Brain & Development最新文献

{"title":"Clinical features and prognostic factors of group B Streptococcus Meningitis in infants","authors":"Wenjie Li ,&nbsp;Xueqian Xia ,&nbsp;Lingyu Zhang ,&nbsp;Xiaoling Peng ,&nbsp;Li Jiang ,&nbsp;Yue Hu","doi":"10.1016/j.braindev.2025.104398","DOIUrl":"10.1016/j.braindev.2025.104398","url":null,"abstract":"<div><h3>Purpose</h3><div>To summarize the clinical features of group B streptococcus (GBS) meningitis in infants and identify the risk factors for poor prognosis.</div></div><div><h3>Methods</h3><div>The clinical data of 52 infants with GBS meningitis treated at Children's Hospital of Chongqing Medical University from January 2012 to December 2021 were retrospectively analyzed.</div></div><div><h3>Results</h3><div>A total of 48 infants (48/52, 92.3 %) presented with symptom onset at ≤90 days of age. Among 52 patients, the most prevalent clinical manifestations were fever (98.1 %), altered mental status (84.6 %) and decreased appetite (63.5 %). Subdural effusion (30/52, 57.7 %) was the most common neurological complication. One patient (1.9 %) died from cerebral herniation. Positive blood culture alone was observed in 41 cases (78.8 %), isolated cerebrospinal fluid (CSF) culture positivity in 5 (9.6 %), and dual blood-CSF culture positivity in 6 (11.5 %). The median hospital stay was 33 days. The most frequently administered antibiotic regimens were vancomycin combined with carbapenems (18/52, 34.6 %) and vancomycin plus third-generation cephalosporins (15/52, 28.8 %). Univariate analysis indicated an association between glucocorticoid use and clinical outcomes; however, multivariate analysis yielded no statistically significant variables (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>GBS meningitis is most common in infants below 3 months. Both clinical manifestations and ancillary tests may be nonspecific, and definitive diagnosis relies on etiological confirmation. The risk of neurological complications is high.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104398"},"PeriodicalIF":1.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune dysregulation in new-onset refractory status epilepticus (NORSE): current insights and therapeutic perspectives","authors":"Aurélie Hanin ,&nbsp;Lawrence J. Hirsch","doi":"10.1016/j.braindev.2025.104406","DOIUrl":"10.1016/j.braindev.2025.104406","url":null,"abstract":"<div><h3>Objective</h3><div>Emerging evidence suggests that cryptogenic new-onset refractory status epilepticus (c-NORSE) arises from innate immunity dysfunction leading to exacerbated inflammation. While immunotherapies have been administered, their efficacy remains variable and unpredictable.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive literature review of studies reporting inflammation biomarkers in patients with NORSE or evaluating targeted immunotherapies. Additionally, we discussed future research directions and therapeutic perspectives.</div></div><div><h3>Results</h3><div>A total of 29 studies reporting inflammation biomarkers in at least five patients were analyzed. Most focused on c-NORSE, frequently describing cerebrospinal fluid pleocytosis, often lymphocytic and usually mild, upon admission. Elevated levels of innate immunity-related pro-inflammatory cytokines were consistently reported in c-NORSE. A large international study further demonstrated significantly higher cytokine levels in c-NORSE compared to other refractory status epilepticus patients, suggesting the importance of innate immunity in c-NORSE pathophysiology. One recent study identified subgroups with distinct inflammatory profiles among c-NORSE, suggesting different treatment approaches.</div><div>More than 30 case series or reports have documented the use of targeted immunotherapies in NORSE. The most commonly used are anakinra (IL1 antagonist) and tocilizumab (IL6 antagonist), both showing seemingly comparable efficacy in seizure control. Recently, intrathecal dexamethasone has gained interest, particularly in pediatric cases, showing promising efficacy with no reported side effects. Other emerging approaches include canakinumab (anti-IL1 antibody), Janus kinase (JAK) inhibitors, and tumor necrosis factor alpha (TNFα) inhibitors.</div></div><div><h3>Conclusions</h3><div>Recent studies have advanced our understanding of innate immunity disturbances in c-NORSE onset and progression. Moreover, they highlight patient heterogeneity, emphasizing the need for personalized strategies targeting specific inflammatory pathways.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104406"},"PeriodicalIF":1.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor: ‘Prevalence and management of gastrointestinal complications of Duchenne muscular dystrophy: A retrospective cohort study’","authors":"Sabri Selcuk Atamanalp","doi":"10.1016/j.braindev.2025.104402","DOIUrl":"10.1016/j.braindev.2025.104402","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104402"},"PeriodicalIF":1.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between epilepsy and attention deficit/hyperactivity disorder – correlation between interictal epileptiform discharges and behavioral disturbances","authors":"Hideaki Kanemura","doi":"10.1016/j.braindev.2025.104403","DOIUrl":"10.1016/j.braindev.2025.104403","url":null,"abstract":"<div><div>A relationship between epileptic activities and neuropsychological dysfunction has been indicated in epileptic children. Epileptic activities including frequent/prolonged seizures and severe EEG abnormalities could be associated with cognitive decline and behavioral disturbances. Frequent, prolonged seizures could induce growth disturbances in the prefrontal cortex, leading to behavioral disturbance. Meanwhile, frequent epileptic seizures or EEG abnormalities, including interictal epileptiform discharges (IEDs), are evident in attention deficit/hyperactivity disorder (ADHD). Subclinical IEDs could lead to neuropsychological dysfunction in epileptic and ADHD children. The concurrence of IED frequency and prolonged periods of high-frequency IEDs may predict the atypical evolution of self-limited epilepsy with centrotemporal spikes. In developmental and epileptic encephalopathy with spike-wave activation during sleep, cognitive/behavioral disturbances correlate with frequent IEDs such as secondary bilateral synchrony (SBS). On the other hand, EEG manifestations, particularly IED locations, could represent important predictors of optimal outcome in epilepsy and ADHD. Abnormal paroxysms in the frontal region could lead to neuropsychological dysfunctions, so frontal IEDs could be associated with cognitive/behavioral disturbances in epilepsy and ADHD. Frontal IEDs could predict atypical clinical features including behavioral disturbance and ultimate neuropsychological outcomes in epileptic/ADHD children. Early remission of clinical seizures and reduction of IEDs might be necessary to accomplish optimal outcomes for children presenting with behavioral disturbances. A therapeutic strategy comprising prompt suppression of IEDs (including frontal IEDs/SBS) could improve quality of life in at least some children with epilepsy and ADHD.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104403"},"PeriodicalIF":1.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recognition of Japanese kanji words in children with specific learning disorders: a preliminary study using magnetoencephalography","authors":"Yuka Egashira ,&nbsp;Yoshimi Kaga ,&nbsp;Atsuko Gunji ,&nbsp;Yousuke Kita ,&nbsp;Motohiro Kimura ,&nbsp;Naruhito Hironaga ,&nbsp;Hiroshige Takeichi ,&nbsp;Sayuri Hayashi ,&nbsp;Yuu Kaneko ,&nbsp;Hidetoshi Takahashi ,&nbsp;Takashi Hanakawa ,&nbsp;Takashi Okada ,&nbsp;Masumi Inagaki","doi":"10.1016/j.braindev.2025.104400","DOIUrl":"10.1016/j.braindev.2025.104400","url":null,"abstract":"<div><h3>Introduction</h3><div>In Western countries, reading disorders are believed to be caused by phonological processing problems. Conversely, Japanese children with developmental dyslexia (DD) and developmental dysgraphia often have difficulty learning kanji that are ideographic characters. It is believed that kanji learning and alphabet learning have different pathologies, as the latter uses phonetic character. In this study, we aimed to clarify the characteristics of kanji word recognition in Japanese children with DD and developmental dysgraphia using magnetoencephalography with high spatial resolution.</div></div><div><h3>Methods</h3><div>Seven Japanese children with learning disorders, including 4 with DD and 3 with developmental dysgraphia, and 14 typically developing Japanese children (TDC) underwent magnetoencephalography while presented with kanji compounds and pseudo-kanji character sequences in their parafoveal visual fields, along with a foveal silent movie.</div></div><div><h3>Results</h3><div>No differences were found between conditions or groups, except significantly smaller source activation in the posterior transverse region of the collateral sulcus (ptCoS) in the patient group, when presenting pseudo-kanji than presenting kanji, or than TDC when presenting deviant pseudo-kanji. The ptCoS activity from kanji exhibited a positive correlation with writing skills in the patient group, independently of attention deficit hyperactivity disorder (ADHD) symptom scores.</div></div><div><h3>Conclusions</h3><div>These results suggest that ptCoS activity during the presentation of kanji characters in Japanese children with DD and developmental dysgraphia reflects their writing ability, regardless of ADHD symptoms. Some forms of ptCoS dysfunction may be related to the neural basis of specific kanji writing functions in Japanese patients with DD and developmental dysgraphia.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104400"},"PeriodicalIF":1.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural history of timed rise from floor in young individuals with Duchenne muscular dystrophy: A single-center retrospective study","authors":"Shota Yoneno ,&nbsp;Eri Takeshita ,&nbsp;Yuko Shimizu-Motohashi ,&nbsp;Mari Oba ,&nbsp;Takatoshi Hara ,&nbsp;Masahiro Hirayama ,&nbsp;Hirofumi Komaki","doi":"10.1016/j.braindev.2025.104396","DOIUrl":"10.1016/j.braindev.2025.104396","url":null,"abstract":"<div><h3>Introduction</h3><div>Motor function in patients with Duchenne muscular dystrophy (DMD) is commonly evaluated using the 6-min walk test, North Star Ambulatory Assessment, and timed function tests. However, few reports have examined the progression of timed rise from floor (TRF) in patients with DMD undergoing steroid therapy in Japan. We investigated the natural history of TRF in patients with DMD treated in Japan.</div></div><div><h3>Methods</h3><div>We retrospectively assessed TRF by age group based on data collected from October 2010 to August 2023. We used Kaplan–Meier curves to analyze the loss of the ability to rise from the floor. Additionally, receiver operating characteristic analysis was performed to predict the loss of the ability to stand up after 1 year.</div></div><div><h3>Results</h3><div>In total, 165 males with DMD were enrolled. The median TRF peaked at 6 years of age and deteriorated thereafter. The median age of the loss of the ability to rise from the floor was 11.9 years (95 % confidence interval = 10.6–13.2). Using a TRF cutoff of 6.2 s, the sensitivity, specificity, and area under the curve for predicting loss of the ability to rise from the floor in 1 year were 71 %, 90 %, and 0.914, respectively.</div></div><div><h3>Conclusion</h3><div>This study provided insights into the deterioration of TRF in patients with DMD receiving steroid treatment in Japan. As a simple and easily measurable parameter, TRF is a useful tool for predicting the progression of motor function.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104396"},"PeriodicalIF":1.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Valproate and lamotrigine combination therapy in children with drug-resistant focal epilepsy: an observational analysis focusing on neuroimaging abnormalities","authors":"Shiena Watanabe ,&nbsp;Takashi Enokizono ,&nbsp;Mitsuyo Nishimura ,&nbsp;Kazushi Maruo ,&nbsp;Tomoya Iwasaki ,&nbsp;Yui Tsunoda ,&nbsp;Yuichi Ueno ,&nbsp;Mai Tanaka ,&nbsp;Yui Takada ,&nbsp;Ryuta Tanaka ,&nbsp;Kota Araki ,&nbsp;Yosuke Masuda ,&nbsp;Eiichi Ishikawa ,&nbsp;Hidetoshi Takada","doi":"10.1016/j.braindev.2025.104395","DOIUrl":"10.1016/j.braindev.2025.104395","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the efficacy of valproate and lamotrigine (VPA–LTG) combination therapy in pediatric patients with drug-resistant focal epilepsy (DRFE), focusing on the presence of neuroimaging abnormalities.</div></div><div><h3>Methods</h3><div>Pediatric patients with epilepsy who visited the University of Tsukuba Hospital and Ibaraki Children's Hospital between October 2021 and September 2024 were included in this retrospective chart review. Patients with DRFE who received VPA–LTG combination therapy were enrolled.</div></div><div><h3>Results</h3><div>Data from 21 patients, including 16 males and 5 females, in the age range of 1.8–13.9 years were examined. The median numbers of previously failed anti-seizure medications (ASMs) and concurrent ASMs were 4 (range: 2–7) and 3 (range: 2–5), respectively. The overall responder rate (defined as the percentage of patients achieving ≥50 % seizure reduction over the last 12 months) was 38 %. The responder rate in patients without MRI abnormalities (67 %) was significantly higher than that in patients with MRI abnormalities (16 %). Patients with MRI abnormalities had more structural etiologies (42 %), whereas those without MRI abnormalities had more unknown etiologies (89 %).</div></div><div><h3>Conclusion</h3><div>Our findings suggest that VPA–LTG combination therapy is a promising option for pediatric patients with DRFE without neuroimaging abnormalities.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104395"},"PeriodicalIF":1.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of withdrawal seizures in children with refractory status epilepticus who responded favorably to continuous midazolam therapy","authors":"Hirokazu Takeuchi ,&nbsp;Kenjiro Kikuchi ,&nbsp;Rikako Takeda ,&nbsp;Yuko Hirata ,&nbsp;Ryuki Matsuura ,&nbsp;Reiko Koichihara ,&nbsp;Ikuya Ueta ,&nbsp;Shin-Ichiro Hamano","doi":"10.1016/j.braindev.2025.104394","DOIUrl":"10.1016/j.braindev.2025.104394","url":null,"abstract":"<div><h3>Background</h3><div>This study investigates the characteristics of children with refractory status epilepticus (RSE) who experienced withdrawal seizures and responded favorably to continuous midazolam (cMDL) therapy.</div></div><div><h3>Methods</h3><div>Patients who experienced RSE and achieved seizure cessation with cMDL were included in the study. Withdrawal seizure was defined as a seizure occurring from the initiation of cMDL tapering until 48 h after the discontinuation of cMDL. The patients were categorized into two groups: seizure cessation and withdrawal seizure groups.</div></div><div><h3>Results</h3><div>Nineteen patients with RSE achieved seizure cessation with cMDL. The seizure cessation group comprised 11 patients, while eight patients (42.1 %) were classified into the withdrawal seizure group. The median maintenance dose of cMDL were 0.1 mg/kg/h (interquartile range [IQR]: 0.1–0.2) for the seizure cessation group, and 0.25 mg/kg/h (IQR: 0.15–0.3) for the withdrawal seizure group. The median maintenance periods were 27 h (IQR: 12–32.5) for the seizure cessation group, and 52.5 h (IQR: 23–65.5) for the withdrawal seizure group. The seizure cessation group had a median cumulative MDL of 2.7 mg/kg (IQR: 1.6–4.9), while the withdrawal seizure group had 11.6 mg/kg (IQR: 4.5–24.5).</div></div><div><h3>Conclusion</h3><div>Although statistical analysis was not conducted due to the small sample size, maintenance dose of cMDL is potentially correlated with withdrawal seizure. A multi-center study with large sample size and statistical analysis of this relationship may contribute to the establishment of an optimized cMDL tapering protocol.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104394"},"PeriodicalIF":1.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the connections between migraine and psychiatric comorbidities: A narrative review","authors":"Jungyon Yum ,&nbsp;Min Kyung Chu","doi":"10.1016/j.braindev.2025.104392","DOIUrl":"10.1016/j.braindev.2025.104392","url":null,"abstract":"<div><div>The close association between migraine and psychiatric comorbidities is well documented. Migraine frequently co-occurs with mood disorders, particularly depression and anxiety, exhibiting a bidirectional relationship across various populations, including children and adolescents. Emerging research has also highlighted significant associations between migraine and bipolar disorder, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Shared pathophysiological mechanisms, including genetic predisposition, neurotransmitter imbalances, hormonal influences, and environmental factors, contribute to these comorbidities. Diagnosing migraine in individuals with ASD and ADHD presents unique challenges due to overlapping symptoms and communication barriers. Furthermore, psychiatric medications may influence migraine symptoms, necessitating careful management. This review explores the relationship between migraine and psychiatric disorders, emphasizing shared mechanisms, diagnostic considerations, and treatment strategies to optimize patient care. This review highlights the necessity for integrated clinical approaches that address both migraine and psychiatric comorbidities, ultimately improving health outcomes for affected individuals.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104392"},"PeriodicalIF":1.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biallelic novel CCDC186 loss-of-function variant disrupting the gene function causes neurodevelopmental phenotype and review of the literature","authors":"Alper Gezdirici ,&nbsp;Sultan Buse Turk ,&nbsp;Tuna Eren Esen ,&nbsp;Cuneyd Yavas ,&nbsp;Ekrem Akbulut ,&nbsp;Halil Ibrahim Yilmaz ,&nbsp;Zeynep Oz Dagdelen ,&nbsp;Pinar Arican ,&nbsp;Mustafa Dogan","doi":"10.1016/j.braindev.2025.104393","DOIUrl":"10.1016/j.braindev.2025.104393","url":null,"abstract":"<div><h3>Background</h3><div>Coiled-coil domain-containing protein 186 (CCDC186) is essential for the transport of secretory dense-core vesicles (DCVs), specialized organelles responsible for storing and releasing neurotransmitters and other modulatory molecules in neurons and endocrine cells, thereby playing a crucial role in physiological processes such as synaptic plasticity, neurotransmission, and hormonal regulation. Resent reports have suggested that biallelic loss-of-function (LOF) variants in <em>CCDC186</em> may be associated with neurodevelopmental disorders and a range of systemic manifestations.</div></div><div><h3>Methods</h3><div>Whole exome sequencing (WES) was performed, and co-segregation analysis of the family was conducted using sanger sequencing. Additionally, five patients with <em>CCDC186</em>-associated phenotypes previously described in the literature were evaluated. Followed by cDNA synthesis and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to analyze gene expression levels. Bioinformatics tools, including RoseTTAFold for protein modeling and STRING for protein-protein interaction networks, were employed to assess the structural and functional consequences of the mutation.</div></div><div><h3>Results</h3><div>We identified a homozygous NM_018017.4:c.535C&gt;T (p.Arg179Ter) nonsense variant in the <em>CCDC186</em> gene. This variant was associated with a marked downregulation of CCDC186 expression in the proband, with moderate reductions observed in heterozygous family members, suggesting dysregulated gene expression resulting from the mutation. Protein modeling indicated structural alterations, including a shift from intrinsically disordered regions to helix-loop-helix motifs in the mutant protein, as well as reduced binding probabilities for most interacting partners.</div></div><div><h3>Conclusion</h3><div>In this study, we presented the comprehensive clinical and genetic profiles of a Turkish child with a novel <em>CCDC186</em> variant, along with five previously reported patients from the literature. Our findings support that the homozygous LOF variants of the <em>CCDC186</em> gene are associated with a novel neurodevelopmental phenotype.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104393"},"PeriodicalIF":1.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}