Child neurology open最新文献

Genetic evaluation of a teenager with seizure found no pathogenic variant in a large gene panel, but an incidental likely pathogenic HNF4A variant, deemed to cause MODY1 diabetes. Diabetes history was absent and glycated hemoglobin normal, but serum calcium was severely low, with abnormally high parathyroid hormone. Thus, pseudohypoparathyroidism was suspected and confirmed by molecular genetic testing. Calcium and calcitriol supplementation led to calcium normalization and neurological symptom improvement. Given the absence of personal or family diabetes history, the HNF4A variant was reassessed and found to encode an alternative transcript with poor expression and activity levels, hence downgraded on expert advice from 'likely pathogenic' to 'likely benign'. Besides illustrating the importance of structured medical workup before launching extensive targeted exome sequencing, this case highlights the need for caution in incidental finding interpretation in patients lacking compatible phenotype or family history, and the value of expert advice in such variant interpretation.

Pediatric chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated disorder of the peripheral nervous system with a number of diagnostic pitfalls. A subset of treatment-resistant CIDP adult patients have been found with antibodies against paranodal proteins. We report the first pediatric case in a 14 year-old adolescent with a severe CIDP phenotype in whom positive anti-neurofascin 155 antibodies were found in his serum. Resistant to conventional therapies, he showed dramatic improvement when treated with Rituximab with mild to moderate functional motor disability at 24 month follow-up. In pediatric CIDP patients that remain refractory to conventional treatments, the presence of antibodies to paranodal proteins warrants investigation as it can have potential therapeutic guidance.

Dystrophinopathies cover a spectrum of X-linked muscle disorders including Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and cardiomyopathy due to pathogenic variants in the DMD gene. Neuropsychiatric manifestations occur approximately in one-third of patients with dystrophinopathy. Epilepsy has been described. Here we report seizure and electroencephalographic features of boys with dystrophinopathy and epilepsy. This is a retrospective chart review of eight patients with dystrophinopathy and epilepsy seen at Arkansas Children's Hospital and University of Rochester Medical center. Six patients had DMD and two had BMD. Five patients had generalized epilepsy. Three patients had focal epilepsy and the seizures were intractable in two of them. Brain imaging was available for five patients and were within normal limits. EEG abnormalities were noted in six patients. Seizures were well controlled on the current antiepileptic medication regimen in all patients. Further research is needed to better elucidate the underlying mechanisms and genotype-phenotype correlations.

We report the case of a 3-year-old boy who presented with recurrent stereotyped transient episodes of left sided weakness consistent with capsular warning syndrome (CWS) which eventually progressed to acute ischemic stroke (AIS). He received thrombolytic therapy with tissue plasminogen activator. Workup was notable for positive CSF varicella (VZV) PCR, and positive CSF and serum VZV IgG and negative IgM. On further history, he was unvaccinated and had a rash consistent with VZV 5 months prior to presentation. This case highlights the importance of recognizing CWS given the increased risk of progression to AIS. In addition, it emphasizes the importance of considering VZV vasculopathy in pediatric AIS and inquiring about infectious history and immunization status despite high rates of vaccination in the United States.

Primary carnitine deficiency (PCD) is caused by pathogenic variants of the SLC22A5 gene, which encodes a transmembrane protein that functions as a high affinity carnitine transporter. Carnitine is essential for the transport of acyl-CoA, produced from fatty acids, into the mitochondria where they are oxidised to produce energy. We present the case history of an 8-year-old boy who presented with fever, lethargy, focal rhythmic (3 Hz) left wrist twitching, and severe encephalopathy. MRI brain showed basal ganglia involvement. Metabolic investigations revealed low serum carnitine; whole genome sequencing confirmed compound heterozygous SLC22A5 mutations. With carnitine replacement, intensive care support, and neurorehabilitation, he made a remarkable recovery, regaining independent breathing, speech, mobility, and hand use. Seizure presentation in PCD is rare and presentation with sustained focal myoclonus has not been previously reported. This case expands the known phenotype of PCD. Prompt carnitine replacement is imperative.

SCN2A, a gene that codes for a sodium channel highly expressed in the cerebellum, has been linked to a heterogeneous phenotype, including episodic ataxia (EA) and epilepsy, among other symptoms¹. Given the rarity of SCN2A-associated EA and its recent description, it is important the genotype-phenotype relationship of SCN2A-associated EA be better defined for prognosis and optimizing future management. Thus, we describe a 2-year-old boy with a SCN2A variant causing an initial prolonged episode of profound ataxia lasting 4 months, cerebellar atrophy, and persistent mild ataxia with episodic exacerbations. Due to the patient's lack of early epilepsy, prolonged initial episode of ataxia, and cerebellar atrophy, this case broadens the scope of the SCN2A variant phenotype. SCN2A should be considered as a cause of early onset ataxia in children with targeted testing or as part of Whole Exome Sequencing (WES) in patients with new onset persistent or EA with or without seizures.

Callosal agenesis is a complex condition with disruption in the steps such as cellular proliferation, migration, axonal growth, guidance, or glial patterning at the midline. Agenesis of the corpus callosum (AgCC) is associated with diverse midline craniofacial malformations affecting the frontal-cranial and midface skeleton. Diagnosing midline abnormalities prenatally can be challenging, especially in twin pregnancies, due to poor resolution of skull base structures on fetal MRI, basal cephalocele could be mistaken for fluid in the nasopharynx, motion limitation, and fetal positioning. Our case highlights the importance of evaluation for other associated midline anomalies when there is callosal agenesis.

Objective: This study aimed to describe shunt malfunction symptoms in children ≤5 years old. Results: In a national survey of 228 caregivers, vomiting (23.1%), irritability (20.8%), and sleepiness (17.2%) were the most frequent symptoms of malfunction. These symptoms also occurred in over 1/3 of "false alarms" experienced by 75% of respondents. Compared with malfunctions, irritability (OR = 1.39, 95% CI [1.05, 1.85], p = 0.022) and fever (OR = 2.22, 95% CI [1.44, 3.44], p < 0.001) were more likely false alarms. Caregivers counseled about "most" symptoms were more confident detecting malfunctions than those informed of "some" (p = 0.036). The majority of caregivers (85%) first contacted a neurosurgeon with concerns about malfunction, followed by neurologists (22%) and family/friends (19%). Most (85%) struggled to differentiate malfunction from regular development. Conclusions: Vomiting, irritability, and sleepiness were the most common symptoms of shunt malfunction and false alarms for children ≤5 years. Most caregivers reported challenges differentiating malfunctions from their child's development.

De novo pathogenic variants in EIF2AK2 have recently been reported as a novel genetic cause of leukoencephalopathy. Here, we describe a male individual who presented in the first year of life with clinical features resembling Pelizaeus-Merzbacher disease (PMD), including nystagmus, hypotonia, and global developmental delay, and which later progressed to include ataxia and spasticity. Brain MRI at the age of two revealed diffuse hypomyelination. This report adds to the limited number of individuals published and further reinforces de novo variants in EIF2AK2 as a molecular cause of a leukodystrophy that clinically and radiologically resembles PMD.