SCN1B Genetic Variants: A Review of the Spectrum of Clinical Phenotypes and a Report of Early Myoclonic Encephalopathy
Background: Pathogenic variants in SCN1B, the gene encoding voltage-gated sodium channel b1/b1B subunits are associated with a spectrum of epileptic disorders. This study describes a child with early myoclonic encephalopathy and a compound heterozygous variant in the SCN1B gene (p.Arg85Cys and c.3G&...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Children |
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| Online Access: | https://www.mdpi.com/2227-9067/9/10/1507 |
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| author | Zahra Zhu Elizabeth Bolt Kyra Newmaster Wendy Osei-Bonsu Stacey Cohen Vishnu Anand Cuddapah Siddharth Gupta Sita Paudel Debopam Samanta Louis T. Dang Paul R. Carney Sunil Naik |
| author_facet | Zahra Zhu Elizabeth Bolt Kyra Newmaster Wendy Osei-Bonsu Stacey Cohen Vishnu Anand Cuddapah Siddharth Gupta Sita Paudel Debopam Samanta Louis T. Dang Paul R. Carney Sunil Naik |
| author_sort | Zahra Zhu |
| collection | DOAJ |
| description | Background: Pathogenic variants in SCN1B, the gene encoding voltage-gated sodium channel b1/b1B subunits are associated with a spectrum of epileptic disorders. This study describes a child with early myoclonic encephalopathy and a compound heterozygous variant in the SCN1B gene (p.Arg85Cys and c.3G>C/p.Met1), along with the child’s clinical response to anti-seizure medications (ASMs) and the ketogenic diet. We reviewed the current clinical literature pertinent to SCN1B-related epilepsy. Methods: We described the evaluation and management of a patient with SCN1B-related developmental and epileptic encephalopathy (DEE). We used the Medline and Pubmed databases to review the various neurological manifestations associated with SCN1B genetic variants, and summarize the functional studies performed on SCN1B variants. Results: We identified 20 families and six individuals (including the index case described herein) reported to have SCN1B-related epilepsy. Individuals with monoallelic pathogenic variants in SCN1B often present with genetic epilepsy with febrile seizures plus (GEFS+), while those with biallelic pathogenic variants may present with developmental and epileptic encephalopathy (DEE). Individuals with DEE present with seizures of various semiologies (commonly myoclonic seizures) and status epilepticus at early infancy and are treated with various antiseizure medications. In our index case, adjunctive fenfluramine was started at 8 months of age at 0.2 mg/kg/day with gradual incremental increases to the final dose of 0.7 mg/kg/day over 5 weeks. Fenfluramine was effective in the treatment of seizures, resulting in a 50% reduction in myoclonic seizures, status epilepticus, and generalized tonic-clonic seizures, as well as a 70–90% reduction in focal seizures, with no significant adverse effects. Following the initiation of fenfluramine at eight months of age, there was also a 50% reduction in the rate of hospitalizations. Conclusions: SCN1B pathogenic variants cause epilepsy and neurodevelopmental impairment with variable expressivity and incomplete penetrance. The severity of disease is associated with the zygosity of the pathogenic variants. Biallelic variants in <i>SCN1B</i> can result in early myoclonic encephalopathy, and adjunctive treatment with fenfluramine may be an effective treatment for <i>SCN1B</i>-related DEE. Further research on the efficacy and safety of using newer ASMs, such as fenfluramine in patients under the age of 2 years is needed. |
| first_indexed | 2024-03-09T20:27:17Z |
| format | Article |
| id | doaj.art-79243c825fe54e0282ed86f278cbacef |
| institution | Directory Open Access Journal |
| issn | 2227-9067 |
| language | English |
| last_indexed | 2024-03-09T20:27:17Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Children |
| spelling | doaj.art-79243c825fe54e0282ed86f278cbacef2023-11-23T23:32:06ZengMDPI AGChildren2227-90672022-10-01910150710.3390/children9101507SCN1B Genetic Variants: A Review of the Spectrum of Clinical Phenotypes and a Report of Early Myoclonic EncephalopathyZahra Zhu0Elizabeth Bolt1Kyra Newmaster2Wendy Osei-Bonsu3Stacey Cohen4Vishnu Anand Cuddapah5Siddharth Gupta6Sita Paudel7Debopam Samanta8Louis T. Dang9Paul R. Carney10Sunil Naik11College of Medicine, Penn State University, Hershey, PA 17033, USACollege of Medicine, Penn State University, Hershey, PA 17033, USACollege of Medicine, Penn State University, Hershey, PA 17033, USACollege of Medicine, Penn State University, Hershey, PA 17033, USAEpilepsy Neurogenetics Initiative, Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USAEpilepsy Neurogenetics Initiative, Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USAKennedy Krieger Institute, Department of Neurology, Johns Hopkins University, Baltimore, MD 21218, USADepartment of Pediatrics and Neurology, Penn State Health Milton Hershey Medical Center, Hershey, PA 17033, USADivision of Pediatric Neurology, Arkansas Children’s Hospital, Little Rock, AR 72202, USADepartment of Pediatrics, Division of Pediatric Neurology, University of Michigan Medical School, Ann Arbor, MI 48109, USAPediatric Neurology Division, University of Missouri Health Care, Columbia, MO 65212, USADepartment of Pediatrics and Neurology, Penn State Health Milton Hershey Medical Center, Hershey, PA 17033, USABackground: Pathogenic variants in SCN1B, the gene encoding voltage-gated sodium channel b1/b1B subunits are associated with a spectrum of epileptic disorders. This study describes a child with early myoclonic encephalopathy and a compound heterozygous variant in the SCN1B gene (p.Arg85Cys and c.3G>C/p.Met1), along with the child’s clinical response to anti-seizure medications (ASMs) and the ketogenic diet. We reviewed the current clinical literature pertinent to SCN1B-related epilepsy. Methods: We described the evaluation and management of a patient with SCN1B-related developmental and epileptic encephalopathy (DEE). We used the Medline and Pubmed databases to review the various neurological manifestations associated with SCN1B genetic variants, and summarize the functional studies performed on SCN1B variants. Results: We identified 20 families and six individuals (including the index case described herein) reported to have SCN1B-related epilepsy. Individuals with monoallelic pathogenic variants in SCN1B often present with genetic epilepsy with febrile seizures plus (GEFS+), while those with biallelic pathogenic variants may present with developmental and epileptic encephalopathy (DEE). Individuals with DEE present with seizures of various semiologies (commonly myoclonic seizures) and status epilepticus at early infancy and are treated with various antiseizure medications. In our index case, adjunctive fenfluramine was started at 8 months of age at 0.2 mg/kg/day with gradual incremental increases to the final dose of 0.7 mg/kg/day over 5 weeks. Fenfluramine was effective in the treatment of seizures, resulting in a 50% reduction in myoclonic seizures, status epilepticus, and generalized tonic-clonic seizures, as well as a 70–90% reduction in focal seizures, with no significant adverse effects. Following the initiation of fenfluramine at eight months of age, there was also a 50% reduction in the rate of hospitalizations. Conclusions: SCN1B pathogenic variants cause epilepsy and neurodevelopmental impairment with variable expressivity and incomplete penetrance. The severity of disease is associated with the zygosity of the pathogenic variants. Biallelic variants in <i>SCN1B</i> can result in early myoclonic encephalopathy, and adjunctive treatment with fenfluramine may be an effective treatment for <i>SCN1B</i>-related DEE. Further research on the efficacy and safety of using newer ASMs, such as fenfluramine in patients under the age of 2 years is needed.https://www.mdpi.com/2227-9067/9/10/1507SCN1Bvoltage-gated sodium channel beta-1Dravet-like syndromeDEEEMEfenfluramine |
| spellingShingle | Zahra Zhu Elizabeth Bolt Kyra Newmaster Wendy Osei-Bonsu Stacey Cohen Vishnu Anand Cuddapah Siddharth Gupta Sita Paudel Debopam Samanta Louis T. Dang Paul R. Carney Sunil Naik SCN1B Genetic Variants: A Review of the Spectrum of Clinical Phenotypes and a Report of Early Myoclonic Encephalopathy Children SCN1B voltage-gated sodium channel beta-1 Dravet-like syndrome DEE EME fenfluramine |
| title | SCN1B Genetic Variants: A Review of the Spectrum of Clinical Phenotypes and a Report of Early Myoclonic Encephalopathy |
| title_full | SCN1B Genetic Variants: A Review of the Spectrum of Clinical Phenotypes and a Report of Early Myoclonic Encephalopathy |
| title_fullStr | SCN1B Genetic Variants: A Review of the Spectrum of Clinical Phenotypes and a Report of Early Myoclonic Encephalopathy |
| title_full_unstemmed | SCN1B Genetic Variants: A Review of the Spectrum of Clinical Phenotypes and a Report of Early Myoclonic Encephalopathy |
| title_short | SCN1B Genetic Variants: A Review of the Spectrum of Clinical Phenotypes and a Report of Early Myoclonic Encephalopathy |
| title_sort | scn1b genetic variants a review of the spectrum of clinical phenotypes and a report of early myoclonic encephalopathy |
| topic | SCN1B voltage-gated sodium channel beta-1 Dravet-like syndrome DEE EME fenfluramine |
| url | https://www.mdpi.com/2227-9067/9/10/1507 |
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