Journal of Child Neurology最新文献

The 5-Domain Niemann Pick Type C Clinical Severity Scale (5DNPCCSS) is used in clinical practice and trials. Although psychometric data support the clinical meaningfulness of the concepts and the scale's interrater reliability, more information is needed to support its construct validity. Here, we evaluated the convergent validity of the Cognition, Speech, and Fine Motor domains. Data from 121 individuals with Niemann-Pick disease type C were drawn from several studies conducted at 2 US sites. Direct standardized assessments included the Nine-Hole pegboard or Purdue pegboard, a portion of the Clinical Evaluation of Language Fundamentals, and the age-appropriate Wechsler IQ test or the Mullen Scales of Early Learning. The 5DNPCCSS domains were significantly related in the expected directions to their respective direct assessments, supporting their construct validity. In combination with previous evidence presented for the Ambulation and Swallow domains, these results support the fitness of purpose of the (5DNPCCSS for clinical studies in Niemann-Pick disease type C. ClinicalTrials.gov: NCT00344331, NCT01747135, NCT02534844.

IntroductionDuchenne muscular dystrophy, the most common inherited neuromuscular disease in children, typically presents its first symptoms at 3-5 years of age with progressive muscular weakness. However, in some boys, the disease manifests earlier in childhood with developmental delays, such as delays in walking and speech, or signs of an autism spectrum disorder.ObjectiveTo analyze and compare the age and time until diagnosis in boys with Duchenne muscular dystrophy, with or without developmental delays as the first sign of disease.Material and MethodsThis is a retrospective descriptive study. Data were collected from 127 boys with Duchenne muscular dystrophy who were followed at the Outpatient Muscle Clinic of Hospital das Clínicas (FMUSP/SP) from 2015 to 2024. To determine the age and time interval between symptom onset and diagnosis, we analyzed the total sample, and 3 separate groups based on initial symptoms.ResultsIn the total sample, the mean age of diagnosis was 6.9 years, with an average interval of 3.6 years between symptom onset and diagnosis. In patients with developmental delays, initial symptoms were observed at an average age of 1.4 years, and despite a diagnosis delay of 3.4 years, these patients were diagnosed an average of 2.7 years earlier than those with normal development.ConclusionOur findings suggest that Duchenne muscular dystrophy should be considered in the differential diagnosis of boys presenting with developmental delays (motor, speech, or cognitive). In such cases, screening with creatine kinase level measurements is crucial.

BackgroundThe transition from pediatric to adult headache care creates an opportunity for changes in care, although the nature of these changes has not been previously explored. We aim to describe the changes in management during this transition period.MethodsA retrospective chart review was conducted on 80 patients who transitioned from pediatric neurology to adult headache clinic within the span of 1 year. The demographics, diagnoses, and treatment regimens were analyzed.ResultsOn average, patients held their first adult headache clinic visit 118 days following their last pediatric visit. More than half of patients experienced changes in either diagnosis or treatment during transition.ConclusionThis research emphasizes the significant influence of care transitions on the management of patients with primary headache disorders.

This retrospective observational study investigates the clinical and neuroimaging profiles of children with cerebral palsy and explores the contribution of genetic factors to its etiology. We reviewed 302 pediatric cases diagnosed with cerebral palsy in Southern Brazil during 2023. Neuroimaging abnormalities were present in 92.1% of cases, with leukomalacia being most frequent. Neonatal encephalopathy emerged as the leading etiology, followed by prematurity and genetic conditions. Genetic testing was performed in 68 patients, identifying 29 distinct genes, notably in cases with preserved imaging or kernicterus. Dyskinetic and ataxic cerebral palsy were more often associated with normal neuroimaging, although not necessarily with positive genetic findings. Some patients with kernicterus also had genetic etiology, especially G6PD. The study reinforces that normal imaging does not exclude underlying genetic causes, especially in patients lacking perinatal complications or exhibiting dyskinetic patterns. These findings emphasize the complementary roles of neuroimaging and genetic in the multifactorial nature of cerebral palsy.

Neuronal ceroid lipofuscinoses are rare, inherited lysosomal storage disorders characterized by progressive neurodegeneration due to aberrant lysosomal function. This study presents 2 cases of CLN7 and CLN8, illustrating the genetic and clinical heterogeneity of neuronal ceroid lipofuscinoses. The first case involves a patient with CLN7, manifesting developmental regression, epilepsy, and motor impairment. The second case presents CLN8, marked by progressive cognitive decline, intractable seizures, and motor dysfunction. Whole exome sequencing confirmed pathogenic mutations in both cases, reinforcing the critical role of genetic diagnostics in precise disease classification. These cases emphasize the necessity of early genetic screening for timely intervention and accurate neuronal ceroid lipofuscinosis subtype classification, which is vital for prognosis and personalized management. Multidisciplinary care, including genetic counseling, neurologic assessment, and supportive therapies, is paramount in optimizing patient outcomes. Documenting these cases contributes to a deeper understanding of neuronal ceroid lipofuscinosis phenotypic variability, supporting ongoing research into genotype-phenotype correlations and potential disease-modifying therapies.

Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder caused by mutations in the SMN1 gene, leading to motor neuron degeneration. This report presents a case of a 22-day-old infant with spinal muscular atrophy who was found to have elevated troponin I level in preparation for administration of a gene therapy with known cardiac adverse effects. Although initial echocardiogram revealed a left-ventricular ejection fraction of 57% at 22 days old, subsequent comprehensive cardiac evaluation revealed improving troponin I levels with a normal left-ventricular ejection fraction of 70% at 34 days of life prior to starting gene therapy. Although not common, elevated troponin I level in an otherwise asymptomatic newborn can be seen in spinal muscular atrophy. This case underscores that elevated troponins may be intrinsic to newborns with spinal muscular atrophy even before starting therapies for spinal muscular atrophy. In addition, we illustrate no further cardiac abnormalities after infusion of the aforementioned gene therapy in a child with asymptomatic elevated troponin I after cardiac clearance.

Introduction16p11.2 microdeletion syndrome is a rare genetic condition with wide clinical heterogeneity. Individuals may present a normal phenotype or neurodevelopmental pathology, often associated with nonspecific dysmorphology, epilepsy, cardiac anomalies and obesity, among other characteristics.Clinical CasesCase 1: Male, 11-year-old, with macrocephaly from 4 months, obesity from 2 years, and speech delay; currently diagnosed with intellectual developmental disorder. Case 2: Female, 13-year-old, referred at 4 years due to language delay; at 6 years, early puberty and obesity were identified; currently recognized as having intellectual developmental disorder and attention-deficit hyperactivity disorder (ADHD). Case 3: Male, 5-year-old, referred at 3 years for global developmental delay, mainly in language; family history of intellectual developmental disorder; currently has global developmental delay. Case 4: Male, 6-year-old, referred at 11 months for motor delay; at 18 months, language delay, motor coordination difficulties, and aggressiveness were noted; recently, he was diagnosed with autism spectrum disorder. Case 5: Male, 14-year-old, with macrocephaly and expressive language delay at 2 years; oppositional behavior and ADHD diagnosed, with learning disabilities and overweight. None of the cases have epilepsy or cardiac pathology. All showed 16p11.2 microdeletion in array-CGH studies and received multidisciplinary follow-up.Discussion/Conclusion16p11.2 microdeletion syndrome shows significant clinical variability, with common neurodevelopmental involvement. Genetic testing via array-CGH helps establish the etiologic diagnosis, making it essential for individuals with global developmental delay / intellectual developmental disorder or autism spectrum disorder. Early diagnosis enables timely intervention and genetic counseling.

Agenesis of the corpus callosum (ACC) has a wide spectrum of anatomic manifestations associated with incompletely understood clinical variability. In this retrospective cohort study, 161 children with ACC were classified into complete ACC and partial ACC. Partial and complete ACC diagnoses were confirmed by postnatal magnetic resonance imaging (MRI) and further classified as isolated or complex (associated with other brain abnormalities or genetic diagnoses). Clinical characteristics, clinical outcomes, and co-occurring genetic variations were collected by chart review. Median age at last neurologic evaluation for the complete and partial ACC cohorts were 2.8 years and 2.3 years, respectively; thus, an average of 2-3 years of follow-up data were analyzed per patient. Results showed that children with complete and partial ACC had similar birth characteristics. Children with complete ACC were more frequently diagnosed prenatally; additionally, complete ACC patients had lower rates of cerebral palsy. When comparing complex complete ACC and complex partial ACC to isolated complete ACC and isolated partial ACC, respectively, the complex subcohorts had a higher level of motor delay, assistive device use, cerebral palsy, ventriculoperitoneal shunt placement, epilepsy, language delay, and cognitive delay than the isolated subcohorts. About 50% of children had genetic variants associated with neurodevelopmental disorders in this cohort. Additionally, >50% of our patients with motor and nonmotor developmental delays, as well as >60% of patients that required assistive devices and had cerebral palsy, were also found to have genetic anomalies. Although research describing ACC and its outcomes is expanding, there is still a need for large cohort studies with robust follow-up data to help further understand the disease.

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare neurodegenerative condition that rapidly progresses with language regression, loss of ambulation, blindness, intractable seizures, and premature death in childhood. Enzyme replacement therapy has transformed the clinical trajectory of CLN2 disease, and early genetic testing is crucial because enzyme replacement therapy cannot reverse clinical progression. Lack of clinician awareness of early clinical symptomatology, initially normal language development, and history of provoked or treatment-responsive seizures may contribute to diagnostic and treatments delays. There remain challenges in equitable enzyme replacement therapy access globally and implementation of dual treatment to address retinopathy. There is a need to better understand the phenotype of CLN2 disease in the era of enzyme replacement therapy, including children who receive treatment presymptomatically. Gene therapy is a promising curative treatment, notwithstanding the mixed clinical evidence on efficacy and challenges achieving widespread brain transgene expression. This review explores our current understanding of early clinical presentation of CLN2 disease, epilepsy phenotype, role of genetic testing, novel biomarkers, and precision treatments including enzyme replacement therapy.