Global Developmental Delay Research Articles

Relationship between fundamental motor skills and physical fitness in children with global developmental delay.

Understanding the significance of motor skills in promoting physical fitness (PF) can offer valuable insights for devising comprehensive intervention and clinical rehabilitation programs for children with global developmental delay (GDD). However, it remains unclear whether fundamental motor skills (FMS) can improve the PF of children with GDD. To investigate the correlation between FMS and PF in children with GDD. A total of 180 children with GDD and 180 typically developing (TD) children aged 3-5 years were selected. All participants completed the Gesell Developmental Schedule, FMS, and PF tests at Beijing Children's Hospital between September 2022 and August 2023. Partial correlation and regression analyses were performed to examine the relationship between FMS and PF. Children with GDD had significantly lower FMS and PF scores compared to TD children (P < 0.05). No significant differences were found between males and females with GDD in FMS and PF score (P > 0.05). A more severe developmental delay was associated with lower FMS and PF scores. The correlation coefficients between individual FMS items and individual PF items, as well as the total PF score, ranged from 0.20 to 0.56. Regression analysis indicated that manual dexterity (β = 0.241, P = 0.029) and body balance (β = 0.399, P = 0.001) significantly predicted the total PF score. In children with GDD, both FMS and PF are underdeveloped. Focusing on motor skills development is vital for promoting their PF.

Biallelic EPB41L3 variants underlie a developmental disorder with seizures and myelination defects.

Erythrocyte Membrane Protein Band 4.1 Like 3 (EPB41L3: NM_012307.5), also known as DAL-1, encodes the ubiquitously expressed, neuronally enriched 4.1B protein, part of the 4.1 superfamily of membrane-cytoskeleton adaptors. 4.1B plays key roles in cell spreading, migration, and cytoskeletal scaffolding that support oligodendrocyte axon adhesions essential for proper myelination. We herein describe six individuals from five unrelated families with global developmental delay, intellectual disability, seizures, hypotonia, neuroregression, and delayed myelination. Exome sequencing identified biallelic variants in EPB41L3 in all affected individuals: two nonsense (c.466C>T, p.(R156*); c.2776C>T, p.(R926*)) and three frameshift (c.666delT, p.(F222Lfs*46); c.2289dupC, p.(V764Rfs*19); c.948_949delTG, p.(A317Kfs*33)). Quantitative-real time PCR and Western blot analysis in human fibroblasts harbouring EPB41L3:c.666delT, p.(F222Lfs*46) indicate ablation of EPB41L3 mRNA and 4.1B protein expression. Inhibition of the nonsense mediated decay (NMD) pathway led to an upregulation of EPB41L3:c.666delT transcripts, supporting NMD as a pathogenic mechanism. Epb41l3-deficient mouse oligodendroglia cells showed significant reduction in mRNA expression of key myelin genes, reduced branching, and increased apoptosis. Our report provides the first clinical description of an autosomal recessive disorder associated with variants in EPB41L3, which we refer to as EPB41L3-associated developmental disorder (EADD). Moreover, our functional studies substantiate the pathogenicity of EPB41L3 hypothesized loss-of-function variants.

Respiratory and Neurodevelopmental Outcomes at 3 Years of Age of Neonates Diagnosed with Sleep-Disordered Breathing.

Objectives: Understanding the long-term consequences of sleep-disordered breathing (SDB) in neonates is crucial. A lack of consensus on diagnostic and treatment thresholds has resulted in limited research in this area. Our study aims to describe the trajectory of SDB in a cohort of high-risk neonates and their respiratory and neurodevelopmental outcomes at 3 years of age, and explore the relationship between SDB during early infancy and neurocognitive outcomes. Methods: A retrospectively identified cohort of neonates with moderate-severe SDB were prospectively followed at 3 years of age. Data collected included last polysomnography (PSG) parameters up to the age of 3 years and sleep physician's recommendations, duration of CPAP use, compliance with treatment, timing of SDB resolution, and neurodevelopmental outcomes. Univariate and multivariate logistic regression analyses were performed to evaluate the association between important respiratory and sleep breathing parameters with the developmental outcomes. Results: Eighty neonates were included. Respiratory and developmental outcomes were available for 58 (72.5%) and 56 (70%) patients, respectively. In most patients (47/58, 81%), SDB had resolved by 3 years of age. Survival without major developmental delay was seen in 32/56 (57%), but a significant proportion (21/56, 37.5%) demonstrated global developmental delay. Following univariate analysis, primary diagnosis, apnoea-hypopnoea index (AHI) at the time of last PSG and SDB outcome was significantly associated with developmental delay. However, these associations were not seen in multivariate analysis. Conclusions: Despite severity at baseline, SDB resolved in the majority of patients with time and treatment. Although statistically insignificant, logistic regression analysis identified some clinically important associations between neonatal SDB and neurodevelopmental outcomes.

Neuronal Migration Disorders in Children; A Case Series highlighting importance of Neuroimaging in diagnosing Epilepsy

Background: Neuronal migration disorders comprise a heterogeneous group of neurological conditions caused by abnormal neuronal positioning during brain development. We aimed to study the clinical profile, neuroimaging features, genetics, and treatment of neuronal migration disorders. Methods: This was a retrospective case series of 15 pediatric patients diagnosed with neuronal migration disorders at a tertiary care hospital over a 5 year period. Detailed clinical evaluation, neuroimaging, EEG, and genetic analysis were performed. Results: Global developmental delay and epilepsy were the most common presenting features. Neuroimaging revealed spectrum of cortical dysgenesis including pachygyria, polymicrogyria, lissencephaly, heterotopia, and schizencephaly, predominantly involving fronto-parietal regions. MRI coupled with clinical findings enabled definitive diagnosis. Genetic analysis identified mutations in PAFAH1B1, ADGRG1, DHDDS, TMTC3, and other genes. Anti-seizure medications like valproate, levetiracetam, and clobazam were the mainstay of therapy. Non-pharmacological interventions including physiotherapy, occupational therapy, and speech therapy were employed. Conclusion: This study demonstrates the diverse clinical, genetic, and radiological spectrum of neuronal migration disorders. Comprehensive evaluation along with neuroimaging and genetic analysis enables accurate diagnosis and guides management. A multimodal approach is required focusing on seizures, neurodevelopmental disabilities, and improving quality of life.

X-Linked Bilateral Polymicrogyria With Epilepsy andIntellectual Disability Associated With a Novel KIF4A Variant.

We studied three brothers and a maternal half-brother featuring global developmental delay, mild to moderate intellectual disability, epilepsy, microcephaly, and strabismus. All had bilateral perisylvian and perirolandic polymicrogyria, while some also had malformations of the hippocampus (malrotation and dysplasia), cerebellum (heterotopias and asymmetric aplasia), corpus callosum dysgenesis, and brainstem asymmetric dysplasia. Exome sequencing showed that all four patients had a novel variant (c.1597C>T:p.Leu533Phe) on the KIF4A gene on chromosome X. We discuss how this variant is possibly pathogenic and could explain the reported phenotype.

Genetic analysis of a child with Dias-Logan syndrome due to variant of BCL11A gene

To analyze the clinical and genetic characteristics of a child featuring Dias-Logan syndrome. A child with speech disorders and delayed psychomotor development from childhood who was admitted to the Rehabilitation Medicine Department of Children's Hospital Affiliated to Zhengzhou University in July 2022 was selected as the research subject. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Potential variant was screened by whole exome sequencing, and candidate variant was verified by Sanger sequencing. The child has presented with global developmental delay, microcephaly, special facial features and behavioral problems. Genetic testing revealed a de novo variant of the BCL11A gene, namely c.561_567delACACGCA (p.Q187fs*7), which was classified as pathogenic (PVS1+PS2+PM2_Supporting). The heterozygous variant of BCL11A gene probably underlay the Dias-Logan syndrome in this child. Above finding has enriched the phenotypic and mutational spectrum of the BCL11A gene and provides a basis for genetic counseling and clinical decision-making.

Chromosome 16p11.2 microdeletion syndrome with microcephaly and Dandy-Walker malformation spectrum: expanding the known phenotype

BackgroundChromosome 16p11.2 deletions and duplications were found to be the second most common copy number variation (CNV) reported in cases with clinical presentation suggestive of chromosomal syndromes. Chromosome 16p11.2 deletion syndrome shows remarkable phenotypic heterogeneity with a wide variability of presentation extending from normal development and cognition to severe phenotypes. The clinical spectrum ranges from neurocognitive and global developmental delay (GDD), intellectual disability, and language defects (dysarthria /apraxia) to neuropsychiatric and autism spectrum disorders. Other presentations include dysmorphic features, congenital malformations, insulin resistance, and a tendency for obesity. Our study aims to narrow the gap of knowledge in Saudi Arabia and the Middle Eastern and Northern African (MENA) region about genetic disorders, particularly CNV-associated disorders. Despite their rarity, genetic studies in the MENA region revealed high potential with remarkable genetic and phenotypic novelty.ResultsWe identified a heterozygous de novo recurrent proximal chromosome 16p11.2 microdeletion by microarray (arr[GRCh38]16p11.2(29555974_30166595)x1) [(arr[GRCh37]16p11.2(29567295_30177916)x1)] and confirmed by whole exome sequencing (arr[GRCh37]16p11.2(29635211_30199850)x1). We report a Saudi girl with severe motor and cognitive disability, myoclonic epilepsy, deafness, and visual impairment carrying the above-described deletion. Our study broadens the known phenotypic spectrum associated with recurrent proximal 16p11.2 microdeletion syndrome to include developmental dysplasia of the hip, optic atrophy, and a flat retina. Notably, the patient exhibited a rare combination of microcephaly, features consistent with the Dandy-Walker spectrum, and a thin corpus callosum (TCC), which are extremely infrequent presentations in patients with the 16p11.2 microdeletion. Additionally, the patient displayed areas of skin and hair hypopigmentation, attributed to a homozygous hypomorphic allele in the TYR gene.ConclusionThis report expands on the clinical phenotype associated with proximal 16p11.2 microdeletion syndrome, highlighting the potential of genetic research in Saudi Arabia and the MENA region. It underscores the importance of similar future studies.

Rubinstein-Taybi Syndrome Clinical Characteristics from the Perspective of Quality of Life and the Impact of the Disease on Family Functioning.

Background/Objectives: Rubinstein-Taybi Syndrome (RSTS-OMIM, #180849) is a rare genetic disorder associated with distinctive clinical features, including a typical craniofacial appearance, global developmental delay, intellectual disability and broad, angular thumbs and fingers. The main aim of the study was to evaluate the health problems of children with RTST, their quality of life and the impact of the disease on family functioning. In addition, we investigate whether comorbidities, autistic behavior and eating problems affect the children's overall QOL. Methods: A cross-sectional study was performed, including a total of 13 caregivers of children diagnosed with RSTS. A self-reported questionnaire [SRQ], medical records and the Pediatric Impact Module PedsQLTM 2.0, the Pediatric Quality of Life PedsQLTM 4.0 were used to obtain data on QOL and the impact of the disease on family functioning. Results: The overall QOL score for children with RSTS was x = 52.40; SD 13.01. The highest QOL was in emotional functioning (EF; x = 59.23; SD 18.69), while the lowest QOL was in physical functioning (PF; x = 48.56; SD 16.32) and social functioning (SF; x = 48.85; SD 18.84). There was a statistically significant negative correlation (p < 0.03; r = -2.01) between the age of the child and their QOL, indicating that older children had lower QOL scores. The mean overall rating for the impact of RSTS on family functioning was x = 50.00; SD 10.91. Caregivers reported the highest scores for cognitive functioning (CF; x = 64.23; SD 23.70) and family relationships (FR; x = 60.00; SD 17.17). The lowest scores were for daily activities (DA; x = 41.03; SD 17.17) and worry (W; x = 37.69; SD 18.55). Conclusions: This study provides the first comprehensive exploration of the QOL of children with RSTS) and its impact on family functioning.

Child and Family Predictors for Mastery Motivation in Children With Developmental Delays.

Motivation is a key factor for child development, but very few studies have examined child and family predictors of both child task and perceived motivation. Thus, the three aims of this 6-month longitudinal study in preschoolers with global developmental delays (GDD) were to explore: 1) differences between task and perceived motivation in cognitive domain; 2) differences among three domains of perceived motivation: cognitive, gross motor, and social; and 3) early child and family predictors of cognitive task motivation and the three domains of perceived motivation 6 months later. Results indicated that preschoolers with GDD showed higher cognitive task motivation than cognitive perceived motivation, and lower perceived cognitive motivation than the other two perceived motivation domains. Different child and family factors predicted cognitive task motivation and the three domains of perceived motivation. Practitioners should educate caregivers on how to observe children's motivation to enhance children's active participation.

Pediatric onset neuronal ceroid lipofuscinoses: Unraveling clinical and genetic specifications.

To unravel the clinical and genetic specifications of Neuronal ceroid lipofuscinosis (NCL). This is a retrospective cross-sectional study conducted in the Department of Pediatric Neurology Children Hospital and University of Child Health Sciences, Lahore, Pakistan from March 2017 to March 2022. The primary outcome was to measure genotype-phenotype correlation by segregation of phenotypes according to genotype. The secondary outcomes included a correlation between genotype and distribution of age(s) of onset. One hundred fifty three patients clinically diagnosed with NCL underwent genetic testing and pathologic mutation was identified in 32.7% of patients. About 59.6% were male and 37.2% had an affected sibling. The median age was 5.46±1.95 years at the onset of the first symptom i.e., myoclonic seizures in 68%, and motor difficulty in 24%. Other features found were global developmental delay (56%), hypotonia (23%), visual impairment (80%), ataxia (22%), and disc pallor (56%). The most common type was CLN6 (Ceroid lipofuscinosis neuronal) (42%), CLN2 (16%) followed by CLN7 (12%). When 50 patients with recognized mutations were compared with 103 patients with no mutation, family history (p=0.049), early visual loss (p=0.016), hypotonia (p=0.001), white matter signals (p=0.026) and pan-atrophy(p=0.047) was statistically significant in the genetically confirmed NCL. Multiple pairwise comparisons indicated that the estimated age of onset for the CLN1 and CLN2 mutation group was significantly lower than other genotypes including CLN6 (p 0.012), CLN10 (p 0.007) and CLN12 (p 0.007). Following a detailed review of NCL symptomatology, a clinically-oriented approach should be used for a rapid diagnosis with confirmation by targeted molecular testing for future genetic counseling.

Socioeconomic Factors and Clinical Characteristics Associated with Age at Autism Spectrum Disorder Diagnosis

Objective: Investigate factors influencing autism spectrum disorder (ASD) diagnosis in children under and over 36 months, and determine the average age for ASD diagnosis at Charoenkrung Pracharak Hospital, Bangkok, Thailand, after implementing ASD screening. Materials and Methods: A retrospective cross-sectional study of 252 children with ASD aged 1-15 years from 2014 to 2023, classified into ≤36 months (n=104) and &gt;36 months (n=148) at diagnosis. Demographic, clinical data and child/family factors were analyzed using multivariate regression analysis. Results: Mean age at ASD diagnosis was 44.77 ± 19.91 months. Attending well-baby clinics (aOR 2.64, p=0.038), higher family income ≥ 814 US dollars per month (aOR 2.33, p=0.020), and higher parental education (aOR 3.43, p=0.011) were significantly associated with diagnosis before 36 months. Hyperactivity as the main complaint (aOR 0.07, p=0.001) and global developmental delay/intellectual disability (aOR 0.45, p=0.023) predicted later diagnosis. Child’s gender, being an only child, sibling order, and parental age had no significant impact. Conclusion: Over half of all ASD diagnoses occurred after age 3, with an average age around 44 months. Regular attendance in well-child clinics allowing ASD screening, and higher socioeconomic status and parental education facilitated earlier diagnosis. In contrast, concerns about hyperactivity and global developmental delay often lead to delayed ASD assessment. Enhancing awareness of ASD among families with limited resources can promote timely diagnosis and access to intervention.

Elucidating the clinical and genetic spectrum of inositol polyphosphate phosphatase INPP4A-related neurodevelopmental disorder

PurposeBiallelic INPP4A variants have recently been associated with severe neurodevelopmental disease in single-case reports. Here, we expand and elucidate the clinical-genetic spectrum and provide a pathomechanistic explanation for genotype-phenotype correlations. MethodsClinical and genomic investigations of 30 individuals were undertaken alongside molecular and in silico modelling and translation reinitiation studies. ResultsWe characterize a clinically variable disorder with cardinal features, including global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs, and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures, and cortical visual impairment. Our studies identify the likely pathomechanism of this genotype-phenotype correlation entailing translational reinitiation in exon 4 resulting in an N-terminal truncated INPP4A protein retaining partial functionality, associated with less severe disease. We also identified identical reinitiation site conservation in Inpp4a−/− mouse models displaying similar genotype-phenotype correlation. Additionally, we show fibroblasts from a single affected individual exhibit disrupted endocytic trafficking pathways, indicating the potential biological basis of the condition. ConclusionOur studies comprehensively characterize INPP4A-related neurodevelopmental disorder and suggest genotype-specific clinical assessment guidelines. We propose that the potential mechanistic basis of observed genotype-phenotype correlations entails exon 4 translation reinitiation.

A case of concurrent malnutrition in maple syrup urine disease: challenges and solutions in Indonesia

BackgroundMaple syrup urine disease (MSUD) is a rare autosomal recessive inborn error of metabolism characterised by the impaired breakdown of branched-chain amino acids. Detecting MSUD in newborns is challenging due to the lack of distinctive signs, especially in resource-limited settings like Indonesia.Case presentationA 2-year-old boy presented to the paediatric metabolic clinic with inactivity, a history of uncontrolled epilepsy, global developmental delay and moderate malnutrition. He was born at 40 weeks of gestation, weighing 3100 g, to consanguineous parents. The patient faced feeding problems and was lethargic after birth, with recurrent episodes of generalised seizure and spasticity. Diagnosed with MSUD at four months, the initial response to thiamine supplementation and MSUD Anamix formula was positive. However, weight loss occurred after switching to unregulated family food, as MSUD-specific infant formula became inaccessible and unsustainable due to high costs for the caregivers. Upon compliance with nutritional advice, the child regained weight and progressed appropriately for his age.ConclusionInborn errors of metabolism like MSUD should be considered in atypical disease presentations. In resource-limited settings, management should be tailored to local product availability and accessibility to ensure effective care.

Deletions in the CDKL5 5' untranslated region lead to CDKL5 deficiency disorder.

Pathogenic variants in the cyclin-dependent kinase-like 5 (CDKL5) gene are associated with CDKL5 deficiency disorder (CDD), a severe X-linked developmental and epileptic encephalopathy. Deletions affecting the 5' untranslated region (UTR) of CDKL5, which involve the noncoding exon 1 and/or alternatively spliced first exons (exons 1a-e), are uncommonly reported. We describe genetic and phenotypic characteristics for 15 individuals with CDKL5 partial gene deletions affecting the 5' UTR. All individuals presented characteristic features of CDD, including medically refractory infantile-onset epilepsy, global developmental delay, and visual impairment. We performed RNA sequencing on fibroblast samples from three individuals with small deletions involving exons 1 and/or 1a/1b only. Results demonstrated reduced CDKL5 mRNA expression with no evidence of expression from alternatively spliced first exons. Our study broadens the genotypic spectrum for CDD by adding to existing evidence that deletions affecting the 5' UTR of the CDKL5 gene are associated with the disorder. We propose that smaller 5' UTR deletions may require additional molecular testing approaches such as RNA sequencing to determine pathogenicity.

Autosomal Recessive Spastic Paraplegia Type 51 Caused by Homozygous Mutation of the AP4E1 Gene: A Case Report of a 17-Years-Old Boy

Autosomal recessive spastic paraplegia-51 (SPG51) is a rare neurodevelopmental disorder caused by a homozygous mutation in the AP4E1 gene, located on chromosome 15q21. Spastic paraplegia-51 (SPG51) is an extremely rare autosomal recessive neurodevelopmental disorder characterized by neonatal hypotonia that progresses to hypertonia and spasticity. Mutations in the AP-4E1 gene on chromosome 15q21.2, which is part of the AP-4 complex, can lead to autosomal recessive spastic paraplegia 51 (SPG51). Different mutations in this gene have been identified in affected individuals, leading to disruption of the AP4 complex and vesicular trafficking processes. The specific characteristics of SPG51 are, due to only few cases, not well understood due to limited reports of affected families. Affected individuals also have global developmental delay with impaired intellectual development and poor or absent speech. Studies linked to an additive symptom of persistent stuttering. Affected individuals typically present with hypotonia in the neonatal period, which progresses to muscular hypertonia, especially in the lower limbs. They may also exhibit contractures, talipes equinovarus, decreased muscle mass, short stature, and microcephaly. Severe mental retardation, absent speech, and dysmorphic facial features are common. Some patients may experience seizures. Neurological examination often reveals spastic paraplegia of the lower limbs, and brain imaging may show atrophy of the cerebellar vermis and cortical atrophy. We present an extremely rare case of a 17 years-old boy with autosomal recessive spastic paraplegia type 51.

X-Linked Intellectual Disability, A Novel KDM5C Variation: A Case Report

Introduction: The Lysine Demethylase 5C gene (KDM5C), located at 11p22, is a crucial gene implicated in X-linked intellectual disability (ID), also known as Claes Jensen syndrome. Mutations in the KDM5C gene can negatively impact H3K4me2/3 modifications, leading to a significant reduction in brain-derived neurotrophic factor (BDNF) and sodium voltage-gated channel alpha subunit 2 (SCN2A), which are associated with both autistic spectrum disorder (ASD) and cognitive impairment. Case Presentation: This study presents a novel KDM5C mutation [rs1569278313, Xp.11.22 (GRCh37); c.807delC exon7/25; Pro269fs], a frameshift deletion at the N terminus in exon 7, in a 7-year-old boy with a history of hypothyroidism and left-hand polydactyly. The primary complaints included seizures, short stature, speech difficulties, restlessness, gait problems, and ID. A brain computerized tomography (CT) scan was normal, while magnetic resonance imaging (MRI) revealed bilateral cerebellar hemisphere atrophy. Multifocal epileptic discharges were observed in the electroencephalogram (EEG), and the auditory brainstem response (ABR) was unremarkable. whole exome sequencing (WES) identified a pathogenic frameshift deletion in the KDM5C gene. Conclusions: This case features a frameshift deletion in exon 7 of the KDM5C gene, manifesting as a syndromic face, short stature, and global developmental delay. Additionally, we discuss the rare KDM5C syndromic features in this patient, providing valuable insight into the pathogenicity and clinical implications of this mutation.

Coordination and Referral Platforms for Children Aged 7 and Under with Suspected Neurodevelopmental Outcome: What Data for Research on Care and Developmental Trajectories?

At the core of the child's medical, social, and educational pathway, coordination and referral platforms (CRPs) for neurodevelopmental disorders (NDDs) have been gradually deployed in France since 2018 and support the early detection of NDDs in children. The 112 nationwide CRPs do not benefit from a common electronic health record system. Our aim was to propose an HER model for CRP to enable real-life data reuse, optimize care pathway management and conduct pre-screening for research. CRP data were collected (n=34) into an application enriched by a NLP tool extracting standardized scales for NDDs assessments from medical and paramedical professionals. NLP tool evaluation presented a precision of 86.4% and recall of 90.5%. CRP support was provided to 195 children included between 1 September 2022 and 31 August 2023, aged 4 years, with a sex ratio of 2.8, with delays reported in language (75%) and concerned by global developmental delays (16%). Children's ND phenotype and care pathway description could be automated by a harmonized and structured EHR. While many clinical situations are at an impasse, real-life data-driven evidence is particularly relevant in the context of NDDs, where early intervention plays such a key role in children's development and prognosis. A harmonized and enriched CRP database could benefit both individual and public health levels with pathway monitoring, intervention proposals and research pre-screenings.

"Ultralow-dose" CT Without Sedation in Pediatric Patients With Neuromuscular Scoliosis.

Children with neuromuscular scoliosis undergoing scoliosis surgery face substantial rates of complications. To mitigate surgical risks such as blood loss in pediatric patients with neuromuscular scoliosis, this study focuses on enabling instrumentation planning for their abnormal vertebral and pelvic anatomy and osteopenia. This study assessed the feasibility of an "ultralow-dose" CT (ULD CT) protocol without sedation in pediatric patients with neuromuscular scoliosis who often have comorbid movement disorders. Our prospective quality improvement study aims: (1) to determine if ULD CT without sedation is feasible in this patient group; (2) to quantify the radiation dose from ULD CT and compare it with preoperative spine radiographs (XR); and (3) to assess if ULD CT allows accurate anatomical assessment and intraoperative navigation given the prevalence of movement disorders. Children with neuromuscular scoliosis underwent spine XR and ULD CT scans. Chart reviews assessed disease etiology and comorbidities. Radiation dose was quantified through Monte-Carlo simulations giving dose indices and effective dose, with statistical analysis done using a paired student's t-test (α=0.05). CT image quality was assessed for its use in preoperative planning and intraoperative navigation. Fourteen patients (5 males, 9 females, average age 14±3y) participated. One patient needed sedation due to autism spectrum disorder and global developmental delay. The radiation dose for spine XR was 0.5±0.2mSv, and ULD CT was 0.6±0.1mSv. There was no statistically significant difference in radiation doses between methods. All ULD CT scans had adequate quality for preoperative assessment of pedicle diameter and orientation, obstacles impeding pedicle entry, S2 Alar-Iliac screw orientation, and intraoperative navigation. ULD CT without sedation is feasible for children with neuromuscular scoliosis. Radiation doses were comparable to standard radiographs. ULD CT provided accurate anatomical assessments and supported intraoperative navigation, proving beneficial despite movement disorders in these patients. Level 2-Development of diagnostic criteria on basis of consecutive patients (with universally applied reference widely accepted standard).

An Algorithmic Approach to MR Imaging of Hypomyelinating Leukodystrophies.

Hypomyelinating leukodystrophies (HLDs) are a heterogeneous group of white matter diseases characterized by permanent deficiency of myelin deposition in brain. MRI is instrumental in the diagnosis and recommending genetic analysis, and is especially useful as many patients have a considerable clinical overlap, with the primary presenting complains being global developmental delay with psychomotor regression. Hypomyelination is defined as deficient myelination on two successive MR scans, taken at least 6 months apart, one of which should have been obtained after 1 year of age. Due to subtle differences in MRI features, the need for a systematic imaging approach to diagnose and classify hypomyelinating disorders is reiterated. The presented article provides an explicit review of imaging features of a myriad of primary and secondary HLDs, using state of the art genetically proven MR cases. A systematic pattern-based approach using MR features and specific clinical clues is illustrated for a quick yet optimal diagnosis of common as well as rare hypomyelinating disorders. The major MR features helping to narrow the differential diagnosis include extent of involvement like diffuse or patchy hypomyelination with selective involvement or sparing of certain white matter structures like optic radiations, median lemniscus, posterior limb of internal capsule and periventricular white matter; cerebellar atrophy; brainstem, corpus callosal or basal ganglia involvement; T2 hypointense signal of the thalami; and presence of calcifications. The authors also discuss the genetic and pathophysiologic basis of HLDs and recent methods to quantify myelin in vivo using advanced neuroradiology tools. The proposed algorithmic approach provides an improved understanding of these rare yet important disorders, enhancing diagnostic precision and improving patient outcomes. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 5.

A Child Carrying a Large Deletion in the 10p.15.3-p12.31 Region

Partial deletion of 10p is a rare disorder. Common features of this disorder include intellectual disability, developmental delay, dysmorphic features, hypoparathyroidism, deafness, and renal anomalies, but the phenotypes can vary between patients. We report an infant girl presented with global developmental delay, distinctive facial features with cleft lip, congenital exotropia, laryngomalacia, atrial septal defect, and sensorineural hearing loss. 46, XX, del (10p→ter) was observed on the G-banded analysis. A chromosomal microarray was performed to obtain more detail on the deletion size and gene involvement that might be related to the clinical phenotypes, medical problems, and management. The deletion involved the region of 10p15.3–p12.31, with an approximate size of 19.528739 Mb. The size of deletion could determine the variability in phenotypes, and microarray is necessary to comprehend the deletion size and gene involvement better.