injuries including retroclival hematomas, as well as diffuse hypoxic brain injury have been identified and described in the recent literature. While AHT is ultimately a clinical diagnosis combining history, exam, and neuroimaging, familiarity with the typical as well as the less‐well known MRI findings will improve recognition of AHT by radiologists.