Developmental surveillance and screening practices in a pediatric oncology clinic: Initial progress of a quality improvement study.

BACKGROUND: Pediatric cancer patients' oncology teams regularly take on a primary care role, but due to the urgent nature of cancer treatment, developmental screenings may be deprioritized. This leaves patients at risk of developmental diagnoses and referrals being delayed. AIMS: Clarify the current developmental surveillance and screening practices of one pediatric oncology team. MATERIALS AND METHODS: Researchers reviewed charts for patients (n = 66) seen at a pediatric oncology clinic in a suburban academic medical center to determine engagement in developmental screening (including functioning around related areas such as speech, neurocognition, etc.) and referrals for care in these areas. RESULTS: Developmental histories were collected from all patients through admission history and physical examination (H&P), but there was no routinized follow-up. Physicians did not conduct regular developmental screening per American Academy of Pediatrics guidelines for any patients but identified n = 3 patients with needs while the psychology team routinely surveilled all patients seen during this time (n = 41) and identified n = 18 patients as having delays. DISCUSSION: Physicians did not routinely screen for development needs beyond H&P and were inconsistent in developmental follow-up/referrals. Integrated psychologists were key in generating referrals for developmental-based care. However, many oncology patients were not seen by psychologists quickly or at all, creating a significant gap in care during a crucial developmental period. CONCLUSION: The case is made for further routinization of ongoing developmental screening in pediatric oncology care.

Is neurodevelopment impaired in Brazilian children with intestinal failure on prolonged parenteral nutrition? A single center study.

PURPOSE: To assess the neurodevelopment outcomes of children younger than 42 months of age with intestinal failure (IF) using prolonged parenteral nutrition (PN) followed by a Pediatric Multidisciplinary Intestinal Rehabilitation Program from a public tertiary hospital in Brazil. METHODS: Bayley III scale was administered in children aged 2 to 42 months with IF and receiving PN for more than 60 days. Composite scores in cognitive, motor, and language domains were analyzed. Developmental delay was defined as a performance 2 standard deviations (SD) below the average at the 3 domains. Association between Bayley III composite scores and clinical variables related to IF were tested. RESULTS: Twenty-four children with median (IQR) age of 17.5 months (9-28.5) were studied, 58.3% were male. Developmental delay was found in 34%, 33% and 27% of the patients in cognitive, motor, and language domains, respectively. There was no significant association between the Bayley-III composite scores and length of hospitalization, prematurity, and number of surgical procedures with anesthesia. CONCLUSION: The study demonstrated impairments in the cognitive, motor and language domains in approximately one-third of young patients with IF on prolonged PN.

TRAPPC11-CDG muscular dystrophy: Review of 54 cases including a novel patient.

The trafficking protein particle (TRAPP) complex is a multisubunit protein complex that functions as a tethering factor involved in intracellular trafficking. TRAPPC11, a crucial subunit of this complex, is associated with pathogenic variants that cause a spectrum of disease, which can range from a limb girdle muscular dystrophy (LGMD) to developmental disability with muscle disease, movement disorder and global developmental delay (GDD)/intellectual disability (ID), or even a congenital muscular dystrophy (CMD). We reviewed the phenotype of all reported individuals with TRAPPC11-opathies, including an additional Mexican patient with novel compound heterozygous missense variants in TRAPPC11 (c.751 T > C and c.1058C > G), restricted to the Latino population. In these 54 patients muscular dystrophy signs are common (early onset muscle weakness, increased serum creatine kinase levels, and dystrophic changes in muscle biopsy). They present two main phenotypes, one with a slowly progressive LGMD with or without GDD/ID (n = 12), and another with systemic involvement characterized by short stature, GDD/ID, microcephaly, hypotonia, poor speech, seizures, cerebral atrophy, cerebellar abnormalities, movement disorder, scoliosis, liver disease, and cataracts (n = 42). In 6 of them CMD was identified. Obstructive hydrocephaly, retrocerebellar cyst, and talipes equinovarus found in the individual reported here has not been described in TRAPPC11 deficiency. As in previous patients, membrane trafficking assays in our patient showed defective abnormal endoplasmic reticulum-Golgi transport as well as decreased expression of LAMP2, and ICAM-1 glycoproteins. This supports previous statements that TRAPPC11-opathies are in fact a congenital disorder of glycosylation (CDG) with muscular dystrophy.

An 11-month-old boy with tuberculous meningitis presenting as progressive limb weakness, fever, developmental retardation, and loss of consciousness: a case report.

BACKGROUND: Tuberculous meningitis (TBM) accounts for about 1% of all tuberculosis cases and about 5% of extrapulmonary tuberculosis cases. However, it poses major importance because approximately half of those affected die or become severely disabled. Herein, the successful treatment of an 11-month-old boy with progressive limb weakness, fever, developmental retardation, and loss of consciousness due to tuberculosis, was reported. CASE PRESENTATION: An 11-month-old (Iranian Turk) boy was referred to Loghman Hakim hospital for progressive limb weakness and loss of previously attained developmental milestones for the past 2 months. He also had persistent fever and loss of consciousness for about 14 to 21 days. Before being referred to our center, the patient had been diagnosed with hydrocephalus at another center due to possible acute bacterial meningitis based on a CT scan and MRI imaging. On physical examination, anterior fontanel bulging and neck stiffness were observed on the admission. His body temperature and heart rate were 38.1 C and 86 beats per minute (bpm), respectively. He had left 6 cranial nerve palsy and spastic quadriparesis with a power of grade 3/5. Other systemic examinations were normal. Endoscopic third ventriculostomy (ETV) (and leptomeningeal biopsy) revealed diffuse thickening of the floor and lateral walls of the 3rd ventricle and also a cobblestone appearance in the form of multiple white patchy lesions was detected on the floor of the 3rd ventricle. CSF analysis and polymerase chain reaction confirmed the TB meningitis. During hospitalization, a temporary EVD (external ventricular drain) was initially inserted. Eventually, defervescence was denoted 5-6 days after initiation of anti-TB medications, and a permanent ventriculoperitoneal shunt was inserted due to hydrocephalus. Gradually his truncal and limb tone and motor function improved, as did his emotional responses to his parents and ability to eat. The patient can walk without help in the 15th month following the operation and resolved hydrocephalus demonstrated on follow-up imaging. CONCLUSION: Over half of treated TB meningitis patients die or suffer severe neurological sequelae, mainly due to late diagnosis. Hence, early diagnosis and prompt initiation of TB treatment offer the best chance of a good neurological outcome.

[Analysis of ADAR gene variants in a Chinese pedigree affected with Dyschromatosis symmetrica hereditaria in conjunct with developmental delay].

OBJECTIVE: To explore the clinical characteristics and genetic etiology for a Chinese pedigree affected with Dyschromatosis symmetrica hereditaria (DSH) in conjunct with developmental delay. METHODS: A child who had presented at the First Affiliated Hospital of Zhengzhou University on May 28 2021 for abnormal skin pigmentation of the extremities and growth retardation for over 2 years was selected as the study subject. Clinical data of the child and his pedigree (11 individuals from three generations) was collected. The child was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing. RESULTS: The child, a two-year-and-seven-month-old male, had hyper- and hypopigmentation on his hands, feet and face, in addition with delayed development. All members of his pedigree had typical presentation of DSH. A heterozygous c.2657G>A variant was found in exon 8 of the ADAR gene in the child, his mother, and elder sister. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as likely pathogenic (PM1+PM2_Supporting+PP1+PP3). CONCLUSION: The c.2657G>A variant of the ADAR gene probably underlay the DSH in this pedigree.

Dual and opposing roles for the kinesin-2 motor, KIF17, in Hedgehog-dependent cerebellar development.

While the kinesin-2 motors KIF3A and KIF3B have essential roles in ciliogenesis and Hedgehog (HH) signal transduction, potential role(s) for another kinesin-2 motor, KIF17, in HH signaling have yet to be explored. Here, we investigated the contribution of KIF17 to HH-dependent cerebellar development, where Kif17 is expressed in both HH-producing Purkinje cells and HH-responding cerebellar granule neuron progenitors (CGNPs). Germline Kif17 deletion in mice results in cerebellar hypoplasia due to reduced CGNP proliferation, a consequence of decreased HH pathway activity mediated through decreased Sonic HH (SHH) protein. Notably, Purkinje cell-specific Kif17 deletion partially phenocopies Kif17 germline mutants. Unexpectedly, CGNP-specific Kif17 deletion results in the opposite phenotype-increased CGNP proliferation and HH target gene expression due to altered GLI transcription factor processing. Together, these data identify KIF17 as a key regulator of HH-dependent cerebellar development, with dual and opposing roles in HH-producing Purkinje cells and HH-responding CGNPs.

The Alberta Infant Motor Scale as an Outcomes Measure of Gross Motor Abilities after Early Complex Cardiac Surgery.

To address the research hypothesis that the Alberta Infant Motor Scale (AIMS) completed following complex cardiac surgery (CCS) is a useful outcomes measure this study determined: (1) AIMS scores at age 8 months after CCS; (2) predictive validity of AIMS at 8 months for Bayley Scales of Infant and Toddler Development-III Gross Motor-scaled scores (GMSS) and diagnosis of cerebral palsy (CP) at 21 months; and (3) predictive demographic and surgical variables of AIMS scores. A prospective cohort study of 250/271 (92.3%) surviving children from Northern Alberta (born 2009-2020) who had CCS at age < 6 months determined AIMS scores at age mean (SD) 8.6 (2.4) and the GMSS at 21.9 (3.8) months. Gross motor delay was defined as AIMS < 5th percentile and GMSS as < 4 (-2SD). Predictions using multiple logistic regressions were expressed as Odds Ratios (OR) and 95% Confidence Interval (CI). Of children, 100/250 (40%) had AIMS < 5th predicting GMSS < 4 (n = 43); sensitivity, specificity, positive, and negative predictive values were 88%, 71%, 40%, and 97%. Hospitalization days were independently associated with AIMS < 5th, OR 1.02 (95% CI 1.007, 1.032; p = 0.005). Excluding hospital days, ventilation days independently predicted AIMS < 5th, OR 1.08 (95% CI 1.038, 1.125, p < 0.001. Gross motor delay determine by AIMS scores of < 5th percentile occurred in 40% of survivors with good prediction of continued delay. Delay determined by AIMS was predicted by longer hospitalization and ventilation; further investigations about the causes are required. AIMS results provide opportunity for early motor intervention.

De novo missense variants in exon 9 of SEPHS1 cause a neurodevelopmental condition with developmental delay, poor growth, hypotonia, and dysmorphic features.

Selenophosphate synthetase (SEPHS) plays an essential role in selenium metabolism. Two mammalian SEPHS paralogues, SEPHS1 and SEPHS2, share high sequence identity and structural homology with SEPHS. Here, we report nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight of these individuals had a recurrent variant at amino acid position 371 of SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were known to be de novo. Structural modeling and biochemical assays were used to understand the effect of these variants on SEPHS1 function. We found that a variant at residue Trp352 results in local structural changes of the C-terminal region of SEPHS1 that decrease the overall thermal stability of the enzyme. In contrast, variants of a solvent-exposed residue Arg371 do not impact enzyme stability and folding but could modulate direct protein-protein interactions of SEPSH1 with cellular factors in promoting cell proliferation and development. In neuronal SH-SY5Y cells, we assessed the impact of SEPHS1 variants on cell proliferation and ROS production and investigated the mRNA expression levels of genes encoding stress-related selenoproteins. Our findings provided evidence that the identified SEPHS1 variants enhance cell proliferation by modulating ROS homeostasis. Our study supports the hypothesis that SEPHS1 plays a critical role during human development and provides a basis for further investigation into the molecular mechanisms employed by SEPHS1. Furthermore, our data suggest that variants in SEPHS1 are associated with a neurodevelopmental disorder.

Assessment of COVID-19 Messaging Strategies to Increase Testing for Students With Intellectual and Developmental Disabilities.

BACKGROUND: Students with intellectual and developmental disabilities (IDD) were disproportionately impacted by the COVID-19 pandemic. This study's goal was to assess the effectiveness of 2 messaging strategies on participation in SARS-CoV-2 weekly testing. METHODS: Cluster randomized trials were conducted at 2 school systems, the special school district (SSD) and Kennedy Krieger Institute (Kennedy) to assess messaging strategies, general versus enhanced, to increase weekly screening for SARS-CoV-2. Testing was offered to staff and students from November 23, 2020 to May 26, 2022. The primary outcomes were percentage of students and staff consented weekly and percentage of study participants who had a test performed weekly. Generalized estimating equation models were utilized to evaluate the primary outcomes. RESULTS: Increases in enrollment and testing occurred during study start up, the beginning of school years, and following surges in both systems. No statistical difference was observed in the primary outcomes between schools receiving standard versus enhanced messaging. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Frequent and consistent communication is vital for families and staff. Weekly screening testing within schools is possible and highlighted the importance of utilizing equitable protocols to provide important testing to students with IDD. CONCLUSION: Enhanced messaging strategies did not increase the number of participants enrolled or the percentage of enrolled participants being tested on a weekly basis.

A 9-year retrospective cohort study of the monitoring and screening of childhood developmental delay in Thailand.

BACKGROUND: Developmental delay in early childhood can have negative long-term cognitive and psychiatric sequelae, along with poor academic achievement, so early screening and surveillance are paramount. The aim of this study is to evaluate the impact of screening and surveillance on child developmental delay using the Developmental Surveillance and Promotion Manual (DSPM) and the Thai Early Developmental Assessment for Intervention (TEDA4I) for Thai children aged 0-5 years old. METHODS: Data were obtained from the routine developmental screening for specific disorders at ages 9, 18, 30, 42 and 60 months conducted using DSPM and TEDA4I from 2013 to 2021. Descriptive statistics were used to analyse the data, and the results are visualised graphically herein. RESULTS: Only 56% of the children were screened for child developmental delay using DSPM. The proportion of children screened increased from <1% in 2013 to 90% in 2021. Suspected developmental delay prevalence increased significantly from 3.91% in 2013-2015 to 10.00% in 2016-2018 and 26.48% in 2019-2021. Moreover, of the children with suspected developmental delay who received developmental stimulation within a month, only 87.9% returned for follow-up visits when they were evaluated again using TEDA4I to ascertain any abnormalities and specific areas of deficit. The overall proportion of children diagnosed with developmental delay was 1.29%. During the pandemic, the proportion of screening tests for child developmental delay at routine vaccination visits and follow-ups decreased but was still at least 80% in each region. CONCLUSIONS: Since 1%-3% of children have suspected developmental delay, early detection is key to treating it as soon as possible. We anticipate that our findings will raise awareness in parents and caregivers about childhood developmental delay and lead to the implementation of early intervention and follow-up at the rural level in Thailand.

Breast (female), colorectal, and lung cancer survival in people with intellectual or developmental disabilities: A population-based retrospective cohort study.

OBJECTIVES: Cancer is a leading cause of death among people living with intellectual or developmental disabilities (IDD). There is little empirical evidence documenting survival or comparing outcomes to those without IDD. This study investigated the association between IDD and cancer survival among adults with breast (female), colorectal, or lung cancer. METHODS: A population-based retrospective cohort study was conducted in Ontario, Canada, with routinely collected data. Patients with breast, colorectal, or lung cancer were included (2007‒2019). IDD status before cancer was determined using an established administrative data algorithm. The outcomes of interest included death from any cause and death from cancer. Cox proportional hazards models and competing events analyses using multivariable cause-specific hazards regression were completed. Analyses were stratified by cancer type. Interactions with age, sex, and stage at diagnosis, as well as sensitivity analyses, were completed. RESULTS: The final cohorts included 123,695 breast, 98,809 colorectal, and 116,232 lung cancer patients. Individuals with IDD experienced significantly worse survival than those without IDD. The adjusted hazard ratios of all-cause death were 2.74 (95% CI 2.41‒3.12), 2.42 (95% CI 2.18‒2.68), and 1.49 (95% CI 1.34‒1.66) times higher for breast, colorectal, and lung cancer patients with IDD relative to those without. These findings were consistent for cancer-specific deaths. With few exceptions, worse survival for people with IDD persisted regardless of stage at diagnosis. CONCLUSION: People with IDD experienced worse cancer survival than those without IDD. Identifying and intervening on the factors and structures responsible for survival disparities is imperative.

RéSUMé: OBJECTIFS: Le cancer est l'une des principales causes de mortalité chez les personnes vivant avec des déficiences intellectuelles ou des troubles du développement (DI/TD). Il y a peu de preuves empiriques décrivant la survie de ces personnes lorsqu'elles sont atteintes d'un cancer ou comparant leurs résultats à ceux des personnes sans DI/TD. Notre étude porte sur l'association entre les DI/TD et la survie au cancer chez les adultes atteints de cancer du sein (femmes), du colorectum ou du poumon. MéTHODE: Une étude de cohorte rétrospective populationnelle a été menée en Ontario, au Canada, à l'aide de données recueillies systématiquement. Nous avons inclus les patientes et les patients atteints de cancer du sein, du colorectum ou du poumon (2007‒2019). Nous avons identifié la présence des DI/TD avant le cancer à l'aide d'un algorithme de traitement de données administratives reconnu. Les résultats d'intérêt étaient les décès de toutes causes et les décès dus au cancer. Nous avons appliqué des modèles des risques proportionnels de Cox et des analyses des événements concurrents en utilisant la régression multivariée des risques par cause. Nos analyses ont été stratifiées selon le type de cancer. Nous avons tenu compte des interactions avec l'âge, le sexe et le stade au diagnostic et effectué des analyses de sensibilité. RéSULTATS: Les cohortes finales ont inclus 123 695 personnes atteintes de cancer du sein, 98 809 atteintes de cancer colorectal et 116 232 atteintes de cancer du poumon. La survie des sujets ayant des DI/TD a été significativement moins bonne que celle des sujets sans DI/TD. Les rapports de risques instantanés ajustés pour les décès de toutes causes étaient 2,74 fois (IC de 95 % 2,41‒3,12), 2,42 fois (IC de 95 % 2,18‒2,68) et 1,49 fois (IC de 95 % 1,34‒1,66) plus élevés chez les personnes atteintes de cancer du sein, du colorectum et du poumon et ayant des DI/TD que chez les personnes sans DI/TD. Ces constatations ressortent pour tous les décès attribuables à des cancers particuliers. Avec peu d'exceptions, la survie moins bonne pour les personnes ayant des DI/TD persistait quel que soit le stade au moment du diagnostic. CONCLUSION: La survie au cancer était moins bonne chez les personnes ayant des DI/TD que chez celles n'ayant pas de DI/TD. Il est impératif d'identifier les facteurs et les structures responsables de ces disparités dans la survie et d'intervenir en conséquence.

The Pivotal Role of Oxytocin's Mechanism of Thermoregulation in Prader-Willi Syndrome, Schaaf-Yang Syndrome, and Autism Spectrum Disorder.

Oxytocin (Oxt) regulates thermogenesis, and altered thermoregulation results in Prader-Willi syndrome (PWS), Schaaf-Yang syndrome (SYS), and Autism spectrum disorder (ASD). PWS is a genetic disorder caused by the deletion of the paternal allele of 15q11-q13, the maternal uniparental disomy of chromosome 15, or defects in the imprinting center of chromosome 15. PWS is characterized by hyperphagia, obesity, low skeletal muscle tone, and autism spectrum disorder (ASD). Oxt also increases muscle tonicity and decreases proteolysis while PWS infants are hypotonic and require assisted feeding in early infancy. This evidence inspired us to merge the results of almost 20 years of studies and formulate a new hypothesis according to which the disruption of Oxt's mechanism of thermoregulation manifests in PWS, SYS, and ASD through thermosensory abnormalities and skeletal muscle tone. This review will integrate the current literature with new updates on PWS, SYS, and ASD and the recent discoveries on Oxt's regulation of thermogenesis to advance the knowledge on these diseases.

Hemizygous splicing variant in CNKSR2 results in X-linked intellectual developmental disorder.

BACKGROUND: Intellectual disability (ID) refers to a childhood-onset neurodevelopmental disorder with a prevalence of approximately 1%-3%. METHODS: We performed whole exome sequencing for the patient with ID. And the splicing variant we found was validated by minigene assay. RESULTS: Here, we report a boy with ID caused by a variant of CNKSR2. His neurological examination revealed hypsarrhythmia via electroencephalography and a right temporal polar arachnoid cyst via brain magnetic resonance imaging. A novel splicing variant in the CNKSR2 gene (NM_014927.5, c.1657+1G>A) was discovered by exome sequencing. The variant caused a 166 bp intron retention between exons 14 and 15, which was validated by a minigene assay. The variant was not reported in public databases such as gnomAD and the Exome Aggregation Consortium. CONCLUSIONS: The variant was predicted to be damaging to correct the translation of the CNKRS2 protein and was classified as likely pathogenic according to the ACMG guidelines.

Loss-of-function of kinesin-5 KIF11 causes microcephaly, chorioretinopathy, and developmental disorders through chromosome instability and cell cycle arrest.

Kinesin motors play a fundamental role in development by controlling intracellular transport, spindle assembly, and microtubule organization. In humans, patients carrying mutations in KIF11 suffer from an autosomal dominant inheritable disease called microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR). While mitotic functions of KIF11 proteins have been well documented in centrosome separation and spindle assembly, cellular mechanisms underlying KIF11 dysfunction and MCLMR remain unclear. In this study, we generate KIF11-inhibition chick and zebrafish models and find that KIF11 inhibition results in microcephaly, chorioretinopathy, and severe developmental defects in vivo. Notably, loss-of-function of KIF11 causes the formation of monopolar spindle and chromosome misalignment, which finally contribute to cell cycle arrest, chromosome instability, and cell death. Our results demonstrate that KIF11 is crucial for spindle assembly, chromosome alignment, and cell cycle progression of progenitor stem cells, indicating a potential link between polyploidy and MCLMR. Our data have revealed that KIF11 inhibition cause microcephaly, chorioretinopathy, and development disorders through the formation of monopolar spindle, polyploid, and cell cycle arrest.

Novel phenotype associated with homozygous likely pathogenic variant in the POP1 gene.

The biallelic variants of the POP1 gene are associated with the anauxetic dysplasia (AAD OMIM 607095), a rare skeletal dysplasia, characterized by prenatal rhizomelic shortening of limbs and generalized joint hypermobility. Affected individuals usually have normal neurodevelopmental milestones. Here we present three cases from the same family with likely pathogenic homozygous POP1 variant and a completely novel phenotype: a girl with global developmental delay and autism, microcephaly, peculiar dysmorphic features and multiple congenital anomalies. Two subsequent pregnancies were terminated due to multiple congenital malformations. Fetal DNA samples revealed the same homozygous variant in the POP1 gene. Expression of the RMRP was reduced in the proband compared with control and slightly reduced in both heterozygous parents, carriers for this variant. To our knowledge, this is the first report of this new phenotype, associated with a novel likely pathogenic variant in POP1. Our findings expand the phenotypic spectrum of POP1-related disorders.

[Catatonia in youth with developmental disabilities: challenges in recognition and management]. / Katatonie bij jongeren met een ontwikkelingsstoornis: uitdagingen in herkenning en aanpak.

Catatonia in children and adolescents is not rare and, as in adults, has a favorable outcome, provided it is recognized and treated promptly. Nevertheless, in clinical practice we encounter several obstacles in terms of diagnosis and treatment in this population of patients. We describe a 14-year-old boy with an intellectually disability and autism spectrum disorder (ASD) in which clinicians did not diagnose catatonia until 1 year after the development of symptoms. Moreover, hesitations surrounding the correct treatment led to its delayed initiation. With this case report we aim to contribute to reduced reluctance and increased alertness in the treatment of catatonia in adolescents with developmental disorders.

The first Turkish family with a novel biallelic missense variant of the ALKBH8 gene: A study on the clinical and variant spectrum of ALKBH8-related intellectual developmental disorders.

ABH8, the protein encoded by the ALKBH8 gene, modifies tRNAs by methylating their anticodon wobble uridine residues. The variations in the ALKBH8 gene are associated with the "intellectual developmental disorder, autosomal recessive type 71" (MIM: 618504) phenotype in the OMIM database. This phenotype is characterized by global developmental delay, facial dysmorphic features, and psychiatric problems. To date, 12 patients from five distinct families carrying variants of the ALKBH8 gene have been reported in the literature. In the present study, we report the first Turkish family harboring a novel homozygous missense variant, NM_138775.3:c.1874G > C (p.Arg625Pro), in the last exon of the ALKBH8 gene. Two affected siblings in this family showed signs of global developmental delay and intellectual disability. Based on the dysmorphological assessment of the cases, fifth finger clinodactyly and fetal fingertip pads were prominent, in addition to the dysmorphic findings similar to those reported in previous studies. Minor dysmorphic limb anomalies in relation to this phenotype have not yet been previously reported in the literature. Our computational studies revealed the potential deleterious effects of the Arg-to-Pro substitution on the structure and stability of the ABH8 methyltransferase domain. In the present report, the first Turkish family with an ultrarare disease associated with the ALKBH8 gene was reported, and a novel deleterious variant in the ALKBH8 gene and additional clinical features that were not reported with this condition have been reported.

Evaluation of neurocognitive and social developments after craniosynostosis surgery.

OBJECTIVE: The study focused on assessing the potential neurocognitive and social developmental issues in children with non-syndromic craniosynostosis (NSC) who received optimal surgical treatment. The primary objective was to determine whether NSC, even after optimal surgical treatment, could have negative effects on brain development. METHODS: The study included a total of 73 pediatric patients aged between 2 and 6 years who had previously undergone surgery for NSC at the Gazi University Faculty of Medicine, Department of Neurosurgery. These patients were carefully matched with 107 healthy children who visited the outpatient clinic of the same department in terms of sociodemographic characteristics such as age, gender, and social status. To assess the neurocognitive and social development of the participants, the child psychologist administered a developmental scale to the child and his/her family via video conference. This scale was adapted from the Bayley-III Infant and Child Development Scale by the Gazi University Faculty of Medicine, Division of Pediatric Neurology. RESULTS: The study found no social or gross motor developmental issues in patients who had undergone optimal surgical treatment for NSC. However, the risk of fine motor developmental deficiencies was 4.79 times higher than that of the normal population, and the risk of language developmental deficiencies was 5.75 times higher than that of the normal population. CONCLUSIONS: Despite timely treatment of NSC, long-term neurocognitive and social development issues may arise in affected children. Therefore, it is crucial to monitor these patients after completing surgical treatment and thoroughly examine their development using a multidisciplinary approach.