Annals of the Child Neurology Society最新文献

This 5-year-old girl presented with approximately 1 year of recurrent episodes of staring with rhythmic eye movements and upper extremity twitching. Development and cognition were normal. Electroencephalogram (EEG) captured typical events of behavioral arrest with staring associated with rhythmic upper body myoclonic jerks time-locked to generalized spike-wave discharges (Video 1/Figure 1). Photic stimulation induced events. Magnetic resonance imaging was normal. An epilepsy gene panel revealed a variant of unknown significance in ADAR/TREX1. Initial treatment with valproic acid (VPA) was unsuccessful, but adding clobazam resolved her seizures. Attempted simplification to monotherapy clobazam was unsuccessful, but she remained seizure-free when combination VPA and clobazam therapy was reintroduced.

Epilepsy with myoclonic absences (EMA) is an epilepsy syndrome characterized by absence seizures accompanied by myoclonic jerks and tonic abduction in the arms often appearing as a ratcheting movement [1]. The condition typically begins in early childhood and can persist into adulthood [2]. Cognitive and developmental impairments may arise from the interplay between the underlying epileptic condition and the effects of frequent seizures [3]. VPA is generally the first-line treatment, often combined with other antiepileptic drugs such as ethosuximide, benzodiazepines, or levetiracetam [1, 4]. However, age, metabolic conditions, and sex may impact first-line medication choice. Zonisamide, levetricetam, clobazam, and several others can be considered as second line or if VPA is not recommended [1, 2]. Primary sodium channel blockers, such as carbamazepine, oxcarbazepine, and phenytoin, should be avoided to prevent exacerbating seizures [5]. Early diagnosis and treatment is crucial for better outcomes, as delayed therapy and the presence of generalized tonic-clonic seizures may indicate a poorer prognosis [2]. Proper medication management of EMA requires consideration of potential side effects and comorbidities.

Samuel Kamoroff: conceptualization, writing – original draft, writing – review and editing, data curation. Harry Abram: writing – review and editing, supervision. Fernando Galan: writing – review and editing, visualization, supervision.

Parental consent was obtained due to the patient being a minor with identifiable physical features included in the video.

The authors declare no conflicts of interest.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder caused by variants of the TSC1 (tuberous sclerosis complex 1) or TSC2 (tuberous sclerosis complex 2) tumor suppressor genes, which regulate cellular proliferation through the mTOR (mammalian target of rapamycin) pathway [1, 2]. TSC has complete genetic penetrance but variable expressivity between patients, which leads to a broad phenotype [1, 3]. Diagnosis is based on major and minor clinical criteria, but identification of a pathogenic genetic variant can be sufficient for early diagnosis in the absence of clinical features [4, 5]. Pathogenic variants are those that prevent protein synthesis or lead to loss of protein function; these are commonly nonsense or frameshift mutations or large deletions [5]. Pathogenic variants have been identified in all other TSC2 exons in the literature; however, variants in exons 25 and 31 have not been associated with loss of protein function or severe symptoms of disease. It has been hypothesized that this occurrence is due to alternative splicing mechanisms in these exons [2].

This 2-month-old boy completed genetic testing shortly after birth due to a family history of TSC. A paternal aunt with hypomelanotic macules was previously diagnosed with TSC, and additional family members had cutaneous features of the disease. Genetic testing of our patient showed a heterozygous frameshift variant in exon 31 of TSC2 (NM_000548.5) c.3786dupA p.Pro1263ThrfsTer59, classified as a likely pathogenic variant (based on the understanding that a frameshift variant is predicted to lead to loss of protein function) although no patients with this variant leading to clinical disease have been documented. Frameshift variants disrupt the reading frame, changing the downstream amino acid codons and resulting in a truncated protein or a protein that is subject to nonsense-mediated decay.

Our patient's paternal aunt had molecular confirmation of the same variant, and the father was considered an obligate carrier with a milder phenotype of the disease. However, parental testing was not completed due to a loss of follow-up. Within the next few months, this patient developed infantile spasms, which were treated with vigabatrin and adrenocorticotropic hormone. Magnetic resonance imaging of the brain at 5 months of age revealed left-sided subependymal nodules, without other abnormalities (Figures 1 and 2). Additional screening (echocardiogram, renal ultrasound, and ophthalmologic evaluation) was completed, and there were no signs of systemic involvement.

The diagnosis of TSC can be challenging during early life due to broad phenotypic variability. Genetic testing can be useful as a screening tool in patients at risk for disease. Our patient, who was diagnosed with TSC by genetic testing, was initially asymptomatic and later developed severe manifesta

This 19-month-old boy with tetralogy of Fallot, repaired at age 6 months, and mild gross motor and language developmental delays presented with new-onset generalized tonic-clonic seizures. Following a brief postictal state, he returned to baseline. Neurological examination was unremarkable. Initial imaging showed diffuse, confluent T2 white matter hyperintensity with associated diffusion restriction and T1 hypointensity. Follow-up imaging at 25 months (Figure 1) revealed progression involving the central corpus callosum. Differential diagnosis for leukodystrophy with diffuse white matter involvement is broad and includes vanishing white matter disease, metachromatic leukodystrophy, and certain mitochondrial disorders. A leukodystrophy gene panel demonstrated homozygous pathogenic sequence variants in EIF2B3, establishing a diagnosis of vanishing white matter disease 3 (VWM3).

VWM is an inherited leukodystrophy that most commonly presents in early childhood with motor deficits following a provoking event (e.g., febrile illness) [1]. VWM3 is caused by biallelic pathogenic variants in the EIF2B3 gene, which encodes a subunit of the enzyme eukaryotic initiation factor 2B (eIF2B). Pathogenic variants in any of the subunit genes lead to reduction in eIF2B activity, causing aberrant activation of the cellular response to physiologic stressors and downstream white matter pathology [2]. Unprovoked seizures and lack of motor manifestations are not typical initial presenting features in this age group [3]. Three-years after his VWM diagnosis, he was also diagnosed with autism.

Olivia Viscuso: conceptualization, writing – original draft, writing – review and editing, resources. Bhairav Patel: conceptualization, writing – review and editing; visualization. James B. Gibson: writing – review and editing. Louisa G. Keith: resources, supervision, writing – review and editing, writing – original draft, conceptualization.

Written consent for publication of clinical details and images was obtained from the patient's legal guardian.

The authors declare no conflicts of interest.