Infants born low birth weight (LBW) and preterm are at risk for developmental delay and cognitive deficits. These deficits can lead to lifelong learning difficulties and high-risk behaviors. Preterm (PT) and full-term (FT) groups were compared across infant and toddler measures of behavior and development to extract early indicators of executive function (EF). The goal was to extract indicators of EF from standardized infant assessments. PT (<2500 grams and <37 weeks) and FT (> 2500 grams and >37 weeks) were compared across assessment and EF components were identified from the BSID-III. A multivariate linear model was used to examine group differences. All children (99 PT and 46 FT) were administered the Bayley III and the DMQ assessments for session 1 (6-8 months). During session 2, N=78 PT and 37 FT (18-20 months), the CBCL was added to previous assessments, and the BRIEF-P was added to previous assessments in session 3, N= 52 PT and 36 FT for session 3 (See Table 1). Significant change scores were found on BSID-III subtests and EF components across all 3 sessions. The PT group also showed significantly more behavioral concerns on the CBCL at 18 months and 36 months and had lower scores on the BRIEF-P than their FT peers. The number of children born PT (N = 27, 52%) who were in Early Intervention (EI) increased across the 3 sessions. Examining early indicators of EFs supported the development of early identification that could lead to decrease adverse outcomes often associated with preterm birth.

Deletions of the long arm of chromosome 20 (20q) are rare, with only 16 reported patients displaying a proximal interstitial 20q deletion. A 1.62 Mb minimal critical region at 20q11.2, encompassing three genes GDF5, EPB41L1, and SAMHD1, is proposed to be responsible for this syndrome. The leading clinical features include growth retardation, intractable feeding difficulties with gastroesophageal reflux, hypotonia and psychomotor developmental delay. Common facial dysmorphisms including triangular face, hypertelorism, and hypoplastic alae nasi were additionally reported. Here, we present the clinical and molecular findings of five new patients with proximal interstitial 20q deletions. We analyzed the phenotype and molecular data of all previously reported patients with 20q11.2q12 microdeletions, along with our five new cases. Copy number variation analysis of patients in our cohort has enabled us to identify the second critical region in the 20q11.2q12 region and redefine the first region that is initially identified. The first critical region spans 359 kb at 20q11.2, containing six MIM genes, including two disease-causing genes, GDF5 and CEP250. The second critical region spans 706 kb at 20q12, encompassing four MIM genes, including two disease-causing genes, MAFB and TOP1. We propose GDF5 to be the primary candidate gene generating the phenotype of patients with 20q11.2 deletions. Moreover, we hypothesize TOP1 as a potential candidate gene for the second critical region at 20q12. Of note, we cannot exclude the possibility of a synergistic role of other genes involved in the deletion, including a contiguous gene deletion syndrome or position effect affecting both critical regions. Further studies focusing on patients with proximal 20q deletions are required to support our hypothesis.

Background  Variants of ubiquitin-specific protease 7 ( USP7 ) gene in humans are associated with a neurodevelopmental disorder-Hao-Fountain syndrome, its core symptoms including developmental delay, intellectual disability, and speech delay. Other variable symptoms can affect multiple systems. In present study, we report two patients with core features from two unrelated consanguineous families originating from the Tianjin Children\'s Hospital. Methods and Results  Genomic DNA was extracted from the peripheral blood samples collected from the probands with their family members and whole-exome sequencing (WES) was used to detect the pathogenic genes in the probands. Suspected variants were subsequently validated by Sanger sequencing. In family 1, WES revealed that the proband carried the de novo variant c.2697A > C (p.Leu899Phe) in USP7 (NM_003470.3). In family 2, WES identified the variant c.3305A > C (p.Asn1102Thr) in USP7 (NM_003470.3) from the proband. Conclusion  We reported two cases of Hao-Fountain syndrome caused by novel USP7 variants. In addition, we report the first case of mosaicism with a USP7 variant in Chinese family. Our findings demonstrate the importance of WES in diagnosis of genetic diseases and expands the USP7 variants spectrum in Hao-Fountain syndrome. Moreover, we summarize the cases caused by USP7 variants in the literature. Our study can provide a vital reference for the diagnosis of future cases.

BACKGROUND: Developmental delay (DD) is a neurodevelopmental disorder characterized by delays in multiple domains. The investigation of brain structure in DD has been enhanced by advanced neuroimaging techniques that can identify regional surface deformities. Neuroimaging studies have identified structural brain abnormalities in individuals with DD, but research specific to the Saudi Arabian population is limited. In this study, we examine the neuroanatomical abnormalities in the cortical and subcortical regions of Saudi Arabian children with DD.
METHODS: A T1-weighted, 1-mm-thick MRI was used to acquire structural brain images of 29 children with DD and age-matched healthy controls.
RESULTS: Analysis of the MRI data revealed significant differences in several cortical and subcortical structures of gray matter (GM) and white matter (WM) in several brain regions of the DD group. Specifically, significant deformities were observed in the caudate nucleus, globus pallidus, frontal gyrus, pars opercularis, pars orbitalis, cingulate gyrus, and subcallosal gyrus. These findings suggest disrupted neurodevelopment in these regions, which may contribute to the cognitive, motor, and behavioral impairments commonly observed in individuals with DD.
CONCLUSIONS: The present study provides valuable insights into the neuroanatomical differences in Saudi Arabian children with DD. Our results provide evidence for cortical and subcortical abnormalities in DD. Deformities in the observed regions may contribute to cognitive impairment, emotional dysregulation, mood disorders, and language deficits commonly observed in DD. The structural analysis may enable the identification of neuroanatomical biomarkers to facilitate the early diagnosis or progression of DD. These results suggest that lower cortical complexity in DD children due to alterations in networks may play a critical role in early brain development.

OBJECTIVE: HCN ion channel family has a widespread expression in neurons, and recently, increasing studies have demonstrated their roles in epilepsies.
METHODS: Clinical data of the patients were gathered in a retrospective study. Exon sequencing was used for the patients with unexplained recurrent seizures and varying levels of developmental delay.
RESULTS: In this study, eight de novo variants of HCN1 genes were uncovered in eight patients, including six missense variants, one nonsense variant and one frameshift insertion variant; five of them were reported for the first time. The onset age for eight patients ranges from one month to one year. Their main clinical manifestations are epilepsy and varying degrees of developmental delay, and the main type of seizure is focal secondary generalized tonic-clonic seizure. Importantly, in our study, one case presented with a form of migrating focal seizure that has not been reported in the literature. Seizures from five of the eight children were effectively controlled with antiepileptic drugs including valproic acid, levetiracetam and oxcarbazepine. One child developed normally and four children developed mild delay. One child was treated with topiramate, and the convulsion was partially controlled and showed moderate to severe developmental delay. The antiepileptic treatment failed for the other two children, and the two children were treated with sodium valproate, oxcarbazepine, lamotrigine, chlorbazan, levetiracetam and nitrodiazepam successively, but their convulsions were not controlled and showed moderate to severe developmental delay.
CONCLUSIONS: Our research reported eight variants in HCN1 gene causing epilepsy; among these variants, five variants were never reported before. HCN1-related epilepsy usually starts infantile period, and focal secondary generalized tonic-clonic seizure is the most common seizure type. Importantly, we reported the case with migrating focal seizure was rarely reported. Our study expanded both genotype and phenotype for HCN1-related epilepsy.

Approximately 40% of children with deafness have an additional developmental disorder or major medical problem, which may delay the age of diagnosis of hearing loss and/or require intervention by other professionals. This situation is referred to as \"deafness with added disability\" (AD+). The reason why the population of hearing-impaired children is more likely to have associated added disabilities is that the risk factors for hearing impairment overlap with those for many other disabilities. These factors can influence various aspects of development, including language acquisition. It is important to check that appropriate care is received, the effectiveness of hearing aids or implants, as well speech therapy intervention strategies, and family adherence to sessions and appointments. The challenge posed by AD+ is early detection, to allow early and appropriate intervention, and the need for fluid transdisciplinary collaboration between all professionals involved, together with the involvement of the family.

UNASSIGNED: The COVID-19 pandemic outbreak have caused increased levels of emotional and behavioral problems, particularly among people with pre-existing mental health conditions. Young individuals with autism spectrum disorders (ASD) and developmental delay (DD) are particularly at risk due to their vulnerability. The purpose of this study was to look into the different effects of the COVID-19 pandemic on 1-6-year-old children with ASD and DD.
UNASSIGNED: Parents and guardians of children with ASD completed an online survey that included questions about their children\'s socio-demographics characteristics, the effects of the COVID-19 outbreak on their health, and what they needed in order to deal with the conditions of the pandemic.
UNASSIGNED: This study compared 4,138 children with ASD to 711 children with DD. Children with ASD had a higher risk of having more emotional and behavioral problems than children with DD (OR 1.38, 95% CI 1.12-1.70). Compared to parent-oriented rehabilitation at home, discontinuing rehabilitation had a higher likelihood of negative emotional and behavioral change (OR 1.67, 95% CI 1.41-1.98). Having teachers\' online support had a higher likelihood of negative emotional and behavioral change for ASD children (OR 1.26, 95% CI 1.03-1.54).
UNASSIGNED: This article provided evidence that children with developmental disabilities, particularly ASD, were at risk for a variety of challenges to their emotional functioning during the COVID-19 period, and that online support was not an ideal way for children with ASD to receive effective educational intervention in China.

We describe a case of a 2-year-old female child who presented as emergency with acute gastroenteritis and severe dehydration. In this patient, there was a history of severe birth asphyxia, and the developmental milestones were delayed. The child was managed as hypotonic cerebral palsy elsewhere with antiepileptic drug and nutritional supplements. However, persistent abnormal pattern of breathing after adequate hydration and noncontributory metabolic profile raised the suspicion of alternate etiology. Later, the diagnosis of Joubert syndrome was established on contrast-enhanced magnetic resonance imaging of brain with findings of \"molar tooth sign\" appearance along with vermian hypoplasia. We present this case to alert the clinicians to explore all the differential diagnoses carefully whenever a child presents with the developmental delay associated with multisystem involvement.

UNASSIGNED: GNAO1 variants have been found to be associated with epileptic encephalopathies, developmental delays (DDs), and movement disorders (MDs). Therapies for patients with GNAO1 variants vary. However, treatments for GNAO1-related diseases are still in their infancy. Previous reports suggest that few pharmacological treatments are effective for patients with GNAO1 variant-related MDs. Deep brain stimulation (DBS) treatment appears to be effective, however surgical procedures and equipment failures pose risks to the patients. Effectiveness for oxcarbazepine (OXC) in GNAO1 variant-related MDs is first reported in our study, and it expand the effective drugs for MD treatment.
UNASSIGNED: We report the case of a 5-year-old male patient with a MD, who suffered from hypotonia and refractory choreoathetosis. The patient was found to have a DD and an intellectual disability. A de-novo variant of the GNAO1 gene (NM_138736: exom6: c.709G>A [p. Glu237Lys]) was identified by whole exome sequencing (WES) when he was 8 months old. The patient visited our hospital at the age of 4 years and 3 months because of fever and recurrent convulsions. Electroencephalogram (EEG) results show abnormal spikes, and magnetic resonance imaging (MRI) showed the enlargement of the lateral ventricles. The administration of tiapride hydrochloride, phenobarbital, midazolam, and hormones had no effect. OXC treatment was then initiated. No MD behaviors, such as rigidity and twisting of the limbs and trunk, or chorea, were observed after 10 days OXC treatment. Eventually, incremental doses of OXC were effective, and our patient achieved good control of his MD.
UNASSIGNED: We are the first to demonstrate the role of OXC in alleviating MDs associated with GNAO1 mutations. This report provides a novel possibility for the clinical treatment of this rare disease. To manage MDs associated with GNAO1 mutations, we recommend that OXC treatment be attempted before invasive surgical therapy.

This study aimed to describe neurodevelopment in fetal growth restriction children at the age of six. Secondly, we tried to demonstrate influencing factors that can improve or exacerbate this development, as well as predictive factors that might select a population at risk to assist with early childhood support.
It was a study of 70 children affected with FGR. FGR was based on these definitions: birth weight below the 3rd percentile or birth weight below the 10th percentile with an abnormal hemodynamic Doppler study. Neurodevelopment was assessed at 6 years old by means of Batelle Development Inventory. A global development quotient under a 100 score was considered a neurodevelopment delay. All variables regarding pregnancy care, delivery episode, postpartum, neonatal care, sociodemographic issues, and the need for support in the first years were studied.
The mean gestational age at diagnosis was 33.14 weeks (standard deviation (SD = 4.31), with 32.9% of early-onset diagnoses. The mean gestational age at delivery was 35.61 (SD = 3.21), and the cesarean rate was 64.3%. The average age of the children at the moment of the evaluation was 76.20-month-old (SD = 3.70). The mean global development quotient was 97.28 (SD = 13.97). We were able to record a 57.1% of global development delay. In the cases of cognition, only 17.1% of the children registered a delay. Motor and communication skills were the most frequently affected. We discovered that socioeconomic status was positively related to the global development quotient, as well as both gestational age at delivery and middle cerebral artery pulsatility index was positively related to the global development quotient.
We found a higher neurodevelopment delay rate (57.1%). We could relate a higher gestational age at delivery and a higher MCA percentile with better global neurodevelopment quotients.