Neurocutaneous melanosis (NCM) and Dandy-Walker malformation (DWM) are both uncommon congenital condition, involving the central nervous system (CNS). Combined NCM with DWM have been reported in a few studies. Potential consequences, including hydrocephalus and CNS malignancies make these illnesses extremely challenging to diagnose and treat. Occurrences of NCM and DWM together, can result in progressive neurological consequences and patients with this condition seems to have really poor prognosis. This case report describes a 5-day-old girl who was born with several large pigmented cutaneous nevi all over her body. She was born at term to non-consanguineous parents who had no family history of similar conditions. Imaging studies, such as brain CT scan, showed cystic dilatation of the fourth ventricle, hypoplasia of the cerebellar vermis, enlargement of the posterior fossa, and possibly secondary hydrocephalus-all of which are indicative of DWM. A biopsy of the nevi confirmed NCM. The patient had no neurological symptoms or systemic complications at the time of presentation. The combination of NCM and DWM is extremely rare, with fewer than 40 reported cases so far. While the exact connection between these two conditions is not fully understood, their coexistence of these conditions might be linked to their shared embryonic origin. Both melanocytes and parts of the CNS come from the neural crest during early development. Since these conditions can have serious neurological and systemic effects, managing them requires multidisciplinary care because of potential consequences of these disorders.
Objectives:This study aimed to develop a structured, culturally responsive neurodevelopmental care framework for preterm infants during the first three months following the neonatal intensive care unit (NICU) discharge, based on research evidence and multidisciplinary expert consensus in Iran. Materials & Methods:A two-phase study was conducted. First, a scoping review (2000-2024) identified key domains and items for post-discharge care. Second, a panel of 24 multidisciplinary experts completed a two-round Delphi survey. Consensus was defined as 75% agreement or higher and a mean Likert score of 3.75 or above on a five-point scale. Quantitative and qualitative analyses were performed in accordance with Delphi study guidelines. Results:The finalized framework comprises 57 items categorized across eight primary domains. Expert agreement ranged from 87% to 95%, with mean Likert scores ranging from 4.42 to 4.65. Positioning and postural care showed the highest agreement (95% t, mean = 4.57). Experts emphasized continuity of care, parent-mediated interventions, and integration of developmental, emotional, and environmental components. Conclusion:This culturally adapted, family-centered framework provides structured post-discharge neurodevelopmental care for preterm infants. It promotes infants' motor, sensory, cognitive, and emotional development while supporting parental empowerment and psychological well-being, potentially optimizing early neurodevelopmental outcomes in home-based care settings.
Objective:Spinal muscular atrophy (SMA) involves the survival motor neuron (SMN) 1 gene, leading to motor neuron degeneration. SMN2 is a homologous gene to SMN1, which can produce SMN protein at lower levels. The new gene-based drugs modify SMN2 pre-messenger RNA splicing, leading to production of functional SMN protein. Materials & Methods:This study aimed to evaluate the effectiveness and safety of Risdiplam and Nusinersen in patients with SMA types I-III. Hammersmith Functional Motor Scale-Expanded (HFMSE) was used for motor evaluation. Results:Results revealed that changes were significant after six months (p< 0.001). Improvements were compared between the two drugs, age groups, and SMA disease types, and no significant differences were found. No severe side effects were experienced and only a few patients reported headaches, and backaches following Nusinersen. Conclusion:both Risdiplam and Nusinersen led to significant improvements in motor function; however, based on cost-effectiveness considerations, we recommend Risdiplam.
Objective:Developmental Coordination Disorder (DCD) affects 5-6% of school-aged children, impairing motor control and coordination. This systematic review and meta-analysis examines the effectiveness of coordination exercises on improving hand function in individuals with DCD. Methods:A comprehensive search was conducted across four databases: Scopus, PubMed, PEDro, and The Cochrane Library for interventional trials published between 2010 and April 2025. PRISMA guidelines were followed for the review, and the methodological quality of studies was assessed using the PEDro scale, GRADE system, Risk of Bias, and Level of Evidence. A random-effects model was used for meta-analysis, calculating standardized mean differences (SMD) with 95% confidence intervals (CI). Results:Seven studies involving 361 children with DCD were included. Meta-analysis revealed a large effect of coordination exercises on hand function compared to control interventions (SMD = 1.13, 95% CI: 0.31 to 1.95, p = 0.0066). Interventions such as haptic perception training, adapted Taekwondo, gaze training, and pegboard tasks showed consistent improvements in fine motor skills. However, moderate-to-high heterogeneity was observed (I² = 70.8%), with sensitivity analysis revealing that two studies contributed over 90% of the total weight. Conclusion:Coordination exercises significantly improve hand function in individuals with DCD, showing a large effect size. These exercises are effective in enhancing fine motor skills and manual dexterity.
Objectives:As permanent hearing loss is irreversible, individuals often rely on hearing aids or cochlear implants as effective rehabilitation solutions. Stem cell therapy has been used this disability at the level of preclinical studies and effectiveness has not been determined to improve of auditory brainstem response (ABR) and restore damaged hair cells of cochlea. This systematic review shows the role of stem cell injection on ABR threshold changes in noise induced hearing loss (NIHL) models. Materials & Methods:Search strategies for Embase, PubMed, and Web of Science were performed based on keywords stem cell, hearing loss, and noise from 2000 to 2024. Nine studies were evaluated for study variables and risk of bias, and only six studies were analyzed to estimate effect size of auditory threshold. Results:The broadband noise was the most common noise to create NIHL model. The improvement of ABR threshold was estimated -2.46, 95% (CI: -3.26, -1.66) after stem cell injection. Significant mean differences were observed in ABR-threshold for local injection (n = 148) and mesenchymal stem cell (MSC) injection (n = 129) with high heterogeneity between studies. Conclusion:According to high heterogeneity between studies, it may be concluded that MSC, systemic injection, and human-derived cells are effective in recovery of auditory brainstem function.
Objectives:Autoimmune Encephalitis (AE) is an immune-mediated inflammatory disorder of the central nervous system with heterogeneous clinical manifestations and variable outcomes. The prognostic significance of antibody status (seropositive vs. seronegative) remains incompletely understood, particularly in Iranian populations. This study aimed to compare clinical characteristics, therapeutic interventions, and prognostic outcomes between seropositive and seronegative patients with AE (≤ 18 years) admitted to two tertiary referral hospitals in Tehran, Iran. Material & Methods:In this study, medical records of 58 patients diagnosed with AE between 2019 and 2024 at Ali Asghar and Hazrat Rasool Hospitals were reviewed. Patients were classified as seropositive or seronegative based on antibody testing. Results:Of the 58 patients, 31 (53.4%) were seropositive and 27 (46.6%) were seronegative. The mean age was 41.94 ± 24.87 months, and 72.4% were male. Seizures were the most common clinical manifestation. No significant differences were observed between seropositive and seronegative groups in initial disease severity, functional outcomes, neurological complications, treatment allocation (all p > 0.05). In multivariable analysis, initial disease severity (OR = 13.3, p = 0.032) and the presence of underlying diseases (OR = 31.4, p = 0.007) were independently associated with poor prognosis, whereas serologic status was not. Conclusion:Serologic status does not significantly influence disease severity, treatment response, or prognosis in patients with AE. Initial clinical severity and comorbidities are the primary determinants of poor outcome. Management strategies should prioritize early recognition, assessment of disease severity, and timely immunotherapy regardless of antibody status.
Objectives:Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by impairments in communication, social interaction, and executive functions. Individuals with High-Functioning Autism (HFA) often demonstrate average or above-average intelligence and typical language development. However, difficulties in social communication persist. Previous studies have indicated that children with HFA exhibit challenges in language, particularly in grammar and vocabulary, which may be associated with executive dysfunction, including deficits in Working Memory (WM). Therefore, the present study aimed to investigate the relationship between verbal WM and grammatical abilities in Persian-speaking children with HFA. Materials & Methods:Twenty monolingual Persian-speaking children diagnosed with HFA, who met the inclusion criteria, were recruited for the study. Morpho-syntactic abilities were assessed through the collection of speech samples analyzed using Persian Developmental Sentence Scoring (PDSS). Additionally, Phonological Working Memory (PWM) tasks, including direct and reverse recall of numbers and repetition of non-words, were administered. Statistical analyses were performed using SPSS software to examine correlations between PWM and grammatical skills. Results:The highest significant correlation was observed between the PDSS and the repetition of three-syllable non-words, while the lowest correlation was found with the immediate repetition of one-syllable non-words. (r = 0.594, p < 0.05). Furthermore, most PDSS subtests demonstrated statistically significant correlations with PWM tasks, with correlation coefficients varying from weak to strong. Conclusion:This study concluded that HFA children experience difficulties in their grammatical skills, and a significant relationship is observed between their PWM and grammatical abilities, underscoring the importance of considering PWM in language intervention strategies, particularly targeting grammatical development in these children.
Objectives:Childhood migraine is a prevalent neurovascular disease in children with a considerable reduction in quality of life and high social cost. Anticonvulsants, such as Valproate and calcium channel blockers, including Cinnarizine are used frequently as preventive medications. This research evaluates the cost-effectiveness and cost-utility of Cinnarizine versus Valproate in managing childhood migraine, based on an Iranian societal perspective. Materials & Methods:A randomized cohort trial was conducted, involving 150 children aged 5 to 17 years at the Imam Reza Clinic in Shiraz, Iran. Patients were administered Cinnarizine (1-2 mg/kg/day) or Valproate (10-20 mg/kg/day) for three months, evaluated by decision-tree models for cost-utility and cost-effectiveness. Effectiveness was measured by reduction in migraine attack frequency and Quality-Adjusted Life Years (QALYs). Costs were obtained from patient medical records, questionnaires, and national datasets, including direct and indirect costs. Sensitivity analysis, such as Monte Carlo simulations, was performed to validate the results. Results:Patients receiving Cinnarizine experienced a mean QALYs of 0.213 versus 0.209 for the Valproate group and a higher rate of response at 26% (Cinnarizine) versus 14% (Valproate). Total costs during the study period favored Cinnarizine ($183 vs. $191) with an Incremental Cost Effectiveness Ratio of $-156 per additional effect and an Incremental Cost Utility Ratio of $-2069 per QALYs. Adverse effects noted were drowsiness (17.8%) for the Cinnarizine and dizziness (13.5%) for the Valproate arm. Probabilistic sensitivity analysis contained an 88.2% probability that Cinnarizine was cost-effective with a willingness-to-pay of $17,922 per QALYs. Conclusion:Cinnarizine was a cheaper option compared to Valproate as a prophylactic agent in pediatric migraine in Iran with higher response rates, lower expenses, and similar effectiveness. Further research with long-term follow-ups and varied populations is needed to validate the results.
Objectives:Evaluating risk factors is essential in the context of hyperbilirubinemia and its clinical outcomes, particularly when attributed to its primary causes: maternal-fetal ABO and Rh incompatibility. This study aims to determine the prevalence rate of predisposing factors and complications of hyperbilirubinemia in newborns with ABO blood group incompatibility, compared to those with Rh incompatibility. Materials & Methods:This is a descriptive-analytical study. The newborns with jaundice who were referred to Ghaem Teaching Hospital affiliated to the Mashhad University of Medical Sciences, Mashhad, Iran, from 2017 to 2019, divided into two groups of ABO incompatibility (n = 83) and Rh incompatibility (n = 81). The neurodevelopmental assessment was performed by Denver Developmental Screening Test II (DDST-II). Following that, a comparison was made between these two groups. Results:The mean age of the ABO incompatibility group was 5.84 days and the Rh incompatibility group was 4.91 days at admission time. The mean values of bilirubin level obtained at 28.26 ± 5.9 and 30.17 ± 8.19 in newborns with ABO and Rh incompatibility (P = 0.089). No significant difference was observed between the two groups regarding age, Apgar score, bilirubin level (P > 0.05), delivery type (χ2 = 1.56; P = 0.21), and gender (χ2 = 0.403; P = 0.52). Among the study population, 45.8% and 89.1% of the infants with Rh incompatibility and with ABO incompatibility had a near-normal neurological development in the first three years of life. A significant difference was found between the two groups regarding developmental status (χ2 = 25.13; P < 0.05). Conclusion:Despite similar bilirubin levels and treatment approaches, neonates with Rh incompatibility experienced significantly higher rates of developmental delay compared to those with ABO incompatibility. By age three, moderate to severe delays were more frequent in the Rh group, underscoring the greater neurodevelopmental risk associated with Rh-mediated hemolysis.
Landau-Kleffner syndrome and related epilepsy-aphasia spectrum disorders are characterized by childhood-onset language regression, sleep-activated epileptiform activity, and frequently refractory seizures. This case report describe a boy with normal early development who developed progressive aphasia and non-motor seizures around age three, with electroencephalographic findings consistent with spike-wave activation during slow sleep, while neuroimaging and metabolic evaluations were normal. Standard antiseizure medications and repeated immunotherapy provided no sustained benefit. Genetic testing at age 12 identified a pathogenic heterozygous GRIN2A gain-of-function missense variant (p.T531M), guiding initiation of targeted therapy with memantine, and an NMDA receptor antagonist. Following memantine treatment, the patient showed marked improvement in speech and social interaction together with reduced sleep-related epileptiform discharges, although some deficits persisted. This case underscores the value of early genetic evaluation in refractory epilepsy-aphasia syndromes and supports the potential role of precision NMDA-modulating therapy in GRIN2A-associated epileptic encephalopathy.
Neurenteric cysts (NCs), also known as endodermal cysts, are rare congenital lesions of endodermal origin. They were thought to originate from a failure of dissolution of the neurenteric canal between the notochord and endoderm during the third week of embryogenesis. The primary clinical symptoms differ from focal pain to paresthesia and weakness based on the cyst's location. This study presents a case of intradural extramedullary NC of the spine at the cervical level. A 10-year-old boy was referred to the hospital, with neck pain and weakness in his left hand. Imaging studies revealed fusion of cervical vertebrae at the levels of C3-C4 and C5-C6. On MRI, a cystic lesion in the intradural extramedullary region compressing the cord was evident. As the preferred treatment option, surgical total resection was completed through the posterior approach, and the definitive diagnosis was made based on the histochemical analysis. NC is a rare lesion and should be kept in mind as a differential diagnosis. Surgical intervention, particularly total resection, frequently improves the sensory and motor deficits associated with NC and is the treatment of choice.
Objectives:Aminoglycoside‑induced ototoxicity is a well‑recognized adverse effect that commonly presents as sensorineural hearing loss. This study investigated hearing damage by administering two doses of Kanamycin, with or without concurrent noise exposure. Auditory function was assessed using auditory brainstem response and cochlear microphonic potential. Materials & Methods:Guinea pigs were divided into six groups: Control, Noise exposure, Kanamycin 300 mg/kg alone (low dose), Kanamycin 300 mg/kg + Noise, Kanamycin 500 mg/kg alone (high dose), and Kanamycin 500 mg/kg + Noise. Auditory threshold shifts were evaluated using click and pure tones at 4, 6, 8, 12, and 16 kHz. The cochlear microphonic amplitude was measured before and after intervention in the study groups. The latency and amplitude of waves I and III were analyzed in the groups without sensorineural hearing loss. Results:Auditory threshold shifts were significantly greater in the low-dose Kanamycin + noise group compared to both the low-dose Kanamycin alone and the noise-only groups across all stimuli (p < 0.05). In contrast, the high-dose Kanamycin alone and the high-dose Kanamycin + noise groups exhibited similar thresholds. They demonstrated significantly higher thresholds than the noise-only group (p < 0.05). Furthermore, no significant difference in the cochlear microphonic amplitude was found among the study groups. Conclusion:Kanamycin at low doses is not inherently ototoxic; however, when combined with noise exposure, it produces a synergistic effect resulting in severe hearing loss. In this model of auditory damage, cochlear microphonic measurements are less informative than auditory brainstem response testing, providing a more reliable assessment of both peripheral and central auditory pathway function.
Objectives:Autism Sspectrum Disorder (ASD) is a kind of neurodevelopmental disease characterized by difficulties in social interactions, verbal and non-verbal communication, movement limitations, and repetitive movement patterns. The goal of this study is to investigate the effects of a Gluten-Free Diet (GFD) on gastrointestinal (GI) and neurological symptoms in patients diagnosed with autism. Materials & Methods:In this study, 120 patients with autism from Tabriz Children's Hospital and Sheikh Al-Rais Clinic were included. Neurologists and psychologists confirmed the diagnosis of autism using the M-CHAT-R/F questionnaire. Based on the patients' clinical history and Rome 3 criteria, GI symptoms such as diarrhea, constipation, vomiting, and abdominal discomfort were detected. A Gluten Free Diet was advised, and the parents received nutrition education and ongoing autism therapies. The control group consisted of children who received specialized medications for autism while maintaining a regular diet. These children were monitored closely. Results:The average age of the patients was 9.27 ± 3.25 years with a median of nine years. Fifty-two patients (47.3%) were boys, and fifty-eight patients (52.7%) were girls. The severity of ASD, as measured by the M-CHAT-R/F scale, was significantly reduced at the 12th month in the intervention group. Furthermore, significant improvements in speech, cognition, and behavior have been observed in patients in the intervention group after using a GFD. Moreover, GI symptoms, including nausea and vomiting, constipation, abdominal pain, and discomfort, were significantly decreased in the intervention group. However, the GI symptoms in the control group did not show any statistically significant difference compared to the 12th month. Conclusion:According to the results obtained in this study, the administration of GFD in children with ASD can significantly lead to the improvement of GI disorders and neurological symptoms regarding the severity of autism in speech, cognition, and behavior.
Objectives: The most common primary headache disorder in children is migraine. Some children with hyperventilation (HV) may exhibit hyperventilation-induced high-amplitude rhythmic slowing (HIHARS) in their electroencephalogram (EEG). The study aims to evaluate the correlation between HIHARS and a child's future migraine onset risk. Materials & Methods: The present study evaluated HIHARS during the HV maneuver in children aged 7 to 12 admitted to the Electroencephalography Monitoring Unit for diverse referral reasons. After six years, the researchers assessed Long-term video-EEG monitoring data for migraine disease according to the International Classification of Headache Disorders, Third Edition (ICHD-3). The clinical and neurophysiological data were analyzed using appropriate statistical methods. Results: The study revealed that among children with HIHARS, migraine was higher (P=0.049) after six years. Additionally, 15 children (68.18%) with HIHARS had a family history of migraine, compared to 12 children (40%) without HIHARS, which was significant (P=0.044). Interestingly, no significant difference was observed between patients with seizures and those without (P=0.1), suggesting that seizures do not act as a confounding factor in this study. Conclusion: This is the first study on the correlation of HIHARS with migraine in children. Patients aged 7 to 12 years old with HIHARS had more susceptibility to migraine headaches. It is suggested that children with HIHARS and a history of migraine in first-degree family members will be more susceptible to developing migraine in life
Objectives:The aim is to compare the occupational priorities of children with Cerebral Palsy (CP) who have mild to moderate motor impairments with those of their caregivers. Additionally, the goal is to explore the connections between these priorities-considering occupation, occupational performance, and satisfaction with performance-and the children's levels of gross motor function and manual ability. Materials & Methods:This cross-sectional study included 58 children with CP aged 6-12 years (mean ± SD: 9.2 ± 2.2) and their 58 caregivers (mean ± SD: 38.5 ± 7). Assessments were conducted using the Canadian Occupational Performance Measure, the Manual Ability Classification System, and the Gross Motor Function Classification System. Data was analyzed using descriptive statistics, Pearson correlations, Fisher's exact tests, and multiple linear regression. Results:The top three occupational priorities, in order, were personal care and functional mobility for both children and caregivers, with active recreation for children and school/study-related activities for caregivers. Significant associations were found between children's occupational priorities areas and manual ability (V = 0.43, p < 0.001) and gross motor function level's (V = 0.32, p = 0.016), caregivers' occupational priorities areas and manual ability level's (V = 0.49, p < 0.001), and children's satisfaction with both caregivers' satisfaction (r = 0.416, p = 0.031) and performance (r = 0.413, p = 0.032 (score. Conclusion:Although children with CP, presenting mild to moderate motor impairment, and caregivers shared two top occupational priorities, differences in other priority emphasize the need to consider children's perspectives in interventions. Children's motor function influenced occupational priorities selection, and their satisfaction was more affected by caregivers' perceptions than by their own performance, highlighting the need to raise caregivers' awareness during therapy.
Objectives: Biotinidase Deficiency (BTD) is an autosomal recessive metabolic disorder caused by mutations in the BTD gene, leading to impaired Biotin metabolism and resulting in severe neurological impairments, including seizures and developmental delays. Early diagnosis and treatment are crucial for improving patient outcomes. This study aims to investigate the clinical outcomes and neuroimaging findings in pediatric patients diagnosed with BTD, emphasizing the importance of early detection and multidisciplinary management. Materials & Methods: This retrospective review was conducted over seven years, analyzing medical records of five patients diagnosed with BTD based on clinical, radiological, and genetic criteria. Brain MRIs were performed, and genetic analyses confirmed the presence of pathogenic mutations in the BTD gene. Results: All patients exhibited characteristic clinical symptoms of BTD, including seizures and developmental delays. MRI findings revealed bilateral symmetrical increased signal intensity on T2-weighted images and low signal intensity on T1-weighted images in subcortical white matter. Treatment with Biotin resolved seizures in all cases; however, irreversible complications such as sensorineural hearing loss were noted in three patients. Early initiation of Biotin therapy correlated with better clinical outcomes. Conclusion: This study highlights the necessity of a multidisciplinary approach to managing BTD, integrating genetic testing, clinical assessments, and neuroimaging. Early diagnosis through newborn screening is vital for improving long-term outcomes in affected children. Future studies should focus on expanding screening initiatives and investigating long-term treatment effects.
Objectives:Depression is a prevalent comorbidity among individuals with epilepsy, significantly impacting quality of life and healthcare costs. Despite its high occurrence, depression in epilepsy often remains undiagnosed due to clinical time constraints and the lack of efficient screening tools. The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) has demonstrated high sensitivity and specificity for detecting depression in adults with epilepsy. However, its effectiveness in adolescents remains underexplored. This study aimed to evaluate the validity and reliability of the Persian version of the NDDI-E in screening for depression among adolescents with epilepsy and to identify potential risk factors associated with depression in this population. Materials & Methods:A cross-sectional study was conducted on 100 consecutively recruited adolescents (aged 12-18 years; 71 females, 29 males) diagnosed with epilepsy at Zahra Mardani Azari Children's Hospital. Participants completed the Persian NDDI-E, and results were compared to diagnoses obtained via the gold-standard K-SADS-PL interview administered by trained clinicians. Reliability was assessed using Cronbach's alpha, and validity was examined through sensitivity, specificity, and predictive values. Statistical analyses were performed using SPSS 26. Results:The NDDI-E demonstrated high sensitivity (81.48%) and specificity (95.89%) in detecting depression. Depression prevalence was 25% based on NDDI-E and 27% based on K-SADS-PL. Cronbach's alpha indicated good internal consistency (α = 0.82). A significant association was found between juvenile myoclonic epilepsy (JME) and depression, while other seizure types showed no correlation. Conclusion:The Persian NDDI-E proves to be a valid and reliable screening tool for depression in adolescents with epilepsy, facilitating early detection and intervention in busy clinical settings. Routine screening is recommended to improve patient outcomes, though larger multicenter studies are needed to confirm these findings.
Objectives:Children with autism spectrum disorder (ASD) frequently experience sensory processing difficulties that interfere with daily functioning, particularly self-care, yet their specific relationships remain underexplored. Therefore, this study aimed to investigate the relationship between sensory processing patterns and self-care skills in children with ASD aged 3-6 years, examining sensory quadrants, sensory sections, and behavioral domains based on the Sensory Profile-second edition (SP-2). Materials & Methods:A cross-sectional design was employed, involving 93 children with ASD. Sensory processing patterns were assessed using the SP-2, while self-care skills were evaluated with the Pediatric Evaluation of Disability Inventory (PEDI). Researchers conducted multiple linear regression analyses to investigate how sensory processing patterns relate to self-care skills. Results:The analysis revealed prevalent sensory processing difficulties in sensory sensitivity (M = 42.2, SD = 13.1), low registration (M = 46.0, SD = 14.4), touch (M = 23.0, SD = 9.2), movement (M = 18.1, SD = 7.4), and body position (M = 16.0, SD = 8.0). Regression analyses showed that overall sensory processing patterns significantly predicted self-care skills (R² = 0.151, p = 0.030). Among specific sensory patterns, the movement domain approached significance (β = -0.289, p = 0.063), suggesting its potential importance in predicting self-care abilities. Conclusion:Sensory processing difficulties may predict self-care skills in young children with ASD. Motor-related sensory challenges seem particularly significant, but it is crucial to approach these findings carefully due to the study's cross-sectional design and dependence on parents' reports. Future research should include longitudinal studies with objective measurements to provide more definitive insights.
Objectives:Approximately 3% of newborns worldwide are affected by Congenital Anomalies (CAs) with or without Intellectual Disability (ID)/Developmental Delay (DD), often caused by genetic factors such as single-gene disorders or chromosome aberrations. Whole Exome Sequencing (WES) has become a highly effective first-tier test for identifying these genetic factors, detecting both Copy Number Variations (CNVs) and Single Nucleotide Polymorphisms (SNPs)/Insertion/Deletion Polymorphisms (INDELs), while conventional cytogenetic analysis can provide additional valuable information to confirm results where applicable. Materials & Methods:The proband DNA was extracted and subjected to WES. Genetic variants were analyzed using the Genome Analysis Toolkit (GATK) following the American College of Medical Genetics and Genomics (ACMG) guidelines. Additionally, karyotyping of the child and her parents was conducted with high-resolution CTG banding after harvesting conventional cell cultures and performing Giemsa banding on metaphase spreads of cultured leukocytes. Results:This study describes a patient with microcephaly, mild intellectual disability, and specific facial features, where initial WES did not identify any causative SNPs/INDELs. However, subsequent WES-based analysis for CNVs revealed the presence of dup (9) (q21.11q22.32). Further chromosomal analysis uncovered unique karyotypes for the patient [46, XX, t (5; 9) (p15.1; q22.1), add (14) (p11.1)] and her father [46, XY, t (5;9)(p15.1;q22.1)], and a normal karyotype for the mother. Conclusion:The present study confirms the effectiveness of utilizing WES-based analysis of CNVs and SNPs/INDELs as the primary diagnostic test for identifying patients with CAs/ID/DD.
Objectives:Understanding normative biometric data of the posterior fossa is imperative to elucidate pathological alterations. Consequently, a reference for normative biometric data on posterior fossa structures in pediatric populations is essential for diagnosing cerebellar hypoplasia and other associated anomalies. However, a comprehensive set of objective, age-stratified biometric ratios for key posterior fossa structures is lacking, limiting diagnostic precision. To the best of our knowledge, only one study has evaluated the biometric data of the posterior fossa components in children. Materials & Methods:The current study is a cross-sectional study conducted among children hospitalized at Imam Hossein Children's Hospital in Isfahan, Iran, in 2022-2023. All magnetic resonance imaging (MRI) examinations, including midline sagittal sections, performed in children ≤ 15 years of age, were included. Patients with a clinical history of posterior fossa involvement or MRI abnormalities were excluded from this study. Two-dimensional (2D) parameters, including the height of the vermian (H-V), anterior-posterior diameter of the vermis (APD-V), anterior-posterior diameter of the midbrain-pons junction (APD-MP), and anterior-posterior diameter of the midpons, were all measured. Four biometric ratios were calculated to normalize posterior fossa morphology across age groups, accounting for individual size variability and providing objective criteria. Results:Four hundred twenty patients, with a mean age of 5.79 ± 4.02 years, were investigated, of whome 222 (52.9%) were boys. All parameters, except APD-V, were significantly higher in boys than in girls. Although boys had a higher mean APD-V than girls, this difference was not statistically significant. In addition, all studied parameters had the fastest growth rates in the first year and continued to grow more slowly until the end of the 15th year. Key findings reveal a mean APD-P/APD-V ratio of 0.77 ± 0.09. The ratio was generally higher in older children, indicating that pontine growth outpaces vermian expansion during development-values near or above 1.00 may suggest pontocerebellar hypoplasia. The H-V/APD-V ratio (mean 1.72 ± 0.18) shows a dip in early childhood, particularly at 1-3 years, suggestingtransient vermian flattening. The H-V/APD-P ratio declines from ~2.30 in infancy to ~2.11 in adolescence, reflecting posterior fossa maturation. Meanwhile, the APD-P/APD-MP ratio remains consistently around 1.91-1.95, aligning with the expected 2:1 anatomical norm, and serving as a reliable reference across age and sex groups. Conclusion:The present study showed that all posterior fossa parameters, except APD-V, were significantly higher in boys. This study establishes normative reference values for key posterior fossa ratios. The APD-P/APD-V ratio (mean 0.77 ± 0.09) increases with age, while the H-V/APD-P ratio declines from ~2.30 to ~2.11. The APD-P/APD-MP ratio remains stable at ~1.91, consistent with the 2:1 anatomical norm. These objective criteria provide quantifiable thresholds for detecting anomalies like pontocerebellar hypoplasia.
