Humans ; Epilepsies, Myoclonic/diagnosis* ; NAV1.1 Voltage-Gated Sodium Channel

Objective: To summarize the genetics and clinical phenotypes of epilepsy children with 2q24.3 microdeletion. Methods: All the patients with 2q24.3 microdeletion were retrospectively collected at the Pediatric Department of Peking University First Hospital from March 2017 to July 2022. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed. Results: There were 13 patients with 2q24.3 microdeletion were included. All 13 patients had de novo copy number variation (CNV) with a deletion size ranged 0.18-7.31 Mb. The main pathogenic genes in the region were SCN3A, SCN2A, TTC21B, SCN1A and SCN9A genes. Among the 13 patients, 7 were boys, and 6 were girls. The onset age of epilepsy was 3.3(2.5, 6.0) months. Multiple seizure types were observed, including focal seizures in 13 patients, generalized tonic-clonic seizures (GTCS) in 6 patients, myoclonic seizures in 3 patients, epileptic spasm in 2 patients, and tonic seizures in 2 patients. Seizures were fever sensitivity in 9 patients. Status epilepticus was observed in 6 patients. One case had normal mental motor development and 12 cases had different degrees of developmental delay. Six patients had craniofacial abnormality, 1 had six-finger deformity of the right thumb, and 1 had multiple system abnormalities. EEG showed focal discharge in 3 cases, multifocal discharges in 5 cases, multifocal and generalized discharges in 1 case. Brain magnetic resonance imaging (MRI) showed enlargement of subarachnoid spaces in the frontal and temporal region in 4 patients, enlargement of lateral ventricle in 4 patients and delayed myelination of white matter in 1 patient. Dravet syndrome was diagnosed in 5 cases. The age at the last follow-up were 2.5(1.4,5.5) years, 1 patient was seizure free longer than 1 year, and 12 patients still had seizures. Conclusions: The epilepsy associated with 2q24.3 microdeletion is mainly induced by the deletion of SCN3A, SCN2A and SCN1A genes. The seizure onset age of 2q24.3 microdeletion related epilepsy was in infancy. Multiple seizure types are observed and the common seizure types include focal seizures and GTCS. Most patients have fever sensitivity and status epilepticus. Most patients have developmental delay. The phenotype of patients with deletion of SCN3A and SCN2A gene is more severe than that of patients with deletion of SCN1A gene only.
Humans ; Abnormalities, Multiple ; Chromosomes ; DNA Copy Number Variations ; Epilepsies, Myoclonic ; Epilepsy ; Fever ; NAV1.7 Voltage-Gated Sodium Channel ; Phenotype ; Retrospective Studies ; Seizures ; Status Epilepticus ; Chromosomes, Human, Pair 2

Objective: To summarize the phenotypes of epilepsy in patients with MBD5 gene variants. Methods: A total of 9 epileptic patients, who were treated in the Department of Pediatrics, Peking University First Hospital from July 2016 to September 2021 and detected with MBD5 gene pathogenic variants, were enrolled. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed retrospectively. Results: Among 9 patients, 6 were male and 3 were female. Age at seizure onset ranged from 5 to 89 months. Multiple seizure types were observed, including generalized tonic clonic seizures (GTCS) in 7 patients, myoclonic seizures in 5 patients, focal seizures in 5 patients, atypical absence seizures in 3 patients, atonic seizures in 2 patients, myoclonus absence seizures in 1 patient, epileptic spasms in 1 patient, and tonic seizures in 1 patient. There were 8 patients with multiple seizure types, 2 patients with sensitivity to fever and 5 patients with clustering of seizures. Two patients had a history of status epilepticus. All patients had developmental delay before seizure onset. Nine patients had obvious language delay, and 6 patients had autism-like manifestations. Five patients had slow background activity in EEG. Interictal EEG showed abnormal discharges in 9 patients. Brain magnetic resonance imaging (MRI) was normal in all patients. A total of 9 epileptic patients carried MBD5 gene variants, all of them were de novo variants. There were MBD5 gene overall heterozygous deletion in 1 patient, large fragment deletions including MBD5 gene in 3 patients and single nucleotide variations (c.300C>A/p.C100X, c.1775delA/p.N592Tfs*29, c.1759C>T/p.Q587X, c.150_151del/p.Lys51Asnfs*6, c.113+1G>C) in 5 patients. The age at last follow-up ranged from 2 years and 9 months to 11 years and 11 months. At the last follow-up, 2 patients were seizure-free for more than 11 months to 4 years 6 months, 7 patients still had seizures. Conclusions: The initial seizure onset in patients with MBD5 gene variants usually occurs in infancy. Most patients have multiple seizure types. The seizures may be fever sensitive and clustered. Developmental delays, language impairments, and autistic behaviors are common. MBD5 gene variants include single nucleotide variations and fragment deletions. Epilepsy associated with MBD5 gene variants is usually refractory.
Child ; Child, Preschool ; DNA-Binding Proteins/genetics* ; Electroencephalography ; Epilepsies, Myoclonic/genetics* ; Epilepsy/genetics* ; Female ; Fever ; Humans ; Infant ; Male ; Nucleotides ; Phenotype ; Retrospective Studies ; Seizures/genetics*

OBJECTIVE: To analyze the clinical features and genetic variants in two patients with Dravet syndrome (DS). METHODS: Peripheral blood samples of the children and their parents were collected for the extraction of genomic DNA and high-throughput sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: By high-throughput sequencing, the two children were found to respectively harbor a c.2135delC frameshifting variant in exon 12 and a c.1522G>T nonsense variant in exon 10 of the SCN1A gene. Both variants were predicted to be pathogenic by bioinformatic analysis. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.2135delC and c.1522G>A variants of the SCN1A gene were predicted to be pathogenic (PVS1+ PS2+ PM2+ PP3). CONCLUSION The variants of the SCN1A gene probably underlay the DS in the patients. Above finding has enriched the variant spectrum and enabled genetic counseling for their families.
Epilepsies, Myoclonic/genetics* ; Genomics ; Humans ; Infant ; Mutation ; NAV1.1 Voltage-Gated Sodium Channel/genetics* ; Pedigree ; Spasms, Infantile/genetics*

Adult ; DNA, Mitochondrial ; genetics ; Electroencephalography ; Humans ; MERRF Syndrome ; genetics ; Male ; Mitochondrial Myopathies ; genetics ; Mutation ; RNA, Transfer, Asn ; genetics

The ketogenic diet (KD) has been used as an effective antiepileptic therapy for intractable childhood epilepsy. However, various adverse effects have been reported with use of the KD. We report a case of a child who developed acute tubular necrosis subsequent to therapy with KD. A 5-year-old girl had myoclonic epilepsy with developmental delay. She was under the treatment with antiepileptic drugs since the age of 3 months and on the KD during the past 18 months. Proteinuria persisted intermittently with the initiation of the KD and subsequently increased in the past 2 months. She was admitted with intermittent mild fever, vomiting, and lethargy for the past 3–4 weeks. At the time of admission, she presented with hypertriglyceridemia, heavy proteinuria, renal Fanconi syndrome, and acute kidney injury. Renal sonography showed a marked increase in the size and parenchymal echogenicity of both kidneys. A renal biopsy revealed acute tubular necrosis accompanied by early interstitial fibrosis. After the withdrawal of the KD and supportive therapy, without changing other anticonvulsants and their dosages, improvement of renal function was observed. Proteinuria had disappeared after 1 month and kidney size returned to normal after 8 months. It is hypothesized that the KD can induce and/or aggravate the renal tubulointerstitial injury in some patients who are under the treatment with anticonvulsants.
Acute Kidney Injury ; Anticonvulsants ; Biopsy ; Child ; Child, Preschool ; Drug Resistant Epilepsy ; Epilepsies, Myoclonic ; Epilepsy ; Fanconi Syndrome ; Female ; Fever ; Fibrosis ; Humans ; Hypertriglyceridemia ; Ketogenic Diet ; Kidney ; Lethargy ; Necrosis ; Proteinuria ; Vomiting

Anticonvulsants ; therapeutic use ; Clonazepam ; therapeutic use ; Female ; Humans ; Levetiracetam ; therapeutic use ; MERRF Syndrome ; drug therapy ; Male ; Myoclonus ; drug therapy

No abstract available.
Acidosis, Lactic ; Brain Diseases ; Humans ; Myoclonic Epilepsy, Juvenile ; Wolff-Parkinson-White Syndrome

Patients with dentatorubral-pallidoluysian atrophy occasionally elicit psychosis. So far, one study reported first generation antipsychotics drugs may provide an effective treatment; however, there is no literature on the benefits of second generation antipsychotics. We report on a 44-year-old man with dentatorubral-pallidoluysian atrophy whose psychotic symptoms were effectively treated with olanzapine. Our observation suggests some second generation antipsychotics provide a therapeutic option for ameliorating psychosis in dentatorubral-pallidoluysian atrophy.
Adult ; Antipsychotic Agents ; Humans ; Myoclonic Epilepsies, Progressive* ; Psychotic Disorders* ; Spinocerebellar Degenerations

BackgroundFacioscapulohumeral muscular dystrophy (FSHD) is characterized by asymmetric muscular deficit of facial, shoulder-girdle muscles, and descending to lower limb muscles, but it exists in several extramuscular manifestations or overlapping syndromes. Herein, we report a "complex disease plus" patient with FSHD1, accompanied by peripheral neuropathy and myoclonic epilepsy.

MethodsStandard clinical assessments, particular auxiliary examination, histological analysis, and molecular analysis were performed through the new Comprehensive Clinical Evaluation Form, pulsed-field gel electrophoresis-based Southern blot, Multiplex Ligation-dependent Probe Amplification (MLPA), whole exome sequencing (WES), and targeted methylation sequencing.

ResultsThe patient presented with mild facial weakness, humeral poly-hill sign, scapular winging, peroneal weakness, drop foot, pes cavus, and myoclonic epilepsy. Furthermore, electrophysiology revealed severely demyelinated and axonal injury. The muscle and nerve biopsy revealed broadly fiber Type II grouping atrophy and myelinated nerve fibers that significantly decreased with thin myelinated fibers and onion bulbs changes. Generalized sharp and sharp-slow wave complexes on electroencephalography support the diagnosis toward myoclonic epilepsy. In addition, molecular testing demonstrated a co-segregated 20-kb 4q35-EcoRI fragment and permissive allele A, which corresponded with D4Z4 hypomethylation status in the family. Both the patient's mother and brother only presented the typical FSHD but lacked overlapping syndromes. However, no mutations for hereditary peripheral neuropathy and myoclonic epilepsy were discovered by MLPA and WES.

ConclusionsThe present study described a "tripe trouble" with FSHD, peripheral neuropathy, and myoclonic epilepsy, adding the spectrum of overlapping syndromes and contributing to the credible diagnosis of atypical phenotype. It would provide a direct clue on medical care and genetic counseling.

Adult ; Child ; Epilepsies, Myoclonic ; complications ; Evoked Potentials, Visual ; Humans ; Male ; Muscle, Skeletal ; Muscular Dystrophy, Facioscapulohumeral ; complications ; Peripheral Nervous System Diseases ; complications