The uptake and efflux of solutes across a plasma membrane is controlled by transporters. There are two main superfamilies of transporters, adenosine 5′-triphosphate (ATP) binding cassettes (ABCs) and solute carriers (SLCs). In the brain, SLC transporters are involved in transporting various solutes across the blood-brain barrier, blood-cerebrospinal fluid barrier, astrocytes, neurons, and other brain cell types including oligodendrocytes and microglial cells. SLCs play an important role in maintaining normal brain function. Hence, mutations in the genes that encode SLC transporters can cause a variety of neurological disorders. We identified the following SLC gene variants in 25 patients in our cohort: SLC1A2,
Epilepsia partialis continua (EPC) is a form of focal motor status epilepticus, associated with multiple etiologies. Etiology-specific treatments, such as hemispherotomy for Rasmussen encephalitis, lesionectomy for focal cortical dysplasia, and metabolic correction for non-ketotic hyperglycemia, have proven to be efficacious in treating EPC, but, in general, EPC is difficult to treat and often drug-resistant, and there is little evidence to guide therapy. We report the successful treatment of EPC with perampanel in two pediatric patients. The first patient was a 12-yearold boy with neuronal ceroid lipofuscinosis (NCL) who started to have EPC around the age of 10 years, characterized by left hemifacial myoclonic twitches and hemibody jerks that were almost continuous throughout the day and disappeared during sleep. He had failed several antiepileptic drugs (AEDs). The EPC stopped within three days of initiating perampanel. The second patient was a six-year-old boy with POLG-related mitochondrial disease who presented to the emergency room with continuous jerky movements of the right arm and face after a trivial head injury. After failing several AEDs, including a midazolam drip, the EPC was controlled with perampanel. Both patients showed dramatic improvement and continue to show sustained efficacy after around five months of follow-up. Based on our observations, perampanel, which has a unique mechanism of action, appears to be a promising therapeutic option for treating EPC.
Background:
Constitutional mismatch repair deficiency (CMMRD) is a rare, autosomal recessive disease caused by a biallelic germline mutation in one of the DNA mismatch repair genes (MLH1, MSH2, MSH6 and PMS2). In addition to colorectal, brain, and hematological malignancies, many additional premalignant and non-malignant features that can point toward the diagnosis of CMMRD have been reported. The report from the CMMRD consortium revealed that all children with CMMRD have café-au-lait macules (CALMs) but the number of CALMs does not reach > 5 in all CMMRD patients, which is one of the diagnostic criterions of NF1. About half of the patients with CMMRD develop brain tumors and up to 40% develop metachronous second malignancies.
Methods:
This is an observational retrospective case series describing five pediatric patients with CMMRD.
Results:
All the five patients in our cohort developed brain tumors and showed a predilection to the frontal lobe. In our cohort, multiple Mongolian spots, coloboma, obesity, CHD, dysmorphism, and clubfoot were also encountered. In all our patients, NF1 and other tumorigenic predisposing syndromes were initially suspected.
Conclusion:
Increasing awareness of this condition and its shared reminiscent NF1 features, particularly CALMs among child neurologists, oncologists, geneticists, and dermatologists can help uncover the tip of the iceberg of CMMRD that carries an important consequence on management.
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